Study on perfume stimulating olfaction with volatile oil of Acorus gramineus for treatment of the Alzheimer's disease rat.

PubMed

Liu, Zhi-Bin; Niu, Wen-Min; Yang, Xiao-Hang; Wang, Yuan; Wang, Wei-Gang

2010-12-01

To probe into the therapeutic effect of perfume stimulating olfaction with volatile oil of Acorus Gramineus on the Alzheimer's disease (AD) rat. Totally 50 adult SD rats, male,weighing 300 +/- 10 g, were randomly divided into 5 groups, normal group (group A), olfactory nerve severing model group (group B), AD model group (group C), AD model plus perfume stimulation group (group D), AD model olfactory nerve severing plus perfume stimulation group (group E), 10 rats in each group. After perfume stimulation, Morris maze test was conducted for valuating the learning and memory ability; Malondaldehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain, and the brain weight were detected. Compared with the AD model group, the average escape latency and swimming distance in 6 days were significantly shorter than those in the group A, B, D (P < 0.01), with no significant differences between the group C and the group E (P > 0.05); Compared with the group A, B and D, MDA content in the group C significantly increased (P < 0.01), and SOD and GSH-Px activities significantly decreased (P < 0.01), and brain weight/body weight decreased significantly in the group C (P < 0.01), with no significant differences between the group C and the group E (P > 0.05). Perfume stimultating olfaction with volatile oil of Acorus Gramineus can significantly increase the learning-memory ability, decrease MDA content and increase SOD and GSH-Px activities and weight of brain in AD rats.

Destruction of white matter integrity in patients with mild cognitive impairment and Alzheimer disease.

PubMed

Sun, Xiaoyan; Salat, David; Upchurch, Kristen; Deason, Rebecca; Kowall, Neil; Budson, Andrew

2014-10-01

Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD). The aim of this research was to study the microstructural integrity of white matter in AD in vivo. Global fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer's Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups. Compared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally. The radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD.

When Cognitive Decline and Depression Coexist in the Elderly: CSF Biomarkers Analysis Can Differentiate Alzheimer's Disease from Late-Life Depression.

PubMed

Liguori, Claudio; Pierantozzi, Mariangela; Chiaravalloti, Agostino; Sancesario, Giulia M; Mercuri, Nicola B; Franchini, Flaminia; Schillaci, Orazio; Sancesario, Giuseppe

2018-01-01

Late-life depression (LLD) and Alzheimer's Disease (AD) are the two most frequent neuropsychiatric disorders affecting elderly. LLD and AD may clinically present with depressive and cognitive symptoms. Therefore, when cognitive decline is coupled with depression in the elderly, the differential diagnosis between LLD and AD could be challenging. The aim of the present study was to evaluate in a population of elderly patients affected by depression and dementia the usefulness of CSF AD biomarkers (tau proteins and β-amyloid 42 -Aβ 42 ) and 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (18FFDG-PET) in early differentiating LLD from AD. Two hundred and fifty-six depressed and demented patients, after performing CSF AD biomarkers and 18FFDG-PET, were distributed in two groups on the basis of the current diagnostic guidelines for AD ( n = 201) and LLD ( n = 55). Patients were then observed for 2 years to verify the early diagnosis. After the 2 year follow-up we compared AD and LLD patients' CSF and 18FFDG-PET data obtained at baseline to a group of age- and sex-matched controls. We found CSF Aβ 42 levels significantly higher in LLD compared to AD patients. Remarkably, CSF Aβ 42 levels of LLD patients (range between 550 and 1204 pg/mL) did not overlap with those of AD patients (range between 82 and 528 pg/mL). Moreover, we documented no differences in CSF AD biomarkers (Aβ 42 and tau proteins) when comparing LLD patients to controls. In addition, AD patients showed the significant reduction of 18FFDG-PET uptake in temporo-parietal regions compared to both controls and LLD. Conversely, LLD and control groups did not differ at 18FFDG-PET analysis, although LLD patients showed heterogeneous patterns of glucose hypometabolism involving cortical and subcortical brain areas. It is noteworthy that at the end of the clinical follow-up, patients owing to AD group showed the expected significant decline of cognitive performances, whereas patients assigned to LLD group improved cognition as depressive symptoms recovered. Hence, in case of co-existence of cognitive impairment and depression in the elderly, we propose CSF AD biomarkers analysis to early differentiate LLD from AD and properly target the patient's therapeutic strategy and clinical follow-up.

Non-Alzheimer's contributions to dementia and cognitive resilience in The 90+ Study.

PubMed

Robinson, John L; Corrada, Maria M; Kovacs, Gabor G; Dominique, Myrna; Caswell, Carrie; Xie, Sharon X; Lee, Virginia M-Y; Kawas, Claudia H; Trojanowski, John Q

2018-06-18

The diagnosis of Alzheimer's disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue. Logistic regression models-adjusting for age, sex and education-determined the association between each pathology and dementia or between subgroups. 53% had dementia, primarily AD or mixed AD; 23% had cognitive impairment without dementia (CIND); 23% were not impaired. Both AD and non-AD pathology was prevalent. 100% had tangles, 81% had plaques, and both tangles and plaques associated with dementia. ARTAG distributed across limbic (70%), brainstem (39%) and cortical regions (24%). 49% had possible CVD and 26% had definite CVD, while HS was noted in 15%. Cortical ARTAG, CVD and HS were each associated with dementia, but limbic and brainstem ARTAGs were not. TDP-43 and Lewy pathologies were found in 36 and 17% and both associated with dementia. No pathology distinguished CIND and the not impaired. By NIA-AA criteria and dementia status, the cohort was subdivided into four groups: those with minimal ADNPC included the not dementia (ND) and Not AD dementia groups; and those with significant ADNPC included the Resilient without dementia and AD dementia groups. Compared to the ND group, the Not AD dementia group had more HS, cortical ARTAG, TDP-43, and Lewy pathology. Compared to the AD dementia group, the Resilient group had less CVD, no HS and less cortical ARTAG, TDP-43 and Lewy pathology. Our findings imply that reductions in non-AD pathologies including CVD contribute to cognitive resilience in the oldest-old.

Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study.

PubMed

Le Heron, Campbell J; Wright, Sarah L; Melzer, Tracy R; Myall, Daniel J; MacAskill, Michael R; Livingston, Leslie; Keenan, Ross J; Watts, Richard; Dalrymple-Alford, John C; Anderson, Tim J

2014-06-01

Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD

Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.

PubMed

Kang, Suna; Moon, Na Rang; Kim, Da Sol; Kim, Sung Hoon; Park, Sunmin

2015-09-01

Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups, whereas during the second part it was suppressed in AD-G as much as Non-AD. In conclusion, central acylated ghrelin in rats prevented the deterioration of memory function, and energy and glucose metabolisms were partially improved, possibly due to less β-amyloid accumulation. This research suggests that interventions such as intermittent fasting to facilitate sustained elevations of acyl-ghrelin should be investigated for cognitive and metabolic benefits, especially in person with early symptoms of memory impairment. Copyright © 2015 Elsevier Inc. All rights reserved.

The relationship of cardiovascular risk factors to Alzheimer disease in Choctaw Indians.

PubMed

Weiner, Myron F; Hynan, Linda S; Rossetti, Heidi; Womack, Kyle B; Rosenberg, Roger N; Gong, Yun-Hua; Qu, Bao-Xi

2011-05-01

To test the hypothesis that cardiovascular risk factors (CRFs) influence predisposition to and the clinical course of Alzheimer disease (AD), the authors compared Choctaw Indians, a group with known high CRF with white persons with AD. In addition to CRF history, the authors investigated the frequency of apolipoprotein E4 (apoE4) genotype andplasma homocysteine (HC) levels. The authors compared 39 Choctaw Indians with AD and 39 Choctaw Indians without AD to 39 white persons with AD with all groups similar in age. CRF history included diabetes, hypertension, high cholesterol or hypolipidemic agent use, or myocardial infarction. The authors also compared plasma HC concentration and apoE4 allele frequency. Choctaw persons with AD differed significantly from white persons with AD in history of hypertension, diabetes, and in HC values but not from Indians without AD. There was a significantly lower apoE4 allele frequency in Choctaw Indian AD than white persons with AD, and both AD groups had an affected first degree relative significantly more often than Indian controls. There was no relationship between the number of CRF and age at onset among Indians or whites, whereas HC concentration was associated with significantly earlier age of onset for Choctaw Indians but not for whites. This small study suggests that in Choctaw Indians modifiable risk factors may play more of a role in disease pathogenesis than in whites and that nonmodifiable risk factors such as apoE4 may play less of a role.

Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults.

PubMed

Berti, Valentina; Walters, Michelle; Sterling, Joanna; Quinn, Crystal G; Logue, Michelle; Andrews, Randolph; Matthews, Dawn C; Osorio, Ricardo S; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S; de Leon, Mony J; Mosconi, Lisa

2018-05-15

To examine in a 3-year brain imaging study the effects of higher vs lower adherence to a Mediterranean-style diet (MeDi) on Alzheimer disease (AD) biomarker changes (brain β-amyloid load via 11 C-Pittsburgh compound B [PiB] PET and neurodegeneration via 18 F-fluorodeoxyglucose [FDG] PET and structural MRI) in midlife. Seventy 30- to 60-year-old cognitively normal participants with clinical, neuropsychological, and dietary examinations and imaging biomarkers at least 2 years apart were examined. These included 34 participants with higher (MeDi+) and 36 with lower (MeDi-) MeDi adherence. Statistical parametric mapping and volumes of interest were used to compare AD biomarkers between groups at cross section and longitudinally. MeDi groups were comparable for clinical and neuropsychological measures. At baseline, compared to the MeDi+ group, the MeDi- group showed reduced FDG-PET glucose metabolism (CMRglc) and higher PiB-PET deposition in AD-affected regions ( p < 0.001). Longitudinally, the MeDi--group showed CMRglc declines and PiB increases in these regions, which were greater than those in the MeDi+ group ( p interaction < 0.001). No effects were observed on MRI. Higher MeDi adherence was estimated to provide 1.5 to 3.5 years of protection against AD. Lower MeDi adherence was associated with progressive AD biomarker abnormalities in middle-aged adults. These data support further investigation of dietary interventions for protection against brain aging and AD. © 2018 American Academy of Neurology.

Neuropsychological Profiles Differentiate Alzheimer Disease from Subcortical Ischemic Vascular Dementia in an Autopsy-Defined Cohort.

PubMed

Ramirez-Gomez, Liliana; Zheng, Ling; Reed, Bruce; Kramer, Joel; Mungas, Dan; Zarow, Chris; Vinters, Harry; Ringman, John M; Chui, Helena

2017-01-01

The aim of this study was to assess the ability of neuropsychological tests to differentiate autopsy-defined Alzheimer disease (AD) from subcortical ischemic vascular dementia (SIVD). From a sample of 175 cases followed longitudinally that underwent autopsy, we selected 23 normal controls (NC), 20 SIVD, 69 AD, and 10 mixed cases of dementia. Baseline neuropsychological tests, including Memory Assessment Scale word list learning test, control oral word association test, and animal fluency, were compared between the three autopsy-defined groups. The NC, SIVD, and AD groups did not differ by age or education. The SIVD and AD groups did not differ by the Global Clinical Dementia Rating Scale. Subjects with AD performed worse on delayed recall (p < 0.01). A receiver operating characteristics analysis comparing the SIVD and AD groups including age, education, difference between categorical (animals) versus phonemic fluency (letter F), and the first recall from the word learning test distinguished the two groups with a sensitivity of 85%, specificity of 67%, and positive likelihood ratio of 2.57 (AUC = 0.789, 95% CI 0.69-0.88, p < 0.0001). In neuropathologically defined subgroups, neuropsychological profiles have modest ability to distinguish patients with AD from those with SIVD. © 2017 S. Karger AG, Basel.

Neuropsychological Profiles Differentiate Alzheimer Disease from Subcortical Ischemic Vascular Dementia in an Autopsy-Defined Cohort

PubMed Central

Ramirez-Gomez, Liliana; Zheng, Ling; Reed, Bruce; Kramer, Joel; Mungas, Dan; Zarow, Chris; Vinters, Harry; Ringman, John M.; Chui, Helena

2018-01-01

Background/Aims The aim of this study was to assess the ability of neuropsychological tests to differentiate autopsy-defined Alzheimer disease (AD) from subcortical ischemic vascular dementia (SIVD). Methods From a sample of 175 cases followed longitudinally that underwent autopsy, we selected 23 normal controls (NC), 20 SIVD, 69 AD, and 10 mixed cases of dementia. Baseline neuropsychological tests, including Memory Assessment Scale word list learning test, control oral word association test, and animal fluency, were compared between the three autopsy-defined groups. Results The NC, SIVD, and AD groups did not differ by age or education. The SIVD and AD groups did not differ by the Global Clinical Dementia Rating Scale. Subjects with AD performed worse on delayed recall (p < 0.01). A receiver operating characteristics analysis comparing the SIVD and AD groups including age, education, difference between categorical (animals) versus phonemic fluency (letter F), and the first recall from the word learning test distinguished the two groups with a sensitivity of 85%, specificity of 67%, and positive likelihood ratio of 2.57 (AUC = 0.789, 95% CI 0.69–0.88, p < 0.0001). Conclusion In neuropathologically defined subgroups, neuropsychological profiles have modest ability to distinguish patients with AD from those with SIVD. PMID:28595184

Meal pattern alterations associated with intermittent fasting for weight loss are normalized after high-fat diet re-feeding.

PubMed

Gotthardt, Juliet D; Bello, Nicholas T

2017-05-15

Alternate day, intermittent fasting (IMF) can be an effective weight loss strategy. However, the effects of IMF on eating behaviors are not well characterized. We investigated the acute and residual effects of IMF for weight loss on meal patterns in adult obese male C57BL/6 mice. After 8weeks of ad libitum high-fat diet to induce diet-induced obesity (DIO), mice were either continued on ad libitum high-fat diet (HFD) or placed on one of 5 diet strategies for weight loss: IMF of high-fat diet (IMF-HFD), pair-fed to IMF-HFD group (PF-HFD), ad libitum low-fat diet (LFD), IMF of low-fat diet (IMF-LFD), or pair-fed to IMF-LFD group (PF-LFD). After the 4-week diet period, all groups were refed the high-fat diet for 6weeks. By the end of the diet period, all 5 groups had lost weight compared with HFD group, but after 6weeks of HFD re-feeding all groups had similar body weights. On (Day 2) of the diet period, IMF-HFD had greater first meal size and faster eating rate compared with HFD. Also, first meal duration was greater in LFD and IMF-LFD compared with HFD. At the end of the diet period (Day 28), the intermittent fasting groups (IMF-HFD and IMF-LFD) had greater first meal sizes and faster first meal eating rate compared with their respective ad libitum fed groups on similar diets (HFD and LFD). Also, average meal duration was longer on Day 28 in the low-fat diet groups (LFD and IMF-LFD) compared with high-fat diet groups (HFD and IMF-HFD). After 6weeks of HFD re-feeding (Day 70), there were no differences in meal patterns in groups that had previously experienced intermittent fasting compared with ad libitum fed groups. These findings suggest that meal patterns are only transiently altered during alternate day intermittent fasting for weight loss in obese male mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparing the driving behaviours of individuals with frontotemporal lobar degeneration and those with Alzheimer's disease.

PubMed

Fujito, Ryoko; Kamimura, Naoto; Ikeda, Manabu; Koyama, Asuka; Shimodera, Shinji; Morinobu, Shigeru; Inoue, Shimpei

2016-01-01

Assessing driving aptitude in dementia patients is critically important for both patient and public safety. However, there have been only a few reports on the driving behaviours and accident risk of patients with dementia, especially frontotemporal lobar degeneration (FTLD). Therefore, we compared the characteristics of driving behaviours in patients with FTLD and those with Alzheimer's disease (AD). The subjects were 28 FTLD and 67 AD patients who visited the Department of Psychiatry, Kochi Medical School Hospital. We conducted semi-structured interviews with their families and caregivers about traffic accident history and changes in patient driving behaviours after dementia onset and then compared the findings between the two groups. Overall changes in driving behaviours were reported in 89% (25/28) and 76% (51/67) of the FTLD and AD patients, respectively (P = 0.17). In the FTLD group, difficulty in judging inter-vehicle distances, ignoring road signs and traffic signals, and distraction were reported in 50% (14/28), 61% (17/28), and 50% (14/28) of patients, respectively, and 75% (21/28) patients had caused a traffic accident after dementia onset. The risk of causing an accident was higher in the FTLD group than in the AD group (odds ratio = 10.4, 95% confidence interval = 3.7-29.1). In addition, the mean duration between dementia onset and a traffic accident was 1.35 years in the FTLD group compared with 3.0 years in the AD group (P < 0.01). Patients with FTLD were more likely to show dangerous driving behaviours than those with AD, and the risk of causing a traffic accident may be higher in patients with FTLD from an early disease stage. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

Imaging discrepancies between magnetic resonance imaging and brain perfusion single-photon emission computed tomography in the diagnosis of Alzheimer's disease, and verification with amyloid positron emission tomography.

PubMed

Yokoyama, Shunichi; Kajiya, Yoriko; Yoshinaga, Takuma; Tani, Atsushi; Hirano, Hirofumi

2014-06-01

In the diagnosis of Alzheimer's disease (AD), discrepancies are often observed between magnetic resonance imaging (MRI) and brain perfusion single-photon emission computed tomography (SPECT) findings. MRI, brain perfusion SPECT, and amyloid positron emission tomography (PET) findings were compared in patients with mild cognitive impairment or early AD to clarify the discrepancies between imaging modalities. Several imaging markers were investigated, including the cortical average standardized uptake value ratio on amyloid PET, the Z-score of a voxel-based specific regional analysis system for AD on MRI, periventricular hyperintensity grade, deep white matter hyperintense signal grade, number of microbleeds, and three indicators of the easy Z-score imaging system for a specific SPECT volume-of-interest analysis. Based on the results of the regional analysis and the three indicators, we classified patients into four groups and then compared the results of amyloid PET, periventricular hyperintensity grade, deep white matter hyperintense signal grade, and the numbers of microbleeds among the groups. The amyloid deposition was the highest in the group that presented typical AD findings on both the regional analysis and the three indicators. The two groups that showed an imaging discrepancy between the regional analysis and the three indicators demonstrated intermediate amyloid deposition findings compared with the typical and atypical groups. The patients who showed hippocampal atrophy on the regional analysis and atypical AD findings using the three indicators were approximately 60% amyloid-negative. The mean periventricular hyperintensity grade was highest in the typical group. Patients showing discrepancies between MRI and SPECT demonstrated intermediate amyloid deposition findings compared with patients who showed typical or atypical findings. Strong white matter signal abnormalities on MRI in patients who presented typical AD findings provided further evidence for the involvement of vascular factors in AD. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

Study of amyloid-β peptide functional brain networks in AD, MCI and HC.

PubMed

Jiang, Jiehui; Duan, Huoqiang; Huang, Zheming; Yu, Zhihua

2015-01-01

One medical challenge in studying the amyloid-β (Aβ) peptide mechanism for Alzheimer's disease (AD) is exploring the law of beta toxic oligomers' diffusion in human brains in vivo. One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD.

Over-representation of the APOE*4 allele in autopsy confirmed early- and late-onset sporadic Alzheimer`s disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamboh, M.I.; DeKosky, S.T.; Ferrell, R.E.

1994-09-01

Apolipoprotein E binds to {beta}-amyloid peptide in senile plaques and neurofibrillary tangles in Alzheimer`s disease (AD). Recent studies have identified the APOE*4 allele as a major predisposing genetic factor for late-onset familial AD as well as in sporadic AD. Most of these association studies are based on clinically diagnosed AD cases with little data available on autopsy confirmed, definite AD. To characterize the distribution of APOE polymorphism in autopsy confirmed sporadic AD cases, we determined APOE genotypes in 111 DNA samples (aged 51-101 years) extracted from brain tissues which were available from the University of Pittsburgh Alzheimer`s Disease Research Center.more » The APOE data was compared between the AD group and 3 samples of population controls from Western Pennsylvania consisting of a young cohort (N=473, aged 18-48 years), middle cohort (N=473, aged 42-50 years) and an old cohort (N=870, aged 65-90 years). The frequency of the APOE*4 allele was similar in the young and middle cohorts (0.12) and slightly lower in the old cohort (0.10). However, the frequency of the APOE*4 allele was three times higher in both early-onset (<65 years; 0.36) and late-onset ({ge}65 years; 0.38) sporadic AD cases compared to the control groups (p<0.0001). In the AD cohort the frequency of the APOE*4 allele was similar across all age groups (<65, 65-75, 76-85, 86+) and so was in men and women (0.40 vs. 0.37). The E*4 homozygosity was observed in 18% of AD cases compared to 1% in each of the three control groups. The E*4 heterozygosity was present in 50% of AD cases compared to 17% in the control old cohort and 22% in both the young and middle control cohorts. These data confirm that the APOE*4 allele is a major risk factor for AD regardless of age-at-diagnosis or family history.« less

Effects of task-irrelevant emotional stimuli on working memory processes in mild cognitive impairment.

PubMed

Berger, Christoph; Erbe, Anna-Katharina; Ehlers, Inga; Marx, Ivo; Hauenstein, Karlheinz; Teipel, Stefan

2015-01-01

Research suggests generally impaired cognitive control functions in working memory (WM) processes in amnestic mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). Little is known how emotional salience of task-irrelevant stimuli may modulate cognitive control of WM performance and neurofunctional activation in MCI and AD individuals. We investigated the impact of emotional task-irrelevant visual stimuli on cortical activation during verbal WM. Twelve AD/MCI individuals and 12 age-matched healthy individuals performed a verbal WM (nback-) task with task-irrelevant emotionally neutral and emotionally negative background pictures during fMRI measurement. AD/MCI individuals showed decreased WM performance compared with controls; both AD/MCI and control groups reacted slower during presentation of negative pictures, regardless of WM difficulty. The AD/MCI group showed increased activation in the left hemispheric prefrontal network, higher amygdala and less cerebellar activation with increasing WM task difficulty compared to healthy controls. Correlation analysis between neurofunctional activation and WM performance revealed a negative correlation between task sensitivity and activation in the dorsal anterior cingulum for the healthy controls but not for the AD/MCI group. Our data suggest compensatory activation in prefrontal cortex and amygdala, but also dysfunctional inhibition of distracting information in the AD/MCI group during higher WM task difficulty. Additionally, attentional processes affecting the correlation between WM performance and neurofunctional activation seem to be different between incipient AD and healthy aging.

Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease.

PubMed

Mosconi, L; Mistur, R; Switalski, R; Brys, M; Glodzik, L; Rich, K; Pirraglia, E; Tsui, W; De Santi, S; de Leon, M J

2009-02-10

At cross-section, cognitively normal individuals (NL) with a maternal history of late-onset Alzheimer disease (AD) have reduced glucose metabolism (CMRglc) on FDG-PET in the same brain regions as patients with clinical AD as compared to those with a paternal and a negative family history (FH) of AD. This longitudinal FDG-PET study examines whether CMRglc reductions in NL subjects with a maternal history of AD are progressive. Seventy-five 50- to 82-year-old NL received 2-year follow-up clinical, neuropsychological, and FDG-PET examinations. These included 37 subjects with negative family history of AD (FH-), 9 with paternal (FHp), and 20 with maternal AD (FHm). Two subjects had parents with postmortem confirmed AD. Statistical parametric mapping was used to compare CMRglc across FH groups at baseline, follow-up, and longitudinally. At both time points, the FH groups were comparable for demographic and neuropsychological characteristics. At baseline and at follow-up, FHm subjects showed CMRglc reductions in the parieto-temporal, posterior cingulate, and medial temporal cortices as compared to FH- and FHp (p < 0.001). Longitudinally, FHm had significant CMRglc declines in these regions, which were significantly greater than those in FH- and FHp (p < 0.05). A maternal history of Alzheimer disease (AD) predisposes normal individuals to progressive CMRglc reductions in AD-vulnerable brain regions, which may be related to a higher risk for developing AD.

Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor (BDNF) tohuman umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) promotescrush-injured rat sciatic nerve regeneration.

PubMed

Hei, Wei-Hong; Almansoori, Akram A; Sung, Mi-Ae; Ju, Kyung-Won; Seo, Nari; Lee, Sung-Ho; Kim, Bong-Ju; Kim, Soung-Min; Jahng, Jeong Won; He, Hong; Lee, Jong-Ho

2017-03-16

This study was designed toinvestigate the efficacy of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) in a rat sciatic nerve crush injury model. BDNF protein and mRNA expression after infection was checked through an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Male Sprague-Dawley rats (200-250g, 6 weeks old) were distributed into threegroups (n=20 each): the control group, UCB-MSC group, and BDNF-adenovirus infected UCB-MSC (BDNF-Ad+UCB-MSC) group. UCB-MSCs (1×10 6 cells/10μl/rat) or BDNF-Ad+UCB-MSCs (1×10 6 cells/10μl/rat)were transplantedinto the rats at the crush site immediately after sciatic nerve injury. Cell tracking was done with PKH26-labeled UCB-MSCs and BDNF-Ad+UCB-MSCs (1×10 6 cells/10μl/rat). The rats were monitored for 4 weeks post-surgery. Results showed that expression of BDNF at both the protein and mRNA levels was higher inthe BDNF-Ad+UCB-MSC group compared to theUCB-MSC group in vitro.Moreover, BDNF mRNA expression was higher in both UCB-MSC group and BDNF-Ad+ UCB-MSC group compared tothe control group, and BDNF mRNA expression in theBDNF-Ad+UCB-MSC group was higher than inboth other groups 5days after surgeryin vivo. Labeled neurons in the dorsal root ganglia (DRG), axon counts, axon density, and sciatic function index were significantly increased in the UCB-MSC and BDNF-Ad+ UCB-MSCgroupscompared to the controlgroup four weeksaftercell transplantation. Importantly,the BDNF-Ad+UCB-MSCgroup exhibited more peripheral nerve regeneration than the other two groups.Our results indicate thatboth UCB-MSCs and BDNF-Ad+UCB-MSCscan improve rat sciatic nerve regeneration, with BDNF-Ad+UCB-MSCsshowing a greater effectthan UCB-MSCs. Copyright © 2017 Elsevier B.V. All rights reserved.

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer's and Parkinson's Diseases.

PubMed

Scharre, Douglas W; Chang, Shu-Ing; Nagaraja, Haikady N; Park, Ariane; Adeli, Anahita; Agrawal, Punit; Kloos, Anne; Kegelmeyer, Deb; Linder, Shannon; Fritz, Nora; Kostyk, Sandra K; Kataki, Maria

2016-10-04

Limited data compares clinical profiles of Lewy Body Dementia (LBD) with Alzheimer's disease (AD) and Parkinson's disease (PD). Twenty-one mildly demented ambulatory LBD subjects were individually matched by MMSE score with 21 AD subjects and by UPDRS motor score with 21 PD subjects. Matched by age, gender, education, and race, pairs were compared using cognitive, functional, behavioral, and motor measures. LBD group performed worse than PD on axial motor, gait, and balance measures. AD had more amnesia and orientation impairments, but less executive and visuospatial deficits than LBD subjects. LBD group had more sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea than AD or PD. Axial motor, gait, and balance disturbances correlated with executive, visuospatial, and global cognition deficits. LBD is differentiated from AD and PD by retrieval memory, visuospatial, and executive deficits; axial motor, gait and balance impairments; sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea.

Ad libitum vs. restricted fluid replacement on hydration and performance of military tasks.

PubMed

Nolte, Heinrich W; Noakes, Timothy D; Nolte, Kim

2013-02-01

The primary objective was to evaluate the effect of ad libitum vs. restricted fluid replacement protocol on hydration markers and performance in selected military tasks. The secondary objective was to determine if 300 ml x h(-1) could be considered a safe minimum fluid intake under the experimental conditions. Data were collected simulating a route march over 16 km. There were 57 subjects who participated in the study. The mean pre-exercise body mass of the ad libitum group was 70.4 +/- 13.3 (SD) kg compared to 69.3 +/- 8.9 kg in the restricted group. The mean total fluid intake of the ad libitum group was 2.1 +/- 0.9 L compared to 1.2 +/- 0.0 L in the restricted group. The ad libitum and restricted intake groups, respectively, lost a mean of 1.05 kg +/- 0.77 (1.5%) and 1.34 kg +/- 0.37 (1.9%). Calculated sweat rate was 608 +/- 93 ml x h(-1) compared to 762 +/- 162 ml x h(-1) in the ad libitum group. There were no significant differences for either urine specific gravity (USG) or urine osmolality (UOsm) before or after the exercise. It is not clear whether fluid intake and calculated sweat rates are causally related or explained by their codependence on a third variable; for example, the exercising metabolic rate. Thus, 300 ml x h(-1) intake could be considered a current safe minimum water intake for soldiers of similar mass under similar experimental conditions, namely similar exercise durations at equivalent exercise intensities in a moderate, dry climate.

Hyperdynamic CSF motion profiles found in idiopathic normal pressure hydrocephalus and Alzheimer's disease assessed by fluid mechanics derived from magnetic resonance images.

PubMed

Takizawa, Ken; Matsumae, Mitsunori; Hayashi, Naokazu; Hirayama, Akihiro; Yatsushiro, Satoshi; Kuroda, Kagayaki

2017-10-18

Magnetic resonance imaging (MRI) does not only ascertain morphological features, but also measures physiological properties such as fluid velocity or pressure gradient. The purpose of this study was to investigate cerebrospinal fluid (CSF) dynamics in patients with morphological abnormalities such as enlarged brain ventricles and subarachnoid spaces. We used a time-resolved three dimensional phase contrast (3D-PC) MRI technique to quantitatively evaluate CSF dynamics in the Sylvian aqueduct of healthy elderly individuals and patients with either idiopathic normal pressure hydrocephalus (iNPH) or Alzheimer's disease (AD) presenting with ventricular enlargement. Nineteen healthy elderly individuals, ten iNPH patients, and seven AD patients (all subjects ≥ 60 years old) were retrospectively evaluated 3D-PC MRI. The CSF velocity, pressure gradient, and rotation in the Sylvian aqueduct were quantified and compared between the three groups using Kolmogorov-Smirnov and Mann-Whitney U tests. There was no statistically significant difference in velocity among the three groups. The pressure gradient was not significantly different between the iNPH and AD groups, but was significantly different between the iNPH group and the healthy controls (p < 0.001), and similarly, between the AD group and the healthy controls (p < 0.001). Rotation was not significantly different between the iNPH and AD groups, but was significantly different between the iNPH group and healthy controls (p < 0.001), and similarly, between the AD group and the healthy controls (p < 0.001). Quantitative analysis of CSF dynamics with time resolved 3D-PC MRI revealed differences and similarities in the Sylvian aqueduct between healthy elderly individuals, iNPH patients, and AD patients. The results showed that CSF motion is in a hyperdynamic state in both iNPH and AD patient groups compared to healthy elderly individuals, and that iNPH patients and AD patients display similar CSF motion profiles.

Symptoms, visual function, and mucin expression of eyes with tear film instability.

PubMed

Shimazaki-Den, Seika; Dogru, Murat; Higa, Kazunari; Shimazaki, Jun

2013-09-01

We examined symptoms, tear stability, visual function, and conjunctival cytology in eyes with an unstable tear film (UTF), expressed as a short tear film breakup time without epithelial damage or low tear secretion, and compared the results with those from eyes with aqueous deficiency (AD) associated with epithelial damage, and healthy eyes. We divided the patients with ocular discomfort into 2 groups according to the breakup time, Schirmer value, and epithelial staining score: UTF group (≤5 seconds, >5 mm, and <3 points; 21 eyes of 21 patients) and AD group (≤5 seconds, ≤5 mm, and ≥3 points; 21 eyes of 21 patients). We examined all patients and 17 healthy subjects for symptoms, tear functions, tear film stability by tear film lipid layer interferometry and tear film analysis system, and functional visual acuity. Conjunctival impression cytology was performed to investigate changes in goblet cell density, squamous metaplasia, and messenger RNA expression of MUC5AC and MUC16. The symptom scores, tear film analysis system index, and functional visual acuity testing were significantly worse in the UTF and AD groups compared with those in the control group (P < 0.05). The messenger RNA expression levels of MUC5AC and MUC16 were significantly lower in UTF and AD eyes compared with those in the control eyes (P < 0.0001). An UTF itself can cause dry eye symptoms and visual disturbance comparable with those of AD dry eyes.

Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

PubMed Central

Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

2008-01-01

Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies. PMID:18669512

Analysis of the posterior cingulate cortex with [18F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods.

PubMed

Coutinho, Artur M N; Porto, Fábio H G; Zampieri, Poliana F; Otaduy, Maria C; Perroco, Tíbor R; Oliveira, Maira O; Nunes, Rafael F; Pinheiro, Toulouse Leusin; Bottino, Cassio M C; Leite, Claudia C; Buchpiguel, Carlos A

2015-01-01

Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.

Analysis of the posterior cingulate cortex with [18F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods

PubMed Central

Coutinho, Artur M.N.; Porto, Fábio H.G.; Zampieri, Poliana F.; Otaduy, Maria C.; Perroco, Tíbor R.; Oliveira, Maira O.; Nunes, Rafael F.; Pinheiro, Toulouse Leusin; Bottino, Cassio M.C.; Leite, Claudia C.; Buchpiguel, Carlos A.

2015-01-01

Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. Objective To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. Methods Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. Results The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. Conclusion rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls. PMID:29213988

Higher education affects accelerated cortical thinning in Alzheimer's disease: a 5-year preliminary longitudinal study.

PubMed

Cho, Hanna; Jeon, Seun; Kim, Changsoo; Ye, Byoung Seok; Kim, Geon Ha; Noh, Young; Kim, Hee Jin; Yoon, Cindy W; Kim, Yeo Jin; Kim, Jung-Hyun; Park, Sang Eon; Kim, Sung Tae; Lee, Jong-Min; Kang, Sue J; Suh, Mee Kyung; Chin, Juhee; Na, Duk L; Kang, Dae Ryong; Seo, Sang Won

2015-01-01

Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD). We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years). As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD. Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.

Physical activity limits the effects of age and Alzheimer's disease on postural control.

PubMed

Debove, Lola; Bru, Noelle; Couderc, Martine; Noé, Frederic; Paillard, Thierry

2017-09-01

The aim was to study the possible influence of physical activity on the postural performance of subjects with Alzheimer's disease (AD). The postural performance (i.e. surface area of the center of foot pressure displacement) of 3 groups was compared: Alzheimer active group (AA), Alzheimer non-active group (ANA) and healthy non-active group (HNA). The AA group's postural performance was superior to that of the ANA and HNA groups. AD disturbed postural performance but participation in regular physical activity made it possible to limit the disturbing effects of AD to a surprising extent, since the postural performance of active AD subjects was also superior to that of healthy subjects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Decline of human tactile angle discrimination in patients with mild cognitive impairment and Alzheimer's disease.

PubMed

Yang, Jiajia; Ogasa, Takashi; Ohta, Yasuyuki; Abe, Koji; Wu, Jinglong

2010-01-01

There is a need to differentiate between patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from normal-aged controls (NC) in the field of clinical drug discovery. In this study, we developed a tactile angle discrimination system and examined whether the ability to discriminate tactile angle differed between patients with MCI and AD and the NC group. Thirty-seven subjects were divided into three groups: NC individuals (n=14); MCI patients (n=10); and probable AD patients (n=13). All subjects were asked to differentiate the relative sizes of the reference angle (60°) and one of eight comparison angles by passive touch. The accuracy of angle discrimination was measured and the discrimination threshold was calculated. We discovered that there were significant differences in the angle discrimination thresholds of AD patients compared to the NC group. Interestingly, we also found that ability to discriminate tactile angle of MCI patients were significantly lower than that of the NC group. This is the first study to report that patients with MCI and AD have substantial performance deficits in tactile angle discrimination compared to the NC individuals. This finding may provide a monitor and therapeutic approach in AD diagnosis and treatment.

Fibrinogen gamma-A chain precursor in CSF: a candidate biomarker for Alzheimer's disease

PubMed Central

Lee, Joung Wook; Namkoong, Hong; Kim, Hyun Kee; Kim, Sanghee; Hwang, Dong Whi; Na, Hae Ri; Ha, Seon-Ah; Kim, Jae-Ryong; Kim, Jin Woo

2007-01-01

Background Cerebrospinal fluid (CSF) may be valuable for exploring protein markers for the diagnosis of Alzheimer's disease (AD). The prospect of early detection and treatment, to slow progression, holds hope for aging populations with increased average lifespan. The aim of the present study was to investigate candidate CSF biological markers in patients with mild cognitive impairment (MCI) and AD and compare them with age-matched normal control subjects. Methods We applied proteomics approaches to analyze CSF samples derived from 27 patients with AD, 3 subjects with MCI and 30 controls. The AD group was subdivided into three groups by clinical severity according to clinical dementia rating (CDR), a well known clinical scale for dementia. Results We demonstrated an elevated level of fibrinogen gamma-A chain precursor protein in CSF from patients with mild cognitive impairment and AD compared to the age-matched normal subjects. Moreover, its expression was more prominent in the AD group than in the MCI and correlated with disease severity and progression. In contrast, fibrinogen gamma-A chain precursor protein was detected very low in the age-matched normal group. Conclusion These findings suggest that the CSF level of fibrinogen gamma-A chain precursor may be a candidate biomarker for AD. PMID:17565664

Adenomatous-Dominant Benign Prostatic Hyperplasia (AdBPH) as a Predictor for Clinical Success Following Prostate Artery Embolization: An Age-Matched Case–Control Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Little, M. W., E-mail: m.little@doctors.org.uk; Boardman, P.; Macdonald, A. C.

PurposeTo investigate the clinical impact of performing prostate artery embolization (PAE) on patients with adenomatous-dominant benign prostatic hyperplasia (AdBPH).Materials and MethodsTwelve patients from the ongoing proSTatic aRtery EmbolizAtion for the treatMent of benign prostatic hyperplasia (STREAM) trial were identified as having AdBPH; defined as two or more adenomas within the central gland of ≥1 cm diameter on multi-parametric MRI (MP-MRI). These patients were age-matched with patients from the STREAM cohort, without AdBPH. Patients were followed up with repeat MP-MRI at 3 months and 1 year. International prostate symptom score (IPSS), international index for erectile function (IIEF), and quality of life assessment from themore » IPSS and EQ-5D-5S questionnaires were recorded pre-PAE and at 6 weeks, 3 months, and 1 year.ResultsThe mean age of patients was 68 (61–76). All patients had PAE as a day-case procedure. The technical success in the cohort was 23/24 (96%). There was a significant reduction in prostate volume following embolization with a median reduction of 34% (30–55) in the AdBPH group, compared to a mean volume reduction of 22% (9–44) in the non-AdBPH group (p = 0.04). There was a significant reduction in IPSS in the AdBPH group following PAE when compared with the control group [AdBPH median IPSS 8 (3–15) vs. non-AdBPH median IPSS 13 (8–18), p = 0.01]. IPSS QOL scores significantly improved in the AdBPH group (p = 0.007). There was no deterioration in sexual function in either group post-PAE.ConclusionsThis is the first time that AdBPH has been identified as being a predictor of clinical success following PAE.« less

Recovery of radiation-induced dry eye and corneal damage by pretreatment with adenoviral vector-mediated transfer of erythropoietin to the salivary glands in mice.

PubMed

Rocha, Eduardo M; Cotrim, Ana P; Zheng, Changyu; Riveros, Paola Perez; Baum, Bruce J; Chiorini, John A

2013-04-01

Therapeutic doses of radiation (RTx) causes dry eye syndrome (DES), dry mouth, and as in other sicca syndromes, they are incurable. The aims of this work are as follows: (a) to evaluate a mouse model of DES induced by clinically relevant doses of radiation, and (b) to evaluate the protective effect of erythropoietin (Epo) in preventing DES. C3H female mice were subjected to five sessions of RTx, with or without pre-RTx retroductal administration of the AdLTR2EF1a-hEPO (AdEpo) vector in the salivary glands (SG), and compared with naïve controls at Day 10 (10d) (8 Gy fractions) and 56 days (56d) (6 Gy fractions) after RTx treatment. Mice were tested for changes in lacrimal glands (LG), tear secretion (phenol red thread), weight, hematocrit (Hct), and markers of inflammation, as well as microvessels and oxidative damage. Tear secretion was reduced in both RTx groups, compared to controls, by 10d. This was also seen at 56d in RTx but not AdEpo+RTx group. Hct was significantly higher in all AdEpo+RTx mice at 10d and 56d. Corneal epithelium was significantly thinner at 10d in the RTx group compared with AdEpo+RTx or the control mice. There was a significant reduction at 10d in vascular endothelial growth factor (VEGF)-R2 in LG in the RTx group that was prevented in the AdEpo+RTx group. In conclusion, RTx is able to induce DES in mice. AdEpo administration protected corneal epithelia and resulted in some recovery of LG function, supporting the value of further studies using gene therapy for extraglandular diseases.

Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial.

PubMed

Dysken, Maurice W; Sano, Mary; Asthana, Sanjay; Vertrees, Julia E; Pallaki, Muralidhar; Llorente, Maria; Love, Susan; Schellenberg, Gerard D; McCarten, J Riley; Malphurs, Julie; Prieto, Susana; Chen, Peijun; Loreck, David J; Trapp, George; Bakshi, Rajbir S; Mintzer, Jacobo E; Heidebrink, Judith L; Vidal-Cardona, Ana; Arroyo, Lillian M; Cruz, Angel R; Zachariah, Sally; Kowall, Neil W; Chopra, Mohit P; Craft, Suzanne; Thielke, Stephen; Turvey, Carolyn L; Woodman, Catherine; Monnell, Kimberly A; Gordon, Kimberly; Tomaska, Julie; Segal, Yoav; Peduzzi, Peter N; Guarino, Peter D

2014-01-01

Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. clinicaltrials.gov Identifier: NCT00235716.

Expression profile of endothelin receptors (ETA and ETB) and microRNAs-155 and -199 in the corpus cavernosum of rats submitted to chronic alcoholism and diabetes mellitus.

PubMed

Gonçalves, F Z; Lizarte Neto, F S; Novais, P C; Gattas, D; Lourenço, L G; de Carvalho, C A M; Tirapelli, D P C; Molina, C A F; Tirapelli, L F; Tucci, S

2018-03-01

Recent evidence shows that chronic ethanol consumption increases endothelin (ET)-1 induced sustained contraction of trabecular smooth muscle cells of the corpora cavernosa in corpus cavernosum of rats by a mechanism that involves increased expression of ETA and ETB receptors. Our goal was to evaluate the effects of alcohol and diabetes and their relationship to miRNA-155, miRNA-199 and endothelin receptors in the corpus cavernosum and blood of rats submitted to the experimental model of diabetes mellitus and chronic alcoholism. Forty-eight male Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D), and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study the protein expression of endothelin receptors by immunohistochemistry and expression of miRNAs-155 and -199 in serum and the cavernous tissue. Immunostaining for endothelin receptors was markedly higher in the A, D, and AD groups than in the C group. Moreover, a significant hypoexpression of the miRNA-199 in the corpus cavernosum tissue from the AD group was observed, compared to the C group. When analyzing the microRNA profile in blood, a significant hypoexpression of miRNA-155 in the AD group was observed compared to the C group. The miRNA-199 analysis demonstrated significant hypoexpression in D and AD groups compared to the C group. Our findings in corpus cavernosum showed downregulated miRNA-155 and miRNA-199 levels associated with upregulated protein expression and unaltered mRNA expression of ET receptors suggesting decreased ET receptor turnover, which can contribute to erectile dysfunction in diabetic rats exposed to high alcohol levels.

Aqueous extract of lavender (Lavandula angustifolia) improves the spatial performance of a rat model of Alzheimer's disease.

PubMed

Kashani, Masoud Soheili; Tavirani, Mostafa Rezaei; Talaei, Sayyed Alireza; Salami, Mahmoud

2011-04-01

Alzheimer's disease (AD) is one of the most important neurodegenerative disorders. It is characterized by dementia including deficits in learning and memory. The present study aimed to evaluate the effects of aqueous extract of lavender (Lavandula angustifolia) on spatial performance of AD rats. Male Wistar rats were first divided into control and AD groups. Rat model of AD was established by intracerebroventricular injection of 10 μg Aβ1-42 20 d prior to administration of the lavender extract. Rats in both groups were then introduced to 2 stages of task learning (with an interval of 20 d) in Morris water maze, each followed by one probe test. After the first stage of spatial learning, control and AD animals received different doses (50, 100 and 200 mg/kg) of the lavender extract. In the first stage of experiment, the latency to locate the hidden platform in AD group was significantly higher than that in control group. However, in the second stage of experiment, control and AD rats that received distilled water (vehicle) showed similar performance, indicating that the maze navigation itself could improve the spatial learning of AD animals. Besides, in the second stage of experiment, control and AD rats that received lavender extract administration at different doses (50, 100, and 200 mg/ kg) spent less time locating the platform (except for the AD rats with 50 mg/kg extract treatment), as compared with their counterparts with vehicle treatment, respectively. In addition, lavender extract significantly improved the performance of control and AD rats in the probe test, only at the dose of 200 mg/kg, as compared with their counterparts with vehicle treatment. The lavender extract can effectively reverse spatial learning deficits in AD rats.

Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

PubMed Central

Krishnan, Vyjayanthi; Andersen, Bo H.; Shoemaker, Christine; Sivko, Gloria S.; Tordoff, Kevin P.; Stark, Gregory V.; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew

2015-01-01

AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 107, 1.5 × 109, or 3.5 × 1010 viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 1010 viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. PMID:25673303

Differentiating between Alzheimer's Disease and Vascular Cognitive Impairment: Is the "Memory Versus Executive Function" Contrast Still Relevant?

PubMed

Andriuta, Daniela; Roussel, Martine; Barbay, Mélanie; Despretz-Wannepain, Sandrine; Godefroy, Olivier

2018-01-01

The contrast between memory versus executive function impairments is commonly used to differentiate between neurocognitive disorders (NCDs) due to Alzheimer's disease (AD) and vascular cognitive impairment (VCI). We reconsidered this question because of the current use of AD biomarkers and the recent revision of the criteria for AD, VCI, and dysexecutive syndrome. To establish and compare the neuropsychological profiles in AD (i.e., with positive CSF biomarkers) and in VCI. We included 62 patients with mild or major NCDs due to pure AD (with positive CSF biomarker assays), and 174 patients (from the GRECogVASC cohort) with pure VCI. The neuropsychological profiles were compared after stratification for disease severity (mild or major NCD). We defined a memory-executive function index (the mean z score for the third free recall and the delayed free recall in the Free and Cued Selective Reminding Test minus the mean z score for category fluency and the completion time in the Trail Making Test part B) and determined its diagnostic accuracy. Compared with VCI patients, patients with AD had significantly greater memory impairments (p = 0.001). Executive function was impaired to a similar extent in the two groups (p = 0.11). Behavioral executive disorders were more prominent in the AD group (p = 0.001). Although the two groups differed significant with regard to the memory-executive function index (p < 0.001), the latter's diagnostic accuracy was only moderate (sensitivity: 63%, specificity: 87%). Although the contrast between memory and executive function impairments was supported at the group level it does not reliably discriminate between AD and VCI at the individual level.

Ethnoracial Differences in the Clinical Characteristics of Alzheimer Disease at Initial Presentation at an Urban Alzheimer’s Disease Center

PubMed Central

Livney, Melissa Gartenberg; Clark, Christopher M.; Karlawish, Jason H.; Cartmell, Su; Negrón, Mirna; Nuñez-Lopez, Jessica; Xie, Sharon X.; Entenza-Cabrera, Fernando; Vega, Irving E.; Arnold, Steven E.

2010-01-01

Objective To compare presentation of Alzheimer disease (AD) at the time of initial evaluation at a university specialty clinic across three ethnoracial groups in order to understand similarities and differences in the demographic, clinical, cognitive, psychiatric, and biologic features. Design Cross-sectional study. Participants A total of 1,341 self-identified African American, Latino (primarily of Caribbean origin), and white non-Hispanic (“WNH”) subjects were recruited from primary care sites or by referral by primary care physicians. Measurements Demographic variables and age of onset of AD, as well as cognitive, functional, and mood impairments at the time of initial presentation and frequencies of apolipoprotein E genotypes, were compared across groups. Results Differences among ethnoracial groups were found for nearly all variables of interest. In particular, the largely immigrant Puerto Rican Latino group had an earlier age of onset of AD, more cognitive impairment, and greater severity of cognitive impairment at the time of initial evaluation in the setting of low average education and socioeconomic status. There was more depression in the Latinos compared with African Americans and WNHs. Greater severity of symptoms was not accounted for by a difference in lag time between onset of symptoms and initial evaluation. The apolipoprotein E-4 genotype was not associated with AD in the Latino cohort. Conclusions Minority groups in Philadelphia, especially Latinos, exhibit a more severe profile of AD at the time of presentation than WNHs. Important potential confounds need to be considered and future research comparing immigrant and nonimmigrant Latino groups will be necessary to elucidate the highly significant differences reported. PMID:21522051

Erythropoietin promotes network formation of transplanted adipose tissue-derived microvascular fragments.

PubMed

Karschnia, P; Scheuer, C; Heß, A; Später, T; Menger, M D; Laschke, M W

2018-05-09

The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF) is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO). Ad-MVF were isolated from green fluorescent protein (GFP)+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL) or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls. Protein expression, cell viability and proliferation of ad-MVF were assessed by proteome profiler array and fluorescence microscopy. GFP+ ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into dorsal skinfold chambers of C57BL/6 mice, to analyse their vascularisation over 14 d by intravital fluorescence microscopy, histology and immunohistochemistry. Cultivation up-regulated the expression of pro- and anti-angiogenic factors within both vehicle- and EPO-treated ad-MVF when compared with non-cultivated controls. Moreover, EPO treatment suppressed cultivation-associated apoptosis and significantly increased the number of proliferating endothelial cells in ad-MVF when compared with vehicle-treated and non-cultivated ad-MVF. Accordingly, implanted matrices seeded with EPO-treated ad-MVF exhibited an improved vascularisation, as indicated by a significantly higher functional microvessel density. The matrices of the three groups contained a comparably large fraction of GFP+ microvessels originating from the ad-MVF, whereas the tissue surrounding the matrices seeded with EPO-treated ad-MVF exhibited a significantly increased microvessel density when compared with the other two groups. These findings indicated that EPO represents a promising cytokine to further boost the excellent vascularisation properties of ad-MVF in tissue-engineering applications.

Added Sugars Intake of Americans: What We Eat in America, NHANES 2013-2014

USDA-ARS?s Scientific Manuscript database

This Data Brief compares the intakes of selected Food Patterns food groups by different demographic groups of Americans, ages 2 years and over, grouped based on their added sugars intake status on day 1 of the What We Eat in America, NHANES 2013-2014 dietary data. There were 8,066 persons in the st...

Motor performance differentiates individuals with Lewy body dementia, Parkinson's and Alzheimer's disease.

PubMed

Fritz, Nora E; Kegelmeyer, Deborah A; Kloos, Anne D; Linder, Shannon; Park, Ariane; Kataki, Maria; Adeli, Anahita; Agrawal, Punit; Scharre, Douglas W; Kostyk, Sandra K

2016-10-01

Differential diagnosis of dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Parkinson's disease (PD) and Alzheimer's disease (AD) is challenging. Comparative motor profiles of these neurodegenerative disorders may aid in earlier diagnosis but have not been extensively studied. Groups were rigorously matched by age, education, and sex. DLB/PDD participants were matched by Mini-Mental State Examination Score to individuals with AD and by Unified Parkinson's Disease Rating Scale motor scores to individuals with PD. Gait, balance, dual task walking and hand dexterity measures were compared between a combined group (n=21) of individuals with Lewy body dementia (LBD) consisting of those with DLB (n=11) and PDD (n=10) to individuals with PD (n=21) or AD (n=21). Individuals at the same disease stage with LBD walked significantly slower with shorter stride lengths (p<0.05), demonstrated poorer balance on both the Tinetti and Berg Balance Scale, and poorer performance on dual-task and figure-of-eight walking compared to PD and AD (p<0.05 for all) groups. Upper extremity coordination on the 9-hole peg test differentiated LBD from both PD and AD and was the only motor test in which individuals with AD performed worse than those with PD. Tinetti balance subscores were significantly lower in PDD compared to DLB participants (10.4±2.3 versus 12.8±2.3; p=0.027). Motor features distinguish individuals with LBD from those with AD and PD. Measures of gait, balance and finger dexterity provide an additional means of differentiating individuals with LBD from those with AD and PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulaic Language in Parkinson's Disease and Alzheimer's Disease: Complementary Effects of Subcortical and Cortical Dysfunction

PubMed Central

Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy

2015-01-01

Purpose The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of formulaic language. Persons with Parkinson's disease (PD), having dysfunctional basal ganglia, were predicted to show impoverished formulaic expressions in contrast to speakers with AD. This study compared participants with PD, participants with AD, and healthy control (HC) participants on protocols probing production and comprehension of formulaic expressions. Method Spontaneous speech samples were recorded from 16 individuals with PD, 12 individuals with AD, and 18 HC speakers. Structured tests were then administered as probes of comprehension. Results The PD group had lower proportions of formulaic expressions compared with the AD and HC groups. Comprehension testing yielded opposite contrasts: participants with PD showed significantly higher performance compared with participants with AD and did not differ from HC participants. Conclusions The finding that PD produced lower proportions of formulaic expressions compared with AD and HC supports the view that subcortical nuclei modulate the production of formulaic expressions. Contrasting results on formal testing of comprehension, whereby participants with AD performed significantly worse than participants with PD and HC participants, indicate differential effects on procedural and declarative knowledge associated with these neurological conditions. PMID:26183940

Distinctive Effect of Donepezil Treatment on P300 and N200 Subcomponents of Auditory Event-Related Evoked Potentials in Alzheimer Disease Patients.

PubMed

Vaitkevičius, Arūnas; Kaubrys, Gintaras; Audronytė, Eglė

2015-07-03

Latency of P300 subcomponent of event-related potentials (ERPs) increases in Alzheimer disease (AD) patients, which correlate well with cognitive impairment. Cholinesterase inhibitors (ChEIs) reduce P300 latency in AD patients with parallel improvement in cognition. It is not known whether N200 response to ChEIs is similar to that of P300. The aim of this study was to evaluate and compare characteristics of P300 and N200 in AD patients, treatment-naïve and on stable donepezil treatment, matched by age, education, sex, and cognitive function. We recruited 22 consecutive treatment-naïve AD patients (AD-N group), 22 AD patients treated with a stable donepezil dose of 10 mg/day for at least 3 months (AD-T group), and 50 healthy controls were recruited. Neuropsychological testing (MMSE, ADAS-Cog, and additional tests) and ERP recording was performed and analyzed. All groups did not differ according to age, duration of education, or sex (p>0.05). AD-N and AD-T groups did not differ according to cognitive function. The AD-T group had longer duration of disease than the AD-N group (p<0.001). The AD-T and AD-N groups did not differ in P300 latencies (p=0.49). N200 latency was longer in the AD-T group (p<0.001). The general linear model showed that significant predictors of P300 latency were age (p=0.019) and AD treatment status (p<0.001). Duration of AD was a significant predictor of N200 latency (p=0.004). The response of N200 latency to donepezil treatment differs from the response of P300. P300 is a better marker of ChEI treatment-dependent cognitive functions. N200 is more dependent on the duration of AD.

Social workers' and nurses' illness representations about Alzheimer disease: an exploratory study.

PubMed

Shinan-Altman, Shiri; Werner, Perla; Cohen, Miri

2014-01-01

Professionals' perceptions of patients' diseases (illness representations) are a major factor influencing the quality of treatment they provide. The aim of the study was to examine and compare Alzheimer disease (AD) illness representations among 2 main professional groups involved in the care of Alzheimer patients. A total of 327 nurses and social workers in Israel were asked to report their cognitive representations (dimensions of identity, cause, timeline, consequences, control, coherence, timeline cycle) and emotional representations. Knowledge about AD, demographic, and occupational characteristics were also obtained. Participants perceived AD as a chronic disease associated with severe consequences. Statistically significant differences were found between the groups, as nurses attributed psychological reasons to AD more than the social workers. Nevertheless, social workers perceived AD as more chronic with severe consequences compared with the nurses. Despite some resemblance, there were differences between the social workers and nurses regarding AD illness representations. Therefore, continuing to distribute materials to professionals regarding AD is recommended, with attention to the unique characteristics of each professional group. Furthermore, the findings encourage the development of training and support programs that will not only deal with the organizational and instrumental levels of treating AD patients but also with the assessment and consequences of professionals' illness representations.

Alfaxalone versus alfaxalone-dexmedetomidine anaesthesia by immersion in oriental fire-bellied toads (Bombina orientalis).

PubMed

Adami, Chiara; d'Ovidio, Dario; Casoni, Daniela

2016-05-01

To determine a dexmedetomidine concentration, to be added to an alfaxalone-based bath solution, that will enhance the anaesthetic and analgesic effects of alfaxalone; and to compare the quality of anaesthesia and analgesia provided by immersion with either alfaxalone alone or alfaxalone with dexmedetomidine in oriental fire-bellied toads (Bombina orientalis). Pilot study followed by a prospective, randomized, experimental trial. Fourteen oriental fire-bellied toads. The pilot study aimed to identify a useful dexmedetomidine concentration to be added to an anaesthetic bath containing 20 mg 100 mL(-1) alfaxalone. Thereafter, the toads were assigned to one of two groups, each comprising eight animals, to be administered either alfaxalone (group A) or alfaxalone-dexmedetomidine (group AD). After immersion for 20 minutes, the toads were removed from the anaesthetic bath and the righting, myotactic and nociceptive reflexes, cardiopulmonary variables and von Frey filaments threshold were measured at 5 minute intervals and compared statistically between groups. Side effects and complications were noted and recorded. In the pilot study, a dexmedetomidine concentration of 0.3 mg 100 mL(-1) added to the alfaxalone-based solution resulted in surgical anaesthesia. The toads in group AD showed higher von Frey thresholds and lower nociceptive withdrawal reflex scores than those in group A. However, in group AD, surgical anaesthesia was observed in two out of eight toads only, and induction of anaesthesia was achieved in only 50% of the animals, as compared with 100% of the toads in group A. The addition of dexmedetomidine to an alfaxalone-based solution for immersion anaesthesia provided some analgesia in oriental fire-bellied toads, but failed to potentiate the level of unconsciousness and appeared to lighten the depth of anaesthesia. This limitation renders the combination unsuitable for anaesthetizing oriental fire-bellied toads for invasive procedures. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

The polymorphism of the ATP-binding cassette transporter 1 gene modulates Alzheimer disease risk in Chinese Han ethnic population.

PubMed

Sun, Yi-Min; Li, Hong-Lei; Guo, Qi-Hao; Wu, Ping; Hong, Zhen; Lu, Chuan-Zhen; Wu, Zhi-Ying

2012-07-01

Recent studies highlight a potential role of cholesterol metabolic disturbance in the pathophysiology of Alzheimer disease (AD). The adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene resides within proximity of linkage peaks on chromosome 9q influence AD and plays a key role in cellular cholesterol efflux in the brain. We studied the role of R219K and V825I polymorphisms of ABCA1 in modulating the risk of AD in 321 AD patients and 349 comparisons of Chinese Han. Genotyping of R219K and V825I were performed by PCR-restriction fragment length polymorphism analysis. The genotype distribution of R219K was different with more RK in total AD group (χ(2) = 8.705, df = 2, p = 0.013), late-onset AD (LOAD) group (χ(2) = 10.636, df = 2, p = 0.005), APOE non-ε4ε4 group (χ(2) = 9.900, df = 2, p = 0.007), and female AD group (χ(2) = 8.369, df = 2, p = 0.015). Logistic regression manifested the risk of AD increased in RK carriers in total AD group (Wald = 6.102, df = 1, p = 0.014, odds ratio [OR]: 1.546, 95% confidence interval [95% CI]: 1.094-2.185), LOAD group (Wald = 7.746, df = 1, p = 0.005, OR: 1.921, 95% CI: 1.213-3.041), and APOE non-ε4ε4 group (Wald = 6.399, df = 1, p = 0.011, OR: 1.586, 95% CI: 1.109-2.266). K allele (RK + KK) also increased the risk of AD compared with RR allele in LOAD group (Wald = 4.750, df = 1, p = 0.029, OR: 1.619, 95% CI: 1.050-2.497). However, no discrepancy was found in V825I. In R219K, age at onset (AAO) was significantly lower by 4.9 years on average in patients of KK genotype than those of RK in APOE ε4 carrying group and higher by 5.5 years in patients of KK genotype than those of RR in APOE ε4 noncarrying group. In V825I, AAO was diseased by 4.3 years in II genotype compared with VV genotype in APOE ε4 noncarrying group and 3.4 years in APOE ε4ε4 noncarrying group. The results indicated that the RK genotype or K allele (RK + KK) of R219K may relate to the development of AD in the east of China.

Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

PubMed

Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

2011-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

Cerebral blood flow reduction associated with orientation for time in amnesic mild cognitive impairment and Alzheimer disease patients.

PubMed

Yamashita, Ken-Ichiro; Taniwaki, Yoshihide; Utsunomiya, Hidetsuna; Taniwaki, Takayuki

2014-01-01

Impairment of orientation for time (OT) is a characteristic symptom of Alzheimer disease (AD). However, the brain regions underlying OT remain to be elucidated. Using single photon emission computed tomography (SPECT), we examined the brain regions exhibiting hypoperfusion that were associated with OT. We compared regional cerebral blood flow (rCBF) differences between AD and amnesic mild cognitive impairment (aMCI) or normal subjects using 3-dimensional stereotactic surface projection (3D-SSP) analysis. AD patients were divided into OT good and poor groups according to their mean OT scores, and rCBF then compared between the groups to elucidate OT-specific brain areas. 3D-SSP analysis showed reduced rCBF in the left superior parietal lobule (SPL) and bilateral inferior parietal lobule (IPL) in AD patients. In the poor OT group, 3D-SSP analysis revealed hypoperfusion in the bilateral SPL, IPL, posterior cingulated cortex (PCC), and precuneus. Among these areas, region of interest analysis revealed a significant higher number of hypoperfused pixels in the left PCC in the OT poor AD group. Our SPECT study suggested that hypoperfusion in the left SPL and bilateral IPL was AD specific, and reduced rCBF in the left PCC was specifically associated with OT. Copyright © 2014 by the American Society of Neuroimaging.

BONE MASS BY QUANTITATIVE ULTRASOUND OF FINGER PHALANGES IN YOUNG KARATE PRACTITIONERS

PubMed Central

Barbeta, Camila Justino de Oliveira; Gonçalves, Ezequiel Moreira; Ribeiro, Keila Donassolo Santos; Ribeiro, Roberto; Roman, Everton Paulo; Guerra-Júnior, Gil

2017-01-01

ABSTRACT Objective: To evaluate bone mass by quantitative ultrasound of the phalanges in young karate practitioners compared to a control group. Methods: Sample composed of 162 karate practitioners (52 females) and 326 healthy controls (110 females) aged 6 to 16 years old, in Western Paraná (Southern Brazil). Weight, height, BMI, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were evaluated. BMI, AD-SoS and BTT values were converted to Z scores. Mann-Whitney, chi-square or Fisher Exact tests and multiple linear regression were applied, with significance level set at p≤0.05. Results: Both genders showed higher values of BTT as Z scores when compared to control group. Females from the control group had higher AD-SoS values (m/s and Z score) compared to female karate practitioners. When relative and absolute frequencies were assessed according to BTT Z score in both groups, male karate practitioners’ bone mass was shown to be adequate more frequently. In female practitioners, age and weight were independent predictors of AD-SoS (R2=0.42) and BTT (R2=0.45), respectively. Among male karate practitioners, age was related to 26% of AD-SoS variances and height was responsible for 36% of BTT variances. Conclusions: Children and adolescents who practice karate were shown to have more bone mass in comparison to the control group, regardless of gender. BTT was more sensitive for this evaluation. PMID:28977128

Effect of dietary carbohydrate source on the development of obesity in agouti transgenic mice.

PubMed

Morris, Kristin L; Zemel, Michael B

2005-01-01

Our objective was to evaluate the effects of a qualitative change in dietary carbohydrate source on body weight and adiposity in a rodent model of diet-induced obesity. We evaluated the effects of high-fat diets (basal) varying in carbohydrate source in aP2-agouti transgenic mice. In the ad libitum study, animals were given free access to the basal diet or one of four test diets for 6 weeks. In two of the diets, dietary carbohydrate was derived from a single source: mung bean noodles (MUNG) or rolled oats (ROLL). The remaining diets were designed to mimic commercially available instant oatmeal with added sugar (IO-S) or flavored instant oatmeal (IO-F). In the energy-restricted study, animals were given ad libitum access to the basal diet for 6 weeks. Subsequently, animals were assigned to one of six treatment groups for 6 weeks. One group was continued on the basal diet ad libitum. The remaining groups were maintained with energy restriction (70% ad libitum) on either the basal, MUNG, ROLL, IO-S, or IO-F diet. Subcutaneous fat pad mass was significantly higher (p<0.05) in the energy-restricted basal and IO-S groups compared with the energy-restricted ROLL diet. Similarly, visceral fat pad mass was significantly lower with ROLL and MUNG diets (p<0.05 for both) compared with basal and IO-S diets, and the insulin:glucose ratio was reduced (by 23% to 34%, p<0.05) in these two diets compared with all others. In ad libitum-fed animals, liver fatty acid synthase expression was 43% to 62% lower (p<0.05) with ROLL and MUNG diets compared with all others. These data suggest that a qualitative change in dietary carbohydrate source modulates body weight and adiposity.

Nicotine dependence syndrome scale and craving: comparing nicotine-dependent individuals with and without comorbid alcohol dependence.

PubMed

Choi, Sam-Wook; Chon, Younghoon; Bhang, Soo-Young; Jang, Yong Lee; Won, Wang-Youn; Choi, Jin Tae; Kim, Dai-Jin

2014-06-01

Although several studies have explored craving for certain drugs, there is limited data describing the relationship between alcohol and nicotine craving from a multidimensional perspective among individuals with comorbid nicotine dependence (ND) and alcohol dependence (AD). We compared a group of male patients diagnosed with ND and AD (n = 160) to a group of male patients diagnosed with ND only (n = 235). Smoking- and drinking-related clinical features were measured, including craving levels and the Nicotine Dependence Syndrome Scale (NDSS), which is a multidimensional questionnaire measuring ND. Subsequently, we studied factors that influenced smoking and alcohol craving in the ND and AD group. Regarding the NDSS, the sum, priority and tolerance scores were significantly higher in the ND and AD group compared with the ND only group (P < 0.000, P < 0.000 and P = 0.001, respectively). In the comorbid group, regression analyses revealed that alcohol craving and Fagerstrom Test for Nicotine Dependence (FTND) scores contributed to nicotine craving (beta coefficient = 0.37, P = 0.005 and beta coefficient = 0.35, P = 0.026, respectively) and these two factors explained 36% of the variance). Nicotine craving appeared to be the only factor that contributed to alcohol craving (beta coefficient = 0.35, P = 0.002), and nicotine craving explained 16% of the variance. This study may help clarify the clinical relationship between comorbid alcohol and nicotine dependence and help guide the development of effective treatment strategies for ND and AD patients. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

Effect of sustained gene delivery of platelet-derived growth factor or its antagonist (PDGF-1308) on tissue-engineered cementum.

PubMed

Anusaksathien, Orasa; Jin, Qiming; Zhao, Ming; Somerman, Martha J; Giannobile, William V

2004-03-01

Cementum, a mineralized tissue lining the tooth root surface, is destroyed during the inflammatory process of periodontitis. Restoration of functional cementum is considered a criterion for successful regeneration of periodontal tissues, including formation of periodontal ligament, cementum, and alveolar bone. Short-term administration of platelet-derived growth factor (PDGF) has been shown to partially regenerate periodontal structures. Nonetheless, the role of PDGF in cementogenesis is not well understood. The aim of the present study was to determine the effect of sustained PDGF gene transfer on cementum formation in an ex vivo ectopic biomineralization model. Osteocalcin (OC) promoter-driven SV40 transgenic mice were used to obtain immortalized cementoblasts (OCCM). The OCCM cells were transduced with adenoviruses (Ad) encoding either PDGF-A, an antagonist of PDGF signaling (PDGF-1308), a control virus (green fluorescent protein, GFP), or no treatment (NT). The transduced cells were incorporated into polymer scaffolds and implanted subcutaneously into severe combined immunodeficient (SCID) mice. The implants were harvested at 3 and 6 weeks for histomorphometric analysis of the newly formed mineralized tissues. Northern blot analysis was performed to determine the expression levels of mineral-associated genes including bone sialoprotein (BSP), OC, and osteopontin (OPN) in the cell-implant specimens at 3 and 6 weeks. The results indicated mineralization was significantly reduced in both the Ad/PDGF-A and Ad/PDGF-1308 treated specimens when compared to the NT or Ad/GFP groups at 3 and 6 weeks (P<0.01). In addition, the size of the implants treated with Ad/PDGF-A and Ad/PDGF-1308 was significantly reduced compared to implants from Ad/GFP and NT groups at 3 weeks (P<0.05). At 6 weeks, the size of implants and mineral formation increased in NT, Ad/GFP, and Ad/PDGF-A groups, while the Ad/PDGF-1308 treated implants continued to decrease in size and mineral formation (P<0.01). Northern blot analysis revealed that in the Ad/PDGF-A treated implants OPN was increased, whereas OC gene expression was downregulated at 3 weeks. In the Ad/PDGF-1308 treated implants, BSP, OC, and OPN were all downregulated at 3 weeks. At 3 weeks, the Ad/PDGF-A treated implants contained significantly higher multinucleated giant cell (MNGC) density compared to NT, Ad/GFP, and Ad/PDGF-1308 specimens. The MNGC density in NT, Ad/GFP, and Ad/PDGF-A treated groups reduced over time, while the Ad/PDGF-1308 transduced implants continued to exhibit significantly higher MNGC density compared with the other treatment groups at 6 weeks. The results showed that continuous exposure to PDGF-A had an inhibitory effect on cementogenesis, possibly via the upregulation of OPN and subsequent enhancement of MNGCs at 3 weeks. On the other hand, Ad/PDGF-1308 inhibited mineralization of tissue-engineered cementum possibly due to the observed downregulation of BSP and OC and a persistence of stimulation of MNGCs. These findings suggest that continuous exogenous delivery of PDGF-A may delay mineral formation induced by cementoblasts, while PDGF is clearly required for mineral neogenesis.

Impaired imitation of gestures in mild dementia: comparison of dementia with Lewy bodies, Alzheimer's disease and vascular dementia.

PubMed

Nagahama, Yasuhiro; Okina, Tomoko; Suzuki, Norio

2015-11-01

To examine whether imitation of gestures provided useful information to diagnose early dementia in elderly patients. Imitation of finger and hand gestures was evaluated in patients with mild dementia; 74 patients had dementia with Lewy bodies (DLB), 100 with Alzheimer's disease (AD) and 52 with subcortical vascular dementia (SVaD). Significantly, more patients with DLB (32.4%) compared with patients with AD (5%) or SVaD (11.5%) had an impaired ability to imitate finger gestures bilaterally. Also, significantly, more patients with DLB (36.5%) compared with patients with AD (5%) or SVaD (15.4%) had lower mean scores of both hands. In contrast, impairment of the imitation of bimanual gestures was comparable among the three patient groups (DLB 50%, AD 42%, SVaD 42.3%). Our study revealed that imitation of bimanual gestures was impaired non-specifically in about half of the patients with mild dementia, whereas imitation of finger gestures was significantly more impaired in patients with early DLB than in those with AD or SVaD. Although the sensitivity was not high, the imitation tasks may provide additional information for diagnosis of mild dementia, especially for DLB. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of Biodistribution and Safety of Adenovirus Vectors Containing Group B Fibers after Intravenous Injection into Baboons

PubMed Central

NI, SHAOHENG; BERNT, KATHRIN; GAGGAR, ANUJ; LI, ZONG-YI; KIEM, HANS-PETER; LIEBER, ANDRÉ

2005-01-01

Vectors containing group B adenovirus (Ad) fibers are able to efficiently transduce gene therapy targets that are refractory to infection with standard Ad serotype 5 (Ad5) vectors, including malignant tumor cells, hematopoietic stem cells, and dendritic cells. Preliminary studies in mice indicate that, after intravenous injection, B-group fiber-containing Ads do not efficiently transduce most organs and cause less acute toxicity than Ad5 vectors. However, biodistribution and safety studies in mice are of limited value because the mouse analog of the B-group Ad receptor, CD46, is expressed only in the testis, whereas in humans, CD46 is expressed on all nucleated cells. Unlike mice, baboons have CD46 expression patterns and levels that closely mimic those in humans. We conducted a biodistribution and toxicity study of group B Ad fiber-containing vectors in baboons. Animals received phosphate-buffered saline, Ad5-bGal (a first-generation Ad5 vector), or B-group fiber-containing Ads (Ad5/35-bGal and Ad5/11-bGal) at a dose of 2 × 1012 VP/kg, and vector biodistribution and safety was analyzed over 3 days. The amount of Ad5/35-bGal and Ad5/11-bGal vector genomes was in most tissues one to three orders of magnitude below that of Ad5. Significant Ad5/35- and Ad5/11-mediated transgene (β-galactosidase) expression was seen only in the marginal zone of splenic follicles. Compared with the animal that received Ad5-bGal, all animals injected with B-group fiber-containing Ad vectors had lower elevations in serum proinflammatory cytokine levels. Gross and histopathology were normal in animals that received B-group Ad fiber-containing Ads, in contrast to the Ad5-infused animal, which showed widespread endothelial damage and inflammation. In a further study, a chimeric Ad5/35 vector carrying proapoptotic TRAIL and Ad E1A genes under tumor-specific regulation was well tolerated in a 30-day toxicity study. No major clinical, serologic, or pathologic abnormalities were noticed in this animal. OVERVIEW SUMMARY B-group Ad fiber-containing vectors are promising tools for gene therapy, for example, for the treatment of metastatic cancer or cardiovascular diseases, or for vaccination/immunotherapy. However, only a few studies of vectors containing B-group Ad fibers in mice have been conducted so far, and little is known about the mechanisms and effects of B-group Ad vector delivery in vivo. Before these vectors can be considered for clinical application, this knowledge gap must be filled. We performed biodistribution and safety studies after intravenous injection of chimeric Ad5 vectors containing Ad35 and Ad11 fibers into baboons. Our study suggests that Ad vectors possessing B-group Ad fibers have a better safety profile after intravenous injection than do conventional Ad5-based vectors. PMID:15960598

[Total flavones derived from Lagotis brevituba maxim reduce the levels of inflammatory cytokines in cerebral cortex and hippocampus of Alzheimer's disease mice].

PubMed

Yang, Bailing; Hou, Qian; Hu, Feng; Zhang, Fan

2016-07-01

Objective To investigate the mechanism behind the treatment of Alzheimer's disease (AD) with total flavones derived from Lagotis brevituba maxim (TF-LBM). Methods Fifty SAMP8 mice (aged 8 months) were randomly divided into 5 groups, (150, 300, 600) mg/kg TF-LBM groups, 0.65 g/kg donepezil HCl group and AD model group; 10 SAMR1 mice (aged 8 months) were used as a control group of normal aging. The AD model group and the normal aging control group were given the same volume of distilled water as TF-LBM groups. Eight weeks after intragastric administration, Morris water maze experiment was conducted to calculate the latency of place navigation. After the behavioral experiment, the brain cortical tissue and hippocampus (CA1 region) of the mice from various groups were taken to observe the morphological changes of the cortical tissue and hippocampus and test IL-1β, IL-6, TNF-α content. Results Compared with the model group, the escape latency of the normal aging group, the high-dose TF-LBM group and the donepezil HCl group were evidently shortened; compared with the normal aging group, IL-1β, IL-6, TNF-αof the model group increased significantly; compared with the model group, IL-1β content of the low-dose TF-LBM group had no obvious difference, while IL-1β content of the median-dose and high-dose TF-LBM groups and the donepezil HCl group decreased significantly; IL-6 content decreased in all TF-LBM groups and the donepezil HCl group; TNF-α level in the low-dose and median-dose TF-LBM groups had no evident difference, while it was reduced significantly in the high-dose TF-LBM group and the donepezil HCl group. Compared with the normal aging group, IL-1β, IL-6 and TNF-α content of the model group increased significantly; compared with the model group, IL-1β, IL-6 and TNF-α content of all TF-LBM groups and the donepezil HCl group decreased. Conclusion TF-LBM can improve the behavior change of SAMP8 mice with AD. TF-LBM can reduce the content of IL-6, IL-1β and TNF-α in cerebral cortex and hippocampus CA1.

Alzheimer's disease and memory-monitoring impairment: Alzheimer's patients show a monitoring deficit that is greater than their accuracy deficit.

PubMed

Dodson, Chad S; Spaniol, Maggie; O'Connor, Maureen K; Deason, Rebecca G; Ally, Brandon A; Budson, Andrew E

2011-07-01

We assessed the ability of two groups of patients with mild Alzheimer's disease (AD) and two groups of older adults to monitor the likely accuracy of recognition judgments and source identification judgments about who spoke something earlier. Alzheimer's patients showed worse performance on both memory judgments and were less able to monitor with confidence ratings the likely accuracy of both kinds of memory judgments, as compared to a group of older adults who experienced the identical study and test conditions. Critically, however, when memory performance was made comparable between the AD patients and the older adults (e.g., by giving AD patients extra exposures to the study materials), AD patients were still greatly impaired at monitoring the likely accuracy of their recognition and source judgments. This result indicates that the monitoring impairment in AD patients is actually worse than their memory impairment, as otherwise there would have been no differences between the two groups in monitoring performance when there were no differences in accuracy. We discuss the brain correlates of this memory-monitoring deficit and also propose a Remembrance-Evaluation model of memory-monitoring. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cu, Zn-Superoxide Dismutase Increases the Therapeutic Potential of Adipose-derived Mesenchymal Stem Cells by Maintaining Antioxidant Enzyme Levels.

PubMed

Yoo, Dae Young; Kim, Dae Won; Chung, Jin Young; Jung, Hyo Young; Kim, Jong Whi; Yoon, Yeo Sung; Hwang, In Koo; Choi, Jung Hoon; Choi, Goang-Min; Choi, Soo Young; Moon, Seung Myung

2016-12-01

In the present study, we investigated the ability of Cu, Zn-superoxide dismutase (SOD1) to improve the therapeutic potential of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) against ischemic damage in the spinal cord. Animals were divided into four groups: the control group, vehicle (PEP-1 peptide and artificial cerebrospinal fluid)-treated group, Ad-MSC alone group, and Ad-MSC-treated group with PEP-1-SOD1. The abdominal aorta of the rabbit was occluded for 30 min in the subrenal region to induce ischemic damage, and immediately after reperfusion, artificial cerebrospinal fluid or Ad-MSCs (2 × 10 5 ) were administered intrathecally. In addition, PEP-1 or 0.5 mg/kg PEP-1-SOD1 was administered intraperitoneally to the Ad-MSC-treated rabbits. Motor behaviors and NeuN-immunoreactive neurons were significantly decreased in the vehicle-treated group after ischemia/reperfusion. Administration of Ad-MSCs significantly ameliorated the changes in motor behavior and NeuN-immunoreactive neuronal survival. In addition, the combination of PEP-1-SOD1 and Ad-MSCs further increased the ameliorative effects of Ad-MSCs in the spinal cord after ischemia. Furthermore, the administration of Ad-MSCs with PEP-1-SOD1 decreased lipid peroxidation and maintained levels of antioxidants such as SOD1 and glutathione peroxidase compared to the Ad-MSC alone group. These results suggest that combination therapy using Ad-MSCs and PEP-1-SOD1 strongly protects neurons from ischemic damage by modulating the balance of lipid peroxidation and antioxidants.

A Multi-Cohort Study of ApoE ɛ4 and Amyloid-β Effects on the Hippocampus in Alzheimer’s Disease

PubMed Central

Khan, Wasim; Giampietro, Vincent; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L.W.; Büchel, Christian; Conrod, Patricia; Flor, Herta; Frouin, Vincent; Garavan, Hugh; Gowland, Penny; Heinz, Anreas; Ittermann, Bernd; Lemaître, Hervé; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Smolka, Michael N.; Ströhle, Andreas; Gallinat, Jeurgen; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Tsolaki, Magda; Mecocci, Patrizia; Spenger, Christian; Villemagne, Victor L.; Masters, Colin L.; Muehlboeck, J-Sebastian; Bäckman, Lars; Fratiglioni, Laura; Kalpouzos, Grégoria; Wahlund, Lars-Olof; Schumann, Gunther; Lovestone, Simon; Williams, Steven C.R.; Westman, Eric; Simmons, Andrew

2017-01-01

The apolipoprotein E (APOE) gene has been consistently shown to modulate the risk of Alzheimer’s disease (AD). Here, using an AD and normal aging dataset primarily consisting of three AD multi-center studies (n = 1,781), we compared the effect of APOE and amyloid-β (Aβ) on baseline hippocampal volumes in AD patients, mild cognitive impairment (MCI) subjects, and healthy controls. A large sample of healthy adolescents (n = 1,387) was also used to compare hippocampal volumes between APOE groups. Subjects had undergone a magnetic resonance imaging (MRI) scan and APOE genotyping. Hippocampal volumes were processed using FreeSurfer. In the AD and normal aging dataset, hippocampal comparisons were performed in each APOE group and in ɛ4 carriers with positron emission tomography (PET) Aβ who were dichotomized (Aβ+/Aβ–) using previous cut-offs. We found a linear reduction in hippocampal volumes with ɛ4 carriers possessing the smallest volumes, ɛ3 carriers possessing intermediate volumes, and ɛ2 carriers possessing the largest volumes. Moreover, AD and MCI ɛ4 carriers possessed the smallest hippocampal volumes and control ɛ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ɛ4 and Aβ positivity had the lowest hippocampal volumes when compared to Aβ- ɛ4 carriers, suggesting a synergistic relationship between APOE ɛ4 and Aβ. However, we found no hippocampal volume differences between APOE groups in healthy 14-year-old adolescents. Our findings suggest that the strongest neuroanatomic effect of APOE ɛ4 on the hippocampus is observed in AD and groups most at risk of developing the disease, whereas hippocampi of old and young healthy individuals remain unaffected. PMID:28157104

Quantitative assessment of finger tapping characteristics in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease.

PubMed

Roalf, David R; Rupert, Petra; Mechanic-Hamilton, Dawn; Brennan, Laura; Duda, John E; Weintraub, Daniel; Trojanowski, John Q; Wolk, David; Moberg, Paul J

2018-06-01

Fine motor impairments are common in neurodegenerative disorders, yet standardized, quantitative measurements of motor abilities are uncommonly used in neurological practice. Thus, understanding and comparing fine motor abilities across disorders have been limited. The current study compared differences in finger tapping, inter-tap interval, and variability in Alzheimer's disease (AD), Parkinson's disease (PD), mild cognitive impairment (MCI), and healthy older adults (HOA). Finger tapping was measured using a highly sensitive light-diode finger tapper. Total number of finger taps, inter-tap interval, and intra-individual variability (IIV) of finger tapping was measured and compared in AD (n = 131), PD (n = 63), MCI (n = 46), and HOA (n = 62), controlling for age and sex. All patient groups had fine motor impairments relative to HOA. AD and MCI groups produced fewer taps with longer inter-tap interval and higher IIV compared to HOA. The PD group, however, produced more taps with shorter inter-tap interval and higher IIV compared to HOA. Disease-specific changes in fine motor function occur in the most common neurodegenerative diseases. The findings suggest that alterations in finger tapping patterns are common in AD, MCI, and PD. In addition, the present results underscore the importance of motor dysfunction even in neurodegenerative disorders without primary motor symptoms.

Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism.

PubMed

Mosconi, Lisa; Brys, Miroslaw; Switalski, Remigiusz; Mistur, Rachel; Glodzik, Lidia; Pirraglia, Elizabeth; Tsui, Wai; De Santi, Susan; de Leon, Mony J

2007-11-27

Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Forty-nine 50- to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[(18)F]fluoro-2-deoxy-d-glucose-positron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH(-)). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH(-) and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH(-) subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.

Atherosclerosis risk factors in American Indians with Alzheimer disease: preliminary findings.

PubMed

Weiner, Myron F; Rosenberg, Roger N; Womack, Kyle B; Svetlik, Doris A; Fuller, Carey; Fields, Julie; Hynan, Linda S

2008-01-01

Factors predisposing to and associated with atherosclerosis may impact the onset and progression of Alzheimer disease (AD). The high prevalence of atherosclerosis and associated risk factors in American Indians makes them ideal subjects to test this association. We compared frequency of history of hypertension, myocardial infarction, stroke, diabetes, and high cholesterol in 34 American Indians with AD with 34 age-matched American Indian controls, and 34 age-matched whites with probable AD. We also measured waist size, height, and weight, and acquired blood for determination of plasma homocysteine and apolipoprotein E genotype. The 3 groups did not differ significantly in age or sex. History of hypertension and diabetes was significantly more common among American Indian AD patients than Indian controls or whites with AD. The 3 groups did not differ in history of stroke or myocardial infarction. Body mass index was significantly greater in both Indian groups than the white AD group. Plasma homocysteine levels were greater, but not significantly so, in the Indian AD than the Indian control group. Thus, there is preliminary evidence of a modest association between history of hypertension and diabetes and AD in a small sample of American Indians. This suggests that changes in lifestyle factors could influence the expression of AD in American Indians.

Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease.

PubMed

Lonie, Jane A; Herrmann, Lucie L; Tierney, Kevin M; Donaghey, Claire; O'Carroll, Ronan; Lee, Andrew; Ebmeier, Klaus P

2009-03-01

Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out-patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.

Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging.

PubMed

Mosconi, Lisa; Berti, Valentina; Quinn, Crystal; McHugh, Pauline; Petrongolo, Gabriella; Varsavsky, Isabella; Osorio, Ricardo S; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S; de Leon, Mony J; Brinton, Roberta Diaz

2017-09-26

This observational multimodality brain imaging study investigates emergence of endophenotypes of late-onset Alzheimer disease (AD) risk during endocrine transition states in a cohort of clinically and cognitively normal women and age-matched men. Forty-two 40- to 60-year-old cognitively normal women (15 asymptomatic perimenopausal by age [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age- and education-matched men were examined. All patients had volumetric MRI, 18 F-fluoro-2-deoxyglucose (FDG)-PET (glucose metabolism), and Pittsburgh compound B-PET scans (β-amyloid [Aβ] deposition, a hallmark of AD pathology). As expected, the MENO group was older than the PERI and CNT groups. Otherwise, groups were comparable on clinical and neuropsychological measures and APOE4 distribution. Compared to CNT women and to men, and controlling for age, PERI and MENO groups exhibited increased indicators of AD endophenotype, including hypometabolism, increased Aβ deposition, and reduced gray and white matter volumes in AD-vulnerable regions ( p < 0.001). AD biomarker abnormalities were greatest in MENO, intermediate in PERI, and lowest in CNT women ( p < 0.001). Aβ deposition was exacerbated in APOE4 -positive MENO women relative to the other groups ( p < 0.001). Multimodality brain imaging indicates sex differences in development of the AD endophenotype, suggesting that the preclinical AD phase is early in the female aging process and coincides with the endocrine transition of perimenopause. These data indicate that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process. © 2017 American Academy of Neurology.

Does Functional Connectivity Provide a Marker for Cognitive Rehabilitation Effects in Alzheimer's Disease? An Interventional Study.

PubMed

Ochmann, Sina; Dyrba, Martin; Grothe, Michel J; Kasper, Elisabeth; Webel, Steffi; Hauenstein, Karlheinz; Teipel, Stefan J

2017-01-01

Cognitive rehabilitation (CR) is a cognitive intervention for patients with Alzheimer's disease (AD) that aims to maintain everyday competences. The analysis of functional connectivity (FC) in resting-state functional MRI has been used to investigate the effects of cognitive interventions. We evaluated the effect of CR on the default mode network FC in a group of patients with mild AD, compared to an active control group. We performed a three-month interventional study including 16 patients with a diagnosis of AD. The intervention group (IG) consisted of eight patients, performing twelve sessions of CR. The active control group (CG) performed a standardized cognitive training. We used a seed region placed in the posterior cingulate cortex (PCC) for FC analysis, comparing scans acquired before and after the intervention. Effects were thresholded at a significance of p < 0.001 (uncorrected) and a minimal cluster size of 50 voxels. The interaction of group by time showed a higher increase of PCC connectivity in IG compared to CG in the bilateral cerebellar cortex. CG revealed widespread, smaller clusters of higher FC increase compared with IG. Across all participants, an increase in quality of life was associated with connectivity increase over time in the bilateral precuneus. CR showed an effect on the FC of the DMN in the IG. These effects need further study in larger samples to confirm if FC analysis may suit as a surrogate marker for the effect of cognitive interventions in AD.

Family history and APOE4 risk for Alzheimer's disease impact the neural correlates of episodic memory by early midlife.

PubMed

Rajah, M N; Wallace, L M K; Ankudowich, E; Yu, E H; Swierkot, A; Patel, R; Chakravarty, M M; Naumova, D; Pruessner, J; Joober, R; Gauthier, S; Pasvanis, S

2017-01-01

Episodic memory impairment is a consistent, pronounced deficit in pre-clinical stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for AD exhibit altered brain function several decades prior to the onset of AD-related symptoms. In the current event-related fMRI study of spatial context memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a family history of late onset AD (MA + FH ), or a combined + FH and apolipoprotein E ε4 allele risk factors for AD (MA + FH + APOE4 ), will exhibit differences in encoding and retrieval-related brain activity, compared to - FH - APOE4 MA controls. We also hypothesized that the two at-risk MA groups will exhibit distinct patterns of correlation between brain activity and memory performance, compared to controls. To test these hypotheses we conducted multivariate task, and behavior, partial least squares analysis of fMRI data obtained during successful context encoding and retrieval. Our results indicate that even though there were no significant group differences in context memory performance, there were significant differences in brain activity and brain-behavior correlations involving the hippocampus, inferior parietal cortex, cingulate, and precuneus cortex in MA with AD risk factors, compared to controls. In addition, we observed that brain activity and brain-behavior correlations in anterior-medial PFC and in ventral visual cortex differentiated the two MA risk groups from each other, and from MA controls . Our results indicate that functional differences in episodic memory-related regions are present by early midlife in adults with + FH and + APOE-4 risk factors for late onset AD, compared to middle-aged controls.

Comparative analysis of autistic traits and behavioral disorders in Prader-Willi syndrome and Asperger disorder.

PubMed

Song, Dae Kwang; Sawada, Masayuki; Yokota, Shingo; Kuroda, Kenji; Uenishi, Hiroyuki; Kanazawa, Tetsufumi; Ogata, Hiroyuki; Ihara, Hiroshi; Nagai, Toshiro; Shimoda, Kazutaka

2015-01-01

Prader-Willi syndrome (PWS) is a neuro-genetic disorder caused by the absence/loss of expression of one or more paternally expressed genes on chromosome 15 (q11-13). In this study, a comparative analysis of intelligence level and autistic traits was conducted between children with PWS (n = 30; 18 males, 12 females; age = 10.6 ± 2.8 years) and those with Asperger disorder (AD; n = 31; 24 males, 7 females; age = 10.5 ± 3.1 years). The children were compared by age group: lower elementary school age (6-8 years), upper elementary school age (9-12 years), and middle school age (13-15 years). As results, the intelligence levels of children with PWS were significantly lower than those with AD across all age groups. Autistic traits, assessed using the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS), revealed that among elementary school age children, those with PWS had less prominent autistic traits than those with AD, however, among middle school age children, those with PWS and AD showed similar prominence. An analysis of the PARS subscale scores by age group showed that while the profiles of autistic traits for children with PWS differed from those of children with AD at elementary school age, the profiles showed no significant differences between the groups at middle school age. The findings suggest that autistic traits in PWS become gradually more prominent with increasing of age and that these autistic traits differ in their fundamental nature from those observed in AD. © 2014 Wiley Periodicals, Inc.

Effect of Canavalia gladiata Extract Fermented with Aspergillus oryzae on the Development of Atopic Dermatitis in NC/Nga Mice.

PubMed

Kim, Ok-Kyung; Chang, Jee-Yun; Nam, Da-Eun; Park, Yoo Kyoung; Jun, Woojin; Lee, Jeongmin

2015-01-01

Canavalia gladiata has been used as a Chinese traditional folk medicine for its anti-inflammatory properties. However, the use of C. gladiata is limited because it contains antinutritional and allergy-causing proteins. We fermented C. gladiata with Aspergillus oryzae and investigated the effects of fermented C. gladiata (FCG) on the development of atopic dermatitis (AD) in mice. The mice were divided into five groups: untreated Balb/c mice; AD control (NC/Nga mice); FCGH (NC/Nga mice fed a dietary supplement of 300 mg/kg fermented C. gladiata water extract); FCG30 (NC/Nga mice fed a dietary supplement of 300 mg/kg of fermented C. gladiata 30% ethanol extract), and FCG80 (NC/Nga mice fed a dietary supplement of 300 mg/kg of fermented C. gladiata 80% ethanol extract). We found increases in the nonessential amino acids and essential amino acid in the FCG compared with the non-FCG. FCG attenuated macroscopic and histopathological changes in dorsal skin of mice when compared with the AD control group. The FCG30 and FCG80 groups, in particular, showed significant decreases in scratching episodes when compared with the AD control group. FCG improved immune responses, including increases in IgE and histamine for AD, through attenuation of Th1/Th2 cytokine imbalance and the production of proinflammatory cytokines and chemokines. We suggest that FCG may have benefits for improvement of AD function by improving the balance of Th1/Th2 cytokines and by producing anti-inflammatory effects. © 2015 S. Karger AG, Basel.

Engaging homeless persons in end of life preparations.

PubMed

Song, John; Wall, Melanie M; Ratner, Edward R; Bartels, Dianne M; Ulvestad, Nancy; Gelberg, Lillian

2008-12-01

There are no prospective studies that have investigated the effects of an intervention to improve end of life (EOL) care in an underserved population. To determine whether homeless persons will complete an advance directive (AD). Randomized trial comparing two modes of providing an opportunity for homeless persons to complete an AD. Half of the subjects were randomized to a self-guided group (SG) who were given an AD and written instructions; the other half were given the same material but, in addition, were offered the opportunity to receive guidance to complete the AD (CG). Fifty-nine homeless persons recruited from a drop-in center. Rate of AD completion and baseline and 3-month follow-up EOL-related knowledge, attitudes, and behaviors. The overall AD completion rate was 44%, with a statistically significant higher completion rate of 59% in the CG group compared to 30% in the self-guided only group. Frequency of worry about death decreased among those who filled out an AD from 50% to 12.5%, and also among those who did not (25% to 12.5%) (p < .05). Among those who filled out an AD, there were increases in plans to write down EOL wishes (56% to 100%; p < .05) and plans to talk about these wishes with someone (63% to 94%; p < .05). This study demonstrates that people living in dire economic and social situations will complete an AD when offered the opportunity. While offering guidance resulted in higher rates of completion; even a simple self-guided AD process can achieve completion of ADs in this population.

Effect of ceramic coating by aerosol deposition on abrasion resistance of a resin composite material.

PubMed

Taira, Yohsuke; Hatono, Hironori; Mizukane, Masahiro; Tokita, Masahiro; Atsuta, Mitsuru

2006-12-01

Aerosol deposition (AD coating) is a novel technique to coat solid substances with a ceramic film. The purpose of the present study was to investigate the effect of AD coating on abrasion resistance of a resin composite material. A 5-microm-thick aluminum oxide layer was created on the polymerized resin composite. The specimen was cyclically abraded using a toothbrush abrasion simulator for 100,000 cycles. Abraded surface was then measured with a profilometer to determine the average roughness (Ra) and maximum roughness (Rmax). It was found that abrasion cycling increased the Ra value of the No-AD-coating group, but decreased the Ra and Rmax values of the AD coating group. Moreover, the AD coating group showed significantly smaller Ra and Rmax values after 100,000 abrasion cycles as compared to the No-coating control group. Microscopic observation supported these findings. In conclusion, the resistance of the resin composite against toothbrush abrasion was improved by AD coating.

Comparing Crowdsourcing and Friendsourcing: A Social Media-Based Feasibility Study to Support Alzheimer Disease Caregivers

PubMed Central

Brady, Erin; Wilkerson, David; Yi, Eun-Hye; Karanam, Yamini; Callahan, Christopher M

2017-01-01

Background In the United States, over 15 million informal caregivers provide unpaid care to people with Alzheimer disease (AD). Compared with others in their age group, AD caregivers have higher rates of stress, and medical and psychiatric illnesses. Psychosocial interventions improve the health of caregivers. However, constraints of time, distance, and availability inhibit the use of these services. Newer online technologies, such as social media, online groups, friendsourcing, and crowdsourcing, present alternative methods of delivering support. However, limited work has been done in this area with caregivers. Objective The primary aims of this study were to determine (1) the feasibility of innovating peer support group work delivered through social media with friendsourcing, (2) whether the intervention provides an acceptable method for AD caregivers to obtain support, and (3) whether caregiver outcomes were affected by the intervention. A Facebook app provided support to AD caregivers through collecting friendsourced answers to caregiver questions from participants’ social networks. The study’s secondary aim was to descriptively compare friendsourced answers versus crowdsourced answers. Methods We recruited AD caregivers online to participate in a 6-week-long asynchronous, online, closed group on Facebook, where caregivers received support through moderator prompts, group member interactions, and friendsourced answers to caregiver questions. We surveyed and interviewed participants before and after the online group to assess their needs, views on technology, and experience with the intervention. Caregiver questions were pushed automatically to the participants’ Facebook News Feed, allowing participants’ Facebook friends to see and post answers to the caregiver questions (Friendsourced answers). Of these caregiver questions, 2 were pushed to crowdsource workers through the Amazon Mechanical Turk platform. We descriptively compared characteristics of these crowdsourced answers with the friendsourced answers. Results In total, 6 AD caregivers completed the initial online survey and semistructured telephone interview. Of these, 4 AD caregivers agreed to participate in the online Facebook closed group activity portion of the study. Friendsourcing and crowdsourcing answers to caregiver questions had similar rates of acceptability as rated by content experts: 90% (27/30) and 100% (45/45), respectively. Rates of emotional support and informational support for both groups of answers appeared to trend with the type of support emphasized in the caregiver question (emotional vs informational support question). Friendsourced answers included more shared experiences (20/30, 67%) than did crowdsourced answers (4/45, 9%). Conclusions We found an asynchronous, online, closed group on Facebook to be generally acceptable as a means to deliver support to caregivers of people with AD. This pilot is too small to make judgments on effectiveness; however, results trended toward an improvement in caregivers’ self-efficacy, sense of support, and perceived stress, but these results were not statistically significant. Both friendsourced and crowdsourced answers may be an acceptable way to provide informational and emotional support to caregivers of people with AD. PMID:28396304

Effect of Mild Cognitive Impairment and Alzheimer Disease on Auditory Steady-State Responses

PubMed Central

Shahmiri, Elaheh; Jafari, Zahra; Noroozian, Maryam; Zendehbad, Azadeh; Haddadzadeh Niri, Hassan; Yoonessi, Ali

2017-01-01

Introduction: Mild Cognitive Impairment (MCI), a disorder of the elderly people, is difficult to diagnose and often progresses to Alzheimer Disease (AD). Temporal region is one of the initial areas, which gets impaired in the early stage of AD. Therefore, auditory cortical evoked potential could be a valuable neuromarker for detecting MCI and AD. Methods: In this study, the thresholds of Auditory Steady-State Response (ASSR) to 40 Hz and 80 Hz were compared between Alzheimer Disease (AD), MCI, and control groups. A total of 42 patients (12 with AD, 15 with MCI, and 15 elderly normal controls) were tested for ASSR. Hearing thresholds at 500, 1000, and 2000 Hz in both ears with modulation rates of 40 and 80 Hz were obtained. Results: Significant differences in normal subjects were observed in estimated ASSR thresholds with 2 modulation rates in 3 frequencies in both ears. However, the difference was significant only in 500 Hz in the MCI group, and no significant differences were observed in the AD group. In addition, significant differences were observed between the normal subjects and AD patients with regard to the estimated ASSR thresholds with 2 modulation rates and 3 frequencies in both ears. A significant difference was observed between the normal and MCI groups at 2000 Hz, too. An increase in estimated 40 Hz ASSR thresholds in patients with AD and MCI suggests neural changes in auditory cortex compared to that in normal ageing. Conclusion: Auditory threshold estimation with low and high modulation rates by ASSR test could be a potentially helpful test for detecting cognitive impairment. PMID:29158880

Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

PubMed Central

Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

2011-01-01

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

Testing messages to reduce smokers' openness to using novel smokeless tobacco products.

PubMed

Popova, Lucy; Neilands, Torsten B; Ling, Pamela M

2014-07-01

Tobacco manufacturers' aggressive promotion of new smokeless tobacco products such as snus warrants a timely and effective public health response. This study tested potential countermarketing messages to discourage current and former smokers from becoming dual users of smokeless tobacco and cigarettes. In a pretest-post-test experiment, 1836 adult current and recently former smokers from a national sample were randomised to view one of six antismokeless tobacco ads followed by a snus ad, to view a control ad followed by a snus ad; or to view two control ads. Perceived effectiveness of ads and actual changes in attitudes and openness to snus were compared across groups using analyses of variance. Some ads that were perceived as most effective did not change attitudes or openness to trying snus, and conversely, some ads not perceived as effective changed attitudes and openness to snus. Ads portraying the negative health effects of smokeless tobacco were perceived as most effective, but ads with antitobacco industry themes significantly decreased favourable attitudes toward snus. Responses to ads were different for smokers who had ever used smokeless tobacco: for this group health effects and humorous/testimonial ads were effective. Measures of perceived effectiveness of antitobacco ads need to be augmented with measures of actual effectiveness to assess countermarketing messages. Some of the developed ads, such as ads with anti-industry themes, were effective for the overall population of smokers whereas humorous/testimonial and health effects ads were particularly effective in changing attitudes of past users of smokeless tobacco. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Content of Television Political Spot Ads for Female Candidates.

ERIC Educational Resources Information Center

Benze, James G.; Declercq, Eugene R.

1985-01-01

Compares the content of female candidates' political spot ads with that of ads for a control group of male candidates in similar contests. Concludes that the biggest differences were in images, with females less likely to stress strength and more likely to stress compassion. (FL)

Preliminary data on the effect of culture on the assessment of Alzheimer's disease-related verbal memory impairment with the International Shopping List Test.

PubMed

Lim, Yen Ying; Pietrzak, Robert H; Snyder, Peter J; Darby, David; Maruff, Paul

2012-03-01

The International Shopping List Test (ISLT) is a measure of verbal learning and memory, developed specifically for use in people from different cultural and linguistic backgrounds. In this report, we describe two studies that examined the ISLT's ability to detect memory impairment and memory decline in patients with mild Alzheimer's disease (AD) from a range of cultural and linguistic backgrounds. In Study 1, the performance of Australian-English-speaking adults with mild AD was compared with that of native Australian-English- and Korean-speaking patients with mild AD. Compared with controls, patients with AD from both language groups showed large but equivalent impairments in total recall, delayed recall, rate of learning, and primacy and retention-weighted recall (RWR) measures on the ISLT. In Study 2, the rate of deterioration in verbal memory over 1 year was examined in groups of native Canadian-English, French, and Korean speakers with mild AD using the total recall, delayed recall, and RWR measures. Rates of change on all three measures were equivalent across the language groups, although the magnitude of deterioration was most pronounced for the total recall and RWR measures. Taken together, these results suggest that the ISLT is valid and reliable for the assessment of verbal learning and memory impairment and decline in patients with mild AD from diverse language groups.

Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.

PubMed

Krishnan, Vyjayanthi; Andersen, Bo H; Shoemaker, Christine; Sivko, Gloria S; Tordoff, Kevin P; Stark, Gregory V; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew; Roberts, M Scot

2015-04-01

AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay.

PubMed

Gersch, Robert P; Fourman, Mitchell S; Phillips, Brett T; Nasser, Ahmed; McClain, Steve A; Khan, Sami U; Dagum, Alexander B; Bui, Duc T

2015-08-01

Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (10(9) pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm(2), P < 0.01 and 12.4 ± 1.2 cm(2), P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm(2)). AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not.

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

PubMed Central

Gersch, Robert P.; Fourman, Mitchell S.; Phillips, Brett T.; Nasser, Ahmed; McClain, Steve A.; Khan, Sami U.; Dagum, Alexander B.

2015-01-01

Background: Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Methods: Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (109 pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. Results: AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm2, P < 0.01 and 12.4 ± 1.2 cm2, P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm2). Conclusions: AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not. PMID:26495207

Oxidative Stress Induced in Nurses by Exposure to Preparation and Handling of Antineoplastic Drugs in Mexican Hospitals: A Multicentric Study

PubMed Central

Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; SanJuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

2014-01-01

The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses. PMID:24719678

Oxidative stress induced in nurses by exposure to preparation and handling of antineoplastic drugs in Mexican hospitals: a multicentric study.

PubMed

Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; Sanjuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

2014-01-01

The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses.

Glutamate-glutamine and GABA in brain of normal aged and patients with cognitive impairment.

PubMed

Huang, Dandan; Liu, Dan; Yin, Jianzhong; Qian, Tianyi; Shrestha, Susan; Ni, Hongyan

2017-07-01

To explore the changes of glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) in the brain in normal old age and cognitive impairment using magnetic resonance spectroscopy (MRS). Seventeen normal young controls (NYC), 15 normal elderly controls (NEC), 21 patients with mild cognitive impairment (MCI) and 17 with Alzheimer disease (AD) patients were included in this study. Glx and GABA+ levels in the anterior cingulate cortex (ACC) and right hippocampus (rHP) were measured by using a MEGA-PRESS sequence. Glx/Cr and GABA+/Cr ratios were compared between NYC and NEC and between the three elderly groups using analysis of covariance (ANCOVA); the tissue fractions of voxels were used as covariates. The relationships between metabolite ratios and cognitive performance were analysed using Spearman correlation coefficients. For NEC and NYC groups, Glx/Cr and GABA+/Cr ratios were lower in NEC in ACC and rHP. For the three elderly groups, Glx/Cr ratio was lower in AD in ACC compared to NEC and MCI; Glx/Cr ratio was lower in AD in rHP compared to NEC. There was no significant decrease for GABA+/Cr ratio. Glx and GABA levels may decrease simultaneously in normal aged, and Glx level decreased predominantly in AD, and it is helpful in the early diagnosis of AD. • Glx and GABA levels may decrease simultaneously in normal aged. • Glx level may decrease predominantly in Alzheimer disease. • The balance in excitatory-inhibitory systems may be broken in AD. • Decreased Glx level may be helpful in early diagnosis of AD.

Conserved Sequences at the Origin of Adenovirus DNA Replication

PubMed Central

Stillman, Bruce W.; Topp, William C.; Engler, Jeffrey A.

1982-01-01

The origin of adenovirus DNA replication lies within an inverted sequence repetition at either end of the linear, double-stranded viral DNA. Initiation of DNA replication is primed by a deoxynucleoside that is covalently linked to a protein, which remains bound to the newly synthesized DNA. We demonstrate that virion-derived DNA-protein complexes from five human adenovirus serological subgroups (A to E) can act as a template for both the initiation and the elongation of DNA replication in vitro, using nuclear extracts from adenovirus type 2 (Ad2)-infected HeLa cells. The heterologous template DNA-protein complexes were not as active as the homologous Ad2 DNA, most probably due to inefficient initiation by Ad2 replication factors. In an attempt to identify common features which may permit this replication, we have also sequenced the inverted terminal repeated DNA from human adenovirus serotypes Ad4 (group E), Ad9 and Ad10 (group D), and Ad31 (group A), and we have compared these to previously determined sequences from Ad2 and Ad5 (group C), Ad7 (group B), and Ad12 and Ad18 (group A) DNA. In all cases, the sequence around the origin of DNA replication can be divided into two structural domains: a proximal A · T-rich region which is partially conserved among these serotypes, and a distal G · C-rich region which is less well conserved. The G · C-rich region contains sequences similar to sequences present in papovavirus replication origins. The two domains may reflect a dual mechanism for initiation of DNA replication: adenovirus-specific protein priming of replication, and subsequent utilization of this primer by host replication factors for completion of DNA synthesis. Images PMID:7143575

Shortened cortical silent period in adductor spasmodic dysphonia: evidence for widespread cortical excitability.

PubMed

Samargia, Sharyl; Schmidt, Rebekah; Kimberley, Teresa Jacobson

2014-02-07

The purpose of this study was to compare cortical inhibition in the hand region of the primary motor cortex between subjects with focal hand dystonia (FHD), adductor spasmodic dysphonia (AdSD), and healthy controls. Data from 28 subjects were analyzed (FHD n=11, 53.25 ± 8.74 y; AdSD: n=8, 56.38 ± 7.5 y; and healthy controls: n=941.67 ± 10.85 y). All subjects received single pulse TMS to the left motor cortex to measure cortical silent period (CSP) in the right first dorsal interosseus (FDI) muscle. Duration of the CSP was measured and compared across groups. A one-way ANCOVA with age as a covariate revealed a significant group effect (p<0.001). Post hoc analysis revealed significantly longer CSP duration in the healthy group vs. AdSD group (p<0.001) and FHD group (p<0.001). These results suggest impaired intracortical inhibition is a neurophysiologic characteristic of FHD and AdSD. In addition, the shortened CSP in AdSD provides evidence to support a widespread decrease in cortical inhibition in areas of the motor cortex that represent an asymptomatic region of the body. These findings may inform future investigations of differential diagnosis as well as alternative treatments for focal dystonias. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Surveillance of home environment in children with atopic dermatitis: a questionnaire survey

PubMed Central

Lee, Jung Hyun; Suh, Jungmin; Kim, Eun Hye; Cho, Joong Bum; Park, Hwa Young; Kim, Jihyun; Cheong, Hae Kwan

2012-01-01

Background The increasing prevalence of atopic dermatitis (AD) suggests a role for environmental factors in triggering a genetic predisposition in sufferers. Objective The purpose of this study was to investigate home environmental factors related to AD severity. Methods We conducted a questionnaire survey about the home environmental factors in 380 children from two daycare centers and the Samsung Medical Center outpatient clinic. AD was diagnosed by Hanifin and Rajka's criteria and its severity was assessed by the Severity Scoring of Atopic Dermatitis index. Children were divided into normal control group, mild AD group and severe AD group. Home environmental factors were compared among the three groups and were statistically analyzed using analysis of variance, Chi-square test, Fisher's exact test, and multiple logistic analysis. Results Indoor remodeling activities, such as painting (p = 0.004), floor covering (p = 0.001) and wallpaper changing (p = 0.002) were associated with severity of AD. Those in the severe AD group were more likely to live in an apartment (p < 0.001). Severe AD was observed more frequently when the monthly income of household (p = 0.027) and final educational status of mother (p = 0.001) were higher. Conclusion Some home environmental factors were associated with AD severity, but its causal relationship is not clear. Further research is needed to confirm these associations and to clarify whether they are causative. PMID:22348208

Neuroprotective Effects of Cistanches Herba Therapy on Patients with Moderate Alzheimer's Disease

PubMed Central

Li, Nan; Wang, Jianping; Ma, Jun; Gu, Zhiqiang; Jiang, Chao; Yu, Lie

2015-01-01

Cistanches Herba (CH) is thought to be a “Yang-invigorating” material in traditional Chinese medicine. We evaluated neuroprotective effects of Cistanches Herba on Alzheimer's disease (AD) patients. Moderate AD participants were divided into 3 groups: Cistanches Herba capsule (CH, n = 10), Donepezil tablet (DON, n = 8), and control group without treatment (n = 6). We assessed efficacy by MMSE and ADAS-cog, and investigated the volume changes of hippocampus by 1.5 T MRI scans. Protein, mRNA levels, and secretions of total-tau (T-tau), tumor necrosis factor-α (TNF-α), and interleukin- (IL) 1β (IL-1β) in cerebrospinal fluid (CSF) were detected by Western blot, RT-PCR, and ELISA. The scores showed statistical difference after 48 weeks of treatment compared to control group. Meanwhile, volume changes of hippocampus were slight in drug treatment groups but distinct in control group; the levels of T-tau, TNF-α, and IL-1β were decreased compared to those in control group. Cistanches Herba could improve cognitive and independent living ability of moderate AD patients, slow down volume changes of hippocampus, and reduce the levels of T-tau, TNF-α, and IL-1β. It suggested that Cistanches Herba had potential neuroprotective effects for moderate AD. PMID:26435722

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial.

PubMed

Park, Kyung Won; Kim, Eun-Joo; Han, Hyun Jeong; Shim, Yong S; Kwon, Jae C; Ku, Bon D; Park, Kee Hyung; Yi, Hyon-Ah; Kim, Kwang K; Yang, Dong Won; Lee, Ho-Won; Kang, Heeyoung; Kwon, Oh Dae; Kim, SangYun; Lee, Jae-Hyeok; Chung, Eun Joo; Park, Sang-Won; Park, Mee Young; Yoon, Bora; Kim, Byeong C; Seo, Sang Won; Choi, Seong Hye

2017-01-01

Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups. Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs. ClinicalTrials.gov NCT01380288.

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer’s dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial

PubMed Central

Kim, Eun-Joo; Han, Hyun Jeong; Shim, Yong S.; Kwon, Jae C.; Ku, Bon D.; Park, Kee Hyung; Yi, Hyon-Ah; Kim, Kwang K.; Yang, Dong Won; Lee, Ho-Won; Kang, Heeyoung; Kwon, Oh Dae; Kim, SangYun; Lee, Jae-Hyeok; Chung, Eun Joo; Park, Sang-Won; Park, Mee Young; Yoon, Bora; Kim, Byeong C.; Seo, Sang Won; Choi, Seong Hye

2017-01-01

Background and objective Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer’s disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. Methods Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. Results Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups. Conclusions Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs. Trial registration ClinicalTrials.gov NCT01380288 PMID:28786987

Differentiating the frontal variant of Alzheimer's disease.

PubMed

Woodward, Michael; Jacova, Claudia; Black, Sandra E; Kertesz, Andrew; Mackenzie, Ian R; Feldman, Howard

2010-07-01

Individuals with a clinical diagnosis of Alzheimer's disease (AD) may have prominent features of executive dysfunction and language impairment as well as behavioral abnormalities early in the disease ('high frontality'). When this occurs differentiation from frontotemporal dementia (FTD) is difficult. It is hypothesized that AD patients with high frontality may have clinical and pathological features that distinguish them from less frontal AD patients. In a well-characterized cohort of people with cognitive impairment, we used the Frontal Behavioral Inventory (FBI) in an attempt to identify AD patients with prominent frontal features (high-FBI AD) and distinguish them from the remainder of AD patients (low-FBI AD). The 18 high-FBI AD patients were compared with the 26 FTD patients who had an FBI performed and the 53 other low FBI AD patients. The individual FBI items did not differ significantly between the FTD and the high-FBI AD patients, and the high FBI AD patients were more like the FTD patients than the other AD patients with respect to presence of a family history of AD, proportion with homozygous apolipoprotein E(4) status, disability as measured by the Disability Assessment for Dementia (DAD) Scale and the Functional Rating Scale (FRS) and neuropsychiatric impairment as measured by the Neuropsychiatric Inventory (NPI). Memory symptom duration was similar in the high FBI AD group compared to the low FBI AD group. There is a subgroup of AD patients with high frontality that can be clinically distinguished from the remainder of AD patients but which requires pathological verification. (c) 2009 John Wiley & Sons, Ltd.

[Effect of lead and selenium on learning and memory ability in rats].

PubMed

Han, Xiaojie; Hu, Xiaoxia; Wei, Qing; Chen, Yilin; Yu, De'e; Hu, Qiansheng

2013-11-01

To study the effect of lead and (or) selenium on learning and memory ability in rats. SPF Wistar rats, after weaning, were divided into six groups, control group, Pb group (respectively Pb exposed), Se group (respectively Se added), Pb-Se group (added Se after Pb exposure), Se-Pb group (added Se before Pb exposure) and Pb + Se group (Pb and Se exposed simultaneously). After intervention for six weeks in rats, the spatial learning and memory of each group rats were measured by Morris water maze assay. Rats in Pb group had significantly longer latency, less site crossings, less percentage of time and distance spent in the target quadrant, and bigger first bearing compared with control group (P < 0.05). Rats in Pb and Se joint exposure groups had significantly shorter latency, more site crossings, less percentage of time and distance spent in the target quadrant, and smaller first bearing compared with Pb group (P < 0.05). There were no significant differences in the indexes of spatial learning and memory ability between the groups of lead and selenium joint exposure groups (P > 0.05). Lead damaged the ability of learning and memory in rats and organic selenium had protective effects on Pb-induced spatial learning and memory deficits in rats.

Linkage of sleep-disordered breathing and acute aortic dissection with patent false lumen.

PubMed

Inami, Toru; Seino, Yoshihiko; Shimura, Tetsuro; Kurihara, Osamu; Kimata, Nakahisa; Murakami, Daisuke; Munakata, Ryo; Takano, Masamichi; Ohba, Takayoshi; Shimizu, Wataru

2016-07-01

Sleep-disordered breathing (SDB) is known as a cardiovascular risk factor and has high prevalence in hypertension, which is a major risk factor of aortic dissection (AD). However, the impact of SDB on AD has not been fully clarified. The aim of this study is to elucidate the impact of SDB on AD, especially on the type of false lumen in AD. We enrolled twenty-three consecutive patients with acute AD (mean age: 66 ± 13 years). All subjects were evaluated by an ambulatory polygraphic sleep monitoring within 1 month from the onset. AD was evaluated by axial images of computed tomography. We comparatively analyzed SDB and AD. 35 % of the subjects presented severe OSA (apnea-hypopnea index: AHI ≥30). The patent false lumen group showed significantly higher systolic and diastolic blood pressure (BP) on arrival and AHI, and lower percutaneous oxygen saturation (SaO2) compared with those in the thrombosed false lumen group. The prevalence of severe SDB was higher in the patent false lumen group (60 vs 15 %, p = 0.039). Systolic BP on arrival was significantly correlated with AHI (r = 0.457, p = 0.033) and the minimum SaO2 (r = -0.537, p = 0.010). The present study revealed close linkage between SDB and AD, and a high prevalence of SDB among AD patients. Severe SDB was related to the development of AD, especially for the patent false lumen type through highly elevated BP which might be easily evoked in the presence of severe SDB. Repetitive occurrence of intrathoracic negative pressure also might influence the repair or closure of false lumen of AD, although the present analysis did not reach statistical significance.

Early differentiation of dementia with Lewy bodies and Alzheimer's disease: Heart rate variability at mild cognitive impairment stage.

PubMed

Kim, Min Seung; Yoon, Jung Han; Hong, Ji Man

2018-05-29

Our study aimed to investigate whether heart rate variability (HRV) could be a useful diagnostic screening tool at MCI (mild cognitive impairment) stage of Dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). This retrospective study used a selected sample from Ajou neurological registry. We identified MCI patients who underwent HRV testing at baseline, and who developed probable DLB (MCI-DLB: n = 23) or AD (MCI-AD: n = 32). The MCI-DLB group exhibited significantly lower levels of almost all HRV parameters compared with the MCI-AD group. Fronto-executive function and visuospatial abilities were poorer in the MCI-DLB group, whereas the extent of verbal memory impairment was greater in the MCI-AD. Verbal memory score was negatively correlated with overall HRV parameters, and visuospatial function was positively correlated with the frequency domain of HRV. Receiver operating curve area under the curve (AUC) analysis revealed that the low frequency component was the best potential diagnostic marker (AUC = 0.88). MCI-DLB patients exhibited greater cardiac autonomic dysfunction (as measured by HRV) and greater fronto-executive and visuospatial deficit compared with MCI-AD patients. HRV may be useful method to differentiate DLB from AD in patients with MCI; this would facilitate early disease-specific intervention. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimer’s Disease patients: A pilot study

PubMed Central

González-Castañeda, Rocío E.; Sánchez-González, Víctor J.; Flores-Soto, Mario; Vázquez-Camacho, Gonzalo; Macías-Islas, Miguel A.; Ortiz, Genaro G.

2013-01-01

Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer’s Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p < 0.05, U test). ChAT protein levels were reduced by 17% (p = 0.02, U test). NRSF gene expression levels were 86% higher in the AD group (p = 0.001, U test) as compared to the control group. In the AD subjects, the NRSF protein levels were 57% higher (p > 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels. PMID:23569405

Risk of Recurrence of Preexisting Ocular Toxoplasmosis during Pregnancy.

PubMed

Reich, Michael; Ruppenstein, Mira; Becker, Matthias D; Mackensen, Friederike

2015-06-01

Comparison between the risk of recurrence during pregnancy with nonpregnant periods in patients with ocular toxoplasmosis (OT). Records of 40 women were retrospectively reviewed. The women were subdivided into either a pregnant group or a control group formed by nonpregnant women during follow-up. Comparable cases from the literature were added. Mean number of recurrences per year was compared. Eleven women with pregnancies could be included. Six cases from the literature were added (total n = 17). Mean number of recurrences per year during versus not during pregnancy was 0.16 (SD 0.39) versus 0.32 (SD 0.30; p = 0.088), respectively. In the control group (n = 29) the mean number of recurrences per year (0.31; SD 0.27) was significantly higher when compared to cases during pregnant periods (p = 0.002). Adding to published series, the presented data do not provide evidence for a relevant impact of pregnancy on recurrence behavior in OT.

Comparison of triglycerides and phospholipids as supplemental sources of dietary long-chain polyunsaturated fatty acids in piglets.

PubMed

Mathews, Susan A; Oliver, William T; Phillips, Oulayvanh T; Odle, Jack; Diersen-Schade, Deborah A; Harrell, Robert J

2002-10-01

Addition of arachidonic acid (AA) and docosahexaenoic acid (DHA) to infant formula promotes visual and neural development. This study was designed to determine whether the source of dietary long-chain polyunsaturated fatty acids (LCPUFA) affected overall animal health and safety. Piglets consumed ad libitum from 1 to 16 d of age a skim milk-based formula with different fat sources added to provide 50% of the metabolizable energy. Treatment groups were as follows: control (CNTL; no added LCPUFA), egg phospholipid (PL), algal/fungal triglyceride (TG) oils, TG plus PL (soy lecithin source) added to match phospholipid treatment (TG + PL) and essential fatty acid deficient (EFAD). Formulas with LCPUFA provided 0.6 and 0.3 g/100 g total fatty acids as AA and DHA, respectively. CNTL piglets had 40% longer ileal villi than PL piglets (P < 0.03), but the TG group was not different from the CNTL group. Gross liver histology did not differ among any of the formula-fed groups (P > 0.1). Apparent dry matter digestibility was 10% greater in CNTL, TG and TG + PL groups compared with PL piglets (P < 0.002). No differences in alanine aminotransferase were detected among treatments, but aspartate aminotransferase was elevated (P < 0.03) in PL piglets compared with TG + PL piglets. Total plasma AA concentration was greater in the TG group compared with CNTL piglets (P < 0.05). Total plasma DHA concentrations were greater in TG piglets compared with PL (P < 0.06) or CNTL (P < 0.02) piglets. These data demonstrate that the algal/fungal TG sources of DHA and AA may be a more appropriate supplement for infant formulas than the egg PL source based on piglet plasma fatty acid profiles and apparent dry matter digestibilities.

Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients

PubMed Central

Corlier, F; Rivals, I; Lagarde, J; Hamelin, L; Corne, H; Dauphinot, L; Ando, K; Cossec, J-C; Fontaine, G; Dorothée, G; Malaplate-Armand, C; Olivier, J-L; Dubois, B; Bottlaender, M; Duyckaerts, C; Sarazin, M; Potier, M-C; Alnajjar-Carpentier, Dr Amer; Logak, Dr Michel; Leder, Dr Sara; Marchal, Dr Dominique; Pitti-Ferandi, Dr Hélène; Brugeilles, Dr Hélene; Roualdes, Dr Brigitte; Michon, Dr Agnes

2015-01-01

Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C11]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker. PMID:26151923

Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections.

PubMed

Krut, Jan Jessen; Zetterberg, Henrik; Blennow, Kaj; Cinque, Paola; Hagberg, Lars; Price, Richard W; Studahl, Marie; Gisslén, Magnus

2013-02-01

The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ(1-42)), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -β). CSF Aβ(1-42), sAPPα and -β, t-tau and p-tau were analysed in bacterial meningitis (n = 12), Lyme neuroborreliosis (n = 13), herpes simplex virus type 1 (HSV-1) encephalitis (n = 10), HIV-associated dementia (HAD) (n = 21), AD (n = 21) and healthy controls (n = 42). Concurrent with AD, Aβ(1-42) was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -β compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aβ(1-42), sAPPα and -β in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aβ(1-42), but differs concerning sAPPα and -β. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis.

Visual Perceptual Organization Ability in Autopsy-Verified Dementia with Lewy Bodies and Alzheimer’s Disease

PubMed Central

Mitolo, Micaela; Hamilton, Joanne M.; Landy, Kelly M.; Hansen, Lawrence A.; Galasko, Douglas; Pazzaglia, Francesca; Salmon, David P.

2018-01-01

Objectives Prominent impairment of visuospatial processing is a feature of dementia with Lewy bodies (DLB), and diagnosis of this impairment may help clinically distinguish DLB from Alzheimer’s disease (AD). The current study compared autopsy-confirmed DLB and AD patients on the Hooper Visual Organization Test (VOT), a test that requires perceptual and mental reorganization of parts of an object into an identifiable whole. The VOT may be particularly sensitive to DLB since it involves integration of visual information processed in separate dorsal and ventral visual “streams”. Methods Demographically similar DLB (n = 28), AD (n = 115), and normal control (NC; n = 85) participants were compared on the VOT and additional neuropsychological tests. Patient groups did not differ in dementia severity at time of VOT testing. High and Low AD-Braak stage DLB subgroups were compared to examine the influence of concomitant AD pathology on VOT performance. Results Both patient groups were impaired compared to NC participants. VOT scores of DLB patients were significantly lower than those of AD patients. The diagnostic sensitivity and specificity of the VOT for patients versus controls was good, but marginal for DLB versus AD. High-Braak and low-Braak DLB patients did not differ on the VOT, but High-Braak DLB performed worse than Low-Braak DLB on tests of episodic memory and language. Conclusions Visual perceptual organization ability is more impaired in DLB than AD but not strongly diagnostic. The disproportionate severity of this visual perceptual deficit in DLB is not related to degree of concomitant AD pathology, which suggests that it might primarily reflect Lewy body pathology. PMID:27221597

Pharmacokinetic and Pharmacodynamic Interaction of Boswellic Acids and Andrographolide with Glyburide in Diabetic Rats: Including Its PK/PD Modeling.

PubMed

Samala, Sujatha; Veeresham, Ciddi

2016-03-01

The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin-induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t1/2, and mean residence time, and decreased the clearance, Vd, markedly as compared with the control group. In rat liver, microsomes BA and AD have shown CYP3A4 inhibitory activity significantly (p < 0.01), compared with the vehicle group. The increase in hypoglycemic action by concomitant administration of glyburide with BA or AD was more in diabetic rats than when the drugs were used singly and with the control group, which suggests the enhancement of glucose reduction capacity of glyburide in diabetic rats along with BA or AD. In PK/PD modeling of BA and AD with glyburide, the predicted PK and PD parameters are in line with the observed PK and PD parameters. The results revealed that BA and AD led to the PK/PD changes because of glyburide-increased bioavailability and because of the inhibition of CYP3A4 enzyme. In conclusion, add-on preparations containing BA or AD may increase the bioavailability of glyburide, and hence the dose should be monitored. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of levothyroxine on learning and memory deficits in a rat model of Alzheimer's disease: the role of BDNF and oxidative stress.

PubMed

Bavarsad, Kowsar; Hadjzadeh, Mousa-Al-Reza; Hosseini, Mahmoud; Pakdel, Roghayeh; Beheshti, Farimah; Bafadam, Soleyman; Ashaari, Zeinab

2018-06-21

The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively. Finally, the rats were euthanized, their blood samples were collected for further thyroxine assessment and their brains were removed after decapitation in order to measure the oxidative stress parameters and brain-derived neurotrophic factor (BDNF). In the MWM, latency (s) increased in the AD rats compared with the normal control group while it decreased in the 10 μg/kg L-T4 injected AD rats compared with the AD group. In the PA, the latency for entering the dark compartment was lower in the AD group than in the normal control group and it decreased in the 10 μg/kg L-T4 injected AD rats. The low dose of L-T4 (10 μg/kg) reduced malondialdehyde concentration but increased thiols concentration, superoxide dismutase, catalase activities and BDNF level in hippocampal tissues of the AD rats. Injection of L-T4 (10 μg/kg) alleviated memory deficits and also improved factors of oxidative stress and BDNF level in the STZ-induced AD rats.

Differential Interactions between Comorbid Anxiety Disorders and Substance Use Disorder in Rapid Cycling Bipolar I or II Disorder

PubMed Central

Gao, Keming; Tolliver, Bryan; Kemp, David E.; Verduin, Marcia L.; Ganocy, Stephen J.; Bilali, Sarah; Brady, Kathleen; Shim, Seong S.; Findling, Robert; Calabrese, Joseph R.

2008-01-01

Objective Anxiety disorders (AD) and substance use disorders (SUD) commonly co-occur with bipolar disorder. This study was undertaken to assess AD-SUD-bipolar subtype interactions. Methods Extensive clinical interview and MINI were used to ascertain DSM-IV diagnoses of rapid cycling bipolar I (RCBPDI) or II (RCBPDII) disorder, SUDs, and ADs including generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD). Data at the initial assessment of four studies was used to compare the prevalence differences in ADs between RCBPDI and RCBPDII by using protocol-defined SUD categories, “Never,” “Lifetime, but not recent,” or “Recent.” Results Five-hundred sixty-six of 568 patients (RCBPDI n=320, RCBPDII n=246) were eligible for analyses. In the “Never” group (n=191), patients with RCBPDI and RCBPDII had similar risk for ADs. In the “Lifetime, but not recent” group (n=195), RCBPDI patients had significantly higher risks for GAD (OR=3.29), PD (OR=2.95), but not OCD, compared with their RCBPDII counterparts. Similarly, in the “Recent” group (n=180), RCBPDI patients also had significantly higher risks for GAD (OR=3.6), PD (OR=3.8), but not OCD, compared with their RCBPDII counterparts. Limitations Data were cross-sectional and not all ADs were included. Conclusion In this large cohort of patients with rapid cycling bipolar disorder, risk for having GAD, PD, but not OCD increased significantly in patients with bipolar I disorder compared to their bipolar II counterparts when a history of SUD was present. However, there were no significant differences in the risk for GAD, PD, or OCD between the subtypes among patients without a history of SUD. PMID:18234350

Everyday problem solving in African Americans and European Americans with Alzheimer's disease: an exploratory study.

PubMed

Ripich, Danielle N; Fritsch, Thomas; Ziol, Elaine

2002-03-01

In this exploratory study, we compared the performance of 10 African American and 26 European American persons with early- to mid-stage Alzheimer's disease (AD) to 20 nondemented elderly (NE), using a shortened version of the Test of Problem Solving (TOPS). The TOPS measures verbal reasoning to solve everyday problems in five areas: explaining inferences, determining causes, answering negative why questions, determining solutions, and avoiding problems. Six linguistic measures were also examined: total utterances, abandoned utterances, length of utterances, maze words, questions, and total words. NE performed better than AD subjects on all but one measure of verbal reasoning ability. AD subjects also showed a trend to use more total utterances and abandoned utterances than NE. For the AD group, no ethnic differences were found for verbal reasoning or linguistic measures. The findings from this preliminary investigation suggest that, compared to European Americans, African American persons with AD demonstrate similar everyday problem solving and linguistic skills. Thus, assessments such as TOPS that examine everyday problem solving may be a useful nonbiased evaluation tool for persons with AD in these two ethnic groups.

Topical Tetracycline Improves MC903-induced Atopic Dermatitis in Mice through Inhibition of Inflammatory Cytokines and Thymic Stromal Lymphopoietin Expression.

PubMed

Liu, Xiao-Jing; Mu, Zhang-Lei; Zhao, Yan; Zhang, Jian-Zhong

2016-06-20

Tetracycline (TET) has been found to have both antibiotic and anti-inflammatory properties. The anti-inflammatory effect of topical TET on atopic dermatitis (AD) has not been reported. The purpose of this study was to explore the potential role of topical TET and its anti-inflammatory effects in a mouse model of AD. The 2% TET was applied topically to ears of MC903-induced AD-like BALB/c mice once a day. AD-like symptoms and severity were evaluated by assessing skin scoring of dermatitis, ear thickness, and frequency of scratching. Serum IgE and thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay. Western blot was used for analyzing the expressions of TSLP, protease-activated receptor 2 (PAR2), and nuclear factor-kappa B (NF-κB) in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of TSLP and inflammatory cytokines including interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-α, and IL-1β in skin lesions. Scoring of dermatitis (9.00 ± 0.63 vs. 6.67 ± 1.03, P = 0.001), ear thickness (0.44 ± 0.02 mm vs. 0.40 ± 0.03 mm, P = 0.018), and serum IgE level (421.06 ± 212.13 pg/ml vs. 244.15 ± 121.39 pg/ml, P = 0.047) were all improved in the 2% TET treatment group compared with AD group. Topical TET significantly reduced the serum level of TSLP (119.04 ± 38.92 pg/ml vs. 65.95 ± 54.61 pg/ml, P = 0.011) and both mRNA and protein expressions of TSLP in skin lesions compared with AD group (P = 0.003 and 0.011, respectively), and NF-κB and PAR2 expression in skin lesions were also suppressed (P = 0.016 and 0.040, respectively). Furthermore, expressions of inflammatory cytokines IL-4, IL-13, and TNF-α in skin lesions were down-regulated in 2% TET group compared with AD group (P = 0.035, 0.008, and 0.044, respectively). Topical TET exerted anti-inflammatory effects through suppression of TSLP and inflammatory cytokines in AD mouse model, suggesting TET as a potential agent for the topical treatment of AD in the future.

Comparing Crowdsourcing and Friendsourcing: A Social Media-Based Feasibility Study to Support Alzheimer Disease Caregivers.

PubMed

Bateman, Daniel Robert; Brady, Erin; Wilkerson, David; Yi, Eun-Hye; Karanam, Yamini; Callahan, Christopher M

2017-04-10

In the United States, over 15 million informal caregivers provide unpaid care to people with Alzheimer disease (AD). Compared with others in their age group, AD caregivers have higher rates of stress, and medical and psychiatric illnesses. Psychosocial interventions improve the health of caregivers. However, constraints of time, distance, and availability inhibit the use of these services. Newer online technologies, such as social media, online groups, friendsourcing, and crowdsourcing, present alternative methods of delivering support. However, limited work has been done in this area with caregivers. The primary aims of this study were to determine (1) the feasibility of innovating peer support group work delivered through social media with friendsourcing, (2) whether the intervention provides an acceptable method for AD caregivers to obtain support, and (3) whether caregiver outcomes were affected by the intervention. A Facebook app provided support to AD caregivers through collecting friendsourced answers to caregiver questions from participants' social networks. The study's secondary aim was to descriptively compare friendsourced answers versus crowdsourced answers. We recruited AD caregivers online to participate in a 6-week-long asynchronous, online, closed group on Facebook, where caregivers received support through moderator prompts, group member interactions, and friendsourced answers to caregiver questions. We surveyed and interviewed participants before and after the online group to assess their needs, views on technology, and experience with the intervention. Caregiver questions were pushed automatically to the participants' Facebook News Feed, allowing participants' Facebook friends to see and post answers to the caregiver questions (Friendsourced answers). Of these caregiver questions, 2 were pushed to crowdsource workers through the Amazon Mechanical Turk platform. We descriptively compared characteristics of these crowdsourced answers with the friendsourced answers. In total, 6 AD caregivers completed the initial online survey and semistructured telephone interview. Of these, 4 AD caregivers agreed to participate in the online Facebook closed group activity portion of the study. Friendsourcing and crowdsourcing answers to caregiver questions had similar rates of acceptability as rated by content experts: 90% (27/30) and 100% (45/45), respectively. Rates of emotional support and informational support for both groups of answers appeared to trend with the type of support emphasized in the caregiver question (emotional vs informational support question). Friendsourced answers included more shared experiences (20/30, 67%) than did crowdsourced answers (4/45, 9%). We found an asynchronous, online, closed group on Facebook to be generally acceptable as a means to deliver support to caregivers of people with AD. This pilot is too small to make judgments on effectiveness; however, results trended toward an improvement in caregivers' self-efficacy, sense of support, and perceived stress, but these results were not statistically significant. Both friendsourced and crowdsourced answers may be an acceptable way to provide informational and emotional support to caregivers of people with AD. ©Daniel Robert Bateman, Erin Brady, David Wilkerson, Eun-Hye Yi, Yamini Karanam, Christopher M Callahan. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 10.04.2017.

Relationship between Delusion of Theft and Cognitive Functions in Patients with Mild Alzheimer's Disease.

PubMed

Na, Hae-Ran; Kang, Dong Woo; Woo, Young-Sup; Bahk, Won-Myong; Lee, Chang-Uk; Lim, Hyun Kook

2018-04-01

Although delusion of theft (DT) is the most frequent type of delusion in Alzheimer's disease (AD), its relationship to cognitive functions remains unclear. The aim of this study was to demonstrate the relationship between DT and cognitive functions in mild AD. Two hundred eighty-nine mild AD patients were enrolled in this study. These subjects were classified into three groups: patients with no delusions (ND, n=82), patients with paranoid delusions (PD, n=114) and patients with DT (n=93). Cognitive functions and their associations with the degree of delusion were compared among the three groups. The results showed that verbal Fluency scores were significantly lower in the PD group than in the DT and ND groups. Word List Recall scores were significantly lower in the DT group than in the PD and ND groups. Interestingly, delusion severity measured with the Neuropsychiatric Inventory delusion subscale correlated negatively with the Word List Recall scores in the DT group. In this study, we demonstrated that episodic memory functions in mild AD patients were associated with DT, but not with PD. Further studies might be needed to clarify the pathophysiology of delusions associated with AD.

Relationship between Delusion of Theft and Cognitive Functions in Patients with Mild Alzheimer’s Disease

PubMed Central

Na, Hae-Ran; Kang, Dong Woo; Woo, Young-Sup; Bahk, Won-Myong; Lee, Chang-Uk; Lim, Hyun Kook

2018-01-01

Although delusion of theft (DT) is the most frequent type of delusion in Alzheimer’s disease (AD), its relationship to cognitive functions remains unclear. The aim of this study was to demonstrate the relationship between DT and cognitive functions in mild AD. Two hundred eighty-nine mild AD patients were enrolled in this study. These subjects were classified into three groups: patients with no delusions (ND, n=82), patients with paranoid delusions (PD, n=114) and patients with DT (n=93). Cognitive functions and their associations with the degree of delusion were compared among the three groups. The results showed that verbal Fluency scores were significantly lower in the PD group than in the DT and ND groups. Word List Recall scores were significantly lower in the DT group than in the PD and ND groups. Interestingly, delusion severity measured with the Neuropsychiatric Inventory delusion subscale correlated negatively with the Word List Recall scores in the DT group. In this study, we demonstrated that episodic memory functions in mild AD patients were associated with DT, but not with PD. Further studies might be needed to clarify the pathophysiology of delusions associated with AD. PMID:29669410

The brain structural and cognitive basis of odor identification deficits in mild cognitive impairment and Alzheimer’s disease

PubMed Central

2014-01-01

Background The objectives of this study were to explore the relationship between olfactory impairment, cognitive measures, and brain structure volumes in healthy elderly individuals, compared to patients with amnestic mild cognitive impairment (aMCI) or early Alzheimer’s disease (AD). The primary aim was to elucidate possible differences in cognitive scores and brain structure volumes between aMCI/AD patients with relatively intact odor identification (OI) ability and those with reduced ability. Methods Twelve patients with aMCI, six with early AD, and 30 control subjects were included. OI abilities were assessed with the Brief Smell Identification Test (B-SIT) and Sniffin Sticks Identification Test (SSIT). Neuropsychological tests of executive functions and memory were performed. Brain structural volumes were obtained from T1 weighted 3D MRI at 3 Tesla. Statistical comparisons between the patients with aMCI and AD indicated no significant differences in performance on most tests. Since the groups were small and AD patients were in an early phase of disease, all patients were subsequently considered together as a single group for studying OI. Patients were subdivided into relatively intact (scores >50%) and reduced OI (≤ 50% score) on the olfactory tests. Results The aMCI/AD group with reduced OI ability, as measured by both B-SIT and SSIT, had significantly smaller hippocampal volume as compared to the patient group with OI scores > 50%. There was a significant association between OI scores and hippocampal volume in the patient (not the control) group. Similar changes with tests of executive function and memory were not found. Low OI scores on B-SIT were associated with conversion from aMCI to AD in patients. The reduced OI patient group was significantly faster on Rey complex figure copying than the fairly intact OI group. Conclusion The results from this pilot study suggest that the reduction in the size of hippocampus in connection with early AD is associated more with loss of OI ability rather than loss of memory, thus demonstrating that impaired OI is an early marker of medial temporal lobe degeneration. PMID:25154749

[Atopic dermatitis and prolonged exclusive breast-feeding].

PubMed

Amri, M; Elhani, I; Doussari, S; Amir, A

2012-04-01

We sought to compare the prevalence of exclusive breastfeeding throughout at least the first 6 months of life in patients presenting atopic dermatitis (AD) with a control group, and to check for a correlation between the duration of exclusive breastfeeding and the severity of AD. We conducted a case-control study with prospective inclusion over a period of 3 years. The study group consisted of 114 patients aged less than 15 years, from an urban area, presenting AD but with no personal or family history of atopy. Each patient was compared with two controls from the same town, matched for age and gender, with no personal or family history of atopy, and free of AD. Data analysis was performed using the SPSS software package, version 15.0. A P-value of less than 0.05 was considered as statistically significant. The prevalence of exclusive breastfeeding for at least the first 6 months of life in the patient group was significantly lower than in the control group (P=0.0413). On the other hand, AD was significantly less severe in patients exclusively breastfed for longer than 9 months (P=0.0079). The correlations recorded in our study do not allow us to draw any definite conclusions about a protective effect of exclusive breastfeeding with regard to AD. However, other benefits of extended exclusive breastfeeding justify supporting breastfeeding in a community with an existing sociocultural predisposition for this feeding method. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Correlation between disease severity and brain electric LORETA tomography in Alzheimer's disease.

PubMed

Gianotti, Lorena R R; Künig, Gabriella; Lehmann, Dietrich; Faber, Pascal L; Pascual-Marqui, Roberto D; Kochi, Kieko; Schreiter-Gasser, Ursula

2007-01-01

To compare EEG power spectra and LORETA-computed intracortical activity between Alzheimer's disease (AD) patients and healthy controls, and to correlate the results with cognitive performance in the AD group. Nineteen channel resting EEG was recorded in 21 mild to moderate AD patients and in 23 controls. Power spectra and intracortical LORETA tomography were computed in seven frequency bands and compared between groups. In the AD patients, the EEG results were correlated with cognitive performance (Mini Mental State Examination, MMSE). AD patients showed increased power in EEG delta and theta frequency bands, and decreased power in alpha2, beta1, beta2 and beta3. LORETA specified that increases and decreases of power affected different cortical areas while largely sparing prefrontal cortex. Delta power correlated negatively and alpha1 power positively with the AD patients' MMSE scores; LORETA tomography localized these correlations in left temporo-parietal cortex. The non-invasive EEG method of LORETA localized pathological cortical activity in our mild to moderate AD patients in agreement with the literature, and yielded striking correlations between EEG delta and alpha1 activity and MMSE scores in left temporo-parietal cortex. The present data support the hypothesis of an asymmetrical progression of the Alzheimer's disease.

Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

PubMed Central

Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

2012-01-01

Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

Comparing Neuropsychological Profiles between Girls with Asperger's Disorder and Girls with Learning Disabilities

ERIC Educational Resources Information Center

McKnight, Megan E.; Culotta, Vincent P.

2012-01-01

Research examining neuropsychological profiles of girls with Asperger's disorder (AD) is sparse. In this study, we sought to characterize neurocognitive profiles of girls with AD compared to girls with learning disabilities (LD). Two groups of school-age girls referred for neuropsychological assessment participated in the study. A total of 23…

Age-related defects in erythrocyte 2,3-diphosphoglycerate metabolism in dementia.

PubMed

Kaminsky, Yury G; Reddy, V Prakash; Ashraf, Ghulam Md; Ahmad, Ausaf; Benberin, Valery V; Kosenko, Elena A; Aliev, Gjumrakch

2013-01-01

Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive "reporter cells" that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA.

Diagnostic performance of the atopy patch test with inhalant allergens.

PubMed

Fuiano, N; Diddi, G; Delvecchio, M; Incorvaia, C

2015-01-01

This study evaluated the diagnostic performance of the atopy patch test (APT) compared with skin prick testing (SPT) and in vitro IgE measurement in a large group of patients with atopic dermatitis (AD) with or without respiratory symptoms (RS). The study included 521 patients (292 males, 229 females; age, 0.5-18 years; median age, 6 years) with AD and RS with different clinical presentations: current AD, 47 patients (Group A); current AD and RS, 72 patients (Group B), past AD and RS, 69 patients (Group C); and RS only, 280 patients (Group D). Fifty-three healthy individuals served as controls. All participants underwent the APT, SPT, and CAP/RAST with the most common inhalant allergens. The presence of a control group allowed calculation of specificity and positive and negative predictive values. A significant difference was found for a positive APT versus both SPT and CAP/RAST (P < .0001) but not for SPT versus CAP/RAST. The differences for APT were significant in all group comparisons except group B vs C and group C vs D. In the control group, the APT was positive in 2% of cases (specificity of 96.2%), SPT was positive in 6% of cases (specificity of 88.4%), and CAP/RAST was positive in 4% of cases (specificity of 92.5%). In young patients sensitized to inhalant allergens with AD in addition to RS, the APT has a superior diagnostic performance to SPT and in vitro IgE measurement.

Brain Metabolic Dysfunction in Capgras Delusion During Alzheimer's Disease: A Positron Emission Tomography Study.

PubMed

Jedidi, H; Daury, N; Capa, R; Bahri, M A; Collette, F; Feyers, D; Bastin, C; Maquet, P; Salmon, E

2015-11-01

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer's disease (AD) and Capgras syndrome was compared with those of 24-healthy elderly participants and 26 patients with AD without delusional syndrome. Comparing the healthy group with the AD group, the patient with AD had significant hypometabolism in frontal and posterior midline structures. In the light of current neural models of face perception, our patients with Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex. © The Author(s) 2013.

Changes of EEG Spectra and Functional Connectivity during an Object-Location Memory Task in Alzheimer's Disease.

PubMed

Han, Yuliang; Wang, Kai; Jia, Jianjun; Wu, Weiping

2017-01-01

Object-location memory is particularly fragile and specifically impaired in Alzheimer's disease (AD) patients. Electroencephalogram (EEG) was utilized to objectively measure memory impairment for memory formation correlates of EEG oscillatory activities. We aimed to construct an object-location memory paradigm and explore EEG signs of it. Two groups of 20 probable mild AD patients and 19 healthy older adults were included in a cross-sectional analysis. All subjects took an object-location memory task. EEG recordings performed during object-location memory tasks were compared between the two groups in the two EEG parameters (spectral parameters and phase synchronization). The memory performance of AD patients was worse than that of healthy elderly adults The power of object-location memory of the AD group was significantly higher than the NC group (healthy elderly adults) in the alpha band in the encoding session, and alpha and theta bands in the retrieval session. The channels-pairs the phase lag index value of object-location memory in the AD group was clearly higher than the NC group in the delta, theta, and alpha bands in encoding sessions and delta and theta bands in retrieval sessions. The results provide support for the hypothesis that the AD patients may use compensation mechanisms to remember the items and episode.

Mindfulness in the Maintenance of Cognitive Capacities in Alzheimer's Disease: A Randomized Clinical Trial.

PubMed

Quintana-Hernández, Domingo J; Miró-Barrachina, María T; Ibáñez-Fernández, Ignacio J; Pino, Angelo Santana-Del; Quintana-Montesdeoca, María P; Rodríguez-de Vera, Bienvenida; Morales-Casanova, David; Pérez-Vieitez, María Del Carmen; Rodríguez-García, Javier; Bravo-Caraduje, Noelia

2016-01-01

The Canary Islands longitudinal study on non-pharmacological treatments showed the overall effectiveness of mindfulness in Alzheimer's disease (AD). However, no specific data on the maintenance of cognitive capacities were presented. To determine whether the practice of mindfulness modifies the course of cognitive impairment in AD. Longitudinal, non-inferiority and equivalence, randomized clinical trial, repeated-measures design, with three experimental groups and one control group. Patients with AD who voluntarily attended the Lidia García Foundation (n = 502). Only those who were treated with donepezil and MMSE ≥18 were included (n = 120). Over a two-year period, each group carried out three weekly sessions of stimulation based on mindfulness, cognitive stimulation therapy, and progressive muscle relaxation. Cognitive assessment CAMDEX-R (MMSE and CAMCOG). Repeated-measures ANOVA (p <  0.05) and the effect size Cohen's d were performed. The mindfulness group showed significant scores compared with the control and muscle relaxation groups (p <  0.05), while mindfulness and cognitive stimulation therapy were equivalent (p≥0.05). Group cognitive stimulation evolved better than the control (p <  0.05) group but not better than the muscle relaxation group (p≥0.05). The effect size compared over two years was large for the mindfulness group (p≥0.80), moderate for the relaxation group (p≥0.50), and low for the cognitive stimulation group (p≥0.20). The practice of mindfulness maintained cognitive function over a period of two years. This longitudinal study suggests that mindfulness can be used as a non-pharmacological treatment to slow cognitive impairment in AD.

Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients.

PubMed

Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

2016-01-19

Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide.

Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients

PubMed Central

Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

2016-01-01

Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide. PMID:26784730

Analysis on Multicast Routing Protocols for Mobile Ad Hoc Networks

NASA Astrophysics Data System (ADS)

Xiang, Ma

As the Mobile Ad Hoc Networks technologies face a series of challenges like dynamic changes of topological structure, existence of unidirectional channel, limited wireless transmission bandwidth, the capability limitations of mobile termination and etc, therefore, the research to mobile Ad Hoc network routings inevitablely undertake a more important task than those to other networks. Multicast is a mode of communication transmission oriented to group computing, which sends the data to a group of host computers by using single source address. In a typical mobile Ad Hoc Network environment, multicast has a significant meaning. On the one hand, the users of mobile Ad Hoc Network usually need to form collaborative working groups; on the other hand, this is also an important means of fully using the broadcast performances of wireless communication and effectively using the limited wireless channel resources. This paper summarizes and comparatively analyzes the routing mechanisms of various existing multicast routing protocols according to the characteristics of mobile Ad Hoc network.

Suppression of colorectal tumorigenesis by recombinant Bacteroides fragilis enterotoxin-2 in vivo.

PubMed

Lv, You; Ye, Tao; Wang, Hui-Peng; Zhao, Jia-Ying; Chen, Wen-Jie; Wang, Xin; Shen, Chen-Xia; Wu, Yi-Bin; Cai, Yuan-Kun

2017-01-28

To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Recombinant proBFT-2 was expressed in Escherichia coli strain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activity via colorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank (BC; n = 10), model (AD; n = 20), model + low-dose toxin (ADLT; n = 20, 10 μg), and a model + high-dose toxin (ADHT; n = 20, 20 μg) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistry determined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa. Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group (21.82 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group (21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 2.16, P < 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group ( P < 0.05, P < 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group (94.44%, P < 0.05, P < 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group (16.67%, P < 0.05, P < 0.05). Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice.

Suppression of colorectal tumorigenesis by recombinant Bacteroides fragilis enterotoxin-2 in vivo

PubMed Central

Lv, You; Ye, Tao; Wang, Hui-Peng; Zhao, Jia-Ying; Chen, Wen-Jie; Wang, Xin; Shen, Chen-Xia; Wu, Yi-Bin; Cai, Yuan-Kun

2017-01-01

AIM To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS). METHODS Recombinant proBFT-2 was expressed in Escherichia coli strain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activity via colorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank (BC; n = 10), model (AD; n = 20), model + low-dose toxin (ADLT; n = 20, 10 μg), and a model + high-dose toxin (ADHT; n = 20, 20 μg) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistry determined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa. RESULTS Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group (21.82 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group (21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 2.16, P < 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group (P < 0.05, P < 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group (94.44%, P < 0.05, P < 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group (16.67%, P < 0.05, P < 0.05). CONCLUSION Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice. PMID:28216966

Physiological falls risk assessment in older people with Alzheimer's disease.

PubMed

Lorbach, Edwina R; Webster, Kate E; Menz, Hylton B; Wittwer, Joanne E; Merory, John R

2007-01-01

Falls are common in people with Alzheimer's disease (AD). There is some evidence that deficits in vision, peripheral sensation, strength, reaction time and balance may be partly responsible for this increased risk. To determine the feasibility and test-retest reliability of a physiological test battery designed to assess falls risk [the Physiological Profile Assessment (PPA)] in people with AD, and to compare their PPA scores to age- and sex-matched controls. Twenty-one community-dwelling people with probable, mild to moderate AD aged 63-91 years, and 21 age- and sex-matched controls underwent the PPA tests and the Mini-Mental State Examination. All tests were then repeated in the AD group to determine test-retest reliability. Most of the PPA tests could be successfully administered to participants with AD. The AD group had a significantly higher overall falls risk score (t(40) = -2.41, p < 0.02), slower hand (t(40) = -4.86, p < 0.01) and foot reaction time (t(40) = -2.26, p < 0.05) and worse coordinated stability (t(40) = -2.40, p < 0.05) than the controls. Physiological falls risk assessment is feasible in older people with mild to moderate AD. Older people with AD demonstrate significant impairments in several physiological domains, particularly reaction time, compared to controls.

An Inverse U-Shaped Curve of Resting-State Networks in Individuals at High Risk of Alzheimer's Disease.

PubMed

Ye, Qing; Chen, Haifeng; Su, Fan; Shu, Hao; Gong, Liang; Xie, Chunming; Zhou, Hong; Bai, Feng

Higher functional connectivity (FC) in resting-state networks has been shown in individuals at risk of Alzheimer's disease (AD) by many studies. However, the longitudinal trajectories of the FC remain unknown. The present 35-month follow-up study aimed to explore longitudinal changes in higher FC in multiple resting-state networks in subjects with the apolipoprotein E ε4 allele (ApoE4) and/or amnestic mild cognitive impairment (aMCI). Fifty-one subjects with aMCI and 64 cognitively normal (CN) subjects underwent neuropsychological tests and resting-state functional magnetic resonance imaging (fMRI) scans twice from April 2011 to June 2015. Subjects were divided into 4 groups according to diagnosis and ApoE4 status. The CN non-ApoE4 group served as a control group, and other groups served as AD risk groups. The cross-sectional and longitudinal patterns of multiple resting-state networks, including default mode network, hippocampus network, executive control network, and salience network, were explored by comparing FC data between groups and between time points, respectively. At baseline, compared with the control group, the AD risk groups showed higher FC with 8 regions in multiple networks. At follow-up, 6 of the regions displayed longitudinally decreased FC in AD risk groups. In contrast, the FC with all of these regions was maintained in the control group. Notably, among the 3 risk groups, most of the higher FC at baseline (5 of the 8 regions) and longitudinally decreased FC at follow-up (4 of the 6 regions) were shown in the aMCI ApoE4 group. Higher resting-state FC is followed by a decline in subjects at AD risk, and this inverse U-shaped trajectory is more notable in subjects with higher risk. © Copyright 2018 Physicians Postgraduate Press, Inc.

Differential Atrophy of Hippocampal Subfields: A Comparative Study of Dementia with Lewy Bodies and Alzheimer Disease.

PubMed

Mak, Elijah; Su, Li; Williams, Guy B; Watson, Rosie; Firbank, Michael; Blamire, Andrew; O'Brien, John

2016-02-01

Dementia with Lewy bodies (DLB) is characterized by relative preservation of the medial temporal lobe compared with Alzheimer disease (AD). The differential involvement of the hippocampal subfields in both diseases has not been clearly established, however. We aim to investigate hippocampal subfield differences in vivo in a clinical cohort of DLB and AD subjects. 104 participants (35 DLBs, 36 ADs, and 35 healthy comparison [HC] subjects) underwent clinical assessment and 3T T1-weighted imaging. A Bayesian model implemented in Freesurfer was used to automatically segment the hippocampus and its subfields. We also examined associations between hippocampal subfields and tests of memory function. Both the AD and DLB groups demonstrated significant atrophy of the total hippocampus relative to HC but the DLB group was characterized by preservation of the cornu ammonis 1 (CA1), fimbria, and fissure. In contrast, all the hippocampal subfields except the fissure were significantly atrophied in AD compared with both DLB and HC groups. Among DLB subjects, CA1 was correlated with the Recent Memory score of the CAMCOG and Delayed Recall subscores of the HVLT. DLB is characterized by milder hippocampal atrophy that was accompanied by preservation of the CA1. The CA1 was also associated with memory function in DLB. Our findings highlight the promising role of hippocampal subfield volumetry, particularly that of the CA1, as a biomarker for the distinction between AD and DLB. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Lipid peroxidation and antioxidant status in rat: effect of food restriction and wheel running.

PubMed

Filaire, Edith; Rouveix, Matthieu; Massart, Alain; Gladine, Cécile; Davicco, Marie Jeanne; Durand, Denys

2009-09-01

Using the activity-based anorexia model, the aim of this investigation was to explore antioxidant enzyme activity (catalase, superoxide dismutase), total antioxidant status (TAS), and alpha-tocopherol in blood, liver, and gastrocnemius muscle associated with the food restriction and voluntary wheel running during 8 days. In addition, lipid peroxidation was measured by measurements of malondialdehyde (MDA). Wistars rats (n = 56) were randomly assigned to one of four groups: an ad lib sedentary group, a control wheel activity group, a food restriction-induced hyperactivity group (1 h/day ad lib food, 23 h/day ad lib wheel access), and a food-restricted sedentary group. The animals were killed when the rats in the food-restricted group had lost 25% of their free feeding weight. Antioxidant enzyme activities and TAS in blood, liver, and gastrocnemius muscle were unaffected by voluntary wheel running. A wheel activity effect (P < 0.05) was obtained for the MDA concentrations in plasma, with lower concentrations in trained animals. Food restriction effects were obtained for antioxidant capacity in liver, as well as for CAT activity in the gastrocnemius muscle and plasma MDA concentrations with lower values in the restricted animals. On the other hand, the food-restricted rats showed higher plasma TAS concentrations (P < 0.05) and higher alpha-tocopherol concentrations in the liver (P < 0.05) when compared to animals fed ad libitum. Our results also showed that food restriction coupled to wheel running decreased antioxidant parameters in liver, and plasmatic MDA concentrations and increased TAS plasma concentrations when compared to the ad libitum sedentary situation.

Effectiveness of a handwriting readiness program in head start: a two-group controlled trial.

PubMed

Lust, Carol A; Donica, Denise K

2011-01-01

This study measured skill improvement in prewriting skills, kindergarten readiness, first-name writing, and handwriting-nonspecific fine motor skills of students at Head Start who participated in Handwriting Without Tears-Get Set for School (HWT-GSS) programming. We conducted a two-group, nonrandomized controlled trial using a pretest-posttest design at a rural Head Start. The effectiveness of adding the HWT-GSS curriculum in one preschool classroom was compared with a control classroom. On posttesting, the experimental group made significant improvements compared with the control group in prewriting, kindergarten readiness, and fine motor skills. Both groups made significant improvements between pretesting and posttesting in prewriting, first name writing, and school readiness. Adding HWT-GSS to the Head Start program would be beneficial in improving handwriting readiness skills.

Lower-extremity function in cognitively healthy aging, mild cognitive impairment, and Alzheimer's disease.

PubMed

Eggermont, Laura H; Gavett, Brandon E; Volkers, Karin M; Blankevoort, Christiaan G; Scherder, Erik J; Jefferson, Angela L; Steinberg, Eric; Nair, Anil; Green, Robert C; Stern, Robert A

2010-04-01

To examine differences in lower-extremity function in cognitive healthy older persons, older persons with mild cognitive impairment (MCI), and older persons with Alzheimer's disease (AD). Descriptive study. University Alzheimer's disease clinical and research program. Older persons (N=66) were studied (mean age, 76.7y); 22 were cognitively normal, 22 were diagnosed with probable MCI, 22 were diagnosed with probable AD. Not applicable. Lower-extremity function was assessed by the four-meter walk test (4MWT), Timed Up & Go (TUG) test, and sit-to-stand (STS) test. Analysis of variance, adjusting for covariates, revealed that performance on the 4MWT was significantly lower in the MCI and AD groups as compared with controls. TUG test performance was worse in the AD group compared with controls. No significant group differences were found for STS performance. These results suggest an association between cognitive impairment and lower-limb function in older persons. Walking speed could be evaluated for its possible utility in screening older persons at risk for cognitive impairment and falls. Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Structural and functional connectional fingerprints in mild cognitive impairment and Alzheimer's disease patients.

PubMed

Son, Seong-Jin; Kim, Jonghoon; Park, Hyunjin

2017-01-01

Regional volume atrophy and functional degeneration are key imaging hallmarks of Alzheimer's disease (AD) in structural and functional magnetic resonance imaging (MRI), respectively. We jointly explored regional volume atrophy and functional connectivity to better characterize neuroimaging data of AD and mild cognitive impairment (MCI). All data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compared regional volume atrophy and functional connectivity in 10 subcortical regions using structural MRI and resting-state functional MRI (rs-fMRI). Neuroimaging data of normal controls (NC) (n = 35), MCI (n = 40), and AD (n = 30) were compared. Significant differences of regional volumes and functional connectivity measures between groups were assessed using permutation tests in 10 regions. The regional volume atrophy and functional connectivity of identified regions were used as features for the random forest classifier to distinguish among three groups. The features of the identified regions were also regarded as connectional fingerprints that could distinctively separate a given group from the others. We identified a few regions with distinctive regional atrophy and functional connectivity patterns for NC, MCI, and AD groups. A three label classifier using the information of regional volume atrophy and functional connectivity of identified regions achieved classification accuracy of 53.33% to distinguish among NC, MCI, and AD. We identified distinctive regional atrophy and functional connectivity patterns that could be regarded as a connectional fingerprint.

Structural and functional connectional fingerprints in mild cognitive impairment and Alzheimer’s disease patients

PubMed Central

Son, Seong-Jin; Kim, Jonghoon

2017-01-01

Regional volume atrophy and functional degeneration are key imaging hallmarks of Alzheimer’s disease (AD) in structural and functional magnetic resonance imaging (MRI), respectively. We jointly explored regional volume atrophy and functional connectivity to better characterize neuroimaging data of AD and mild cognitive impairment (MCI). All data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compared regional volume atrophy and functional connectivity in 10 subcortical regions using structural MRI and resting-state functional MRI (rs-fMRI). Neuroimaging data of normal controls (NC) (n = 35), MCI (n = 40), and AD (n = 30) were compared. Significant differences of regional volumes and functional connectivity measures between groups were assessed using permutation tests in 10 regions. The regional volume atrophy and functional connectivity of identified regions were used as features for the random forest classifier to distinguish among three groups. The features of the identified regions were also regarded as connectional fingerprints that could distinctively separate a given group from the others. We identified a few regions with distinctive regional atrophy and functional connectivity patterns for NC, MCI, and AD groups. A three label classifier using the information of regional volume atrophy and functional connectivity of identified regions achieved classification accuracy of 53.33% to distinguish among NC, MCI, and AD. We identified distinctive regional atrophy and functional connectivity patterns that could be regarded as a connectional fingerprint. PMID:28333946

Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression.

PubMed

Zetterberg, Henrik; Skillbäck, Tobias; Mattsson, Niklas; Trojanowski, John Q; Portelius, Erik; Shaw, Leslie M; Weiner, Michael W; Blennow, Kaj

2016-01-01

The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons. To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. A commercially available immunoassay was used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (β = -4177, P = .003), ventricular volume (β = 1835, P < .001), and hippocampus volume (β = -54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (β = -1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (β = 2.30, P < .001); and faster white matter intensity change (β = 598.7, P < .001). Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time. This finding corroborates the contention that degeneration of large-caliber axons is an important feature of AD neurodegeneration.

Implications of comorbidity on costs for patients with Alzheimer disease.

PubMed

Kuo, Tzu-Chun; Zhao, Yang; Weir, Sharada; Kramer, Marilyn Schlein; Ash, Arlene S

2008-08-01

No prior studies have used a comprehensive clinical classification system to examine the effect of differences in overall illness burden and the presence of other diseases on costs for patients with Alzheimer disease (AD) when compared with demographically matched nondemented controls. Of a total of 627,775 enrollees who were eligible for medical and pharmacy benefits for 2003 and 2004 in the MarketScan Medicare Supplemental and Coordination of Benefits Database, we found 25,109 AD patients. For each case, 3 demographically matched nondemented controls were selected using propensity scores. Applying the diagnostic cost groups (DCGs) model to all enrollees, 2003 diagnoses were used to estimate prospective relative risk scores (RRSs) that predict 2004 costs from all illness other than AD. RRSs were then used to control for illness burden to estimate AD's independent effect on costs. Compared with the control group, the AD cohort has more comorbid conditions (8.1 vs. 6.5) and higher illness burden (1.23 vs. 1.04). Individuals with AD are more likely to have mental health conditions, neurologic conditions, cognitive disorders, cerebrovascular disease, diabetes with acute complications, and injuries. Annual costs for AD patients are $3567 (34%) higher than for controls. Excess costs attributable to AD, after controlling for non-AD illness burden, are estimated at $2307 per year with outpatient pharmacy being the key driver ($1711 in excess costs). AD patients are sicker and more expensive than demographically matched controls. Even after adjusting for differences in illness burden, costs remain higher for AD patients.

Moderate Changes in the Circadian System of Alzheimer's Disease Patients Detected in Their Home Environment.

PubMed

Weissová, Kamila; Bartoš, Aleš; Sládek, Martin; Nováková, Marta; Sumová, Alena

2016-01-01

Alzheimer's disease (AD) is a neurodegenerative disease often accompanied with disruption of sleep-wake cycle. The sleep-wake cycle is controlled by mechanisms involving internal timekeeping (circadian) regulation. The aim of our present pilot study was to assess the circadian system in patients with mild form of AD in their home environment. In the study, 13 elderly AD patients and 13 age-matched healthy control subjects (the patient's spouses) were enrolled. Sleep was recorded for 21 days by sleep diaries in all participants and checked by actigraphy in 4 of the AD patient/control couples. The samples of saliva and buccal mucosa were collected every 4 hours during the same 24 h-interval to detect melatonin and clock gene (PER1 and BMAL1) mRNA levels, respectively. The AD patients exhibited significantly longer inactivity interval during the 24 h and significantly higher number of daytime naps than controls. Daily profiles of melatonin levels exhibited circadian rhythms in both groups. Compared with controls, decline in amplitude of the melatonin rhythm in AD patients was not significant, however, in AD patients more melatonin profiles were dampened or had atypical waveforms. The clock genes PER1 and BMAL1 were expressed rhythmically with high amplitudes in both groups and no significant differences in phases between both groups were detected. Our results suggest moderate differences in functional state of the circadian system in patients with mild form of AD compared with healthy controls which are present in conditions of their home dwelling.

Detection of Alzheimer's disease using group lasso SVM-based region selection

NASA Astrophysics Data System (ADS)

Sun, Zhuo; Fan, Yong; Lelieveldt, Boudewijn P. F.; van de Giessen, Martijn

2015-03-01

Alzheimer's disease (AD) is one of the most frequent forms of dementia and an increasing challenging public health problem. In the last two decades, structural magnetic resonance imaging (MRI) has shown potential in distinguishing patients with Alzheimer's disease and elderly controls (CN). To obtain AD-specific biomarkers, previous research used either statistical testing to find statistically significant different regions between the two clinical groups, or l1 sparse learning to select isolated features in the image domain. In this paper, we propose a new framework that uses structural MRI to simultaneously distinguish the two clinical groups and find the bio-markers of AD, using a group lasso support vector machine (SVM). The group lasso term (mixed l1- l2 norm) introduces anatomical information from the image domain into the feature domain, such that the resulting set of selected voxels are more meaningful than the l1 sparse SVM. Because of large inter-structure size variation, we introduce a group specific normalization factor to deal with the structure size bias. Experiments have been performed on a well-designed AD vs. CN dataset1 to validate our method. Comparing to the l1 sparse SVM approach, our method achieved better classification performance and a more meaningful biomarker selection. When we vary the training set, the selected regions by our method were more stable than the l1 sparse SVM. Classification experiments showed that our group normalization lead to higher classification accuracy with fewer selected regions than the non-normalized method. Comparing to the state-of-art AD vs. CN classification methods, our approach not only obtains a high accuracy with the same dataset, but more importantly, we simultaneously find the brain anatomies that are closely related to the disease.

Magnetoencephalography for the Detection of Intervention Effects of a Specific Nutrient Combination in Patients with Mild Alzheimer’s Disease: Results from an Exploratory Double-Blind, Randomized, Controlled Study

PubMed Central

van Straaten, Elisabeth C. W.; de Waal, Hanneke; Lansbergen, Marieke M.; Scheltens, Philip; Maestu, Fernando; Nowak, Rafal; Hillebrand, Arjan; Stam, Cornelis J.

2016-01-01

Synaptic loss is an early pathological finding in Alzheimer’s disease (AD) and correlates with memory impairment. Changes in macroscopic brain activity measured with electro- and magnetoencephalography (EEG and MEG) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials. EEG peak frequency and functional networks have shown, in addition to improved memory performance, to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn® Connect, which is designed to enhance synapse formation and function. Here, we explore the value of MEG, with higher spatial resolution than EEG, in identifying intervention effects of the nutrient combination by comparing MEG spectral measures, functional connectivity, and networks between an intervention and a control group. Quantitative markers describing spectral properties, functional connectivity, and graph theoretical aspects of MEG from the exploratory 24-week, double-blind, randomized, controlled Souvenir II MEG sub-study (NTR1975, http://www.trialregister.nl) in drug naïve patients with mild AD were compared between a test group (n = 27), receiving Souvenaid, and a control group (n = 28), receiving an isocaloric control product. The groups were unbalanced at screening with respect to Mini-Mental State Examination. Peak frequencies of MEG were compared with EEG peak frequencies, recorded in the same patients at similar time points, were compared with respect to sensitivity to intervention effects. No consistent statistically significant intervention effects were detected. In addition, we found no difference in sensitivity between MEG and EEG peak frequency. This exploratory study could not unequivocally establish the value of MEG in detecting interventional effects on brain activity, possibly due to small sample size and unbalanced study groups. We found no indication that the difference could be attributed to a lack of sensitivity of MEG compared with EEG. MEG in randomized controlled trials is feasible but its value to disclose intervention effects of Souvenaid in mild AD patients needs to be studied further. PMID:27799918

Magnetoencephalography for the Detection of Intervention Effects of a Specific Nutrient Combination in Patients with Mild Alzheimer's Disease: Results from an Exploratory Double-Blind, Randomized, Controlled Study.

PubMed

van Straaten, Elisabeth C W; de Waal, Hanneke; Lansbergen, Marieke M; Scheltens, Philip; Maestu, Fernando; Nowak, Rafal; Hillebrand, Arjan; Stam, Cornelis J

2016-01-01

Synaptic loss is an early pathological finding in Alzheimer's disease (AD) and correlates with memory impairment. Changes in macroscopic brain activity measured with electro- and magnetoencephalography (EEG and MEG) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials. EEG peak frequency and functional networks have shown, in addition to improved memory performance, to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn ® Connect, which is designed to enhance synapse formation and function. Here, we explore the value of MEG, with higher spatial resolution than EEG, in identifying intervention effects of the nutrient combination by comparing MEG spectral measures, functional connectivity, and networks between an intervention and a control group. Quantitative markers describing spectral properties, functional connectivity, and graph theoretical aspects of MEG from the exploratory 24-week, double-blind, randomized, controlled Souvenir II MEG sub-study (NTR1975, http://www.trialregister.nl) in drug naïve patients with mild AD were compared between a test group ( n  = 27), receiving Souvenaid, and a control group ( n  = 28), receiving an isocaloric control product. The groups were unbalanced at screening with respect to Mini-Mental State Examination. Peak frequencies of MEG were compared with EEG peak frequencies, recorded in the same patients at similar time points, were compared with respect to sensitivity to intervention effects. No consistent statistically significant intervention effects were detected. In addition, we found no difference in sensitivity between MEG and EEG peak frequency. This exploratory study could not unequivocally establish the value of MEG in detecting interventional effects on brain activity, possibly due to small sample size and unbalanced study groups. We found no indication that the difference could be attributed to a lack of sensitivity of MEG compared with EEG. MEG in randomized controlled trials is feasible but its value to disclose intervention effects of Souvenaid in mild AD patients needs to be studied further.

[Effects of the association of sulbutiamine with an acetylcholinesterase inhibitor in early stage and moderate Alzheimer disease].

PubMed

Ollat, H; Laurent, B; Bakchine, S; Michel, B-F; Touchon, J; Dubois, B

2007-01-01

The efficacy of the inhibitors of acetylcholinesterase in Alzheimer's Disease (AD) is moderated and some patients do not respond to these treatments. Sulbutiamine potentializes cholinergic and glutamatergic transmissions, mainly in hippocampus and prefrontal cortex. This multicentric, randomized and double-blind trial evaluates the effects of the association of sulbutiamine to an anticholinesterasic drug in cognitive functions in patients with AD at an early stage (episodic memory, working memory, executive functions, attention). Patients had first donepezil (D) or sulbutiamine (S) during three months. During this period, only attention improved in both groups. During the three following months, a placebo (P) in patients D and donepezil in patients S were added. Compared to entry results, episodic memory decreased in group D + P but improved in group S + D. At the same time the improvement of attention persisted in both groups. Daylife activities only improved in group S + D. In conclusion sulbutiamine can be an adjuvant to treatment in early stage and moderate AD by anticholinesterasic drugs.

Prevalence of Comorbidity in Patients With Young-Onset Alzheimer Disease Compared With Late-Onset: A Comparative Cohort Study.

PubMed

Gerritsen, Adrie A J; Bakker, Christian; Verhey, Frans R J; de Vugt, Marjolein E; Melis, René J F; Koopmans, Raymond T C M

2016-04-01

With the lack of a cure for Alzheimer disease (AD), the identification of comorbidity is important to reduce the possibility of excess disability. Although comorbidity in patients with late-onset AD (LO-AD) is common, for people with young-onset AD (YO-AD), it is unclear how often comorbidity occurs. Furthermore, it is uncertain whether comorbidity in patients with YO-AD differs from that in patients with LO-AD. The aim of this study was to explore the prevalence, types of morbidity, and morbidity profiles in patients with YO-AD compared with those of patients with LO-AD. Explorative cohort study from 2 separate Dutch cohorts (Needs in Young-onset Dementia [NeedYD] and the Clinical Course of Cognition and Comorbidity-Dementia Study [4C-Dementia study]). Participants were recruited in 2007 and 2008 from (1) the memory clinics of 3 Dutch Alzheimer centers, (2) the memory clinics of general hospitals, (3) mental health services in the southern part of the Netherlands, and (4) young-onset dementia specialized day care facilities. A comparison group of community-dwelling, elderly patients with AD was selected from the 4C-Dementia study. Patients in this study were recruited in 2010 and 2011 from the aforementioned Alzheimer centers. The prevalence rates of comorbidity were compared between 177 patients with YO-AD and 155 patients with LO-AD. Comorbidity was classified using the International Classification of Diseases, 10th Revision (ICD-10). The total amount of comorbidity was established by counting the number of existing diseases (ICD categories or chapters) and comorbidity was also dichotomized as present or absent. Furthermore, a hierarchical cluster analysis was performed to study clusters of comorbidity. Compared with LO-AD, patients with YO-AD showed less (P < .001) overall comorbidity (58.2% vs 86.5%) and had lower prevalence rates of diabetes, obesity, and circulatory diseases; however, the prevalence rates of diseases of the nervous system in YO-AD (6.2%) were higher compared with those of patients with LO-AD (4.5%). The cluster analysis revealed a distinctive group of patients with YO-AD with either no comorbidity or with a disease of the nervous system. Endocrine, nutritional, and metabolic diseases and diseases of the circulatory system were present in 34% of the patients with YO-AD. Comorbidity is less common in YO-AD than in LO-AD. However, general practitioners should be aware that approximately one-third of the patients with YO-AD suffer from or have endocrine, nutritional, and metabolic diseases and/or diseases of the circulatory system. Treatment should therefore not only focus on dementia but also on comorbidity. This attention may slow the functional decline in AD. These exploratory analyses suggested a higher prevalence of nervous system diseases in YO-AD compared with LO-AD. However, the finding did not reach statistical significance and in combination with the exploratory nature of the analyses justifies further investigation. If verified, this finding may help to decrease the time to diagnosis of AD and, subsequently, support in young patients with a neurological disease. Further investigation is needed to gain more insight into the association between comorbidity and AD in younger people. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Taste detection and recognition thresholds in Japanese patients with Alzheimer-type dementia.

PubMed

Ogawa, Takao; Irikawa, Naoya; Yanagisawa, Daijiro; Shiino, Akihiko; Tooyama, Ikuo; Shimizu, Takeshi

2017-04-01

Alzheimer-type dementia (AD) is pathologically characterized by massive neuronal loss in the brain, and the taste cortex is thought to be affected. However, there are only a few reports regarding the gustatory function of AD patients, and the conclusions of this research are inconsistent. This prospective study enrolled 22 consecutive patients with mild to moderately severe Alzheimer-type dementia (AD) with mean age of 84.0 years, and 49 elderly volunteers without dementia with mean age of 71.0 years as control subjects. The control subjects were divided into two groups according to age: a younger group (N=28, mean age: 68.5) and an older group (N=21, mean age: 83.0). The gustatory function was investigated using the filter paper disc method (FPD) and electrogustometry (EGM). The gustatory function as measured by the FPD was significantly impaired in patients with AD as compared with age-matched control subjects; no such difference was found between the younger and the older control groups. On the other hand, as for the EGM thresholds, there were no differences between the AD patient group and the age-matched controls. The FPD method demonstrated decreased gustatory function in AD patients beyond that of aging. On the other hand, EGM thresholds did not differ between the AD patient group and the age-matched controls. These results suggest that failure of taste processing in the brain, but not taste transmission in the peripheral taste system, occurs in patients with AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Asian sand dust aggregate causes atopic dermatitis-like symptoms in Nc/Nga mice.

PubMed

Takeshita, Sayaka; Tokunaga, Takahiro; Tanabe, Yoshiko; Arinami, Tadao; Ichinose, Takamichi; Noguchi, Emiko

2015-01-01

Asian sand dust (ASD) originates from the arid and semiarid areas of China, and epidemiologic studies have shown that ASD exposure is associated with various allergic and respiratory symptoms. However, few studies have been performed to assess the relationship between skin inflammation and ASD exposure. Twelve-week-old NC/Nga mice were divided into 6 groups (n = 8 for each group): hydrophilic petrolatum only (control); hydrophilic petrolatum plus ASD (ASD); hydrophilic petrolatum and heat inactivated-ASD (H-ASD); Dermatophagoides farinae extract (Df); Df and ASD (Df + ASD), and; Df and H-ASD (Df + H-ASD). The NC/Nga mice in each group were subjected to treatment twice a week for 4 weeks. We evaluated skin lesions by symptoms, pathologic changes, and serum IgE levels. ASD alone did not induce atopic dermatitis (AD)-like skin symptoms. However, Df alone, Df + H-ASD and Df + ASD all induced AD-like symptoms, and dermatitis scores in the group of Df + ASD group were significantly greater than that of the Df group (P = 0.0011 at day 21; and P = 0.017 at day 28). Mean serum IgE was markedly increased in the Df and Df + ASD groups, compared to the ASD and control groups (P < 0.0001), and serum IgE levels in the Df + ASD group were significantly higher compared to the Df group (P = 0.003). ASD alone did not cause AD-like symptoms in NC/Nga mice. However, AD-like symptoms induced by Df, a major allergen, were enhanced by adding ASD. Although no epidemiological studies have been conducted for the association between ASD and symptoms of dermatitis, our data suggest that it is likely that ASD may contribute to the exacerbation of not only respiratory symptoms, but also skin diseases, in susceptible individuals.

Evaluating the Effectiveness of GTM-1, Rapamycin, and Carbamazepine on Autophagy and Alzheimer Disease.

PubMed

Zhang, Lijuan; Wang, Lina; Wang, Run; Gao, Yuan; Che, Haoyue; Pan, Yonghua; Fu, Peng

2017-02-14

BACKGROUND This study was proposed to compare the efficacy and safety of GTM-1, Rapamycin (Rap), and Carbamazepine (CBZ) in managing Alzheimer disease (AD). The impact of the above mentioned therapeutic drugs on autophagy was also investigated in our study. MATERIAL AND METHODS Firstly, 3×Tg AD mice were randomly allocated into 4 groups (each group with 10 mice), in which AD mice were separately treated with dimethylsulfoxide (DMSO, vehicle group), GTM-1 (6 mg/kg), Rap (1 mg/kg), and CBZ (100 mg/kg). Then spatial memory and learning ability of mice was tested using the Morris water maze. Routine blood tests were performed to evaluate the toxicity of these drugs. Amyloid-β42 (Aβ42) concentration was detected by ELISA and immunohistochemistry. Proteins related to autophagy were detected by Western blot. RESULTS GTM-1, Rap, and CBZ significantly improved the spatial memory of 3×Tg AD mice compared to that in the vehicle group (all P<0.05). Moreover, this study revealed that CBZ dosage was related to toxicity in mice. All of the above drugs significantly increased the expression of LC3-II and reduced Aβ42 levels in hippocampi of 3×Tg AD mice (all P<0.05). On the other hand, neither GTM-1 nor CBZ had significant influence on the expression of proteins on the mTOR pathway. CONCLUSIONS GTM-1 can alleviate the AD syndrome by activating autophagy in a manner that is dependent on the mTOR pathway and it therefore can be considered as an alternative to Rap.

Cognitive-behavioural group therapy improves a psychophysiological marker of stress in caregivers of patients with Alzheimer's disease.

PubMed

Aboulafia-Brakha, T; Suchecki, D; Gouveia-Paulino, F; Nitrini, R; Ptak, R

2014-01-01

Family caregivers of patients with dementia frequently experience psychological stress, depression and disturbed psychophysiological activity, with increased levels of diurnal cortisol secretion. To compare the effects of a cognitive-behavioural group therapy (CBT) to a psychoeducation group programme (EDUC) on cortisol secretion in caregivers of patients with moderate Alzheimer's disease (AD). Caregivers of AD outpatients were semi-randomly allocated to one of two intervention programmes (CBT or EDUC) consisting of eight weekly sessions. Twenty-six participants completed the study. Before and after intervention, salivary cortisol was collected at four different times of the day. Effects of the interventions were evaluated with self-report psychological scales and questionnaires related to functional abilities and neuropsychiatric symptoms of the AD relative. Only in the CBT group did salivary cortisol levels significantly decrease after intervention, with a large effect size and high achieved power. Both groups reported a reduction of neuropsychiatric symptoms of their AD relative after intervention. Psychoeducation for caregivers may contribute to a reduction of neuropsychiatric symptoms of AD patients while CBT additionally attenuates psychophysiological responses to stressful situations in caregivers, by reducing diurnal cortisol levels. This may lead to a positive impact in the general health of the caregiver, eventually resulting in better care of the AD patient.

Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer's Disease.

PubMed

Cacciamani, Federica; Tandetnik, Caroline; Gagliardi, Geoffroy; Bertin, Hugo; Habert, Marie-Odile; Hampel, Harald; Boukadida, Laurie; Révillon, Marie; Epelbaum, Stéphane; Dubois, Bruno

2017-01-01

Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer's disease (AD). In this study, we searched for a specific pattern of SCD in asymptomatic individuals at risk for AD. Cognitively normal older adults (N = 318) reporting SCD and their informants were enrolled in the INSIGHT-PreAD cohort. We examined the relationship between six SCD measures and both cognitive scores and AD neuroimaging markers (amyloid burden, hippocampal atrophy and brain hypometabolism). An awareness of cognitive decline index (ACDI) has been introduced based on the subject-informant discrepancy in a questionnaire of SCD and participants with low versus high awareness were compared. Scores in the INSIGHT-PreAD SCD questionnaires did not correlate with AD neuroimaging markers. As well, no correlation has been found between SCD measures and cognitive scores. Comparing subjects with a low (n = 19) and high (n = 86) level of awareness, no significant difference in terms of demography, neuropsychiatric symptoms, autonomy, quality of life, cognition, and hippocampal volume was found. However, the "low awareness" group showed greater amyloid burden and lower cortical metabolism, compared to the "high awareness" group. This study provided additional evidence that reporting SCD by itself is not a specific symptom of preclinical AD. Conversely, a low cognitive awareness (namely, when subjects report fewer difficulties than their relatives do) may represent a very early form of anosognosia and serve as a specific indicator of preclinical AD. This finding is of key importance as an enrichment factor to consider in both clinical practice and research trials.

Reconstructing the Geomagnetic Field in West Africa: First Absolute Intensity Results from Burkina Faso

NASA Astrophysics Data System (ADS)

Kapper, Lisa; Donadini, Fabio; Serneels, Vincent; Tema, Evdokia; Goguitchaichvili, Avto; Julio Morales, Juan

2017-03-01

We present absolute geomagnetic intensities from iron smelting furnaces discovered at the metallurgical site of Korsimoro, Burkina Faso. Up to now, archaeologists recognized four different types of furnaces based on different construction methods, which were related to four subsequent time periods. Additionally, radiocarbon ages obtained from charcoal confine the studied furnaces to ages ranging from 700-1700 AD, in good agreement with the archaeologically determined time periods for each type of furnace. Archaeointensity results reveal three main groups of Arai diagrams. The first two groups contain specimens with either linear Arai diagrams, or slightly curved diagrams or two phases of magnetization. The third group encompasses specimens with strong zigzag or curvature in their Arai diagrams. Specimens of the first two groups were accepted after applying selection criteria to guarantee the high quality of the results. Our data compared to palaeosecular variation curves show a similar decreasing trend between 900-1500 AD. However, they reveal larger amplitudes at around 800 AD and 1650 AD than the reference curves and geomagnetic field models. Furthermore, they agree well with archaeomagnetic data from Mali and Senegal around 800 AD and with volcanic data around 1700 AD.

Reconstructing the Geomagnetic Field in West Africa: First Absolute Intensity Results from Burkina Faso

PubMed Central

Kapper, Lisa; Donadini, Fabio; Serneels, Vincent; Tema, Evdokia; Goguitchaichvili, Avto; Julio Morales, Juan

2017-01-01

We present absolute geomagnetic intensities from iron smelting furnaces discovered at the metallurgical site of Korsimoro, Burkina Faso. Up to now, archaeologists recognized four different types of furnaces based on different construction methods, which were related to four subsequent time periods. Additionally, radiocarbon ages obtained from charcoal confine the studied furnaces to ages ranging from 700–1700 AD, in good agreement with the archaeologically determined time periods for each type of furnace. Archaeointensity results reveal three main groups of Arai diagrams. The first two groups contain specimens with either linear Arai diagrams, or slightly curved diagrams or two phases of magnetization. The third group encompasses specimens with strong zigzag or curvature in their Arai diagrams. Specimens of the first two groups were accepted after applying selection criteria to guarantee the high quality of the results. Our data compared to palaeosecular variation curves show a similar decreasing trend between 900–1500 AD. However, they reveal larger amplitudes at around 800 AD and 1650 AD than the reference curves and geomagnetic field models. Furthermore, they agree well with archaeomagnetic data from Mali and Senegal around 800 AD and with volcanic data around 1700 AD. PMID:28350006

[Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol].

PubMed

Robaczyk, Maciej G

2002-01-01

The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk when compared to OTY subjects. Absolute LEP levels were correlated with trunk BF in CUS patients whereas in KON and AD groups these levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM-corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP levels were lower than in controls. No correlation was found between plasma levels of F and LEP in CUS and AD groups. This correlation was negative in KON (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups demonstrated a negative correlation between plasma ACTH and LEP levels. CUS patients showed positive, BFM-independent correlations between LEP levels, FIRI and G values, and a positive, BFM-dependent correlation between IRI and LEP levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI and LEP levels. In these and in AD patients, a positive, BFM-independent correlation between IRI and LEP levels was found. Moreover, a negative, BFM-dependent correlation between GH and LEP levels was found in OTY patients. In this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in the AD group, a midnight increase in leptin levels was observed. In conclusion, upregulation of leptin levels in relation to body fat in Cushing's syndrome is independent of the source of hypercortisolism. Apparently, it results from insulin resistance and hyperglycaemia and contributes to coexisting metabolic abnormalities. In Addison's disease, downregulation of leptin may reflect an adaptation mechanism to cortisol deficiency and result from low insulin and extremely high adrenocorticotrophin levels. In women with normal cortisol levels, irrespectively of nutritional status; leptin levels reflect body fat content. In obese subjects, leptin levels may be influenced by cortisol levels, high levels of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone. Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not directly influence diurnal variation in plasma leptin levels. In Cushing's syndrome, visceral fat may be a predominant source of leptin, whereas in women with normal or low cortisol levels peripherally accumulated fat may determine leptin secretion.

Free and Cued Selective Reminding Test is superior to the Wechsler Memory Scale in discriminating mild cognitive impairment from Alzheimer's disease.

PubMed

Lemos, Raquel; Cunha, Catarina; Marôco, João; Afonso, Ana; Simões, Mário R; Santana, Isabel

2015-08-01

The Logical Memory (LM) and the Verbal Paired Associative Learning (VPAL) are subtests from the Wechsler Memory Scale commonly used to characterize the memory deficit of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). The Free and Cued Selective Reminding Test (FCSRT) was suggested to assess the memory impairment of AD spectrum patients by the International Working Group on AD. In the present study, we compared the properties of the tests and their accuracy in classifying aMCI and AD. A group of aMCI patients (n = 85) and AD patients (n = 43) were included. The reliability and the validity of the three tests were analyzed. AD patients showed a significant pattern of worse impairment on all tests than aMCI. The FCSRT was able to classify more patients as having memory impairment in the aMCI group rather than the WMS subtests. The FCSRT proved to be good in discriminating the two groups in both lower and higher educational levels, whereas the LM was more useful in higher educated patients. Although the instruments had good results, the FCSRT was more accurate in discriminating MCI from AD, and less influenced by the educational level. © 2014 Japan Geriatrics Society.

Formaldehyde-Induced Aggravation of Pruritus and Dermatitis Is Associated with the Elevated Expression of Th1 Cytokines in a Rat Model of Atopic Dermatitis

PubMed Central

Back, Seung Keun; Lee, Hyunkyoung; Lee, JaeHee; Kim, Hye young; Kim, Hee Jin; Na, Heung Sik

2016-01-01

Atopic dermatitis is a complex disease of heterogeneous pathogenesis, in particular, genetic predisposition, environmental triggers, and their interactions. Indoor air pollution, increasing with urbanization, plays a role as environmental risk factor in the development of AD. However, we still lack a detailed picture of the role of air pollution in the development of the disease. Here, we examined the effect of formaldehyde (FA) exposure on the manifestation of atopic dermatitis and the underlying molecular mechanism in naive rats and in a rat model of atopic dermatitis (AD) produced by neonatal capsaicin treatment. The AD and naive rats were exposed to 0.8 ppm FA, 1.2 ppm FA, or fresh air (Air) for 6 weeks (2 hours/day and 5 days/week). So, six groups, namely the 1.2 FA-AD, 0.8 FA-AD, Air-AD, 1.2 FA-naive, 0.8 FA-naive and Air-naive groups, were established. Pruritus and dermatitis, two major symptoms of atopic dermatitis, were evaluated every week for 6 weeks. After that, samples of the blood, the skin and the thymus were collected from the 1.2 FA-AD, the Air-AD, the 1.2 FA-naive and the Air-naive groups. Serum IgE levels were quantified with ELISA, and mRNA expression levels of inflammatory cytokines from extracts of the skin and the thymus were calculated with qRT-PCR. The dermatitis and pruritus significantly worsened in 1.2 FA-AD group, but not in 0.8 FA-AD, compared to the Air-AD animals, whereas FA didn't induce any symptoms in naive rats. Consistently, the levels of serum IgE were significantly higher in 1.2 FA-AD than in air-AD, however, there was no significant difference following FA exposure in naive animals. In the skin, mRNA expression levels of Th1 cytokines such as TNF-α and IL-1β were significantly higher in the 1.2 FA-AD rats compared to the air-AD rats, whereas mRNA expression levels of Th2 cytokines (IL-4, IL-5, IL-13), IL-17A and TSLP were significantly higher in 1.2 FA-naive group than in the Air-naive group. These results suggested that 1.2 ppm of FA penetrated the injured skin barrier, and exacerbated Th1 responses and serum IgE level in the AD rats so that dermatitis and pruritus were aggravated, while the elevated expression of Th2 cytokines by 1.2 ppm of FA in naive rats was probably insufficient for clinical manifestation. In conclusion, in a rat model of atopic dermatitis, exposure to 1.2 ppm of FA aggravated pruritus and skin inflammation, which was associated with the elevated expression of Th1 cytokines. PMID:28005965

A comparison of two methods for assessing awareness of antitobacco television advertisements.

PubMed

Luxenberg, Michael G; Greenseid, Lija O; Depue, Jacob; Mowery, Andrea; Dreher, Marietta; Larsen, Lindsay S; Schillo, Barbara

2016-05-01

This study uses an online survey panel to compare two approaches for assessing ad awareness. The first uses a screenshot of a television ad and the second shows participants a full-length video of the ad. We randomly assigned 1034 Minnesota respondents to view a screenshot or a streaming video from two antitobacco ads. The study used one ad from ClearWay Minnesota's ITALIC! We All Pay the Price campaign, and one from the Centers for Disease Control ITALIC! Tips campaign. The key measure used to assess ad awareness was aided ad recall. Multivariate analyses of recall with cessation behaviour and attitudinal beliefs assessed the validity of these approaches. The respondents who saw the video reported significantly higher recall than those who saw the screenshot. Associations of recall with cessation behaviour and attitudinal beliefs were stronger and in the anticipated direction using the screenshot method. Over 20% of the respondents assigned to the video group could not see the ad. People who were under 45 years old, had incomes greater than $35,000 and women were reportedly less able to access the video. The methodology used to assess recall matters. Campaigns may exaggerate the successes or failures of their media campaigns, depending on the approach they employ and how they compare it to other media campaign evaluations. When incorporating streaming video, researchers should consider accessibility and report possible response bias. Researchers should fully define the measures they use, specify any viewing accessibility issues, and make ad comparisons only when using comparable methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Age-Related Defects in Erythrocyte 2,3-Diphosphoglycerate Metabolism in Dementia

PubMed Central

Kaminsky, Yury G.; Reddy, V. Prakash; Ashraf, Ghulam Md; Ahmad, Ausaf; Benberin, Valery V.; Kosenko, Elena A.; Aliev, Gjumrakch

2013-01-01

Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive “reporter cells” that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA. PMID:24124630

Which types of televised anti-tobacco campaigns prompt more quitline calls from disadvantaged groups?

PubMed

Durkin, Sarah J; Wakefield, Melanie A; Spittal, Matthew J

2011-12-01

To examine the efficacy of different types of mass media ads in driving lower socio-economic smokers (SES) to utilize quitlines. This study collected all 33 719 calls to the Victorian quitline in Australia over a 2-year period. Negative binomial regressions examined the relationship between weekly levels of exposure to different types of anti-smoking ads and quitline calls, after adjusting for covariates. Interaction terms were added to determine whether relationships differed by SES. In total, smokers were exposed 88.39 times to anti-smoking ads over the 2-year period, as estimated by target audience ratings points. Higher emotion narrative ad exposure had the strongest association with quitline calls, increasing call rates by 13% for every additional ad exposure per week (per 100 points, rate ratio = 1.132, P = 0.001). Substantially, greater increases in calls to quitline from lower SES groups were observed when higher emotion narrative ads were on air compared with when other ad types were on air, and this advantage was not as strong among higher SES groups. Airing higher emotion narrative anti-smoking ads may contribute to reducing, but not eliminating, socio-economic disparities in calls to the quitline through maximizing the responses of the lower SES smokers.

The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

PubMed

de Waal, Hanneke; Stam, Cornelis J; Lansbergen, Marieke M; Wieggers, Rico L; Kamphuis, Patrick J G H; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C W

2014-01-01

Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. 179 drug-naïve mild AD patients who participated in the Souvenir II study. Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Dutch Trial Register NTR1975.

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

PubMed Central

de Waal, Hanneke; Stam, Cornelis J.; Lansbergen, Marieke M.; Wieggers, Rico L.; Kamphuis, Patrick J. G. H.; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C. W.

2014-01-01

Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Trial registration Dutch Trial Register NTR1975. PMID:24475144

Evaluating driving performance of outpatients with Alzheimer disease.

PubMed

Cox, D J; Quillian, W C; Thorndike, F P; Kovatchev, B P; Hanna, G

1998-01-01

Alzheimer disease (AD) is a progressive disease, with multiple physiologic, psychologic, and social implications. A critical issue in its management is when to recommend restrictions on autonomous functioning, such as driving an automobile. This study evaluates driving performance of patients with AD and its relation to patient scores on the Mini-Mental State Exam (MMSE). This study compared 29 outpatients with probable AD with 21 age-matched control participants on an interactive driving simulator to determine how the two groups differed and how such differences related to mental status. Patients with AD (1) were less likely to comprehend and operate the simulator cognitively, (2) drove off the road more often, (3) spent more time driving considerably slower than the posted speed limit, (4) spent less time driving faster than the speed limit, (5) applied less brake pressure in stop zones, (6) spent more time negotiating left turns, and (7) drove more poorly overall. There were no observed differences between AD patients and the control group in terms of crossing the midline and driving speed variability. Among the AD patients, those who could not drive the simulator because of confusion and disorientation (n = 10) had lower MMSE scores and drove fewer miles annually. Those AD patients who had stopped driving also scored lower on their MMSE but did not perform more poorly on the driving simulator. Factor analysis revealed five driving factors associated with AD, explaining 93 percent of the variance. These five factors correctly classified 27 (85 percent) of 32 AD patients compared with the control group. Of the 15 percent who were improperly classified, there were three false positives (control participants misclassified as AD patients) and two false negatives (AD patients misclassified as control participants). The computed total driving score correlated significantly with MMSE scores (r = -.403, P = 0.011). Driving simulators can provide an objective means of assessing driving safety.

Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine-needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations.

PubMed

Song, Dae Hyun; Lee, Boram; Shin, Yooju; Choi, In Ho; Ha, Sang Yun; Lee, Jae Jun; Hong, Min Eui; Choi, Yoon-La; Han, Joungho; Um, Sang-Won

2015-07-01

Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutation in pulmonary adenocarcinoma is clinically important due to its association with resistance to EGFR inhibitors and poor prognosis. To our knowledge, there has not been a comparative study focusing on cytological nuclear features of pulmonary adenocarcinoma harboring KRAS mutation (KRAS-AD). Hence, we compared the cytomorphology of metastatic KRAS-AD and EGFR-positive adenocarcinoma (EGFR-AD) in aspiration specimens from lymph nodes. Forty lymph node aspiration specimens from forty KRAS-AD patients were collected at Samsung Medical Center (Seoul, Korea) from 2009 to 2013. As a control group, 40 EBUS-FNA lymph node specimens from 20 EGFR-AD patients were collected. EGFR-AD specimens were evaluated at Samsung Medical Center (Seoul, Korea) from 2012 to 2013. All 80 specimens were histologically confirmed to metastatic adenocarcinoma. Two pathologists performed a blinded review of all specimens. Compared with EGFR-AD, KRAS-AD exhibited more severe nuclear pleomorphism (P < 0.001), coarse chromatin (P = 0.001), cherry-red nucleoli (P < 0.001) and naked tumor cells (P = 0.002) with necrotic (P < 0.001) and neutrophilic (P = 0.008) background. Our study provides the first demonstration of cytomorphologic differentiation between metastatic KRAS-AD and metastatic EGFR-AD in lymph node aspiration specimens. © 2014 Wiley Periodicals, Inc.

Comparative analysis of the electroencephalogram in patients with Alzheimer's disease, diffuse axonal injury patients and healthy controls using LORETA analysis.

PubMed

Ianof, Jéssica Natuline; Fraga, Francisco José; Ferreira, Leonardo Alves; Ramos, Renato Teodoro; Demario, José Luiz Carlos; Baratho, Regina; Basile, Luís Fernando Hindi; Nitrini, Ricardo; Anghinah, Renato

2017-01-01

Alzheimer's disease (AD) is a dementia that affects a large contingent of the elderly population characterized by the presence of neurofibrillary tangles and senile plaques. Traumatic brain injury (TBI) is a non-degenerative injury caused by an external mechanical force. One of the main causes of TBI is diffuse axonal injury (DAI), promoted by acceleration-deceleration mechanisms. To understand the electroencephalographic differences in functional mechanisms between AD and DAI groups. The study included 20 subjects with AD, 19 with DAI and 17 healthy adults submitted to high resolution EEG with 128 channels. Cortical sources of EEG rhythms were estimated by exact low-resolution electromagnetic tomography (eLORETA) analysis. The eLORETA analysis showed that, in comparison to the control (CTL) group, the AD group had increased theta activity in the parietal and frontal lobes and decreased alpha 2 activity in the parietal, frontal, limbic and occipital lobes. In comparison to the CTL group, the DAI group had increased theta activity in the limbic, occipital sublobar and temporal areas. The results suggest that individuals with AD and DAI have impairment of electrical activity in areas important for memory and learning.

The effects of cognitive rehabilitation on Alzheimer's dementia patients' cognitive assessment reference diagnosis system performance based on level of cognitive functioning.

PubMed

Hwang, Jung-Ha; Cha, Hyun-Gyu; Cho, Hyuk-Shin

2015-09-01

[Purpose] The purpose of this study is to apply cognitive rehabilitation according to Alzheimer's disease (AD) patients' level of cognitive functioning to compare changes in Cognitive Assessment Reference Diagnosis System performance and present standards for effective intervention. [Subjects] Subjects were 30 inpatients diagnosed with AD. Subjects were grouped by Clinical Dementia Rating (CDR) class (CDR-0.5, CDR-1, or CDR-2, n = 10 per group), which is based on level of cognitive functioning, and cognitive rehabilitation was applied for 50 minutes per day, five days per week, for four weeks. [Methods] After cognitive rehabilitation intervention, CARDS tests were conducted to evaluate memory. [Results] Bonferroni tests comparing the three groups revealed that the CDR-0.5 and CDR-1 groups showed significant increases in Delayed 10 word-list, Delayed 10 object-list, Recognition 10 object, and Recent memory performance compared to the CDR-2 group. In addition, the CDR-0.5 group showed significant decreases in Recognition 10 word performance compared to the CDR-1 group. [Conclusion] Cognitive rehabilitation, CDR-0.5 or CDR-1 subjects showed significantly greater memory improvements than CDR-2 subjects. Moreover, was not effective for CDR-2 subjects.

A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

PubMed

Hafkemeijer, Anne; Möller, Christiane; Dopper, Elise G P; Jiskoot, Lize C; van den Berg-Huysmans, Annette A; van Swieten, John C; van der Flier, Wiesje M; Vrenken, Hugo; Pijnenburg, Yolande A L; Barkhof, Frederik; Scheltens, Philip; van der Grond, Jeroen; Rombouts, Serge A R B

2017-01-01

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy. We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63.8±5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups. At baseline, connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls. We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found.

Impact of cognitive task on the posture of elderly subjects with Alzheimer's disease compared to healthy elderly subjects.

PubMed

Manckoundia, Patrick; Pfitzenmeyer, Pierre; d'Athis, Philippe; Dubost, Véronique; Mourey, France

2006-02-01

The aims of this study were to analyze the effects of cognitive task on static posture in Alzheimer's disease (AD) and in healthy elderly (HE) subjects and to evaluate whether those effects were greater in AD subjects than in HE subjects. We performed a posturographic analysis on 13 subjects with mild AD (mean age, 79.7+/-5.1 years, Mini-Mental State Examination scores between 18 and 23) and on 17 HE subjects (mean age, 78.5+/-4.4 years). After watching a video sequence, the subjects were asked to maintain a stable upright posture while standing on a force platform. Then, the postural sway was measured during the following two conditions: (1) quiet standing and (2) both standing and answering questions about the video sequence. We were interested in the center of pressure (CoP) area and path. For each group, the single task was compared to the dual task for the CoP area and path. We also compared the variability of both CoP area (variation of the CoP area between the single and the dual task) and path (variation of the CoP path between the single and the dual task) between the two groups. We showed that there was no significant difference between the single and the dual task in HE subjects concerning the CoP area and path, in contrast to the AD group, and that variability of both the CoP area and path were significantly greater in the AD subjects than in the HE subjects. This finding may contribute to the risk of falls in AD patients. Copyright (c) 2005 Movement Disorder Society.

Parental Meta-Emotion Philosophy and Emotion Coaching in Families of Children and Adolescents with an Anxiety Disorder.

PubMed

Hurrell, Katherine E; Houwing, Frances L; Hudson, Jennifer L

2017-04-01

Using a multi-method approach, this study examined differences in parental meta-emotional philosophy (including, parental emotional awareness and emotion coaching) for families with anxiety disordered (AD; n = 74) and non-AD (n = 35) children (aged 7 to 15). Further, it was investigated whether children's emotion regulation (ER) varied across the AD and non-AD groups. Parent(s) were interviewed about their awareness of emotions and emotion coaching; completed a battery of questionnaires that included a measure assessing children's emotion regulation; and engaged in a parent-child discussion task. Results indicated that compared to parents of non-AD youth, parents of AD youth were less aware of their own emotions and their children's emotions, and these results varied by emotion type. Parents of AD youth engaged in significantly less emotion coaching than parents of non-AD youth. AD youth were identified as having significantly greater difficulty regulating their emotions when compared to non-AD youth. Implications for the role of parental meta-emotional philosophy and AD youth's emotion regulation are discussed.

The prevention of hip fracture with risedronate and ergocalciferol plus calcium supplementation in elderly women with Alzheimer disease: a randomized controlled trial.

PubMed

Sato, Yoshihiro; Kanoko, Tomohiro; Satoh, Kei; Iwamoto, Jun

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer disease (AD), who are prone to falls and have osteoporosis. We previously found that deficiency of 25-hydroxyvitamin D and compensatory hyperparathyroidism cause reduced bone mineral density in female patients with AD. We address the possibility that treatment with risedronate sodium and ergocalciferol plus calcium supplementation may reduce the incidence of nonvertebral fractures in elderly women with AD. A total of 500 elderly women with AD were randomly assigned to daily treatment with 2.5 mg of risedronate sodium or a placebo, combined with 1000 IU of ergocalciferol and 1200 mg of elementary calcium, and followed up for 18 months. At baseline, patients of both groups showed 25-hydroxyvitamin D deficiency with compensatory hyperparathyroidism. During the study period, bone mineral density in the risedronate group increased by 4.1% and decreased by 0.9% in the control group. Vertebral fractures occurred in 29 patients (24 hip fractures) in the control group and 8 patients (5 hip fractures) in the risedronate group. The relative risk in the risedronate group compared with the control group was 0.28 (95% confidence interval, 0.13-0.59). Elderly patients with AD hypovitaminosis D are at increased risk for hip fracture. Treatment with risedronate and ergocalciferol may be safe and effective in reducing the risk of a fracture in elderly patients with AD.

A blinded, randomized clinical trial comparing the efficacy and safety of oclacitinib and ciclosporin for the control of atopic dermatitis in client-owned dogs

PubMed Central

Little, Peter R; King, Vickie L; Davis, Kylie R; Cosgrove, Sallie B; Stegemann, Michael R

2015-01-01

Background Ciclosporin is approved for the treatment of atopic dermatitis (AD) in dogs and has been shown to be safe and effective. Placebo-controlled studies suggest that oclacitinib is a safe and effective alternative therapy. Hypothesis/Objectives To evaluate the efficacy and safety of oclacitinib, in comparison to ciclosporin, for the control of AD in a blinded, randomized clinical trial, incorporating a noninferiority test at day 28. Animals A total of 226 client-owned dogs with a history of AD from eight sites were enrolled. Methods Enrolled animals were randomized to receive oral oclacitinib (0.4–0.6 mg/kg twice daily for 14 days, then once daily) or oral ciclosporin (3.2–6.6 mg/kg once daily) for 12 weeks. Owners assessed pruritus using an enhanced visual analog scale (VAS), and veterinarians assessed dermatitis using the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-02. Results On days 1, 2, 7, 14, 28, 56 and 84, the percentage reduction from baseline for owner-assessed pruritus changed from 25.6 to 61.0% in the oclacitinib group compared with 6.5 to 61.5% in the ciclosporin group; differences were significant at all time points up to day 28. On day 56, ciclosporin-treated dogs showed a similar decrease in pruritus to oclacitinib-treated dogs. On day 14, the percentage reduction from baseline CADESI-02 was significantly greater in the oclacitinib group (58.7%) than in the ciclosporin group (43.0%). Three times as many adverse events attributed to gastrointestinal signs were reported in the ciclosporin group compared with the oclacitinib group. Conclusions and clinical importance In this study of treatment for canine AD, oclacitinib had a faster onset of action and a lower frequency of gastrointestinal side effects compared with ciclosporin. PMID:25496303

Quantitative evaluation of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Duchesne, S.; Frisoni, G. B.

2009-02-01

We propose a single, quantitative metric called the disease evaluation factor (DEF) and assess its efficiency at estimating disease burden in normal, control subjects (CTRL) and probable Alzheimer's disease (AD) patients. The study group consisted in 75 patients with a diagnosis of probable AD and 75 age-matched normal CTRL without neurological or neuropsychological deficit. We calculated a reference eigenspace of MRI appearance from reference data, in which our CTRL and probable AD subjects were projected. We then calculated the multi-dimensional hyperplane separating the CTRL and probable AD groups. The DEF was estimated via a multidimensional weighted distance of eigencoordinates for a given subject and the CTRL group mean, along salient principal components forming the separating hyperplane. We used quantile plots, Kolmogorov-Smirnov and χ2 tests to compare the DEF values and test that their distribution was normal. We used a linear discriminant test to separate CTRL from probable AD based on the DEF factor, and reached an accuracy of 87%. A quantitative biomarker in AD would act as an important surrogate marker of disease status and progression.

Cerebrovascular Smooth Muscle Actin Is Increased in Non-Demented Subjects with Frequent Senile Plaques at Autopsy: Implications for the Pathogenesis of Alzheimer Disease

PubMed Central

Hulette, Christine M.; Ervin, John F.; Edmonds, Yvette; Antoine, Samantha; Stewart, Nicolas; Szymanski, Mari H.; Hayden, Kathleen M; Pieper, Carl F.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2009-01-01

We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared to brains of non-demented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: non-demented subjects without significant AD type pathology (“Normal”, n = 20); non-demented subjects with frequent senile plaques at autopsy (“Preclinical AD”, n = 20); and subjects with frontotemporal dementia, (“FTD”, n = 10). The groups were matched for gender and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described. Surprisingly, SMA expression in arachnoid, cerebral cortex and white matter arterioles was greater in the Preclinical AD group than in the Normal and FTD groups. The plaques were not associated with amyloid angiopathy or other vascular disease in this group. SMA expression in the brains of the Normal group was intermediate between the Preclinical AD and FTD groups. All 3 groups exhibited much greater SMA expression than in our previous report. The presence of frequent plaques and increased arteriolar SMA expression in the brains of non-demented subjects suggest that increased SMA expression might represent a physiologic response to neurodegeneration that could prevent or delay overt expression dementia in AD. PMID:19287310

Self-Regulation of Beer Advertising: A Comparative Analysis of Perceived Violations by Adolescents and Experts.

PubMed

Vendrame, Alan; Silva, Rebeca; Xuan, Ziming; Sparks, Robert; Noel, Jonathan; Pinsky, Ilana

2015-09-01

We assessed the impact of the 2010 revisions to Brazil's self-regulatory alcohol marketing code using expert and adolescent raters. Five popular TV beer ads were selected. Ads were rated based on the 2010 Brazilian self-regulatory marketing code. The expert group (N = 31) represented health-related professions; the adolescent group (N = 110) were public high school students. At least 1 ad violated 11 of 17 guidelines included in the study. Ratings by experts and adolescents were similar. Both found violations in all sections of the self-regulatory code, but significant group differences were seen in applying the section that prohibits the promotion of excessive alcohol consumption, with experts identifying more violations than adolescents. Beer ads in the sample systematically violated the self-regulatory standards for alcohol advertising in Brazil according to both experts and youth. Public policies for more effective restrictions and prohibitions in alcohol ads should be considered. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Total recognition discriminability in Huntington's and Alzheimer's disease.

PubMed

Graves, Lisa V; Holden, Heather M; Delano-Wood, Lisa; Bondi, Mark W; Woods, Steven Paul; Corey-Bloom, Jody; Salmon, David P; Delis, Dean C; Gilbert, Paul E

2017-03-01

Both the original and second editions of the California Verbal Learning Test (CVLT) provide an index of total recognition discriminability (TRD) but respectively utilize nonparametric and parametric formulas to compute the index. However, the degree to which population differences in TRD may vary across applications of these nonparametric and parametric formulas has not been explored. We evaluated individuals with Huntington's disease (HD), individuals with Alzheimer's disease (AD), healthy middle-aged adults, and healthy older adults who were administered the CVLT-II. Yes/no recognition memory indices were generated, including raw nonparametric TRD scores (as used in CVLT-I) and raw and standardized parametric TRD scores (as used in CVLT-II), as well as false positive (FP) rates. Overall, the patient groups had significantly lower TRD scores than their comparison groups. The application of nonparametric and parametric formulas resulted in comparable effect sizes for all group comparisons on raw TRD scores. Relative to the HD group, the AD group showed comparable standardized parametric TRD scores (despite lower raw nonparametric and parametric TRD scores), whereas the previous CVLT literature has shown that standardized TRD scores are lower in AD than in HD. Possible explanations for the similarity in standardized parametric TRD scores in the HD and AD groups in the present study are discussed, with an emphasis on the importance of evaluating TRD scores in the context of other indices such as FP rates in an effort to fully capture recognition memory function using the CVLT-II.

Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer's Disease.

PubMed

Jiang, Jing; Liu, Gang; Shi, Suhua; Li, Zhigang

2016-01-01

Objectives . To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer's disease. Methods . In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer's disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer's disease (AD), and normal (N) groups were assessed. Results . The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and A β amyloid content in the frontal lobe, compared with the AD group ( P < 0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD. Conclusion . MEA therapy may be superior to EA in treating Alzheimer's disease as demonstrated in SAMP8 mice.

Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer's Disease

PubMed Central

Jiang, Jing; Liu, Gang

2016-01-01

Objectives. To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer's disease. Methods. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer's disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer's disease (AD), and normal (N) groups were assessed. Results. The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and Aβ amyloid content in the frontal lobe, compared with the AD group (P < 0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD. Conclusion. MEA therapy may be superior to EA in treating Alzheimer's disease as demonstrated in SAMP8 mice. PMID:27974974

Histidine-tryptophan-ketoglutarate solution with added ebselen augments myocardial protection in neonatal porcine hearts undergoing ischemia/reperfusion.

PubMed

Chen, Yan; Liu, Jinping; Li, Shoujun; Yan, Fuxia; Xue, Qinghua; Wang, Huiying; Sun, Peng; Long, Cun

2015-02-01

Whether modified histidine-tryptophan-ketoglutarate (HTK) solution offers myocardial protection to newborn heart has not been documented. The purpose of this study was to compare myocardial protection using HTK added by ebselen with HTK in a piglet model of cardiopulmonary bypass (CPB). Fifteen piglets were randomly assigned to three groups: the control group (C group, n = 5), HTK solution group (HTK group, n = 5), and HTK added by 10 nM ebselen group (HTK+E group, n = 5). Animals in the two experimental groups were placed on hypothermic CPB, after which the ascending aorta had been clamped for 2 h. The control animals underwent normothermic CPB without cardiac arrest. Myocardial antioxidant activities, myocytes apoptosis and mitochondrial structures, as well as the release of cytochrome c and the expression of Bax, Bcl-2, and HSP72 protein in myocardium were measured. Increased myocardial superoxide dismutase (SOD) and Mn-SOD activities, decreased TUNEL-positive cells, and reduced release of cytochrome c were noted in the HTK+E group compared with those in the HTK group (P = 0.021, P = 0.020, P = 0.045, and P = 0.010, respectively). The Bax/Bcl-2 ratio in the HTK group was significantly higher than that in the C group (P = 0.024). The expression of HSP72 protein and mRNA in the HTK+E group was higher than that in the HTK group (P = 0.039 and P = 0.035, respectively). Mitochondrial score under electron microscope in the HTK+E group was lower than that in the HTK group (P = 0.047). Improved antioxidant defense, reduced myocytes apoptosis, and better preserved mitochondrial structure were observed in the HTK+E group. Ebselen added to HTK provides better myocardioprotection to HTK solution for the neonatal heart. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Comparing the PPAT Drawings of Boys with AD/HD and Age-Matched Controls Using the Formal Elements Art Therapy Scale.

ERIC Educational Resources Information Center

Munley, Maripat

2002-01-01

Explores whether children with AD/HD respond differently to a specific art directive. Using the Formal Elements Art Therapy Scale to evaluate the drawings, results indicate three elements that would most accurately predict the artists into the AD/HD group: color prominence, details of objects and environments, and line quality. (Contains 29…

Intratumoral delivery of docetaxel enhances antitumor activity of Ad-p53 in murine head and neck cancer xenograft model.

PubMed

Yoo, George H; Subramanian, Geetha; Ezzat, Waleed H; Tulunay, Ozlem E; Tran, Vivian R; Lonardo, Fulvio; Ensley, John F; Kim, Harold; Won, Joshua; Stevens, Timothy; Zumstein, Louis A; Lin, Ho-Sheng

2010-01-01

The aim of this study is to determine the ability of intratumorally delivered docetaxel to enhance the antitumor activity of adenovirus-mediated delivery of p53 (Ad-p53) in murine head and neck cancer xenograft model. A xenograft head and neck squamous cell carcinoma mouse model was used. Mice were randomized into 4 groups of 6 mice receiving 6 weeks of biweekly intratumoral injection of (a) diluent, (b) Ad-p53 (1 x 10(10) viral particles per injection), (c) docetaxel (1 mg/kg per injection), and (d) combination of Ad-p53 (1 x 10(10) viral particles per injection) and docetaxel (1 mg/kg per injection). Tumor size, weight, toxicity, and overall and disease-free survival rates were determined. Intratumoral treatments with either docetaxel alone or Ad-p53 alone resulted in statistically significant antitumor activity and improved survival compared with control group. Furthermore, combined delivery of Ad-p53 and docetaxel resulted in a statistically significant reduction in tumor weight when compared to treatment with either Ad-p53 or docetaxel alone. Intratumoral delivery of docetaxel enhanced the antitumor effect of Ad-p53 in murine head and neck cancer xenograft model. The result of this preclinical in vivo study is promising and supports further clinical testing to evaluate efficacy of combined intratumoral docetaxel and Ad-p53 in treatment of head and neck cancer. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Association between Diabetes and Risk of Aortic Dissection: A Case-Control Study in a Chinese Population.

PubMed

He, Xingwei; Liu, Xintian; Liu, Wanjun; Wang, Bei; Liu, Yujian; Li, Zhuxi; Wang, Tao; Tan, Rong; Gao, Bo; Zeng, Hesong

2015-01-01

It is well-recognized that diabetes represents a powerful independent risk factor for cardiovascular diseases. However, very few studies have investigated the relationship between diabetes and risk of aortic dissection (AD). The aim of this case-control study was to evaluate the association between diabetes and risk of AD in Chinese population. A hospital-based case-control study, consisting of 2160 AD patients and 4320 controls, was conducted in a Chinese population. Demographic, clinical characteristics and risk factors were collected. Diabetes rate of patients with overall AD, Stanford type A AD and type B AD group was compared with that of corresponding matched control groups. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between diabetes and AD risk. The prevalence of diabetes was lower in AD cases than that of control subjects, whether it is the overall AD, type A AD or type B AD group (4.7% vs. 10.0%, 2.9% vs. 8.8%, 5.9% vs. 10.9%, all P<0.001). Furthermore, in multivariate model, diabetes was found to be associated with lower AD risk, which not only applies to the overall AD (OR = 0.2, 95%CI: 0.15-0.26), but also type A AD (OR = 0.12, 95% CI: 0.07-0.20) and type B AD (OR = 0.25, 95%CI: 0.18-0.33). We observed the paradoxical inverse relationship between DM and risk of AD in the Chinese population. These results suggest diabetes may play a protective role in the development of AD. However, further studies are needed to enrich related evidence, especially with regard to underlying mechanisms for these trends.

Synthesis and Solution Properties of Adamantane Containing Quaternary Ammonium Salt-type Cationic Surfactants: Hydrocarbon-based, Fluorocarbonbased and Bola-type.

PubMed

Yoshimura, Tomokazu; Okada, Mari; Matsuoka, Keisuke

2016-10-01

Quaternary ammonium salt-type cationic surfactants with an adamantyl group (hydrocarbon-type; C n AdAB, fluorocarbon-type; C m F C 3 AdAB, bola-type; Ad-s-Ad, where n, m and s represent hydrocarbon chain lengths of 8-16, fluorocarbon chain lengths of 4-8, and spacer chain length of 10-12) were synthesized via quaternization of N, N-dimethylaminoadamantane and n-alkyl bromide or 1, n-dibromoalkane. Conductivity and surface tension were measured to characterize the solution properties of the synthesized adamantyl group-containing cationic surfactants. In addition, the effects of hydrocarbon and fluorocarbon chain lengths and spacer chain length between headgroups on the measured properties were evaluated by comparison with those of conventional cationic surfactants. The critical micelle concentration (CMC) of C n AdAB and Ad-s-Ad was 2/5 of that for the corresponding conventional surfactants C n TAB and bola-type surfactants with similar number of carbons in the alkyl or alkylene chain; this was because of the increased hydrophobicity due to the adamantyl group. A linear relationship between the logarithm of CMC and the hydrocarbon chain length for C n AdAB was observed, as well as for C n TAB. The slope of the linear correlation for both surfactants was almost the same, indicating that the adamantyl group does not affect the CMC with variations in the hydrocarbon chain length. Similar to conventional surfactants C n TAB, the hydrocarbon-type C n AdAB is highly efficient in reducing the surface tension of water, despite the large occupied area per molecule resulting from the relatively bulky structure of the adamantane skeleton. On the other hand, the bola-type Ad-s-Ad resulted in increased surface tension compared to C n AdAB, indicating that the curved chain between adamantyl groups leads to poor adsorption and orientation at the air-water interface.

Abnormal functional connectivity of the posterior cingulate cortex is associated with depressive symptoms in patients with Alzheimer’s disease

PubMed Central

Zhang, Jiangtao; Guo, Zhongwei; Liu, Xiaozheng; Jia, Xize; Li, Jiapeng; Li, Yaoyao; Lv, Danmei; Chen, Wei

2017-01-01

Background Depressive symptoms are significant and very common psychiatric complications in patients with Alzheimer’s disease (AD), which can aggravate the decline in social function. However, changes in the functional connectivity (FC) of the brain in AD patients with depressive symptoms (D-AD) remain unclear. Objective To investigate whether any differences exist in the FC of the posterior cingulate cortex (PCC) between D-AD patients and non-depressed AD patients (nD-AD). Materials and methods We recruited 15 D-AD patients and 17 age-, sex-, educational level-, and Mini-Mental State Examination (MMSE)-matched nD-AD patients to undergo tests using the Neuropsychiatric Inventory, Hamilton Depression Rating Scale, and 3.0T resting-state functional magnetic resonance imaging. Bilateral PCC were selected as the regions of interest and between-group differences in the PCC FC network were assessed using Student’s t-test. Results Compared with the nD-AD group, D-AD patients showed increased PCC FC in the right amygdala, right parahippocampus, right superior temporal pole, right middle temporal lobe, right middle temporal pole, and right hippocampus (AlphaSim correction; P<0.05). In the nD-AD group, MMSE scores were positively correlated with PCC FC in the right superior temporal pole and right hippocampus (false discovery rate corrected; P<0.05). Conclusion Differences were detected in PCC FC between nD-AD and D-AD patients, which may be related to depressive symptoms. Our study provides a significant enhancement to our understanding of the functional mechanisms underlying D-AD. PMID:29066900

Long-term effectiveness of rivastigmine patch or capsule for mild-to-severe Alzheimer's disease: a meta-analysis.

PubMed

Su, Jiangli; Liu, Yang; Liu, Yu; Ren, Liqun

2015-01-01

To evaluate the long-term effectiveness of rivastigmine patch or capsule on mild to severe Alzheimer's disease (AD). We performed a meta-analysis of 17 studies regarding the treatment effectiveness of rivastigmine patch or capsule on mild-to-severe AD. Significant difference exists between treatment with rivastigmine patch or capsule and placebo groups (p-value < 0.001). In the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score evaluation, a negative weighted mean difference (WMD) was observed in overall and mild-moderate groups after rivastigmine treatment. And in ADAS-ADL score evaluation, a positive WMD was observed in overall groups after rivastigmine treatment. Moreover, WMD value is lower in patch administration subgroup compared to that of capsule administration subgroup. Rivastigmine treatment shows a positive result of improving the condition of patients with mild-to-severe AD. Patch administration shows a stronger effect on decreasing ADAS-Cog score compared to capsule administration.

Treatment and post-treatment effects of functional therapy on the sagittal pharyngeal dimensions in Class II subjects.

PubMed

Pavoni, Chiara; Cretella Lombardo, Elisabetta; Franchi, Lorenzo; Lione, Roberta; Cozza, Paola

2017-10-01

To evaluate the craniofacial changes induced by functional appliances with special regard to the oro and nasopharyngeal sagittal airway dimensions in subjects with dentoskeletal Class II malocclusions when compared with an untreated Class II control group immediately after therapy and at long-term observation. A group of 40 patients (21 females and 19 males) with Class II malocclusion treated consecutively either with a Bionator or an Activator followed by fixed appliances was compared with a matched control group of 31 subjects (16 females and 15 males) with untreated Class II malocclusion. The treated sample was evaluated at T1, start of treatment (mean age: 9.9 ± 1.4 years); T2, end of functional treatment and prior to fixed appliances (mean age: 11.9 ± 1.3 years); and T3, long-term observation at the end of growth (mean age: 18.2 ± 2.1 years). Statistical comparisons were performed with independent sample t tests at T1 (baseline characteristics) and for the T1-T2, T2-T3, and T1-T3 changes. During active treatment the treated group showed a significant increment in lower airway dimension (PNS-AD1), as well as a significant improvement in the upper airway dimension (PNS-AD2). A significant decrease in the upper adenoid size (AD2-H) was also found. In the longterm evaluation, a significant increase in both lower and upper airway thickness (PNS-AD1; PNS-AD2) and a significant decrease in the upper adenoid thickness were still present in the treated group. The treatment with functional appliances produced significant favorable changes during active treatment in the oro- and nasopharyngeal sagittal airway dimensions in dentoskeletal Class II subjects when compared with untreated controls, and these changes were stable in the long-term. Copyright © 2017 Elsevier B.V. All rights reserved.

The neural correlates of auditory and visuospatial span in logopenic progressive aphasia and Alzheimer's disease.

PubMed

Foxe, David; Leyton, Cristian E; Hodges, John R; Burrell, James R; Irish, Muireann; Piguet, Olivier

2016-10-01

Logopenic progressive aphasia (lv-PPA) is a form of primary progressive aphasia and is predominantly associated with Alzheimer's disease (AD) pathology. The neuropsychological profiles of lv-PPA and typical clinical AD are, however, distinct. In particular, these two syndromes differ on attention span measures, where auditory attention span is more impaired in lv-PPA than in AD and visuospatial span appears more impaired in AD than in lv-PPA. The neural basis of these span profiles, however, remains unclear. Sixteen lv-PPA and 21 AD matched patients, and 15 education-matched healthy controls were recruited. All participants were assessed by a neurologist and completed a neuropsychological assessment that included the Wechsler Memory Scale-III Digit and Spatial Span tasks, and underwent a high-resolution structural brain MRI to conduct cortical thickness analyses. Patient groups were impaired on all span tasks compared to Controls. In addition, performance on Digit Span Forward (DSF) was significantly lower in the lv-PPA than the AD group, while Spatial Span Forward (SSF) was significantly lower in the AD than the lv-PPA group. No differences were found between patient groups on the Digit or Spatial Span Backward tasks. Neuroimaging analyses revealed that reduced DSF performance correlated to thinning of the left superior temporal gyrus in the lv-PPA group, whereas reduced SSF performance was related to bilateral precentral sulcus and parieto-occipital thinning in the AD group. Analyses of the backward span tasks revealed that reduced Spatial Span Backward (SSB) performance in the lv-PPA group related to cortical thinning of the left superior parietal lobule. This study demonstrates that while lv-PPA and AD commonly share the same underlying neuropathology, their span profiles are distinct and are mediated by divergent patterns of cortical degeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuropathology of dementia with Lewy bodies in advanced age: a comparison with Alzheimer disease.

PubMed

Ubhi, Kiren; Peng, Kevin; Lessig, Stephanie; Estrella, Jennilyn; Adame, Anthony; Galasko, Douglas; Salmon, David P; Hansen, Lawrence A; Kawas, Claudia H; Masliah, Eliezer

2010-11-26

Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder of the aging population characterized by α-synuclein accumulation in cortical and subcortical regions. Although neuropathology in advanced age has been investigated in dementias such as Alzheimer Disease (AD), severity of the neuropathology in the oldest old with DLB remains uncharacterized. For this purpose we compared characteristics of DLB cases divided into three age groups 70-79, 80-89 and ≥ 90 years (oldest old). Neuropathological indicators and levels of synaptophysin were assessed and correlated with clinical measurements of cognition and dementia severity. These studies showed that frequency and severity of DLB was lower in 80-89 and ≥ 90 year cases compared to 70-79 year old group but cognitive impairment did not vary with age. The extent of AD neuropathology correlated with dementia severity only in the 70-79 year group, while synaptophysin immunoreactivity more strongly associated with dementia severity in the older age group in both DLB and AD. Taken together these results suggest that the oldest old with DLB might represent a distinct group. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Knowledge, attitudes and behaviour of Greek adults towards salt consumption: a Hellenic Food Authority project.

PubMed

Marakis, Georgios; Tsigarida, Eirini; Mila, Spyridoula; Panagiotakos, Demosthenes B

2014-08-01

To investigate the knowledge, attitudes and behaviour of Greek adults towards salt as well as their differences with respect to gender, age and level of education. Cross-sectional, observational survey. Voluntary participation to a telephone interview, using a seventeen-item questionnaire. Greek adults aged over 25 years (n 3609), nationally representative according to age, gender and geographical distribution of the Greek population, were interviewed. More women of all age groups compared with men reported adding salt during cooking (P < 0·001), while less reported adding salt on the plate (P < 0·001). Also, more women believed that salt added during cooking was the main source of salt in the diet (P < 0·001). Participants aged 25-34, 35-44 and 45-54 years old had better knowledge of the harmful effects of salt on health compared with the 55+ years age group (P = 0·002, P = 0·001, P < 0·001, respectively); respondents in the aforementioned age groups also knew that children should consume less salt than adults compared with 55+ years age group (P = 0·004, P < 0·001, P < 0·001, respectively). Respondents with secondary and higher educational status were more likely to avoid consumption of processed foods (P < 0·001) and to check the nutrition information on food packaging as compared with respondents having basic education status (P < 0·001). Awareness needs to be raised regarding salt recommendations for adults and children, sources of sodium in the diet and adding less salt during cooking, as well as reading food labels. Future campaigns for salt reduction should consider gender, age and level of education differences regarding knowledge, attitudes and behaviour towards salt.

Biomarker validation of a decline in semantic processing in preclinical Alzheimer's disease.

PubMed

Papp, Kathryn V; Mormino, Elizabeth C; Amariglio, Rebecca E; Munro, Catherine; Dagley, Alex; Schultz, Aaron P; Johnson, Keith A; Sperling, Reisa A; Rentz, Dorene M

2016-07-01

Differentially worse performance on category versus letter fluency suggests greater semantic versus retrieval difficulties. This discrepancy, combined with reduced episodic memory, has widespread clinical utility in diagnosing Alzheimer's disease (AD). Our objective was to investigate whether changes in semantic processing, as measured by the discrepancy between category and letter fluency, was detectable in preclinical AD: in clinically normal older adults with abnormal β-amyloid (Aβ) deposition on positron emission tomography (PET) neuroimaging. Clinically normal older adults (mean Mini Mental State Exam (MMSE) score = 29) were classified as Aβ+ (n = 70) or Aβ- (n = 205) using Pittsburgh Compound B-(PET) imaging. Participants completed letter fluency (FAS; word generation to letters F-A-S) and category fluency (CAT; word generation to animals, vegetables, fruits) annually (mean follow-up = 2.42 years). The effect of Aβ status on fluency over time was examined using linear mixed models controlling for age, sex, and education. To dissociate effects related to semantic (CAT) versus retrieval processes (CAT and FAS), we repeated models predicting CAT over time, controlling for FAS and likewise for CAT controlling for FAS. At baseline, the Aβ+ group performed better on FAS compared with the Aβ- group but comparably on CAT. Longitudinally, the Aβ+ group demonstrated greater decline on CAT compared with the Aβ- group (p = .0011). This finding remained significant even when covarying for FAS (p = .0107). Aβ+ participants similarly declined compared with Aβ- participants on FAS (p = .0112), but this effect became insignificant when covarying for CAT (p = .1607). These findings provide biomarker validation for the greater specificity of declines in category versus letter fluency to underlying AD pathology. Our results also suggest that changes in semantic processing occur earlier in the AD trajectory than previously hypothesized. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A direct comparison of popular models of normal memory loss and Alzheimer's disease in samples of African Americans, Mexican Americans, and refugees and immigrants from the former Soviet Union.

PubMed

Schrauf, Robert W; Iris, Madelyn

2011-04-01

To understand how people differentiate normal memory loss from Alzheimer's disease (AD) by investigating cultural models of these conditions. Ethnographic interviews followed by a survey. Cultural consensus analysis was used to test for the presence of group models, derive the "culturally correct" set of beliefs, and compare models of normal memory loss and AD. Chicago, Illinois. One hundred eight individuals from local neighborhoods: African Americans, Mexican Americans, and refugees and immigrants from the former Soviet Union. Participants responded to yes-or-no questions about the nature and causes of normal memory loss and AD and provided information on ethnicity, age, sex, acculturation, and experience with AD. Groups held a common model of AD as a brain-based disease reflecting irreversible cognitive decline. Higher levels of acculturation predicted greater knowledge of AD. Russian speakers favored biological over psychological models of the disease. Groups also held a common model of normal memory loss, including the important belief that "normal" forgetting involves eventual recall of the forgotten material. Popular models of memory loss and AD confirm that patients and clinicians are speaking the same "language" in their discussions of memory loss and AD. Nevertheless, the presence of coherent models of memory loss and AD, and the unequal distribution of that knowledge across groups, suggests that clinicians should include wider circles of patients' families and friends in their consultations. These results frame knowledge as distributed across social groups rather than simply the possession of individual minds. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease.

PubMed

Shinto, Lynne; Quinn, Joseph; Montine, Thomas; Dodge, Hiroko H; Woodward, William; Baldauf-Wagner, Sara; Waichunas, Dana; Bumgarner, Lauren; Bourdette, Dennis; Silbert, Lisa; Kaye, Jeffrey

2014-01-01

Oxidative stress, inflammation, and increased cholesterol levels are all mechanisms that have been associated with Alzheimer's disease (AD) pathology. Several epidemiologic studies have reported a decreased risk of AD with fish consumption. This pilot study was designed to evaluate the effects of supplementation with omega-3 fatty acids alone (ω-3) or omega-3 plus alpha lipoic acid (ω-3 + LA) compared to placebo on oxidative stress biomarkers in AD. The primary outcome measure was peripheral F2-isoprostane levels (oxidative stress measure). Secondary outcome measures included performance on: Mini-Mental State Examination (MMSE), Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL), and Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Thirty-nine AD subjects were randomized to one of three groups: 1) placebo, 2) ω-3, or 3) ω-3 + LA for a treatment duration of 12 months. Eighty seven percent (34/39) of the subjects completed the 12-month intervention. There was no difference between groups at 12 months in peripheral F2-isoprostane levels (p = 0.83). The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog (p = 0.98, p = 0.86) and in ADL (p = 0.15, p = 0.82). Compared to placebo, the ω-3 + LA showed less decline in MMSE (p < 0.01) and IADL (p = 0.01) and the ω-3 group showed less decline in IADL (p < 0.01). The combination of ω-3 + LA slowed cognitive and functional decline in AD over 12 months. Because the results were generated from a small sample size, further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted.

A Randomized Placebo-Controlled Pilot Trial of Omega-3 Fatty Acids and Alpha Lipoic Acid in Alzheimer’s Disease

PubMed Central

Shinto, Lynne; Quinn, Joseph; Montine, Thomas; Dodge, Hiroko H.; Woodward, William; Baldauf-Wagner, Sara; Waichunas, Dana; Bumgarner, Lauren; Bourdette, Dennis; Silbert, Lisa; Kaye, Jeffrey

2013-01-01

Oxidative stress, inflammation, and increased cholesterol levels are all mechanisms that have been associated with Alzheimer’s disease (AD) pathology. Several epidemiologic studies have reported a decreased risk of AD with fish consumption. This pilot study was designed to evaluate the effects of supplementation with omega-3 fatty acids alone (ω-3) or omega-3 plus alpha lipoic acid (ω-3 +LA) compared to placebo on oxidative stress biomarkers in AD. The primary outcome measure was peripheral F2-isoprostane levels (oxidative stress measure). Secondary outcome measures included performance on: Mini-Mental State Examination (MMSE), Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL), and Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Thirty-nine AD subjects were randomized to one of three groups: 1) placebo, 2) ω-3, or 3) ω-3 + LA for a treatment duration of 12 months. Eighty seven percent (34/39) of the subjects completed the 12-month intervention. There was no difference between groups at 12 months in peripheral F2-isoprostane levels (p = 0.83). The ω-3 +LA and ω-3 were not significantly different than the placebo group in ADAS-cog (p = 0.98, p = 0.86) and in ADL (p = 0.15, p = 0.82). Compared to placebo, the ω-3+LA showed less decline in MMSE (p< 0.01) and IADL (p= 0.01) and the ω-3 group showed less decline in IADL (p < 0.01). The combination of ω-3+LA slowed cognitive and functional decline in AD over 12 months. Because the results were generated from a small sample size, further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted. PMID:24077434

One cigarette is one too many: evaluating a light smoker-targeted media campaign.

PubMed

Jasek, John P; Johns, Michael; Mbamalu, Ijeoma; Auer, Kari; Kilgore, Elizabeth A; Kansagra, Susan M

2015-07-01

Light smokers represent an increasing share of adult smokers in various parts of the world including New York City (NYC). Since 2007, the NYC Department of Health and Mental Hygiene has aired hard-hitting antitobacco media campaigns paired with time-limited nicotine replacement therapy (NRT) giveaways. We evaluated an original antitobacco media campaign, developed to increase awareness of smoking risks and encourage cessation service use among light smokers in NYC. We compared cessation service request volume during the campaign to historical periods without ads targeting light smokers. We used a cross-sectional online panel survey to assess the ad's perceived effectiveness and its impact on learning something new, quit intentions and concern for smoking-related health risks among non-daily, light daily and heavy daily smokers. The proportion of light smokers among smokers requesting cessation services increased 50% (from 13% to 20%) relative to previous time-limited NRT giveaways. Compared to heavy daily smokers, non-daily (aOR: 1.95, p<0.05) and light daily (aOR: 2.27, p<0.05) smokers were more likely to express increased concern about smoking-related health risks after viewing the ad. Perceived effectiveness of the ad did not differ by smoker type. This study provides evidence that light smokers were receptive to a targeted antitobacco message encouraging use of cessation services. The campaign appears to have been particularly effective in increasing smoking-related health concerns in this group. The lack of difference in perceived ad effectiveness by smoker type suggests the potential to develop such ads without sacrificing broad impact. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of Cholinergic Deficiency in Preclinical Alzheimer's Disease Using Pupillometry

PubMed Central

Robinson, Liam; Rowe, Christopher C.; Ames, David; Masters, Colin L.; Taddei, Kevin; Rainey-Smith, Stephanie R.; Martins, Ralph N.; Kanagasingam, Yogesan

2017-01-01

Cortical cholinergic deficiency is prominent in Alzheimer's disease (AD), and published findings of diminished pupil flash response in AD suggest that this deficiency may extend to the visual cortical areas and anterior eye. Pupillometry is a low-cost, noninvasive technique that may be useful for monitoring cholinergic deficits which generally lead to memory and cognitive disorders. The aim of the study was to evaluate pupillometry for early detection of AD by comparing the pupil flash response (PFR) in AD (N = 14) and cognitively normal healthy control (HC, N = 115) participants, with the HC group stratified according to high (N = 38) and low (N = 77) neocortical amyloid burden (NAB). Constriction phase PFR parameters were significantly reduced in AD compared to HC (maximum acceleration p < 0.05, maximum velocity p < 0.0005, average velocity p < 0.005, and constriction amplitude p < 0.00005). The high-NAB HC subgroup had reduced PFR response cross-sectionally, and also a greater decline longitudinally, compared to the low-NAB subgroup, suggesting changes to pupil response in preclinical AD. The results suggest that PFR changes may occur in the preclinical phase of AD. Hence, pupillometry has a potential as an adjunct for noninvasive, cost-effective screening for preclinical AD. PMID:28894607

Improved exercise capacity and reduced systemic inflammation after adenoviral-mediated SERCA-2a gene transfer.

PubMed

Gupta, Dipin; Palma, Jon; Molina, Ezequiel; Gaughan, John P; Long, Walter; Houser, Steven; Macha, Mahender

2008-04-01

We hypothesized that sarcoplasmic reticulum Ca2+ ATPase pump (SERCA-2a) gene delivery would have beneficial effects upon exercise capacity and markers of inflammation in the setting of heart failure. A pressure-overload model of experimental heart failure was used in rats. Following a decrease in fractional shortening of >or=25%, animals underwent intracoronary adenoviral-mediated gene transfection using SERCA-2a. Heart failure animals were randomized to receive the SERCA-2a gene, the beta galactosidase (control) gene, or followed without any further intervention. Exercise and hemodynamic testing were performed, and myocardial and systemic markers of inflammation were assayed after 7 and 21 d. Animals receiving Ad.SERCA-2a showed an increase in exercise tolerance (499.0 +/- 14.9 versus 312.8 +/- 10.5 s, P < 0.0001) relative to Ad.Gal group. Groups treated with Ad.SERCA-2a had significantly decreased serum levels of the inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor-alpha compared with Ad.Gal-treated animals. Serum levels of atrial natriuretic peptide were decreased in animals receiving Ad.SERCA-2a compared with animals receiving Ad.Gal at day 7 (0.35 +/- 0.03 versus 0.52 +/- 0.11 pg/mL, P = 0.001). Myocardial levels of the proapoptotic protein bax were reduced in Ad.SERCA-2a -treated animals compared with those receiving Ad.Gal at day 7 (protein level/actin: 0.24 +/- 0.05 versus 0.33 +/- 0.04, P = 0.04) and day 21 (protein level/actin: 0.61 +/- 0.04 versus 0.69 +/- 0.01, P = 0.001). Genetic modulation of heart failure using the SERCA-2a gene was associated with improvement in cardiac function and exercise capacity as well as improvements in heart-failure associated inflammatory markers.

A generalized estimating equations approach for resting-state functional MRI group analysis.

PubMed

D'Angelo, Gina M; Lazar, Nicole A; Eddy, William F; Morris, John C; Sheline, Yvette I

2011-01-01

An Alzheimer's fMRI study has motivated us to evaluate inter-regional correlations between groups. The overall objective is to assess inter-regional correlations at a resting-state with no stimulus or task. We propose using a generalized estimating equation (GEE) transition model and a GEE marginal model to model the within-subject correlation for each region. Residuals calculated from the GEE models are used to correlate brain regions and assess between group differences. The standard pooling approach of group averages of the Fisher-z transformation assuming temporal independence is a typical approach used to compare group correlations. The GEE approaches and standard Fisher-z pooling approach are demonstrated with an Alzheimer's disease (AD) connectivity study in a population of AD subjects and healthy control subjects. We also compare these methods using simulation studies and show that the transition model may have better statistical properties.

Plasma BDNF levels are correlated with aggressiveness in patients with amnestic mild cognitive impairment or Alzheimer disease.

PubMed

Nagata, Tomoyuki; Kobayashi, Nobuyuki; Shinagawa, Shunichiro; Yamada, Hisashi; Kondo, Kazuhiro; Nakayama, Kazuhiko

2014-04-01

In the present study, we examined whether neuropsychiatric symptoms were correlated with plasma brain-derived neurotrophic factor (BDNF) levels as a state marker or were associated with the BDNF polymorphism Val66Met in patients with amnestic mild cognitive impairment (A-MCI) or Alzheimer disease (AD). One hundred and seventy-six outpatients with AD (n = 129) or A-MCI (n = 47) were selected and their plasma BDNF concentrations measured. Next, we investigated the correlation between the plasma BDNF level and the Behavioral Pathology in Alzheimer Disease (Behave-AD) subscale scores, which reflect neuropsychiatric symptoms. We also compared the plasma BDNF level and the Behave-AD subscale scores among the BDNF Val66Met genotypic groups. Among the seven Behave-AD subscale scores, aggressiveness was positively correlated with the plasma BDNF level (ρ = 0.237, P < 0.005), but did not differ significantly among the three BDNF Val66Met genotypic groups. The Behave-AD total and other subscale scores did not differ significantly among the BDNF Val66Met genotypic groups and were not associated with the plasma BDNF level. Moreover, the plasma BDNF level did not differ significantly among the three BDNF Val66Met genotypic groups or between patients with A-MCI and those with AD. The plasma BDNF level was robustly correlated with aggressiveness, implying that the plasma BDNF level might be useful as a behavioral state marker in patients with AD or A-MCI.

Assessment of free and cued recall in Alzheimer's disease and vascular and frontotemporal dementia with 24-item Grober and Buschke test.

PubMed

Cerciello, Milena; Isella, Valeria; Proserpi, Alice; Papagno, Costanza

2017-01-01

Alzheimer's disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) are the most common forms of dementia. It is well known that memory deficits in AD are different from those in VaD and FTD, especially with respect to cued recall. The aim of this clinical study was to compare the memory performance in 15 AD, 10 VaD and 9 FTD patients and 20 normal controls by means of a 24-item Grober-Buschke test [8]. The patients' groups were comparable in terms of severity of dementia. We considered free and total recall (free plus cued) both in immediate and delayed recall and computed an Index of Sensitivity to Cueing (ISC) [8] for immediate and delayed trials. We assessed whether cued recall predicted the subsequent free recall across our patients' groups. We found that AD patients recalled fewer items from the beginning and were less sensitive to cueing supporting the hypothesis that memory disorders in AD depend on encoding and storage deficit. In immediate recall VaD and FTD showed a similar memory performance and a stronger sensitivity to cueing than AD, suggesting that memory disorders in these patients are due to a difficulty in spontaneously implementing efficient retrieval strategies. However, we found a lower ISC in the delayed recall compared to the immediate trials in VaD than FTD due to a higher forgetting in VaD.

Mild cognitive impairment due to alzheimer disease is less likely under the age of 65.

PubMed

Shin, Soojeong; Kim, Jong Hun; Cho, Jeong Hee; Kim, Gyu Sik; Choi, Sun-Ah; Lee, Jun Hong

2015-01-01

Patients with amnestic mild cognitive impairment (aMCI) are considered to have a high risk for Alzheimer dementia (AD). Even high positive predictive values, however, cannot be guaranteed even by tests with high sensitivity and specificity when disease prevalence is low. If we regard the clinical criteria for aMCI as a test for predicting aMCI due to AD, the positive predictive value of the criteria will be low by definition in young patients with aMCI (age below 65 years) because of the low prevalence of AD in this age group. To test this hypothesis, we compared CSF biomarkers for AD between young (age below 65 years) and old (age 65 years or older) age groups of normal cognition, aMCI, and AD of the Alzheimer's Disease Neuroimaging Initiative database. Using these biomarkers, we observed that the prevalence of aMCI due to AD differed significantly between the young and the old. For example, only 28.2% young aMCI, but 63.2% old aMCI, had abnormal CSF amyloid measures consistent with AD pathology. As posited, the presence of aMCI due to AD was lower in young aMCI than in old aMCI. Given that the likelihood of aMCI due to AD is reduced in younger subjects, more attention to and evaluation of alternative diagnoses need to be considered in this group.

Altered expression of γ-secretase components in animal model of major depressive disorder induced by reserpine administration.

PubMed

Lee, Hye-Ryun; Hwang, In-Sik; Kim, Ji-Eun; Choi, Sun-Il; Lee, Young-Ju; Goo, Jun-Seo; Lee, Eon-Pil; Choi, Hae-Wook; Kim, Hong-Sung; Lee, Jae-Ho; Jung, Young-Jin; Hwang, Dae-Youn

2012-06-01

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of γ-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of γ-secretase components decreased (P<0.03). Among the three components of the γ-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.

Home-Based Exercise Program Improves Balance and Fear of Falling in Community-Dwelling Older Adults with Mild Alzheimer's Disease: A Pilot Study.

PubMed

Padala, Kalpana P; Padala, Prasad R; Lensing, Shelly Y; Dennis, Richard A; Bopp, Melinda M; Roberson, Paula K; Sullivan, Dennis H

2017-01-01

Balance problems are common in older adults with Alzheimer's disease (AD). The objective was to study the effects of a Wii-Fit interactive video-game-led physical exercise program to a walking program on measures of balance in older adults with mild AD. A prospective randomized controlled parallel-group trial (Wii-Fit versus walking) was conducted in thirty community-dwelling older adults (73±6.2 years) with mild AD. Home-based exercises were performed under caregiver supervision for 8 weeks. Primary (Berg Balance Scale, BBS) and secondary outcomes (fear of falls and quality of life) were measured at baseline, 8 weeks (end of intervention), and 16 weeks (8-weeks post-intervention). At 8 weeks, there was a significantly greater improvement (average inter-group difference [95% CI]) in the Wii-Fit group compared to the walking group in BBS (4.8 [3.3-6.2], p < 0.001), after adjusting for baseline. This improvement was sustained at 16 weeks (3.5 [2.0-5.0], p < 0.001). Analyses of the secondary outcome measures indicated that there was a significantly greater improvement in the Wii-Fit group compared to walking group in Activity-specific Balance Confidence scale (6.5 [3.6-9.4], p < 0.001) and Falls Efficacy Scale (-4.8 [-7.6 to -2.0], p = 0.002) at 8 weeks. However, this effect was not sustained at 16 weeks. Quality of life improved in both groups at 8 weeks; however, there were no inter-group differences (p = 0.445). Home-based, caregiver-supervised Wii-Fit exercises improve balance and may reduce fear of falling in community-dwelling older adults with mild AD.

Comparison of low-abundance biomarker levels in capillary-collected nonstimulated tears and washout tears of aqueous-deficient and normal patients.

PubMed

Guyette, Nicole; Williams, Larezia; Tran, My-Tho; Than, Tammy; Bradley, John; Kehinde, Lucy; Edwards, Clara; Beasley, Mark; Fullard, Roderick

2013-05-01

Low tear volume limits the use of nonstimulated (NS) microcapillary tear collection in aqueous-deficient (AD) patients. Adding a small amount of "washout" fluid to the eye prior to tear collection is a potentially viable alternative method for abundant proteins, but is relatively untested for low-abundance biomarkers. This study determined the feasibility of the washout (WO) method as an NS alternative for low-abundance biomarkers. NS and WO biomarker profiles were compared between AD patients and non-AD controls to determine if the two methods identify the same intergroup differences. Matching NS and WO tears were collected from 48 patients by micropipette, the WO sample after instillation of 10 μL saline. Tear cytokine levels were measured by 27-Plex Bio-Rad assay. Bland-Altman analyses for each biomarker determined the agreement between tear sample types. Patients were grouped as AD or non-AD based on Schirmer score to determine if NS profile between-group differences were preserved in WO tears. Bland-Altman plots showed good biomarker level agreement between NS and WO tears for most cytokines. Five biomarkers, among those most often cited as differing in AD dry eye, differed significantly between non-AD and AD groups in both tear types. Additional biomarker differences were seen in NS tears only. The WO tear collection method is a viable alternative to NS tears for many low-abundance biomarkers and is able to replicate major NS tear differences between dry eye groups. More subtle intergroup differences are lost in WO samples because of reduced statistical power.

Nonbranded or branded direct-to-consumer prescription drug advertising-which is more effective?

PubMed

Rollins, Brent L; King, Karen; Zinkhan, George; Perri, Matthew

2011-01-01

Recently, pharmaceutical manufacturers have increased the amount of nonbranded, disease-education focused, direct-to-consumer advertisements. A comparison to branded, product-specific, ads was examined through a series of survey questions measuring consumer attitudes and the role of involvement. Nonbranded ads compared favorably to branded ads and should remain a viable part of the marketing mix. Consumers' level of disease state involvement was the strongest determinant of attitudes overall and within the two ad groupings, as highly involved consumers had significantly more positives attitudes regarding the nonbranded ads. Regardless of involvement level, however, nonbranded ads maintained positive attitude levels.

Cultural Variation in Antismoking Video Ads between the United States, Taiwan, and China

ERIC Educational Resources Information Center

Wong, Tzu-Jung; King, Jessica L.; Pomeranz, Jamie L.

2016-01-01

Antitobacco advertisement components, including types of messages and advertising appeals, have not been evaluated among multinational groups. This study identified and compared the content of antismoking video ads across three countries. We reviewed 86 antismoking video advertisements for the following information: severity of the consequences of…

Cognitive Behavioral Insomnia Therapy for Those With Insomnia and Depression: A Randomized Controlled Clinical Trial

PubMed Central

Edinger, Jack D.; Kuchibhatla, Maragatha; Lachowski, Angela M.; Bogouslavsky, Olya; Krystal, Andrew D.; Shapiro, Colin M.

2017-01-01

Abstract Study Objective: To compare cognitive behavioral therapy for insomnia (CBT-I) + antidepressant medication (AD) against treatments that target solely depression or solely insomnia. Design: A blinded, randomized split-plot experimental study. Setting: Two urban academic clinical centers. Participants: 107 participants (68% female, mean age 42 ± 11) with major depressive disorder and insomnia. Interventions: Randomization was to one of three groups: antidepressant (AD; escitalopram) + CBT-I (4 sessions), CBT-I + placebo pill, or AD + 4-session sleep hygiene control (SH). Measurements and Results: Subjective sleep was assessed via 2 weeks of daily sleep diaries (use of medication was covaried in all analyses); although there were no statistically significant group differences detected, all groups improved from baseline to posttreatment on subjective sleep efficiency (SE) and total wake time (TWT) and the effect sizes were large. Objective sleep was assessed via overnight polysomnographic monitoring at baseline and posttreatment; analyses revealed both CBT groups improved on TWT (p = .03), but the AD + SH group worsened. There was no statistically significant effect for PSG SE (p = .07). There was a between groups medium effect observed for the AD + SH and CBT + placebo group differences on diary TWT and both PSG variables. All groups improved significantly from baseline to posttreatment on the Hamilton Rating Scale for Depression (HAMD-17); the groups did not differ. Conclusions: Although all groups self-reported sleeping better after treatment, only the CBT-I groups improved on objective sleep, and AD + SH’s sleep worsened. This suggests that we should be treating sleep in those with depression with an effective insomnia treatment and relying on self-report obscures sleep worsening effects. All groups improved on depression, even a group with absolutely no depression-focused treatment component (CBT-I + placebo). The depression effect in CBT-I only group has been reported in other studies, suggesting that we should further investigate the antidepressant properties of CBT-I. PMID:28199710

The prevention of hip fracture with menatetrenone and risedronate plus calcium supplementation in elderly patients with Alzheimer disease: a randomized controlled trial.

PubMed

Sato, Yoshihiro; Honda, Yoshiaki; Umeno, Kazuo; Hayashida, Norimasa; Iwamoto, Jun; Takeda, Tsuyoshi; Matsumoto, Hideo

2011-01-01

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer disease (AD), who are prone to falls and have osteoporosis. We previously found that vitamin K deficiency and low 25-hydroxyvitamin D (25-OHD) with compensatory hyperparathyroidism cause reduced bone mineral density (BMD) in female patients with AD. This may modifiable by intervention with menatetrenone (vitamin K2) and risedronate sodium; we address the possibility that treatment with menatetrenone, risedronate and calcium may reduce the incidence of nonvertebral fractures in elderly patients with AD. A total of 231 elderly patients with AD were randomly assigned to daily treatment with 45 mg of menatetrenone or a placebo combined with once weekly risedronate sodium, and followed up for 12 months. At baseline, patients of both groups showed high undercarboxylated osteocalcin (ucOC) and low 25-OHD insufficiency with compensatory hyperparathyroidism. During the study period, BMD in the treatment group increased by 5.7% and increased by 2.1% in the control group. Nonvertebral fractures occurred in 15 patients (10 hip fractures) in the control group and 5 patients (2 hip fractures) in the treatment group. The relative risk in the treatment group compared with the control group was 0.31 (95% confidence interval, 0.12-0.81). Elderly AD patients with hypovitaminosis K and D are at increased risk for hip fracture. The study medications were well tolerated with relatively few adverse events and effective in reducing the risk of a fracture in elderly patients with AD.

Aerobic Exercise Sustains Performance of Instrumental Activities of Daily Living in Early-Stage Alzheimer Disease.

PubMed

Vidoni, Eric D; Perales, Jaime; Alshehri, Mohammed; Giles, Abdul-Mannaan; Siengsukon, Catherine F; Burns, Jeffrey M

2017-12-28

Individuals with Alzheimer disease (AD) experience progressive loss of independence-performing activities of daily living. Identifying interventions to support independence and reduce the economic and psychosocial burden of caregiving for individuals with AD is imperative. The purpose of this analysis was to examine functional disability and caregiver time in individuals with early-stage AD. This was a secondary analysis of a randomized controlled trial of 26 weeks of aerobic exercise (AEx) versus stretching and toning (ST). We measured functional dependence using the Disability Assessment for Dementia, informal caregiver time required using the Resources Utilization in Dementia Lite, and cognition using a standard cognitive battery. We saw a stable function in the AEx group compared with a significant decline in the ST group (4%; F = 4.2, P = .04). This was especially evident in more complex, instrumental activities of daily living, with individuals in the AEx group increasing 1% compared with an 8% loss in the ST group over 26 weeks (F = 8.3, P = .006). Change in memory was a significant predictor of declining instrumental activities of daily living performance (r = 0.28, 95% confidence interval = 0.08 ∞, P = .01). Informal caregiver time was not different between the AEx and ST groups. Our analysis extends recent work by revealing specific benefits for instrumental activities of daily living for individuals in the early stages of AD and supports the value of exercise for individuals with cognitive impairment.

Distinguishing Depressive Pseudodementia from Alzheimer Disease: A Comparative Study of Hippocampal Volumetry and Cognitive Tests

PubMed Central

Sahin, Sevki; Okluoglu Önal, Tugba; Cinar, Nilgun; Bozdemir, Meral; Çubuk, Rahmi; Karsidag, Sibel

2017-01-01

Background and Aim Depressive pseudodementia (DPD) is a condition which may develop secondary to depression. The aim of this study was to contribute to the differential diagnosis between Alzheimer disease (AD) and DPD by comparing the neurocognitive tests and hippocampal volume. Materials and Methods Patients who met criteria of AD/DPD were enrolled in the study. All patients were assessed using the Wechsler Memory Scale (WMS), clock-drawing test, Stroop test, Benton Facial Recognition Test (BFRT), Boston Naming Test, Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS). Hippocampal volume was measured by importing the coronal T1-weighted magnetic resonance images to the Vitrea 2 workstation. Results A significant difference was found between the AD and DPD groups on the WMS test, clock-drawing test, Stroop test, Boston Naming Test, MMSE, GDS, and left hippocampal volume. A significant correlation between BFRT and bilateral hippocampal volumes was found in the AD group. No correlation was found among parameters in DPD patients. Conclusions Our results suggest that evaluation of facial recognition and left hippocampal volume may provide more reliable evidence for distinguishing DPD from AD. Further investigations combined with functional imaging techniques including more patients are needed. PMID:28868066

Neuropathologic features associated with Alzheimer disease diagnosis

PubMed Central

Grinberg, L.T.; Miller, B.; Kawas, C.; Yaffe, K.

2011-01-01

Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods: We conducted a cross-sectional analysis of 2,014 older adults (≥70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made ≤1 year before death, n = 419) or AD (at ≥65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70–74 years: c statistic, 95% confidence interval: 0.93, 0.89–0.96; 75–84 years: 0.95, 0.87–0.95; ≥85 years: 0.83, 0.80–0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004). Conclusion: Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. PMID:22031532

Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial.

PubMed

Craft, Suzanne; Claxton, Amy; Baker, Laura D; Hanson, Angela J; Cholerton, Brenna; Trittschuh, Emily H; Dahl, Deborah; Caulder, Erin; Neth, Bryan; Montine, Thomas J; Jung, Youngkyoo; Maldjian, Joseph; Whitlow, Christopher; Friedman, Seth

2017-01-01

Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD. This randomized, double-blind, placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD. Participants received placebo (n = 12), 40 IU of insulin detemir (n = 12), or 40 IU of regular insulin (n = 12) daily for four months, administered with a nasal delivery device. A cognitive battery was administered at baseline and after two and four months of treatment. MRI was administered for all participants and lumbar puncture for a subset (n = 20) at baseline and four months. The primary outcome was change from baseline to four months on a memory composite (sum of Z scores for delayed list and story recall). Secondary outcomes included: global cognition (Alzheimer's Disease Assessment Scale-Cognition), daily functioning (Dementia Severity Rating Scale), MRI volume changes in AD-related regions of interest, and cerebrospinal fluid AD markers. The regular insulin treated group had better memory after two and four months compared with placebo (p < 0.03). No significant effects were observed for the detemir-assigned group compared with the placebo group, or for daily functioning for either group. Regular insulin treatment was associated with preserved volume on MRI. Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio. Future research is warranted to examine the mechanistic basis of treatment differences, and to further assess the efficacy and safety of intranasal insulin.

Time to achieve target mean arterial pressure during resuscitation from experimental anaphylactic shock in an animal model. A comparison of adrenaline alone or in combination with different volume expanders.

PubMed

Tajima, K; Zheng, F; Collange, O; Barthel, G; Thornton, S N; Longrois, D; Levy, B; Audibert, G; Malinovsky, J M; Mertes, P M

2013-11-01

Anaphylactic shock is a rare, but potentially lethal complication, combining life-threatening circulatory failure and massive fluid shifts. Treatment guidelines rely on adrenaline and volume expansion by intravenous fluids, but there is no solid evidence for the choice of one specific type of fluid over another. Our purpose was to compare the time to achieve target mean arterial pressure upon resuscitation using adrenaline alone versus adrenaline with different resuscitation fluids in an animal model and to compare the tissue oxygen pressures (PtiO2) with the various strategies. Twenty-five ovalbumin-sensitised Brown Norway rats were allocated to five groups after anaphylactic shock induction: vehicle (CON), adrenaline alone (AD), or adrenaline with isotonic saline (AD+IS), hydroxyethyl starch (AD+HES) or hypertonic saline (AD+HS). Time to reach a target mean arterial pressure value of 75 mmHg, cardiac output, skeletal muscle PtiO2, lactate/pyruvate ratio and cumulative doses of adrenaline were recorded. Non-treated rats died within 15 minutes. The target mean arterial pressure value was reached faster with AD+HES (median: 10 minutes, range: 7.5 to 12.5 minutes) and AD+IS (median: 17.5 minutes, range: 5 to 25 minutes) versus adrenaline alone (median: 25 minutes, range: 20-30 minutes). There were also reduced adrenaline requirements in these groups. The skeletal muscle PtiO2 was restored only in the AD+HES group. Although direct extrapolation to humans should be made with caution, our results support the combined use of adrenaline and volume expansion for resuscitation from anaphylactic shock. When used with adrenaline the most effective fluid was hydroxyethyl starch, whereas hypertonic saline was the least effective.

A Group Based Key Sharing and Management Algorithm for Vehicular Ad Hoc Networks

PubMed Central

Moharram, Mohammed Morsi; Azam, Farzana

2014-01-01

Vehicular ad hoc networks (VANETs) are one special type of ad hoc networks that involves vehicles on roads. Typically like ad hoc networks, broadcast approach is used for data dissemination. Blind broadcast to each and every node results in exchange of useless and irrelevant messages and hence creates an overhead. Unicasting is not preferred in ad-hoc networks due to the dynamic topology and the resource requirements as compared to broadcasting. Simple broadcasting techniques create several problems on privacy, disturbance, and resource utilization. In this paper, we propose media mixing algorithm to decide what information should be provided to each user and how to provide such information. Results obtained through simulation show that fewer number of keys are needed to share compared to simple broadcasting. Privacy is also enhanced through this approach. PMID:24587749

Buccal Cell Cytokeratin 14 Correlates with Multiple Blood Biomarkers of Alzheimer's Disease Risk.

PubMed

Leifert, Wayne R; Nguyen, Tori; Rembach, Alan; Martins, Ralph; Rainey-Smith, Stephanie; Masters, Colin L; Ames, David; Rowe, Christopher C; Macaulay, S Lance; François, Maxime; Fenech, Michael F

2015-01-01

Mild cognitive impairment (MCI) may reflect early stages of neurodegenerative disorders such as Alzheimer's disease (AD). Our hypothesis was that cytokeratin 14 (CK14) expression could be used with blood-based biomarkers such as homocysteine, vitamin B12, and folate to identify individuals with MCI or AD from the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging. Buccal cells from 54 individuals were analyzed by a newly developed method that is rapid, automated, and quantitative for buccal cell CK14 expression levels. CK14 was negatively correlated with plasma Mg²⁺ and LDL, while positively correlated with vitamin B12, red cell hematocrit/volume, and basophils in the MCI group and positively correlated with insulin and vitamin B12 in the AD group. The combined biomarker panel (CK14 expression, plasma vitamin B12, and homocysteine) was significantly lower in the MCI (p = 0.003) and AD (p = 0.0001) groups compared with controls. Receiver-operating characteristic curves yielded area under the curve (AUC) values of 0.829 for the MCI (p = 0.002) group and 0.856 for the AD (p = 0.0003) group. These complex associations of multiple related parameters highlight the differences between the MCI and AD cohorts and possibly an underlying metabolic pathology associated with the development of early memory impairment. The changes in buccal cell CK14 expression observed in this pilot study supports previous results suggesting the peripheral biomarkers and metabolic changes are not restricted to brain pathology alone in MCI and AD and could prove useful as a potential biomarker in identifying individuals with an increased risk of developing MCI and eventually AD.

Validation of an Alzheimer’s disease assessment battery in Asian participants with mild to moderate Alzheimer’s disease

PubMed Central

Shen, Joan HQ; Shen, Qi; Yu, Holly; Lai, Jin-Shei; Beaumont, Jennifer L; Zhang, Zhenxin; Wang, Huali; Kim, Seong Yoon; Chen, Christopher; Kwok, Timothy; Wang, Shuu-Jiun; Lee, Dong Young; Harrison, John; Cummings, Jeffrey

2014-01-01

There is a lack of validated tools for assessing Alzheimer’s disease (AD) across Asia. This study evaluates the psychometric properties of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Disability Assessment for Dementia (DAD), and Neuropsychological Test Battery (NTB) in Asian participants. Participants with mild to moderate AD (n=251) and healthy controls (n=51) from Mainland China, Taiwan, Singapore, Hong Kong, and South Korea completed selected instruments at several time points. Test-retest reliability was better than 0.70 for all tests. AD participants performed significantly more poorly than controls on every score. Within the AD group, greater disease severity corresponded to significantly poorer performance. The AD group test performance worsened over time and there was a trend for worse performance in AD compared to healthy controls over time. The ADAS-Cog, DAD, and NTB are reliable, valid, and responsive measures in this population and could be used for clinical trials across Asian countries/regions. PMID:25628967

Distance-informed metric learning for Alzheimer's disease staging.

PubMed

Shi, Bibo; Wang, Zhewei; Liu, Jundong

2014-01-01

Identifying intermediate biomarkers of Alzheimer's disease (AD) is of great importance for diagnosis and prognosis of the disease. In this study, we develop a new AD staging method to classify patients into Normal Controls (NC), Mild Cognitive Impairment (MCI), and AD groups. Our solution employs a novel metric learning technique that improves classification rates through the guidance of some weak supervisory information in AD progression. More specifically, those information are in the form of pairwise constraints that specify the relative Mini Mental State Examination (MMSE) score disparity of two subjects, depending on whether they are in the same group or not. With the imposed constraints, the common knowledge that MCI generally sits in between of NC and AD can be integrated into the classification distance metric. Subjects from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; 56 AD, 104 MCI, 161 controls) were used to demonstrate the improvements made comparing with two state-of-the-art metric learning solutions: large margin nearest neighbors (LMNN) and relevant component analysis (RCA).

Analysis of word number and content in discourse of patients with mild to moderate Alzheimer's disease.

PubMed

de Lira, Juliana Onofre; Minett, Thaís Soares Cianciarullo; Bertolucci, Paulo Henrique Ferreira; Ortiz, Karin Zazo

2014-01-01

Alzheimer's disease (AD) is characterized by impairments in memory and other cognitive functions such as language, which can be affected in all aspects including discourse. A picture description task is considered an effective way of obtaining a discourse sample whose key feature is the ability to retrieve appropriate lexical items. There is no consensus on findings showing that performance in content processing of spoken discourse deteriorates from the mildest phase of AD. To compare the quantity and quality of discourse among patients with mild to moderate AD and controls. A cross-sectional study was designed. Subjects aged 50 years and older of both sexes, with one year or more of education, were divided into three groups: control (CG), mild AD (ADG1) and moderate AD (ADG2). Participants were asked to describe the "cookie theft" picture. The total number of complete words spoken and information units (IU) were included in the analysis. There was no significant difference among groups in terms of age, schooling and sex. For number of words spoken, the CG performed significantly better than both the ADG 1 and ADG2, but no difference between the two latter groups was found. CG produced almost twice as many information units as the ADG1 and more than double that of the ADG2. Moreover, ADG2 patients had worse performance on IUs compared to the ADG1. Decreased performance in quantity and content of discourse was evident in patients with AD from the mildest phase, but only content (IU) continued to worsen with disease progression.

Putative Gonadotropin Releasing Hormone Agonist Therapy and Dementia: An Application of Medicare Hospitalization Claims Data.

PubMed

Smith, Mark A; Bowen, Richard L; Nguyen, Richard Q; Perry, George; Atwood, Craig S; Rimm, Alfred A

2018-05-16

Estrogen and hormone replacement therapies to reduce Alzheimer's disease (AD) have yielded conflicting results. However, this study proposes that the well-characterized increase in serum gonadotropins following menopause or andropause are accountable for the increased risk of developing AD among the elderly population. To determine the role of gonadotropins in the development of AD and investigate gonadotropin-releasing hormone (GnRH) agonist therapy as a potential preventative and/or disease-modifying approach to AD management. Male Medicare beneficiaries aged 67 to 75 and hospitalized with prostate cancer (n = 115,789) were compared to three control groups: men of the same demographics undergoing a cholecystectomy (n = 97,267), herniorrhaphy (n = 68,778), or transurethral prostatectomy (n = 267,691). A proportion of the patients hospitalized with prostate cancer were assumed to have low concentrations of serum gonadotropins and sex steroids as a result of GnRH agonist therapy, while those in the control groups were assumed to have elevated gonadotropin but lowered sex steroid levels that are associated with andropause in this age group. The rates of development of select diagnoses of dementia, including AD, over a twelve-year follow-up period following surgery. When compared to control patients, men hospitalized with prostate cancer have a protection against dementia after twelve years of follow-up, with relative risks ranging from 0.48 to 0.83. Patients with prostate cancer are treated with the GnRH analogue leuprolide acetate, our data suggest that leuprolide acetate may be therapeutic for AD via its downregulation of serum gonadotropins.

Analysis of word number and content in discourse of patients with mild to moderate Alzheimer's disease

PubMed Central

de Lira, Juliana Onofre; Minett, Thaís Soares Cianciarullo; Bertolucci, Paulo Henrique Ferreira; Ortiz, Karin Zazo

2014-01-01

Alzheimer's disease (AD) is characterized by impairments in memory and other cognitive functions such as language, which can be affected in all aspects including discourse. A picture description task is considered an effective way of obtaining a discourse sample whose key feature is the ability to retrieve appropriate lexical items. There is no consensus on findings showing that performance in content processing of spoken discourse deteriorates from the mildest phase of AD. Objective To compare the quantity and quality of discourse among patients with mild to moderate AD and controls. Methods A cross-sectional study was designed. Subjects aged 50 years and older of both sexes, with one year or more of education, were divided into three groups: control (CG), mild AD (ADG1) and moderate AD (ADG2). Participants were asked to describe the "cookie theft" picture. The total number of complete words spoken and information units (IU) were included in the analysis. Results There was no significant difference among groups in terms of age, schooling and sex. For number of words spoken, the CG performed significantly better than both the ADG 1 and ADG2, but no difference between the two latter groups was found. CG produced almost twice as many information units as the ADG1 and more than double that of the ADG2. Moreover, ADG2 patients had worse performance on IUs compared to the ADG1. Conclusion Decreased performance in quantity and content of discourse was evident in patients with AD from the mildest phase, but only content (IU) continued to worsen with disease progression. PMID:29213912

Examining the Screen for Child Anxiety-Related Emotional Disorder-71 as an assessment tool for anxiety in children with high-functioning autism spectrum disorders.

PubMed

van Steensel, Francisca J A; Deutschman, Amber A C G; Bögels, Susan M

2013-11-01

The psychometric properties of a questionnaire developed to assess symptoms of anxiety disorders (SCARED-71) were compared between two groups of children: children with high-functioning autism spectrum disorder and comorbid anxiety disorders (ASD-group; n = 115), and children with anxiety disorders (AD-group; n = 122). Anxiety disorders were established with a semi-structured interview (ADIS-C/P), using child- as well as parent-report. Internal consistency, construct validity, sensitivity, specificity, and discriminant validity of the SCARED-71 was investigated. Results revealed that the psychometric properties of the SCARED-71 for the ASD-group were quite comparable to the AD-group, however, the discriminant validity of the SCARED-71 child-report was less in the ASD-group. Raising the parental cutoffs of the SCARED-71 resulted in higher specificity rates, which suggests that research should focus more on establishing alternative cutoffs for the ASD-population.

CATEGORICAL AND CORRELATIONAL ANALYSES OF BASELINE FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IMAGES FROM THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE (ADNI)

PubMed Central

Langbaum, Jessica B.S.; Chen, Kewei; Lee, Wendy; Reschke, Cole; Bandy, Dan; Fleisher, Adam S.; Alexander, Gene E.; Foster, Norman L.; Weiner, Michael W.; Koeppe, Robert A.; Jagust, William J.; Reiman, Eric M.

2010-01-01

In mostly small single-center studies, Alzheimer’s disease (AD) is associated with characteristic and progressive reductions in fluorodeoxyglucose positron emission tomography (PET) measurements of the regional cerebral metabolic rate for glucose (CMRgl). The AD Neuroimaging Initiative (ADNI) is acquiring FDG PET, volumetric magnetic resonance imaging, and other biomarker measurements in a large longitudinal multi-center study of initially mildly affected probable AD (pAD) patients, amnestic mild cognitive impairment (aMCI) patients, who are at increased AD risk, and cognitively normal controls (NC), and we are responsible for analyzing the PET images using statistical parametric mapping (SPM). Here we compare baseline CMRgl measurements from 74 pAD patients and 142 aMCI patients to those from 82 NC, we correlate CMRgl with categorical and continuous measures of clinical disease severity, and we compare apolipoprotein E (APOE) ε4 carriers to non-carriers in each of these subject groups. In comparison with NC, the pAD and aMCI groups each had significantly lower CMRgl bilaterally in posterior cingulate, precuneus, parietotemporal and frontal cortex. Similar reductions were observed when categories of disease severity or lower Mini-Mental State Exam (MMSE) scores were correlated with lower CMRgl. However, when analyses were restricted to the pAD patients, lower MMSE scores were significantly correlated with lower left frontal and temporal CMRgl. These findings from a large, multi-site study support previous single-site findings, supports the characteristic pattern of baseline CMRgl reductions in AD and aMCI patients, as well as preferential anterior CMRgl reductions after the onset of AD dementia. PMID:19349228

Adding Paracetamol to Ibuprofen for the Treatment of Patent Ductus Arteriosus in Preterm Infants: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.

PubMed

Hochwald, Ori; Mainzer, Gur; Borenstein-Levin, Liron; Jubran, Huda; Dinur, Gil; Zucker, Meirav; Mor, Malka; Khoury, Asaad; Kugelman, Amir

2018-05-21

 The objective of this study was to compare the closure rate of hemodynamically significant patent ductus arteriosus (hsPDA) of intravenous ibuprofen + paracetamol (acetaminophen) versus ibuprofen + placebo, in preterm infants of 24 to 31 6/7 weeks postmenstrual age.  This is a single-center, double-blind, randomized controlled pilot study. Infants were assigned for treatment with either intravenous ibuprofen + paracetamol ( n  = 12) or ibuprofen + placebo ( n  = 12).  There was no statistical difference in baseline characteristics of the two groups. Echocardiography parameters were comparable before treatment in both groups. There was a trend toward higher hsPDA closure rate in the paracetamol group in comparison to the placebo group (83 vs. 42%, p  = 0.08). No adverse effects, clinical or laboratory, were associated with adding paracetamol.  Our pilot study was unable to detect a beneficial effect by adding intravenous paracetamol to ibuprofen for the treatment of hsPDA. Larger prospective studies are needed to explore the positive tendency suggested by our results and to assure safety. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluation of the antigingivitis effect of a chlorhexidine mouthwash with or without an antidiscoloration system compared to placebo during experimental gingivitis.

PubMed

Li, Wen; Wang, Ren E; Finger, Martin; Lang, Niklaus P

2014-02-01

The aim of the present study was to evaluate the effectiveness of chlorhexidine (CHX) with an antidiscoloration system (ADS) on stain, plaque accumulation, and gingivitis. A randomized, controlled clinical trial was conducted in 26 students. After a preparatory period, the students were randomly assigned to either group P (placebo), group T1 (0.12% CHX without an ADS), or group T2 (0.12% CHX with an ADS). During the 3-week experimental period, all mechanical oral hygiene was abolished. Rinsing with 10 mL mouthwash or placebo was performed twice daily under supervision. The parameters assessed on days 0, 7, 14, and 21 included the Discoloration Index (DI), Plaque Index (PII), and Gingival Index (GI). There were no significant mean differences in the DI, PII, or GI between groups T2 and P. Significant mean differences existed in the DI between groups T2 and T1 on days 14 and 21. Significant mean differences existed in the PI between groups T2 and T1 on days 7, 14, and 21. Likewise, significant mean differences existed in the GI between groups T2 and T1 on days 14 and 21. CHX with an ADS did not prevent plaque or gingivitis development. In fact, the CHX mouthwash with an ADS showed no superior effect over placebo on oral hygiene or the prevention of gingivitis. © 2013 Wiley Publishing Asia Pty Ltd.

Unplanned gait termination in individuals with multiple sclerosis.

PubMed

Roeing, Kathleen L; Moon, Yaejin; Sosnoff, Jacob J

2017-03-01

Despite the pervasive nature of gait impairment in multiple sclerosis (MS), there is limited information concerning the control of gait termination in individuals with MS. The purpose of this investigation was to examine unplanned gait termination with and without cognitive distractors in individuals with MS compared to healthy controls. Thirty-one individuals with MS and 14 healthy controls completed a series of unplanned gait termination tasks over a pressure sensitive walkway under distracting and non-distracting conditions. Individuals with MS were further broken down into groups based on assistive device use: (no assistive device (MS noAD ) n=18; and assistive device (MS AD ) n=13). Individuals with MS who walked with an assistive device (MS AD : 67.8±15.1cm/s) walked slower than individuals without an assistive device (MS noAD : 110.4±32.3cm/s, p<0.01) and controls (120.0±30.0cm/s; p<0.01). There was a significant reduction in velocity in the cognitively distracting condition (93.4±32.1cm/s) compared to the normal condition [108.8±36.2cm/s; F(1,43)=3.4, p=0.04]. All participants took longer to stop during the distracting condition (1.7±0.6s) than the non-distracting condition (1.4±0.4s; U=673.0 p<0.01). After controlling for gait velocity, post-hoc analysis revealed the MS AD group took significantly longer to stop compared to the control group (p=0.05). Further research investigating the control of unplanned gait termination in MS is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the Effects of a Sweetened Beverage Intervention on Self-Selected Food Intake

USDA-ARS?s Scientific Manuscript database

Evidence suggests that the intake of added sugar increases the risk of chronic disease and should be targeted for reduction. It is unclear if all types of added sugar have equivalent effects on food intake. This prospective, blinded intervention study compared parallel groups consuming one of five t...

Visual rating method and tensor-based morphometry in the diagnosis of mild cognitive impairment and Alzheimer's disease: a comparative magnetic resonance imaging study.

PubMed

Tuokkola, Terhi; Koikkalainen, Juha; Parkkola, Riitta; Karrasch, Mira; Lötjönen, Jyrki; Rinne, Juha O

2016-03-01

Atrophy of the medial temporal lobe (MTL) is the main structural magnetic resonance imaging (MRI) finding in the brain of patients with Alzheimer's disease (AD). However, evaluating the degree of atrophy is still demanding. The visual rating method (VRM) was compared with multi-template tensor-based morphometry (TBM), in terms of its efficacy in diagnosing of mild cognitive impairment (MCI) and AD. Forty-seven patients with MCI, 80 patients with AD and 84 controls were studied. TBM seems to be more sensitive than VRM at the early stage of dementia in the areas of MTL and ventricles. The methods were equally good in distinguishing controls and the MCI group from the AD group. At the frontal areas TBM was better than VRM in all comparisons. A user-friendly VRM is still useful for the clinical evaluation of MCI patients, but multi-template TBM is more sensitive for diagnosing the early stages of dementia. However, TBM is currently too demanding to use for daily clinical work. © The Foundation Acta Radiologica 2015.

Left ventricular remodeling and change of systolic function after closure of patent ductus arteriosus in adults: device and surgical closure.

PubMed

Jeong, Young-Hoon; Yun, Tae-Jin; Song, Jong-Min; Park, Jung-Jun; Seo, Dong-Man; Koh, Jae-Kon; Lee, Se-Whan; Kim, Mi-Jeong; Kang, Duk-Hyun; Song, Jae-Kwan

2007-09-01

Left ventricular (LV) remodeling and predictors of LV systolic function late after closure of patent ductus arteriosus (PDA) in adults remain to be clearly demonstrated. In 45 patients with PDA, including 28 patients who received successful occlusion using the Amplatzer device (AD group) (AGA, Golden Valley, MN) and 17 patients who received surgical closure (OP group), echocardiography studies were performed before closure and 1 day (AD group) or within 7 days (OP group) after closure, and then were repeated at > or = 6 months (17 +/- 13 months). In both groups, LV ejection fraction (EF) and end-diastolic volume index were significantly decreased immediately after closure, whereas end-systolic volume index did not change. During the long-term follow-up period, end-systolic as well as end-diastolic volume indices decreased significantly in both groups and LV EF recovered compared to the immediate postclosure state. However, LV EF remained low compared to the preclosure state. Five patients (11.1%) including 3 patients in the AD group and 2 patients in the OP group showed persistent late LV systolic dysfunction (EF <50%). In stepwise, multiple logistic regression analysis, preclosure EF was the only independent predictor of late normal postclosure EF (odds ratio, 1.230; 95% CI, 1.054-1.434; P = .008). Receiver operating characteristic curve analysis showed that preclosure EF > or = 62% had a sensitivity of 72% and a specificity of 83% for predicting late normal LV EF after closure. Left ventricular EF remains low late after PDA closure compared with preclosure state in adults. Preclosure LV EF is the best index to predict late postclosure LV EF.

Double dissociation of social functioning in frontotemporal dementia

PubMed Central

Rankin, Katherine P.; Kramer, Joel H.; Mychack, Paula; Miller, Bruce L.

2009-01-01

Background Efforts to characterize changes in social functioning in frontotemporal dementia (FTD) have failed to elicit clear dissociation between frontal and temporal variants of the disease based on behavioral measures. Methods This study obtained premorbid and current first-degree relative ratings using an established measure of interpersonal functioning, the Interpersonal Adjectives Scales, to measure personality change in 16 patients with frontal variant (FLV) and 13 with temporal variant (TLV) FTD, and in a control group of 16 patients with AD. Results All three groups showed significant change over time in multiple domains, including increased introversion (FG) and submissiveness (HI). However, patients with both FTD subtypes evidenced significantly greater increases in overall interpersonal pathology vector length [VL] than did patients with AD, who remained within the normal range on all scores. Patients with FLV showed a 2 SD increase in submissiveness (HI), but their cold-heartedness (DE) change scores were not significantly different from those of patients with AD. Conversely, the TLV cold-heartedness (DE) score increased 2 SD compared to minimal change for the AD and FLV groups, yet change in submissiveness (HI) did not differentiate between AD and TLV groups. Conclusions The Interpersonal Adjectives Scales differentiated both FTD groups from patients with AD on the basis of both degree and direction of personality change. Also, the two subtypes of FTD showed distinctly different patterns of change in social functioning: patients with temporal variant shifted toward severe interpersonal coldness with mild loss of dominance, whereas patients with frontal variant showed the opposite pattern. PMID:12552042

Cognitively normal individuals with AD parents may be at risk for developing aging-related cortical thinning patterns characteristic of AD.

PubMed

Reiter, Katherine; Alpert, Kathryn I; Cobia, Derin J; Kwasny, Mary J; Morris, John C; Csernansky, John C; Wang, Lei

2012-07-02

Children of Alzheimer's disease (AD) patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. In this study, we assessed the earliest cortical changes associated with AD in 71 cognitively healthy, adult children of AD patients (AD offspring) as compared with 69 with no family history of AD (non-AD offspring). Cortical thickness measures were obtained using FreeSurfer from 1.5T magnetic resonance (MR) scans. ApoE genotyping was obtained. Primary analyses examined family history and ApoeE4 effects on cortical thickness. Secondary analyses examined age effects within groups. All comparisons were adjusted using False Discovery Rate at a significance threshold of p<0.05. There were no statistically significant differences between family history and ApoE4 groups. Within AD offspring, increasing age was related to reduced cortical thickness (atrophy) over large areas of the precuneus, superior frontal and superior temporal gyri, starting at around age 60. Further, these patterns existed within female and maternal AD offspring, but were absent in male and paternal AD offspring. Within non-AD offspring, negative correlations existed over small regions of the superior temporal, insula and lingual cortices. These results suggest that as AD offspring age, cortical atrophy is more prominent, particularly if the parent with AD is mother or if the AD offspring is female. Copyright © 2012 Elsevier Inc. All rights reserved.

COGNITIVELY NORMAL INDIVIDUALS WITH AD PARENTS MAY BE AT RISK FOR DEVELOPING AGING-RELATED CORTICAL THINNING PATTERNS CHARACTERISTIC OF AD

PubMed Central

Reiter, Katherine; Alpert, Kathryn I.; Cobia, Derin J.; Kwasny, Mary J.; Morris, John C.; Csernansky, John C.; Wang, Lei

2012-01-01

Children of Alzheimer's Disease (AD) patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. In this study, we assessed the earliest cortical changes associated with AD in 71 cognitively healthy, adult children of AD patients (AD offspring) as compared with 69 with no family history of AD (non-AD offspring). Cortical thickness measures were obtained using FreeSurfer from 1.5T magnetic resonance (MR) scans. ApoE genotyping was obtained. Primary analyses examined family history and ApoeE4 effects on cortical thickness. Secondary analyses examined age effects within groups. All comparisons were adjusted using False Discovery Rate at a significance threshold of p < 0.05. There were no statistically significant differences between family history and ApoE4 groups. Within AD offspring, increasing age was related to reduced cortical thickness (atrophy) over large areas of the precuneus, superior frontal and superior temporal gyri, starting at around age 60. Further, these patterns existed within female and maternal AD offspring, but were absent in male and paternal AD offspring. Within non-AD offspring, negative correlations existed over small regions of the superior temporal, insula and lingual cortices. These results suggest that as AD offspring age, cortical atrophy is more prominent, particularly if the parent with AD is mother or if the AD offspring is female. PMID:22503937

Hippocampal volumes among older Indian adults: Comparison with Alzheimer's disease and mild cognitive impairment

PubMed Central

Dhikav, Vikas; Duraisamy, Sharmila; Anand, Kuljeet Singh; Garga, Umesh Chandra

2016-01-01

Background: Hippocampal volume data from India have recently been reported in younger adults. Data in older adults are unknown. The present paper describes hippocampal volume from India among older adults and compares the same with patients having Alzheimer's disease (AD) and mild cognitive impairment (MCI). Materials and Methods: A total of 32 cognitively normal subjects, 20 patients with AD, and 13 patients with MCI were enrolled. Patients were evaluated for the diagnosis of AD/MCI using the National Institute of Neurological and Communicative Disorders and Stroke and the Related Disorders Association criteria and the Clinical Dementia Rating (CDR) Scale (score = 0.5), respectively. Hippocampal volume was measured using magnetic resonance imaging (MRI) machine by manual segmentation (Megnatom Symphony 1.5T scanner) three-dimensional (3D) sequences. Results: Age and duration of illness in the MCI group were 70.6 ± 8.6 years and 1.9 ± 0.9 years, respectively. In the AD group, age and duration of illness were 72 ± 8.1 years and 3.1 ± 2.2 years, respectively. In cognitively normal subjects, the age range was 45-88 years (66.9 ± 10.32) years. Mean mini–mental status examination (MMSE) score of healthy subjects was 28.28 ± 1.33. In the MCI group, MMSE was 27.05 ± 1.79. In the AD group, MMSE was 13.32 ± 5.6. In the healthy group, the hippocampal volume was 2.73 ± 0.53 cm3 on the left side and 2.77 ± 0.6 cm3 on the right side. Likewise, in MCI, the volume on the left side was 2.35 ± 0.42 cm3 and the volume on the right side was 2.36 ± 0.38 cm3. Similarly, in the AD group, the volume on the right side was 1.64 ± 0.55 cm3 and on the left side it was 1.59 ± 0.55 cm3. Post hoc analysis using Tukey's honestly significant difference (HSD) showed, using analysis of variance (ANOVA) that there was a statistically significant difference between healthy and AD (P ≤ 0.01), and between healthy and MCI (P ≤ 0.01) subjects. There was a correlation between MMSE score and hippocampal volume in the AD group. Conclusion: The volume of the hippocampus in older Indian adults was 2.77 ± 0. 6 cm3 on the right side and 2.73 ± 0.52 cm3 on the left side. There was a significant hippocampal volume loss in MCI/AD compared to cognitively normal subjects. PMID:27293329

A novel dietary restriction method for group-housed rats: weight gain and clinical chemistry characterization.

PubMed

Kasanen, I H E; Inhilä, K J; Nevalainen, J I; Väisänen, S B; Mertanen, A M O; Mering, S M; Nevalainen, T O

2009-04-01

Laboratory rodents are usually fed ad libitum. Moderate dietary restriction decreases mortality and morbidity compared with ad libitum feeding. There are, however, problems in achieving dietary restriction. Traditional methods of restricted feeding may interfere with the diurnal rhythms of the animals and are not compatible with group-housing of rodents. We have invented a novel method, the diet board, for restricting the feed intake of laboratory rats. The use of the diet board moderately decreased weight gain of rats when compared with ad libitum-fed animals. The diet board retarded skeletal growth only minimally, whereas major differences were found in body fat depositions. Serum free fatty acid, triglyceride and cholesterol values were lower in diet-restricted rats, while the opposite was true for serum creatine kinase. There were no differences in total protein, albumin or alanine aminotransferase. Moreover, differences in interindividual variances in parameters were not detected between the groups; hence this study could not combine the diet board with reduction potential. The diet board provides mild to moderate dietary restriction for group-housed rats and is unlikely to interfere with the diurnal eating rhythm. The diet board can also be seen as a cage furniture item, dividing the open cage space and increasing the structural complexity of the environment. In conclusion, the diet board appears to possess refinement potential when compared with traditional methods of dietary restriction.

320-row CT renal perfusion imaging in patients with aortic dissection: A preliminary study.

PubMed

Liu, Dongting; Liu, Jiayi; Wen, Zhaoying; Li, Yu; Sun, Zhonghua; Xu, Qin; Fan, Zhanming

2017-01-01

To investigate the clinical value of renal perfusion imaging in patients with aortic dissection (AD) using 320-row computed tomography (CT), and to determine the relationship between renal CT perfusion imaging and various factors of aortic dissection. Forty-three patients with AD who underwent 320-row CT renal perfusion before operation were prospectively enrolled in this study. Diagnosis of AD was confirmed by transthoracic echocardiography. Blood flow (BF) of bilateral renal perfusion was measured and analyzed. CT perfusion imaging signs of AD in relation to the type of AD, number of entry tears and the false lumen thrombus were observed and compared. The BF values of patients with type A AD were significantly lower than those of patients with type B AD (P = 0.004). No significant difference was found in the BF between different numbers of intimal tears (P = 0.288), but BF values were significantly higher in cases with a false lumen without thrombus and renal arteries arising from the true lumen than in those with thrombus (P = 0.036). The BF values measured between the true lumen, false lumen and overriding groups were different (P = 0.02), with the true lumen group having the highest. Also, the difference in BF values between true lumen and false lumen groups was statistically significant (P = 0.016), while no statistical significance was found in the other two groups (P > 0.05). The larger the size of intimal entry tears, the greater the BF values (P = 0.044). This study shows a direct correlation between renal CT perfusion changes and AD, with the size, number of intimal tears, different types of AD, different renal artery origins and false lumen thrombosis, significantly affecting the perfusion values.

Effect of pranayama on rate pressure product in mild hypertensives.

PubMed

Goyal, Rajni; Lata, Hem; Walia, Lily; Narula, Manjit K

2014-07-01

The modern living life-style is known to produce various physical and psychological stresses resulting in increased blood pressure (BP) and heart rate (HR). This can lead to increased myocardial oxygen demand (MVO2). MVO2 correlated best with rate pressure product (RPP). RPP is a product of HR and systolic BP. The present study was conducted to evaluate the effect of relaxation in the form of pranayama on RPP in mild hypertensives. Mild hypertensive patients were divided into two groups. Group A received antihypertensive drugs for 6 weeks and Group B received antihypertensive drugs along with pranayama training for 6 weeks. BP decreased significantly in Group B (148 ± 8.09-127 ± 12.10 mm of Hg) where pranayama was added. The decrease was significant as compared to Group A. HR decreased significantly in both the groups as compared to baseline, however the decrease was similar in both groups. RPP decreased significantly in both groups as compared to baseline, however the decrease was significantly more (P < 0.01) when pranayama was added to antihypertensive drugs (96.73 ± 20.53) when compared to antihypertensive drugs alone (114.66 ± 26.30). The pranayama produces relaxed state and in this state parasympathetic activity overrides sympathetic activity. Hence, addition of pranayama can be a useful addition to antihypertensive drugs for better control of hypertension in mild hypertensives.

Neurometabolic characteristics in the anterior cingulate gyrus of Alzheimer's disease patients with depression: a (1)H magnetic resonance spectroscopy study.

PubMed

Guo, Zhongwei; Zhang, Jiangtao; Liu, Xiaozheng; Hou, Hongtao; Cao, Yulin; Wei, Fuquan; Li, Japeng; Chen, Xingli; Shen, Yuedi; Chen, Wei

2015-12-02

Depression is a common comorbid psychiatric symptom in patients with Alzheimer's disease (AD), and the prevalence of depression is higher among people with AD compared with healthy older adults. Comorbid depression in AD may increase the risk of cognitive decline, impair patients' function, and reduce their quality of life. However, the mechanisms of depression in AD remain unclear. Here, our aim was to identify neurometabolic characteristics in the brain that are associated with depression in patients with mild AD. Thirty-seven patients were evaluated using the Neuropsychiatric Inventory (NPI) and Hamilton Depression Rating Scale (HAMD-17), and divided into two groups: 17 AD patients with depression (D-AD) and 20 non-depressed AD patients (nD-AD). Using proton magnetic resonance spectroscopy, we characterized neurometabolites in the anterior cingulate gyrus (ACG) of D-AD and nD-AD patients. Compared with nD-AD patients, D-AD patients showed lower N-acetylaspartate/creatine (NAA/Cr) and higher myo-inositol/creatine (mI/Cr) in the left ACG. NPI score correlated with NAA/Cr and mI/Cr in the left ACG, while HAMD correlated with NAA/Cr. Our findings show neurometabolic alterations in D-AD patients. Thus, D-AD pathogenesis may be attributed to abnormal activity of neurons and glial cells in the left ACG.

Malonyl-CoA decarboxylase (MCD) is differentially regulated in subcellular compartments by 5'AMP-activated protein kinase (AMPK). Studies using H9c2 cells overexpressing MCD and AMPK by adenoviral gene transfer technique.

PubMed

Sambandam, Nandakumar; Steinmetz, Michael; Chu, Angel; Altarejos, Judith Y; Dyck, Jason R B; Lopaschuk, Gary D

2004-07-01

Malonyl-CoA, a potent inhibitor of carnitine pamitoyl transferase-I (CPT-I), plays a pivotal role in fuel selection in cardiac muscle. Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, removes a potent allosteric inhibition on CPT-I and thereby increases fatty acid oxidation in the heart. Although MCD has several Ser/Thr phosphorylation sites, whether it is regulated by AMP-activated protein kinase (AMPK) has been controversial. We therefore overexpressed MCD (Ad.MCD) and constitutively active AMPK (Ad.CA-AMPK) in H9c2 cells, using an adenoviral gene delivery approach in order to examine if MCD is regulated by AMPK. Cells infected with Ad.CA-AMPK demonstrated a fourfold increase in AMPK activity as compared with control cells expressing green fluorescent protein (Ad.GFP). MCD activity increased 40- to 50-fold in Ad.MCD + Ad.GFP cells when compared with Ad.GFP control. Co-expressing AMPK with MCD further augmented MCD expression and activity in Ad.MCD + Ad.CA-AMPK cells compared with the Ad.MCD + Ad.GFP control. Subcellular fractionation further revealed that 54.7 kDa isoform of MCD expression was significantly higher in cytosolic fractions of Ad.MCD + Ad.CA-AMPK cells than of the Ad.MCD +Ad.GFP control. However, the MCD activities in cytosolic fractions were not different between the two groups. Interestingly, in the mitochondrial fractions, MCD activity significantly increased in Ad.MCD + Ad.CA-AMPK cells when compared with Ad.MCD + Ad.GFP cells. Using phosphoserine and phosphothreonine antibodies, no phosphorylation of MCD by AMPK was observed. The increase in MCD activity in mitochondria-rich fractions of Ad.MCD + Ad.CA-AMPK cells was accompanied by an increase in the level of the 50.7 kDa isoform of MCD protein in the mitochondria. This differential regulation of MCD expression and activity in the mitochondria by AMPK may potentially regulate malonyl-CoA levels at sites nearby CPT-I on the mitochondria.

Shiatsu as an adjuvant therapy for depression in patients with Alzheimer's disease: A pilot study.

PubMed

Lanza, Giuseppe; Centonze, Stella Silvia; Destro, Gera; Vella, Veronica; Bellomo, Maria; Pennisi, Manuela; Bella, Rita; Ciavardelli, Domenico

2018-06-01

Among the complementary and alternative medicine, Shiatsu might represent a feasible option for depression in Alzheimer's disease (AD). We evaluated Shiatsu on mood, cognition, and functional independence in patients undergoing physical activity. Single-blind randomized controlled study. Dedicated Community Center for patients with AD. AD patients with depression were randomly assigned to the "active group" (Shiatsu + physical activity) or the "control group" (physical activity alone). Shiatsu was performed by the same therapist once a week for ten months. Global cognitive functioning (Mini Mental State Examination - MMSE), depressive symptoms (Geriatric Depression Scale - GDS), and functional status (Activity of Daily Living - ADL, Instrumental ADL - IADL) were assessed before and after the intervention. We found a within-group improvement of MMSE, ADL, and GDS in the active group. However, the analysis of differences before and after the interventions showed a statistically significant decrease of GDS score only in the active group. The combination of Shiatsu and physical activity improved depression in AD patients compared to physical activity alone. The pathomechanism might involve neuroendocrine-mediated effects of Shiatsu on neural circuits implicated in mood and affect regulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Memory and metamemory performance in Alzheimer's disease and healthy elderly: the Contextual Memory Test (CMT).

PubMed

Gil, N; Josman, N

2001-08-01

The purpose of the present study was to examine the ability of the Contextual Memory Test (CMT) to differentiate between elderly people suffering from Alzheimer's disease (AD) in comparison to healthy elderly people. Specifically, the objectives were to compare for differences between and within the groups on components of memory, including immediate and delayed recall as well as recognition. In addition, parameters of metamemory skills, such as general awareness, self-prediction of memory capacity, self-estimation, strategy use and use of contextual information, as well as the correlation between self-awareness and actual performance in both groups, were investigated. The sample consisted of 60 elderly participants, including 30 people diagnosed with AD who were assigned to the research group and 30 people matched for age, gender and educational level who were assigned to the control group. The results provide support for the hypothesis positing differences in memory performance between healthy elderly participants and those suffering from AD, particularly in immediate and delayed recall as well as in recognition. Moreover, findings indicate an improvement in memory performance under the cued condition (contextual), whereas improvement in the AD group proved to be significant only for immediate recall. The findings point to a distinct overestimation of memory ability predicted by both the AD and control groups. Following the memory task, however, the participants accurately estimated the number of items they remembered. In addition, significant correlations between the use of contextual and association strategies and the number of items remembered by both groups were obtained, in immediate as well as in delayed recall. Therefore, these findings support the CMT as a valuable memory and metamemory assessment tool for use with the AD population.

Skin reaction and regeneration after single sodium lauryl sulfate exposure stratified by filaggrin genotype and atopic dermatitis phenotype.

PubMed

Bandier, J; Carlsen, B C; Rasmussen, M A; Petersen, L J; Johansen, J D

2015-06-01

Filaggrin is key for the integrity of the stratum corneum. Mutations in the filaggrin gene (FLGnull) play a prominent role in atopic dermatitis (AD) pathogenesis. People with AD have increased susceptibility to irritants. However, little is known about the effect of filaggrin genotype and AD phenotype on irritant response and skin regeneration. To investigate the role of FLGnull and AD groups for skin reaction and recovery after sodium lauryl sulfate (SLS) irritation. This is a case-control study comprising 67 subjects, including healthy controls and patients with and without FLGnull and AD. Reactivity to different doses of SLS at 24, 48, 72 and 145 h after SLS application was measured by transepidermal water loss (TEWL) and laser Doppler flowmetry (LDF). Reactivity was assessed univariately and by pattern analysis. All patient groups showed a higher degree of skin-barrier disruption and inflammation than did controls in response to SLS. Assessing reactivity by the delta value of the area under the curve for both TEWL and LDF showed significant differences between healthy controls and those with the AD phenotype, irrespective of filaggrin mutation. The poorest regeneration was among those with the AD phenotype. The two AD phenotype groups were separated by multivariate technique, due to earlier inflammatory reactivity among subjects with FLGnullplus AD compared with the AD phenotype alone. Both skin reaction and regeneration were significantly different between the patient population and the healthy controls. Additionally, response severity and regeneration depended more on AD phenotype than on filaggrin genotype, whereas the response was more rapid among the FLGnullplus AD individuals. © 2015 British Association of Dermatologists.

Impact of auditory-visual bimodality on lexical retrieval in Alzheimer's disease patients.

PubMed

Simoes Loureiro, Isabelle; Lefebvre, Laurent

2015-01-01

The aim of this study was to generalize the positive impact of auditory-visual bimodality on lexical retrieval in Alzheimer's disease (AD) patients. In practice, the naming skills of healthy elderly persons improve when additional sensory signals are included. The hypothesis of this study was that the same influence would be observable in AD patients. Sixty elderly patients separated into three groups (healthy subjects, stage 1 AD patients, and stage 2 AD patients) were tested with a battery of naming tasks comprising three different modalities: a visual modality, an auditory modality, and a visual and auditory modality (bimodality). Our results reveal the positive influence of bimodality on the accuracy with which bimodal items are named (when compared with unimodal items) and their latency (when compared with unimodal auditory items). These results suggest that multisensory enrichment can improve lexical retrieval in AD patients.

Concurrent white and gray matter degeneration of disease-specific networks in early-stage Alzheimer's disease and behavioral variant frontotemporal dementia.

PubMed

Steketee, Rebecca M E; Meijboom, Rozanna; de Groot, Marius; Bron, Esther E; Niessen, Wiro J; van der Lugt, Aad; van Swieten, John C; Smits, Marion

2016-07-01

This study investigates regional coherence between white matter (WM) microstructure and gray matter (GM) volume and perfusion measures in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) using a correlational approach. WM-GM coherence, compared with controls, was stronger between cingulum WM and frontotemporal GM in AD, and temporoparietal GM in bvFTD. In addition, in AD compared with controls, coherence was stronger between inferior fronto-occipital fasciculus WM microstructure and occipital GM perfusion. In this first study assessing regional WM-GM coherence in AD and bvFTD, we show that WM microstructure and GM volume and perfusion measures are coherent, particularly in regions implicated in AD and bvFTD pathology. This indicates concurrent degeneration in disease-specific networks. Our methodology allows for the detection of incipient abnormalities that go undetected in conventional between-group analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy increased pro-angiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium.

PubMed

Suresh, Sumanth C; Selvaraju, Vaithinathan; Thirunavukkarasu, Mahesh; Goldman, Joshua W; Husain, Aaftab; Alexander Palesty, J; Sanchez, Juan A; McFadden, David W; Maulik, Nilanjana

2015-12-15

Engraftment of mesenchymal stem cells (MSCs) has emerged as a powerful candidate for mediating myocardial repair. In this study, we genetically modified MSCs with an adenovector encoding thioredoxin-1 (Ad.Trx1). Trx1 has been described as a growth regulator, a transcription factor regulator, a cofactor, and a powerful antioxidant. We explored whether engineered MSCs, when transplanted, are capable of improving cardiac function and angiogenesis in a rat model of myocardial infarction (MI). Rat MSCs were cultured and divided into MSC, MSC+Ad.LacZ, and MSC+Ad.Trx1 groups. The cells were assayed for proliferation, and differentiation potential. In addition, rats were divided into control-sham (CS), control-MI (CMI), MSC+Ad.LacZ-MI (MLZMI), and MSC+Ad.Trx1-MI (MTrxMI) groups. MI was induced by left anterior descending coronary artery (LAD) ligation, and MSCs preconditioned with either Ad.LacZ or Ad.Trx1 were immediately administered to four sites in the peri-infarct zone. The MSC+Ad.Trx1 cells increased the proliferation capacity and maintained pluripotency, allowing them to divide into cardiomyocytes, smooth muscle, and endothelial cells. Western blot analysis, 4 days after treatment showed increased vascular endothelial growth factor (VEGF), heme oxygenase-1 (HO-1), and C-X-C chemokine receptor type 4 (CXCR4). Also capillary density along with myocardial function as examined by echocardiography was found to be increased. Fibrosis was reduced in the MTrxMI group compared to MLZMI and CMI. Visualization of Connexin-43 by immunohistochemistry confirmed increased intercellular connections in the MTrxMI rats compared to MLZMI. Engineering MSCs to express Trx1 may prove to be a strategic therapeutic modality in the treatment of cardiac failure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Malassezia Yeast and Cytokine Gene Polymorphism in Atopic Dermatitis

PubMed Central

Das, Shukla; Ramachandran, V.G.; Saha, Rumpa; Bhattacharya, S.N.; Dar, Sajad

2017-01-01

Introduction Atopic Dermatitis (AD) is a recurrent chronic condition associated with microorganism and their interaction with the susceptible host. Malassezia yeast is a known commensal which is thought to provoke the recurrent episodes of symptoms in atopic dermatitis patients. Malassezia immunomodulatory properties along with defective skin barrier in such host, results in disease manifestation. Here, we studied Single Nucleotide Polymorphism (SNP) in IL10 and IFN γ genes of the host and its relation with susceptibility to Malassezia infection. Aim To isolate Malassezia yeast from AD patients and compare the genetic susceptibility of the host by correlating the cytokine gene polymorphism with the control subjects. Materials and Methods Study was conducted from January 2012 to January 2013. It was a prospective observational study done in Department of Microbiology and Department of Dermatology and Venereology in University College of Medical Sciences and GTB Hospital, Delhi. Sample size comprised of 38 cases each of AD. Skin scrapings were used for fungal culture on Sabouraud Dextrose Agar (SDA) and Modified Dixon Agar (MDA) and isolated were identified as per conventional phenotypic methods. Genomic DNA was extracted from blood samples collected from all study subjects. Cytokine genotyping was carried out by Amplification Refractory Mutations System- Polymerase Chain Reaction (ARMS-PCR) with sequence specific primers. Three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN-γ+874A/T) in two cytokine genes were assessed in all the patients and healthy controls. Statistical Analysis Chi-Square Test or Fisher’s-Exact Test and Bonferroni’s correction. Results In AD group, Malassezia yeasts were cultured in 24 out of 38 samples and thus the identification rate was 63.1 percent as compared to healthy group, 52.6 percent (20/38). Significant difference in allele, or genotype distribution were observed in IL10-819/592C/T and IFN-γ+874A/T gene polymorphism in AD group. Conclusion Higher isolation rate in cases as compared to control group highlights the implication of Malassezia in AD. Association between specific cytokine gene polymorphism and clinical outcome was found to be significant in study group. The result of cytokine gene polymorphism in the present study demonstrated susceptibility of host to Malassezia infection. PMID:28511379

A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease.

PubMed

Nascimento, Carla M C; Teixeira, Camila V L; Gobbi, Lilian T B; Gobbi, Sebastião; Stella, Florindo

2012-06-01

To analyze the influence of a six-month exercise program on neuropsychiatric disorders and on the performance of instrumental activities in elderly patients with Alzheimer's disease (AD). The study included 20 patients with AD in the mild to moderate stages of the Clinical Dementia Rating (CDR) divided into two groups: the experimental group, composed of 10 women who participated in the six-month exercise program, and the control group, composed of the 10 remaining AD patients who did not take part in an exercise program during the same period. All participants were evaluated using the Mini-Mental State Exam for global cognitive function, the Neuropsychiatric Inventory Questionnaire for neuropsychiatric disorders, and the Pfeffer Functional Activities Questionnaire for the degree of functional impairment. The control group showed functional and neuropsychiatric deterioration in the comparisons between pre- and post-intervention times and between groups. The experimental group showed a propensity for less deterioration in neuropsychiatric disorders and performance of instrumental activities compared to the sedentary group.

Graph theoretic analysis of structural connectivity across the spectrum of Alzheimer's disease: The importance of graph creation methods

PubMed Central

Phillips, David J.; McGlaughlin, Alec; Ruth, David; Jager, Leah R.; Soldan, Anja

2015-01-01

Graph theory is increasingly being used to study brain connectivity across the spectrum of Alzheimer's disease (AD), but prior findings have been inconsistent, likely reflecting methodological differences. We systematically investigated how methods of graph creation (i.e., type of correlation matrix and edge weighting) affect structural network properties and group differences. We estimated the structural connectivity of brain networks based on correlation maps of cortical thickness obtained from MRI. Four groups were compared: 126 cognitively normal older adults, 103 individuals with Mild Cognitive Impairment (MCI) who retained MCI status for at least 3 years (stable MCI), 108 individuals with MCI who progressed to AD-dementia within 3 years (progressive MCI), and 105 individuals with AD-dementia. Small-world measures of connectivity (characteristic path length and clustering coefficient) differed across groups, consistent with prior studies. Groups were best discriminated by the Randić index, which measures the degree to which highly connected nodes connect to other highly connected nodes. The Randić index differentiated the stable and progressive MCI groups, suggesting that it might be useful for tracking and predicting the progression of AD. Notably, however, the magnitude and direction of group differences in all three measures were dependent on the method of graph creation, indicating that it is crucial to take into account how graphs are constructed when interpreting differences across diagnostic groups and studies. The algebraic connectivity measures showed few group differences, independent of the method of graph construction, suggesting that global connectivity as it relates to node degree is not altered in early AD. PMID:25984446

Relative added value: what are the tools to evaluate it?

PubMed

Le Jeunne, Claire; Woronoff-Lemsi, Marie-Christine; David, Nadine; de Sahb, Rima

2008-01-01

The relative added value of a drug is currently evaluated in France by the Transparency Commission (TC) of the National Health Authority (HAS), by assigning a level of Improvement in Actual Benefit (IAB). IAB is based on two parameters, efficacy and safety of the product, in a defined target population, either as compared to one or more other drugs with similar indications, or within therapeutic strategy. The items used for evaluation, including the level of clinical effect, the relevance of the comparator, the choice of comparison criteria and the methodology used (indirect comparison, non-inferiority studies, etc.), have been reviewed by the working group in Giens with regard to an analysis of the opinion on TC issued between 2004 and 2007 in several therapeutic areas First of all, this attempt at rationalisation based on the criteria used to assess the relative added value demonstrated the rareness of direct comparative data, and was followed by a discussion on the possible broadening of the evaluation criteria. The group discussed taking into account the Public Health Impact (PHI), which has now been incorporated into the assessment of Actual Benefit (AB). The group believes that PHI seems to be more related to the notion of IAB than to that of AB. Indeed, it is frequently the relative added value of a new drug that produces an impact in public health. Conversely, considering the comparative evaluation criteria of PHI, which are not systematically taken into account in IMSR (such as improvement in the health of the population, meeting a public health need or impact on the healthcare system), PHI could legitimately be included in the assessment of the relative added value of a drug. Other parameters such as compliance or impact on professional practice have been considered. Thus, the notion of relative added value, evaluated at initial registration, could be based on an expected improvement in medical service. The notion of expected medical service leads to the requirement of producing additional data in real life (post-registration studies), which would support the definitive notion of improvement in actual benefit at the time of renewed registration, while taking into account the place occupied by the drug in the therapeutic strategy.

Probiotics improve insulin resistance status in an experimental model of Alzheimer's disease.

PubMed

Athari Nik Azm, Somayeh; Djazayeri, Abolghassem; Safa, Majid; Azami, Kian; Djalali, Mahmoud; Sharifzadeh, Mohammad; Vafa, Mohammadreza

2017-01-01

Background: Nowadays, Alzheimer's disease (AD) is considered as Type 3 diabetes in which insulin resistance is the common cause of both diseases. Disruption of insulin signaling cascade and insulin resistance can induce AD; and central insulin resistance causes systemic alterations in serum insulin, FBS levels, and lipid profile. Studies have shown that probiotics ( Lactobacillus and Bifidobacterium species) can be used as a nutritional approach to improve these metabolic changes. We assessed the probiotic effect (4 species of Lactobacillus and Bifidobacterium ) on insulin resistance biomarkers in an experimental model of AD. Methods: A total of 60 rats were divided into 5 groups: (1) a control group without surgical and dietary intervention; (2) a controlprobiotics group receiving probiotics for 8 weeks, but not receiving any surgical intervention; (3) a group receiving a sham operation in which PBS was injected intrahippocampus but without dietary intervention; (4) an Alzheimer group for which Amyloid-ß (Aß) 1- 42 was injected intrahippocampus but without dietary intervention; (5) and an Alzheimer-probiotics group for which Aß1-42 was injected intrahippocampus and given 2g probiotics for 8 weeks. The FBS levels and lipid profile were measured by a calorimetric method, insulin levels were detected by an ELISA kit, and HOMA-IR was calculated using a formula. ANOVA (one way analysis of variance followed by Bonferroni comparisons post hoc) was used to compare all the variables between groups. Results: Serum glucose, insulin levels, and HOMA-IR index increased in the Alzheimer group compared to the control (p<0.001), while probiotics decreased only insulin level and HOMA-IR index in AP group compared to Alzheimer group (p<0.001). Also, TG levels increased in the Alzheimer group (p<0.001), but no significant difference was detected between Alzheimer and Alzheimerprobiotics group. Conclusion: It seems that probiotics play an effective role in controlling glycemic status of Alzheimer's disease.

Phenomenological Characteristics of Future Thinking in Alzheimer's Disease.

PubMed

Moustafa, Ahmed A; El Haj, Mohamad

2018-05-11

This study investigates phenomenological reliving of future thinking in Alzheimer's disease (AD) patients and matched controls. All participants were asked to imagine in detail a future event, and afterward, were asked to rate phenomenological characteristics of their future thinking. As compared to controls, AD participants showed poor rating for reliving, travel in time, visual imagery, auditory imagery, language, and spatiotemporal specificity. However, no significant differences were observed between both groups in emotion and importance of future thinking. Results also showed lower rating for visual imagery relative to remaining phenomenological features in AD participants compared to controls; conversely, these participants showed higher ratings for emotion and importance of future thinking. AD seems to compromise some phenomenological characteristics of future thinking, especially, visual imagery; however, other phenomenological characteristics, such as emotion, seem to be relatively preserved in these populations. By highlighting the phenomenological experience of future thinking in AD, our paper opens a unique window into the conscious experience of the future in AD patients.

Exploring the bulk in AdS /CFT : A covariant approach

NASA Astrophysics Data System (ADS)

Engelhardt, Netta

2017-03-01

I propose a general, covariant way of defining when one region is "deeper in the bulk" than another. This definition is formulated outside of an event horizon (or in the absence thereof) in generic geometries; it may be applied to both points and surfaces, and it may be used to compare the depth of bulk points or surfaces relative to a particular boundary subregion or relative to the entire boundary. Using the recently proposed "light-cone cut" formalism, the comparative depth between two bulk points can be determined from the singularity structure of Lorentzian correlators in the dual field theory. I prove that, by this definition, causal wedges of progressively larger regions probe monotonically deeper in the bulk. The definition furthermore matches expectations in pure AdS and in static AdS black holes with isotropic spatial slices, where a well-defined holographic coordinate exists. In terms of holographic renormalization group flow, this new definition of bulk depth makes contact with coarse graining over both large distances and long time scales.

In Search of Sleep Biomarkers of Alzheimer’s Disease: K-Complexes Do Not Discriminate between Patients with Mild Cognitive Impairment and Healthy Controls

PubMed Central

Reda, Flaminia; Gorgoni, Maurizio; Lauri, Giulia; Truglia, Ilaria; Cordone, Susanna; Scarpelli, Serena; Mangiaruga, Anastasia; D’Atri, Aurora; Ferrara, Michele; Lacidogna, Giordano; Marra, Camillo; Rossini, Paolo Maria; De Gennaro, Luigi

2017-01-01

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer’s disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioration. PMID:28468235

Small vessel disease, but neither amyloid load nor metabolic deficit, is dependent on age at onset in Alzheimer's disease.

PubMed

Ortner, Marion; Kurz, Alexander; Alexopoulos, Panagiotis; Auer, Florian; Diehl-Schmid, Janine; Drzezga, Alexander; Förster, Stefan; Förstl, Hans; Perneczky, Robert; Sorg, Christian; Yousefi, Behrooz H; Grimmer, Timo

2015-04-15

There is controversy concerning whether Alzheimer's disease (AD) with early onset is distinct from AD with late onset with regard to amyloid pathology and neuronal metabolic deficit. We hypothesized that compared with patients with early-onset AD, patients with late-onset AD have more comorbid small vessel disease (SVD) contributing to clinical severity, whereas there are no differences in amyloid pathology and neuronal metabolic deficit. The study included two groups of patients with probable AD dementia with evidence of the AD pathophysiologic process: 24 patients with age at onset <60 years old and 36 patients with age at onset >70 years old. Amyloid deposition was assessed using carbon-11-labeled Pittsburgh compound B positron emission tomography, comorbid SVD was assessed using magnetic resonance imaging, and neuronal metabolic deficit was assessed using fluorodeoxyglucose positron emission tomography. Group differences of global and regional distribution of pathology were explored using region of interest and voxel-based analyses, respectively, carefully controlling for the influence of dementia severity, apolipoprotein E genotype, and in particular SVD. The pattern of cognitive impairment was determined using z scores of the subtests of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery. Patients with late-onset AD showed a significantly greater amount of SVD. No statistically significant differences in global or regional amyloid deposition or neuronal metabolic deficit between the two groups were revealed. However, when not controlling for SVD, subtle differences in fluorodeoxyglucose uptake between early-onset AD and late-onset AD groups were detectable. There were no significant differences regarding cognitive functioning. Age at onset does not influence amyloid deposition or neuronal metabolic deficit in AD. The greater extent of SVD in late-onset AD influences the association between neuronal metabolic deficit and clinical symptoms. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Comparison of child-parent and parent-only cognitive-behavioral therapy programs for anxious children aged 5 to 7 years: short- and long-term outcomes.

PubMed

Monga, Suneeta; Rosenbloom, Brittany N; Tanha, Azadeh; Owens, Mary; Young, Arlene

2015-02-01

Childhood anxiety disorders (AD) are prevalent, debilitating disorders. The most effective treatment approach for children less than 8 years old requires further investigation. The study's primary objective was to compare 2 cognitive-behavioral therapy (CBT) group programs. CBT was delivered to children 5 to 7 years old and their parents (child-parent) or only to parents (parent-only), whereas children attended group sessions but did not receive CBT. Using a prospective, repeated measures, longitudinal study design, 77 children (29 male, mean age = 6.8 years; SD = 0.8 year) with AD and their parents participated in either a 12-week child-parent or parent-only CBT group treatment after a 3-month no-treatment wait-time. Well-validated treatment outcome measures were completed at 5 assessment time points: initial assessment, pretreatment, immediately posttreatment, 6 months, and 12 months posttreatment. A mixed models analysis was used to assess change in AD severity and global functioning improvements from baseline within each treatment and between treatments. No significant changes were noted in child-parent or parent-only treatment during the 3-month no-treatment wait time. Both treatments saw significant improvements posttreatment and at longer-term follow-up with significant reductions in AD severity measured by clinician and parent report and increases in global functioning. Significantly greater improvements were observed in the child-parent compared to the parent-only treatment. This study suggests that both parent-only and child-parent group CBT improves AD severity in children 5 to 7 years old. Study results suggest that involvement of both children and parents in treatment is more efficacious than working with parents alone. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

African Descent and Glaucoma Evaluation Study (ADAGES)

PubMed Central

Girkin, Christopher A.; Sample, Pamela A.; Liebmann, Jeffrey M.; Jain, Sonia; Bowd, Christopher; Becerra, Lida M.; Medeiros, Felipe A.; Racette, Lyne; Dirkes, Keri A.; Weinreb, Robert N.; Zangwill, Linda M.

2010-01-01

Objective To define differences in optic disc, retinal nerve fiber layer, and macular structure between healthy participants of African (AD) and European descent (ED) using quantitative imaging techniques in the African Descent and Glaucoma Evaluation Study (ADAGES). Methods Reliable images were obtained using stereoscopic photography, confocal scanning laser ophthalmoscopy (Heidelberg retina tomography [HRT]), and optical coherence tomography (OCT) for 648 healthy subjects in ADAGES. Findings were compared and adjusted for age, optic disc area, and reference plane height where appropriate. Results The AD participants had significantly greater optic disc area on HRT (2.06 mm2; P<.001) and OCT (2.47 mm2; P<.001) and a deeper HRT cup depth than the ED group (P<.001). Retinal nerve fiber layer thickness was greater in the AD group except within the temporal region, where it was significantly thinner. Central macular thickness and volume were less in the AD group. Conclusions Most of the variations in optic nerve morphologic characteristics between the AD and ED groups are due to differences in disc area. However, differences remain in HRT cup depth, OCT macular thickness and volume, and OCT retinal nerve fiber layer thickness independent of these variables. These differences should be considered in the determination of disease status. PMID:20457974

Electromagnetic pulse exposure induces overexpression of beta amyloid protein in rats.

PubMed

Jiang, Da-peng; Li, Jing; Zhang, Jie; Xu, Sheng-long; Kuang, Fang; Lang, Hai-yang; Wang, Ya-feng; An, Guang-zhou; Li, Jin-hui; Guo, Guo-zhen

2013-04-01

With the developing and widely used electromagnetic field (EMF) technology, more and more studies are focusing on the relationship between EMF and Alzheimer's disease (AD). Electromagnetic pulse (EMP) is one type of widely used EMF. This study aimed to clarify whether EMP exposure could induce cognitive and memory impairment, thus finding a possible relationship between EMP and AD. Forty healthy male Sprague Dawley rats were randomly divided into four groups. Animals, respectively, received 100, 1000, and 10,000 pulses EMP (field strength 50 kV/m, repetition rate 100 Hz) exposure and sham exposure when 2 months old. Monthly Morris water maze (MWM) was used to test the changes of cognitive and memory ability. Superoxide dismutase (SOD) activity and glutathione (GSH) content were used as oxidative stress indexes. Expressions of some types of Alzheimer's disease-related proteins were also detected. After exposure, EMP exposure caused clear cognitive and memory impairment compared with sham exposure group (p <0.05). Determination of oxidation indexes showed decreased SOD activity and GSH content in exposure groups compared with sham group. Immunohistochemical (IHC) staining showed increased beta amyloid protein (Aβ) in EMP exposure groups compared with sham group. Western blot experiments showed increased expressions of Aβ oligomer and beta amyloid protein precursor (APP) in EMP exposure groups. Increased expression of microtubule-associated protein 1 light chain 3-II (LC3-II) was also found. The present results showed that EMP exposure can cause long-term impairment in impaired cognition and memory of rats, resulting in AD-like symptoms. This may be induced by enhancing oxidative stress and is related to autophagy dysfunction. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Impact of Adult Day Services on Behavioral and Psychological Symptoms of Dementia

ERIC Educational Resources Information Center

Femia, Elia E.; Zarit, Steven H.; Stephens, Mary Ann Parris; Greene, Rick

2007-01-01

Purpose: This study explored whether adult day service (ADS) use was associated with reductions in behavioral and psychological symptoms of dementia (BPSD) in individuals with dementia. Design and Methods: We used a quasi-experimental design to compare a group of 133 persons with dementia (PWDs) who initially enrolled in an ADS program to a…

Effect of Ganoderma Lucidum Preparation on the Behavior,Biochemistry,and Autoimmune Parameters of Mouse Models of APP/PS1 Double Transgenic Alzheimer's Disease.

PubMed

Qin, Chuan; Wu, Shanqiu; Chen, Baosheng; Wu, Xiaoxian; Qu, Kunyao; Liu, Junmin; Zhang, Guifang; Xu, Yanfeng; Shu, Shunli; Sun, Lihua; Li, Yanhong; Zhu, Hua; Huang, Lan; Ma, Chunmei; Xu, Yuhuan; Han, Yunlin; Lu, Yaozeng

2017-06-20

Objective To evaluate the efficacy of Ganoderma lucidum preparation on the behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1 double transgenic Alzheimer's disease(AD).Methods A total of 44 4-month-old APP/PS-1 double transgenic AD mice were randomly divided into AD model group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month-old C57BL/6 mice were used as the control group.Water maze test was conducted to observe the behavior changes,and the protein expressions in brain tissues were detected by Western blot analysis.The autoimmune indicators were detected by indirect immunofluorescence method.Results In the navigation experiment,the time of finding the platform was gradually shortened since the 2 nd day in the control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD model group gradually increased.On the 5 th day,the time of finding platform was significantly shorter in control group (t=5.607,P=0.000) and LZ-H group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the number of crossing the target platform(t=2.452,P=0.025)and the residence time in the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly smaller/shorter than those in control group;in addition,the number of crossing the target platform in the AD model group was significantly smaller than that in LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ-H group;the number of crossing through the target platform quadrant(t=2.493,P=0.022)and residence time in the target quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept group.Western blot analysis showed that the expression of ApoA1 in the brain tissues of mice in LZ-H and LZ-M groups were significantly higher than those in AD model group(P<0.01,P<0.05);Aβ-40 expression in LZ-H group was significantly lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1 in brain tissues of mice in LZ-H group were significantly higher than those in model group(P<0.01,P<0.05).The plasma IgG level in Aricept group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H group(t=4.689,P=0.001)were significantly higher than that in the control group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the expression of Aβ-40 protein,and improve the autoimmune function.

Clinical, behavioral, and treatment differences in nursing facility residents with dementia, with and without pseudobulbar affect symptomatology.

PubMed

Zarowitz, Barbara J; O'Shea, Terrence

2013-11-01

Characterize the prevalence and impact of crying and tearfulness as symptoms that may be suggestive of pseudobulbar affect (PBA) in residents of nursing facilities, including those with Alzheimer's disease (AD) and non-AD [non-AD-associated] associated dementia. Data were extracted retrospectively from a large repository of de-identified and linked Minimum Data Set 2.0 (MDS) and prescription claims records for the period between October 1, 2009, and September 30, 2010. A score of 1 or 2 on MDS item E1m ("crying, tearfulness") was used to identify potential PBA. 19,000 nursing facilities in 48 states. Prescription and MDS records of nursing facility residents. Comparison of concomitant diagnoses, MDS mood, and behavioral indicators, and psychopharmacologic medication use, in residents with crying/tearfulness to a control group matched for age, gender, diagnosis of AD or non-AD dementia, and diagnosis of depression. A total of 137,829 residents underwent at least one MDS assessment during the study period. Of these, 12,595 (9.1%) had item E1m ("crying, tearfulness") scored as a 1 or 2 on their MDS assessments. Ten thousand residents were then randomly selected from this group and matched to 10,000 controls without "crying, tearfulness" (MDS E1m = 0) for analysis. A total of 4,786 (47.9%) unique residents with "crying, tearfulness" had a diagnosis of AD (8.8%), non-AD dementia (31.5%), or both (7.6%). All of the MDS mood indicators were at least twice as prevalent in this group compared with those without "crying, tearfulness" Additionally, mood symptoms such as anger, worried/pained facial expressions, and repetitive verbalizations; and behavioral symptoms such as verbal/physical abuse and socially inappropriate/disruptive behavior, were more than twice as frequent in the "crying, tearfulness" group. Antipsychotic medications were also used more often in this group (50% vs. 36.1%), as were antidepressants (59.1% vs. 49.8%). In the absence of an International Classification of Diseases 9th edition, Clinical Modification code, the presence of "crying, tearfulness" on MDS 2.0 item E1m was used as a proxy to identify potential PBA. Nursing facility residents with "crying, tearfulness" had a higher prevalence of all mood and behavior indicators as well as psychopharmacological medication use, compared with matched controls without "crying, tearfulness." Similar results were seen in the subgroup of residents with an underlying diagnosis of AD and/or non-AD dementia. Further research should validate the actual prevalence of PBA in this population, and the corresponding impact on resident outcomes.

Effect of automated ultraviolet C-emitting device on decontamination of hospital rooms with and without real-time observation of terminal room disinfection.

PubMed

Penno, Katie; Jandarov, Roman A; Sopirala, Madhuri M

2017-11-01

We studied the effectiveness of an ultraviolet C (UV-C) emitter in clinical settings and compared it with observed terminal disinfection. We cultured 22 hospital discharge rooms at a tertiary care academic medical center. Phase 1 (unobserved terminal disinfection) included cultures of 11 high-touch environmental surfaces (HTSs) after terminal room disinfection (AD) and after the use of a UV-C-emitting device (AUV). Phase 2 (observed terminal disinfection) included cultures before terminal room disinfection (BD), AD, and AUV. Zero-inflated Poisson regression compared mean colony forming units (CFU) between the groups. Two-sample proportion tests identified significance of the observed differences in proportions of thoroughly cleaned HTSs (CFU < 5). Significant P value was determined using the Bonferroni corrected threshold of α = .05/12 = .004. We obtained 594 samples. Risk of overall contamination was 0.48 times lower in the AUV group than in the AD group (P < .001), with 1.04 log 10 reduction. During phase 1, overall proportion of HTSs with <5 CFUs increased in AUV versus AD by 0.12 (P = .001). During phase 2, it increased in AD versus BD by 0.45 (P < .001), with no significant difference between AD and AUV (P = .02). Use of UV-C with standard cleaning significantly reduced microbial burden and improved the thoroughness of terminal disinfection. We found no further benefit to UV-C use if standard terminal disinfection was observed. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

A small-group functional balance intervention for individuals with Alzheimer disease: a pilot study.

PubMed

Ries, Julie D; Drake, Jamie Michelle; Marino, Christopher

2010-03-01

Individuals with Alzheimer disease (AD) have a higher risk of falls than their cognitively intact peers. This pilot study was designed to assess the feasibility and effectiveness of a small-group balance exercise program for individuals with AD in a day center environment. Seven participants met the inclusion criteria: diagnosis of AD or probable AD, medical stability, and ability to walk (with or without assistive device). We used an exploratory pre- and post-test study design. Participants engaged in a functional balance exercise program in two 45-minute sessions each week for eight weeks. Balance activities were functional and concrete, and the intervention was organized into constant, blocked, massed practice. Outcome measures included Berg Balance Scale (BBS), Timed Up and Go (TUG), and gait speed (GS; self-selected and fast assessed by an instrumented walkway). Data were analyzed by comparing individual change scores with previously identified minimal detectable change scores at the 90% confidence level (MDC90). Pre- and post-test data were acquired for five participants (two participants withdrew). The BBS improved in all five participants, and improved > or = 6.4 points (the MDC90 for the BBS in three participants. Four participants improved their performance on the TUG, and three participants improved > or = 4.09 seconds (the MDC90 for the TUG). Self-selected GS increased > or = 9.44 cm/sec (the MDC90 for gait speed) in three participants. Two participants demonstrated post-test self-selected GS comparable with their pretest fast GS. This pilot study suggests that a small-group functional balance intervention for individuals with AD is feasible and effective. Although participants had no explicit memory of the program, four of five improved in at least two outcome measures. Larger scale functional balance intervention studies with individuals with AD are warranted.

Decision making measured by the Iowa Gambling Task in alcohol use disorder and gambling disorder: a systematic review and meta-analysis.

PubMed

Kovács, Ildikó; Richman, Mara J; Janka, Zoltán; Maraz, Aniko; Andó, Bálint

2017-12-01

Gambling disorder (GD) and alcohol use disorder (AD) have similar features, such as elevated impulsivity and decision-making deficits, which are directly linked to relapse and poor therapeutic outcomes. Our aim was to assess decision-making characteristics in GD and AD patients compared to healthy controls (HC) based on one of the most frequently used measures of decision-making: the Iowa Gambling Task (IGT). In our systematic literature search of three databases, we identified 1198 empirical articles that mentioned decision-making deficits with the use of the IGT in patients diagnosed with either AD or GD. Possible effects were calculated using meta-analysis. In the end, 17 studies (including 1360 participants) were suitable for inclusion in the meta-analysis reporting data for 23 group contrasts. The random effects estimate indicated impaired IGT performance in both AD patients (N=500; d=-0.581, CI:-89.5<δ<-26.6%) and an even greater deficit in GD patients (N=292; d=-1.034, CI:-156.1<δ<50.7%) compared to HCs. Sampling variances were calculated for both AD (v 1 =0.0056) and GD groups (v 2 =0.0061), from which the z-score was calculated (z=-21.0785; p<0.05), which indicates a statistically significant difference between AD and GD groups. No significant moderating effects of age, gender or education were found. There is enough evidence to support that decision-making deficit associated with addictive disorders, and that the deficit is more expressed in gambling disorder than in alcohol use disorder. Impaired decision-making plays an important part in poor therapeutic outcomes, thus provides a promising opportunity for cognitive intervention. Copyright © 2017 Elsevier B.V. All rights reserved.

Cognitive Behavioral Insomnia Therapy for Those With Insomnia and Depression: A Randomized Controlled Clinical Trial.

PubMed

Carney, Colleen E; Edinger, Jack D; Kuchibhatla, Maragatha; Lachowski, Angela M; Bogouslavsky, Olya; Krystal, Andrew D; Shapiro, Colin M

2017-04-01

To compare cognitive behavioral therapy for insomnia (CBT-I) + antidepressant medication (AD) against treatments that target solely depression or solely insomnia. A blinded, randomized split-plot experimental study. Two urban academic clinical centers. 107 participants (68% female, mean age 42 ± 11) with major depressive disorder and insomnia. Randomization was to one of three groups: antidepressant (AD; escitalopram) + CBT-I (4 sessions), CBT-I + placebo pill, or AD + 4-session sleep hygiene control (SH). Subjective sleep was assessed via 2 weeks of daily sleep diaries (use of medication was covaried in all analyses); although there were no statistically significant group differences detected, all groups improved from baseline to posttreatment on subjective sleep efficiency (SE) and total wake time (TWT) and the effect sizes were large. Objective sleep was assessed via overnight polysomnographic monitoring at baseline and posttreatment; analyses revealed both CBT groups improved on TWT (p = .03), but the AD + SH group worsened. There was no statistically significant effect for PSG SE (p = .07). There was a between groups medium effect observed for the AD + SH and CBT + placebo group differences on diary TWT and both PSG variables. All groups improved significantly from baseline to posttreatment on the Hamilton Rating Scale for Depression (HAMD-17); the groups did not differ. Although all groups self-reported sleeping better after treatment, only the CBT-I groups improved on objective sleep, and AD + SH's sleep worsened. This suggests that we should be treating sleep in those with depression with an effective insomnia treatment and relying on self-report obscures sleep worsening effects. All groups improved on depression, even a group with absolutely no depression-focused treatment component (CBT-I + placebo). The depression effect in CBT-I only group has been reported in other studies, suggesting that we should further investigate the antidepressant properties of CBT-I. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Bone density and brain atrophy in early Alzheimer's disease.

PubMed

Loskutova, Natalia; Honea, Robyn A; Vidoni, Eric D; Brooks, William M; Burns, Jeffrey M

2009-01-01

Studies suggest a link between bone loss and Alzheimer's disease. To examine bone mineral density (BMD) in early Alzheimer's disease (AD) and its relationship to brain structure and cognition, we evaluated 71 patients with early stage AD (Clinical Dementia Rating (CDR) 0.5 and 1) and 69 non-demented elderly control participants (CDR 0). Measures included whole body BMD by dual energy x-ray absorptiometry (DXA) and normalized whole brain volumes computed from structural MRI scans. Cognition was assessed with a standard neuropsychological test battery. Mean BMD was lower in the early AD group (1.11 +/- 0.13) compared to the non-demented control group (1.16 +/- 0.12, p = 0.02), independent of age, gender, habitual physical activity, smoking, depression, estrogen replacement, and apolipoprotein E4 carrier status. In the early AD group, BMD was related to whole brain volume (b = 0.18, p = 0.03). BMD was also associated with cognitive performance, primarily in tests of memory (logical memory [b = 0.15, p = 0.04], delayed logical memory [b = 0.16, p = 0.02], and the selective reminding task - free recall [b = 0.18, p = 0.009]). BMD is reduced in the earliest clinical stages of AD and associated with brain atrophy and memory decline, suggesting that central mechanisms may contribute to bone loss in early AD.

CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients.

PubMed

Skillbäck, Tobias; Delsing, Louise; Synnergren, Jane; Mattsson, Niklas; Janelidze, Shorena; Nägga, Katarina; Kilander, Lena; Hicks, Ryan; Wimo, Anders; Winblad, Bengt; Hansson, Oskar; Blennow, Kaj; Eriksdotter, Maria; Zetterberg, Henrik

2017-11-01

A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271). We compared CSF/serum albumin ratio to 2 healthy control groups (n = 292, n = 20), between dementia diagnoses, and tested biomarker associations. Patients in DLB, LAD, VaD, MIX, other, and NOS groups had higher CSF/serum albumin ratio than controls. CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers. Our data show that BBB leakage is common in dementias. The lack of association between CSF/serum albumin ratio and AD biomarkers suggests that BBB dysfunction is not inherent to AD but might represent concomitant cerebrovascular pathology. Copyright © 2017 Elsevier Inc. All rights reserved.

A randomized, double-blind, placebo-controlled study to evaluate the efficacy in AD of liquid soap containing 12% ammonium lactate + 20% urea.

PubMed

Amichai, B; Grunwald, M H

2009-12-01

Atopic dermatitis (AD) is a common chronic skin disease, which mainly affects children. Xerosis is one of the most troublesome signs of the disease. The aim of this study was to evaluate the efficacy of liquid soap containing 12% ammonium lactate + 20% urea in patients with AD. In a randomized, double-blind study, 36 patients (both male and female patients; age range 3-40 years) with mild to moderate AD were enrolled. Patients were divided randomly into two groups, in a ratio of 2:1 (active:placebo). The prescribed soap was used on a daily basis during a shower for 3 weeks. All patients continued all other systemic or topical medication but avoided any other soap or emollients. After 3 weeks of treatment, efficacy was assessed both by clinician and patient. There were significant improvements in scaling (P < 0.0001), skin dryness (P < 0.0001) and redness (P = 0.03) as rated by the investigator, and subjective patient assessment of itch also improved (P < 0.001) in the study group compared with the control group. The liquid soap was found to be effective in patients with AD, as use of this soap in patients with stable mild to moderate AD improved the parameters studied.

Evaluation of recombinant adenovirus vaccines based on glycoprotein D and truncated UL25 against herpes simplex virus type 2 in mice.

PubMed

Liu, Wei; Zhou, Yan; Wang, Ziyan; Zhang, Zeqiang; Wang, Qizhi; Su, Weiheng; Chen, Yan; Zhang, Yan; Gao, Feng; Jiang, Chunlai; Kong, Wei

2017-05-01

The high prevalence of herpes simplex virus 2 (HSV-2) infections in humans necessitates the development of a safe and effective vaccine that will need to induce vigorous T-cell responses to control viral infection and transmission. We designed rAd-gD2, rAd-gD2ΔUL25, and rAd-ΔUL25 to investigate whether recombinant replication-defective adenoviruses vaccine could induce specific T-cell responses and protect mice against intravaginal HSV-2 challenge compared with FI-HSV-2. In the present study, recombinant adenovirus-based HSV-2 showed higher reductions in mortality and stronger antigen-specific T-cell responses compared with FI-HSV-2 and the severity of genital lesions in mice immunized with rAd-gD2ΔUL25 was significantly decreased by eliciting IFN-γ-secreting T-cell responses compared with rAd-gD2 and rAd-ΔUL25 groups. Our results demonstrated the immunogenicity and protective efficacy of recombinant adenovirus vaccines in acute HSV-2 infection following intravaginal challenge in mice. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

An integrated workflow for multiplex CSF proteomics and peptidomics-identification of candidate cerebrospinal fluid biomarkers of Alzheimer's disease.

PubMed

Hölttä, Mikko; Minthon, Lennart; Hansson, Oskar; Holmén-Larsson, Jessica; Pike, Ian; Ward, Malcolm; Kuhn, Karsten; Rüetschi, Ulla; Zetterberg, Henrik; Blennow, Kaj; Gobom, Johan

2015-02-06

Many disease processes in the brain are reflected in the protein composition of the cerebrospinal fluid (CSF). In addition to proteins, CSF also contains a large number of endogenous peptides whose potential as disease biomarkers largely remains to be explored. We have developed a novel workflow in which multiplex isobaric labeling is used for simultaneous quantification of endogenous CSF peptides and proteins by liquid chromatography coupled with mass spectrometry. After the labeling of CSF samples, endogenous peptides are separated from proteins by ultrafiltration. The proteins retained on the filters are trypsinized, and the tryptic peptides are collected separately. We evaluated this technique in a comparative pilot study of CSF peptide and protein profiles in eight patients with Alzheimer's disease (AD) and eight nondemented controls. We identified several differences between the AD and control group among endogenous peptides derived from proteins known to be associated with AD, including neurosecretory protein VGF (ratios AD/controls 0.45-0.81), integral membrane protein 2B (ratios AD/controls 0.72-0.84), and metallothionein-3 (ratios AD/controls 0.51-0.61). Analysis of tryptic peptides identified several proteins that were altered in the AD group, some of which have previously been reported as changed in AD, for example, VGF (ratio AD/controls 0.70).

Comparison of intraluminal radiofrequency ablation and stents vs. stents alone in the management of malignant biliary obstruction.

PubMed

Cui, Wei; Wang, Yu; Fan, Wenzhe; Lu, Mingjian; Zhang, Yingqiang; Yao, Wang; Li, Jiaping

2017-11-01

To retrospectively evaluate the added benefit of adding intraluminal radiofrequency ablation (RFA) to biliary metal stent placement for patients with malignant biliary obstruction (MBO). From November 2013 to December 2015, 89 patients with MBO who had undergone percutaneous intraluminal RFA and stent placement (RFA-stent group, n = 50) or stent placement only (stent group, n = 39) were included. Outcomes were compared according to the type of tumour: cholangiocarcinoma or non-cholangiocarcinoma. Primary and secondary stent patency (PSP, SSP) were significantly higher for the RFA-stent group than the stent group (PSP: 7.0 months vs. 5.0 months, p = 0.006; SSP: 10.0 months vs. 5.6 months, p < 0.001), with overall survival being comparable (5.0 months vs. 4.7 months, p = 0.068). In subgroup analysis, RFA-stent showed significant PSP benefits compared to stent alone in patients with cholangiocarcinoma (7.4 months vs. 4.3 months; p = 0.009), but with comparable outcomes in patients with non-cholangiocarcinoma (6.3 months vs. 5.2 months; p = 0.266). The SSP was improved in both subgroups (cholangiocarcinoma, 12.6 months vs. 5.0 months, p < 0.001; non-cholangiocarcinoma, 10.3 months vs. 5.5 months, p = 0.013). Technical success and clinical success were not significantly different between the two groups. The rate of complication was higher for the RFA-stent group, but tolerable when compared to the stent group. Although survival was comparable between the groups, RFA-stent confers therapeutic benefits to patients with MBO in terms of stent patency compared to stent placement alone, especially in those with cholangiocarcinoma.

Quantifying the eating abnormalities in frontotemporal dementia.

PubMed

Ahmed, Rebekah M; Irish, Muireann; Kam, Jonathan; van Keizerswaard, Jolanda; Bartley, Lauren; Samaras, Katherine; Hodges, John R; Piguet, Olivier

2014-12-01

Presence of eating abnormalities is one of the core criteria for the diagnosis of behavioral variant frontotemporal dementia (bvFTD), yet their occurrence in other subtypes of frontotemporal dementia (FTD) and effect on metabolic health is not known. To define and quantify patterns of eating behavior and energy, sugar, carbohydrate, protein, and fat intake, as well as indices of metabolic health in patients with bvFTD and semantic dementia (SD) compared with patients with Alzheimer disease (AD) and healthy control participants. Prospective case-controlled study involving patient and caregiver completion of surveys. Seventy-five participants with dementia (21 with bvFTD, 26 with SD, and 28 with AD) and 18 age- and education-matched healthy controls were recruited from FRONTIER, the FTD research clinic at Neuroscience Research Australia in Sydney. Caregivers of patients with FTD and AD completed validated questionnaires on appetite, eating behaviors, energy consumption, and dietary macronutrient composition. All participants completed surveys on hunger and satiety. Body mass index and weight measurements were prospectively collected. The bvFTD group had significant abnormalities in the domains of appetite (U = 111.0, z = 2.7, P = .007), eating habits (U = 69.5, z = 3.8, P = .001), food preferences (U = 57.0, z = 4.1, P = .001), swallowing (U = 109.0, z = 3.0, P = .003), and other oral behaviors (U = 141.0, z = 2.6, P = .009) compared with the AD group. The bvFTD and SD groups tended to have increased energy consumption. Compared with controls, the bvFTD group had significantly increased carbohydrate intake (251 vs 170 g/d; P = .05) and the SD group had significantly increased sugar intake (114 vs 76 g/d; P = .049). No significant differences in total fat or protein intake between the groups were found. Despite similar energy intake, the SD group had lower hunger and satiety scores compared with the bvFTD group. In contrast, hunger and satiety scores did not differ between the bvFTD group and controls. The abnormal eating behavior was found in the 2 groups (bvFTD and SD) with the highest body mass index (F = 4.2, P = .008) and waist circumference (F = 6.4, P = .001). Abnormal eating behaviors are prominent in patients with bvFTD and those with SD and are not limited to increased appetite. The observed higher intake of sugar and carbohydrates was found in patients with the FTD subtypes and those with higher body mass index and waist circumference and was not explained simply by increased hunger or lower satiety.

Testing messages to reduce smokers’ openness to using novel smokeless tobacco products

PubMed Central

Popova, Lucy; Neilands, Torsten B.; Ling, Pamela M.

2013-01-01

Introduction Tobacco manufacturers’ aggressive promotion of new smokeless tobacco products such as snus warrants a timely and effective public health response. This study tested potential counter-marketing messages to discourage current and former smokers from becoming dual users of smokeless tobacco and cigarettes. Methods In a pretest – post-test experiment, 1,836 adult current and recently former smokers from a national sample were randomized to view one of six anti-smokeless tobacco ads followed by a snus ad, to view a control ad followed by a snus ad; or to view two control ads. Perceived effectiveness of ads and actual changes in attitudes and openness to snus were compared across groups using analyses of variance. Results Some ads that were perceived as most effective did not change attitudes or openness to trying snus, and conversely, some ads not perceived as effective changed attitudes and openness to snus. Ads portraying the negative health effects of smokeless tobacco were perceived as most effective, but ads with anti-tobacco industry themes significantly decreased favorable attitudes toward snus. Responses to ads were different for smokers who had ever used smokeless tobacco: for this group health effects and humorous/testimonial ads were effective. Conclusions Measures of perceived effectiveness of anti-tobacco ads need to be augmented with measures of actual effectiveness to assess counter-marketing messages. Some of the developed ads, such as ads with anti-industry themes, were effective for the overall population of smokers whereas humorous/testimonial and health effects ads were particularly effective in changing attitudes of past users of smokeless tobacco. PMID:23467655

Allele doses of apolipoprotein E type {epsilon}4 in sporadic late-onset Alzheimer`s disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucotte, G.; Aouizerate, A.; Gerard, N.

1995-12-18

Apoliprotein E, type {epsilon}4 allele (ApoE-{epsilon}4) is associated with late-onset sporadic Alzheimer`s disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-{epsilon}4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging. 26 refs., 2 figs., 1 tab.

RNA Interference Silencing of Glycogen Synthase Kinase 3β Inhibites Tau Phosphorylation in Mice with Alzheimer Disease.

PubMed

Bian, Hong; Bian, Wei; Lin, Xiaoying; Ma, Zhaoyin; Chen, Wen; Pu, Ying

2016-09-01

To explore the effect of glycogen synthase kinase 3β (GSK-3β) silencing on Tau-5 phosphorylation in mice suffering Alzheimer disease (AD). GSK-3β was firstly silenced in human neuroblastoma SH-SY5Y cells using special lentivirus (LV) and the content of Tau (A-12), p-Tau (Ser396) and p-Tau (PHF-6) proteins. GSK-3β was also silenced in APP/PS1 mouse model of AD mice, which were divided into three groups (n = 10): AD, vehicle, and LV group. Ten C57 mice were used as control. The memory ability of mice was tested by square water maze, and the morphological changes of hippocampus and neuron death were analyzed by haematoxylin-eosin staining. Moreover, the levels of Tau and phosphorylated Tau (p-Tau) were detected by western blotting and immunohistochemistry, respectively. The lentivirus-mediated GSK-3β silencing system was successfully developed and silencing GSK-3β at the cellular level reduced Tau phosphorylation obviously. Moreover, GSK-3β silence significantly improved the memory ability of AD mice in LV group compared with AD group (P < 0.05) according to the latency periods and error numbers. As for the hippocampus morphology and neuron death, no significant change was observed between LV group and normal control. Immunohistochemical detection and western blotting revealed that the levels of Tau and p-Tau were significantly down-regulated after GSK-3β silence. Silencing GSK-3β may have a positive effect on inhibiting the pathologic progression of AD through down-regulating the level of p-Tau.

Balance and gait of adults with very mild Alzheimer disease.

PubMed

Gras, Laura Z; Kanaan, Saddam F; McDowd, Joan M; Colgrove, Yvonne M; Burns, Jeffrey; Pohl, Patricia S

2015-01-01

Studies have shown that adults with Alzheimer disease (AD) have gait and balance deficits; however, the focus has been on those with mild to severe disease. The purpose of this study was to determine whether balance and gait deficits are present in those with very mild AD. Thirteen adults (72.9±4.7 years old) with very mild AD and 13 age-matched (72.6±4.6 years old) and sex-matched (10 males and 3 females) participants in a control group without AD performed balance and gait tests. All participants were living in the community and independent in community ambulation. Participants with very mild AD had shorter times in tandem stance with eyes open (P<0.001) and with eyes closed (P=0.007) compared with participants in the control group. Those with AD also took longer to complete the Timed "Up & Go" Test (P<0.001). Gait deficits were found for those with AD as demonstrated by slower velocities in the 10-m walk at a comfortable pace (P=0.029) and on an instrumented walkway (P<0.001). Stance times were longer for those with AD (P<0.001) and step length was shorter (P=0.001). There were no group differences in the 10-m walk at a fast pace. The gait velocity of participants in the control group was faster on the instrumented walkway than in the 10-m walk at a comfortable pace (P=0.031). In contrast, the gait velocity of those with AD was significantly slower on the instrumented walkway than in the 10-m walk at a comfortable pace (P=0.024). Balance and gait deficits may be present in those in the very early stages of AD. Novel surfaces may affect gait speed in those with very mild AD. Identifying mobility deficits early in the progression of AD may provide an opportunity for early physical therapy intervention, thus promoting continued functional independence. Adults in the very early stages of AD may show signs of balance and gait deficits. Recognition of these problems early with subsequent physical therapy may slow the progression of further balance and gait dysfunction.

Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer's disease.

PubMed

Silva, Aderbal R T; Santos, Ana Cecília Feio; Farfel, Jose M; Grinberg, Lea T; Ferretti, Renata E L; Campos, Antonio Hugo Jose Froes Marques; Cunha, Isabela Werneck; Begnami, Maria Dirlei; Rocha, Rafael M; Carraro, Dirce M; de Bragança Pereira, Carlos Alberto; Jacob-Filho, Wilson; Brentani, Helena

2014-01-01

Alzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) "clinical-pathological AD" (CP-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and clinical dementia (CDR ≥ 2, IQCODE>3.8); II) "pathological AD" (P-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE<3.2); and III) "normal aging" (N)--subjects without neuropathological AD (Braak ≤ II and CERAD 0 or A) and with normal cognitive function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.

Which Neuropsychological Tests Predict Progression to Alzheimer’s Disease in Hispanics?

PubMed Central

Weissberger, Gali H.; Salmon, David P.; Bondi, Mark W.; Gollan, Tamar H.

2013-01-01

Objective To investigate which neuropsychological tests predict eventual progression to Alzheimer’s disease (AD) in both Hispanic and non-Hispanic individuals. Although our approach was exploratory, we predicted that tests that underestimate cognitive ability in healthy aging Hispanics might not be sensitive to future cognitive decline in this cultural group. Method We compared first-year data of 22 older adults (11 Hispanic) who were diagnosed as cognitively normal but eventually developed AD (decliners), to 60 age- and education-matched controls (27 Hispanic) who remained cognitively normal. To identify tests that may be culturally biased in our sample, we compared Hispanic with non-Hispanic controls on all tests and asked which tests were sensitive to future decline in each cultural group. Results Compared to age-, education-, and gender-matched non-Hispanic controls, Hispanic controls obtained lower scores on tests of language, executive function, and some measures of global cognition. Consistent with our predictions, some tests identified non-Hispanic, but not Hispanic, decliners (vocabulary, semantic fluency). Contrary to our predictions, a number of tests on which Hispanics obtained lower scores than non-Hispanics nevertheless predicted eventual progression to AD in both cultural groups (e.g., Boston Naming Test [BNT], Trails A and B). Conclusions Cross-cultural variation in test sensitivity to decline may reflect greater resistance of medium difficulty items to decline and bilingual advantages that initially protect Hispanics against some aspects of cognitive decline commonly observed in non-Hispanics with preclinical AD. These findings highlight a need for further consideration of cross-cultural differences in neuropsychological test performance and development of culturally unbiased measures. PMID:23688216

Cognitive Profiles on the Severe Impairment Battery Are Similar in Alzheimer Disease and Down Syndrome With Dementia.

PubMed

Dick, Malcolm B; Doran, Eric; Phelan, Michael; Lott, Ira T

2016-01-01

Previous research has revealed similarities in the neuropathology, clinical presentation, and risk factors between persons with Alzheimer disease from the general population (GP-AD) and those with Down syndrome (DS-AD). Less is known, however, about the extent of similarities and differences in the cognitive profiles of these 2 populations. Fifty-one moderate to severely demented GP-AD and 59 DS-AD individuals participated in this study which compared the cognitive profiles of these 2 populations on the Severe Impairment Battery (SIB), controlling for sex as well as level of functional ability using a modified version of the Bristol Activities of Daily Living Scale. Overall, the neuropsychological profiles of the higher-functioning individuals within the DS-AD and advanced GP-AD groups, as represented by mean difference scores on the SIB as a whole and across the 9 separate cognitive domains, were very similar to one another after adjusting for sex and functional impairment. To our knowledge, this is the first study to directly compare the cognitive profiles of these 2 populations on the SIB. Findings suggest that the underlying dementia in GP-AD and DS-AD may have corresponding and parallel effects on cognition.

Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia.

PubMed

Sabbagh, Marwan N; Chen, Kewei; Rogers, Joseph; Fleisher, Adam S; Liebsack, Carolyn; Bandy, Dan; Belden, Christine; Protas, Hillary; Thiyyagura, Pradeep; Liu, Xiaofen; Roontiva, Auttawut; Luo, Ji; Jacobson, Sandra; Malek-Ahmadi, Michael; Powell, Jessica; Reiman, Eric M

2015-08-01

Down syndrome (DS) is associated with amyloid b (Ab) deposition. We characterized imaging measurements of regional fibrillar Ab burden, cerebral metabolic rate for glucose (rCMRgl), gray matter volumes (rGMVs), and age associations in 5 DS with dementia (DS/AD1), 12 DS without dementia (DS/AD2), and 9 normal controls (NCs). There were significant group differences in mean standard uptake value ratios (SUVRs) for florbetapir with DS/AD1 having the highest, followed by DS/AD2, followed by NC. For [18F]-fluorodeoxyglucose positron emission tomography, posterior cingulate rCMRgl in DS/AD1 was significantly reduced compared with DS/AD2 and NC. For volumetric magnetic resonance imaging (vMRI), hippocampal volumes were significantly reduced for the DS/AD1 compared with DS/AD2 and NC. Age-related SUVR increases and rCMRgl reductions were greater in DS participants than in NCs. DS is associated with fibrillar Ab, rCMRgl, and rGMV alterations in the dementia stage and before the presence of clinical decline. This study provides a foundation for the studies needed to inform treatment and prevention in DS. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Comparison of the Psychological Impacts of Asymptomatic and Symptomatic Cutaneous Diseases: Vitiligo and Atopic Dermatitis

PubMed Central

Noh, Seongmin; Kim, Miri; Park, Chang Ook; Hann, Seung-Kyung

2013-01-01

Background Vitiligo and atopic dermatitis (AD) are common dermatological disorders which may cause significant psychological and social distress leading to impaired quality of life (QoL) in patients. Objective We evaluated the degree of psychological stress and impairment of QoL in vitiligo patients as compared with AD patients and normal controls (NCs). Methods A total of 60 patients from each group and 60 NCs were enrolled. Five questionnaires on depression (Beck depression inventory, BDI), state anxiety (SA) and trait anxiety (TA), interaction anxiousness (IAS), private body consciousness (PBC) and dermatologic QoL were used. Results The vitiligo patients had a significantly higher level of TA (p<0.01), PBC (p<0.001) and impaired QoL (p<0.001) than NCs, but not BDI, SA and IAS. The AD patients had significantly higher scores for all five questionnaire items compared with NCs. In the comparison between the AD and vitiligo groups, all of the indexes except body consciousness were higher in AD patients than in vitiligo patients: BDI (p<0.01), SA (p<0.05), TA (p<0.001), IAS (p<0.01) and impaired QoL (p<0.001). Exposure of vitiligo lesions was not a significant variable in the analysis of the contribution of clinical variables of vitiligo on psychological stress and QoL. Conclusion Vitiligo, which is not accompanied by any symptoms, involves less psychological impact than AD, which is accompanied by itching. Compared to NCs, however, the elevated general anxiety and body consciousness in patients with vitiligo suggests that they may be more concerned with the aggravation of hypopigmented patches than difficulties in social interactions. PMID:24371393

Cholinergic Receptor Binding in Alzheimer Disease and Healthy Aging: Assessment In Vivo with Positron Emission Tomography Imaging.

PubMed

Sultzer, David L; Melrose, Rebecca J; Riskin-Jones, Hannah; Narvaez, Theresa A; Veliz, Joseph; Ando, Timothy K; Juarez, Kevin O; Harwood, Dylan G; Brody, Arthur L; Mandelkern, Mark A

2017-04-01

To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms. Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied. PET imaging of α4β2* nicotinic cholinergic receptor binding using 2-[ 18 F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2FA) and clinical measures of global cognition, attention/processing speed, verbal memory, visuospatial memory, and neuropsychiatric symptoms were used. 2FA binding was lower in the AD group compared with the C group in the medial thalamus, medial temporal cortex, anterior cingulate, insula/opercula, inferior caudate, and brainstem (p < 0.05, corrected cluster), but binding was not associated with cognition. The C group had significant inverse correlations between 2FA binding in the thalamus (left: r s  = -0.55, p = 0.008; right: r s  = -0.50, p = 0.02; N = 22) and hippocampus (left: r s  = -0.65, p = 0.001; right: r s  = -0.55, p = 0.009; N = 22) and the Trails A score. The AD group had inverse correlation between 2FA binding in anterior cingulate (left: r s  = -0.50, p = 0.01; right: r s  = -0.50, p = 0.01; N = 24) and Neurobehavioral Rating Scale agitation/disinhibition factor score. Cholinergic receptor binding is reduced in specific brain regions in mild to moderate AD and is related to neuropsychiatric symptoms. Among healthy older adults, lower receptor binding may be associated with slower processing speed. Cholinergic receptor binding in vivo may reveal links to other key brain changes associated with aging and AD and may provide a potential molecular treatment target. Published by Elsevier Inc.

Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children.

PubMed

Wahn, Ulrich; Bos, Jan D; Goodfield, Mark; Caputo, Ruggero; Papp, Kim; Manjra, Ahmed; Dobozy, Attila; Paul, Carle; Molloy, Stephen; Hultsch, Thomas; Graeber, Michael; Cherill, Robert; de Prost, Yves

2002-07-01

Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion. BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously. Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively). There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months. Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids.

Effect on post-cryopreserved semen characteristics of Holstein bulls of adding combinations of vitamin C and either catalase or reduced glutathione to Tris extender.

PubMed

Eidan, Sajeda M

2016-04-01

This study was undertaken to investigate the influence of adding combinations of vitamin C to Tris extender with either catalase or reduced glutathione on post-cryopreserved semen characteristics of Holstein bulls for different preservation periods (cooling at 5°C, 48 h, 1, 2 and 3 months post cryopreservation, PC). Seven Holstein bulls of 2.5-3 years of age were used in this experiment. Semen was collected via artificial vagina in one ejaculate per bull per week for the 7 week experimental period. Pooled semen was equally divided into three treatments using Tris extender. Combinations of vitamin C (2.5mM) were added with either catalase (100 IU/ml, T2) or reduced glutathione (2mM, T3) to Tris extender and comparisons in response were made with the control group (Tris extender, T1). Individual sperm motility (IM), viability (V), plasma membrane integrity (PMI), and acrosome integrity (AI) were assessed during all periods of the study along with Malondialdehyde (MDA) concentrations and freezing ability. The IM was greater (P ≤ 0.01) in the T2 as compared with the T1 group at all periods of the study. Furthermore, the IM were greater (P ≤ 0.01) in the T3 as compared with the T1 group at the 48 h time period and at 3 months PC. The V, PMI and AI were greater (P ≤ 0.01) in T2 and T3 as compared with the T1 group at all the experimental periods. The MDA was greater (P ≤ 0.01) in the T2 as compared with the T1 group at 3 months PC. In conclusion, there was improved semen quality if semen of Holstein bulls was collected and stored in combinations of vitamin C with either catalase (T2) or reduced glutathione (T3) being added to Tris extender. Copyright © 2016 Elsevier B.V. All rights reserved.

Human figure drawing distinguishes Alzheimer's patients: a cognitive screening test study.

PubMed

Stanzani Maserati, Michelangelo; D'Onofrio, Renato; Matacena, Corrado; Sambati, Luisa; Oppi, Federico; Poda, Roberto; De Matteis, Maddalena; Naldi, Ilaria; Liguori, Rocco; Capellari, Sabina

2018-05-01

To study human figure drawing in a group of Alzheimer's disease (AD) patients and compare it with a group of patients with mild cognitive impairment (MCI) and controls. We evaluated consecutive outpatients over a one-year period. Patients were classified as affected by AD or by MCI. All patients and controls underwent a simplified version of the human-figure drawing test and MMSE. A qualitative and quantitative analysis of all human figures was obtained. 112 AD, 100 MCI patients and 104 controls were enrolled. AD patients drew human figures poor in details and globally smaller than MCI patients and controls. Human figures drawn by MCI patients are intermediate in body height between those of the AD patients and the healthy subjects. The head-to-body ratio of human figures drawn by AD patients is greater than controls and MCI patients, while the human figure size-relative-to-page space index is significantly smaller. Body height is an independent predictor of cognitive impairment correlating with its severity and with the number of the figure's details. Human figures drawn by AD patients are different from those drawn by healthy subjects and MCI patients. Human figure drawing test is a useful tool for orienting cognitive impairment's diagnosis.

A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging.

PubMed

Balachandar, R; John, J P; Saini, J; Kumar, K J; Joshi, H; Sadanand, S; Aiyappan, S; Sivakumar, P T; Loganathan, S; Varghese, M; Bharath, S

2015-05-01

Alzheimer's disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD. Fifteen mild AD subjects and 15 cognitively healthy controls (CHc) matched for age and gender, underwent detailed neurocognitive assessment and magnetic resonance imaging (MRI) of resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Rest fMRI was analyzed using dual regression approach and DTI by voxel wise statistics. Patients with mild AD had significantly lower functional connectivity (FC) within the default mode network and increased FC within the executive network. The mild AD group scored significantly lower in all domains of cognition compared with CHc. But fractional anisotropy did not significantly (p < 0.05) differ between the groups. Resting state functional connectivity alterations are noted during initial stages of cognitive decline in AD, even when there are no significant white matter microstructural changes. Copyright © 2014 John Wiley & Sons, Ltd.

Wii-Fit for Improving Gait and Balance in an Assisted Living Facility: A Pilot Study

PubMed Central

Padala, Kalpana P.; Padala, Prasad R.; Malloy, Timothy R.; Geske, Jenenne A.; Dubbert, Patricia M.; Dennis, Richard A.; Garner, Kimberly K.; Bopp, Melinda M.; Burke, William J.; Sullivan, Dennis H.

2012-01-01

Objectives. To determine the effects on balance and gait of a Wii-Fit program compared to a walking program in subjects with mild Alzheimer's dementia (AD). Methods. A prospective randomized (1 : 1) pilot study with two intervention arms was conducted in an assisted living facility with twenty-two mild AD subjects. In both groups the intervention occurred under supervision for 30 minutes daily, five times a week for eight weeks. Repeated measures ANOVA and paired t-tests were used to analyze changes. Results. Both groups showed improvement in Berg Balance Scale (BBS), Tinetti Test (TT) and Timed Up and Go (TUG) over 8 weeks. However, there was no statistically significant difference between the groups over time. Intragroup analysis in the Wii-Fit group showed significant improvement on BBS (P = 0.003), and TT (P = 0.013). The walking group showed a trend towards improvement on BBS (P = 0.06) and TUG (P = 0.07) and significant improvement in TT (P = 0.06). Conclusion. This pilot study demonstrates the safety and efficacy of Wii-Fit in an assisted living facility in subjects with mild AD. Use of Wii-Fit resulted in significant improvements in balance and gait comparable to those in the robust monitored walking program. These results need to be confirmed in a larger, methodologically sound study. PMID:22745909

Does eating good-tasting food influence body weight?

PubMed

Tordoff, Michael G; Pearson, Jordan A; Ellis, Hillary T; Poole, Rachel L

2017-03-01

Does eating good-tasting food influence body weight? To investigate, we first established some concentrations of sucralose and mineral oil in chow that mice strongly preferred. Then, in Experiment 1, we compared groups of 16 mice fed plain chow (i.e., chow with no additives) to groups fed chow with added (a) sucralose, (b) mineral oil, (c) sucralose and mineral oil, or (d) sucralose on odd days and mineral oil on even days. During a 6-week test, the body weights and body compositions of the five groups never differed. In Experiment 2, we compared groups of 18 mice fed plain chow or plain high-fat diet to groups fed these diets with added sucralose. During a 9-week test, the high-fat diet caused weight gain, but the body weights of mice fed the sucralose-sweetened diets did not differ from those fed the corresponding plain versions. Two-cup choice tests conducted at the end of each experiment showed persisting strong preferences for the diets with added sucralose and/or mineral oil. In concert with earlier work, our results challenge the hypothesis that the orosensory properties of a food influence body weight gain. A good taste can stimulate food intake acutely, and guide selection toward nutrient-dense foods that cause weight gain, but it does not determine how much is eaten chronically. Copyright © 2016 Elsevier Inc. All rights reserved.

Does eating good-tasting food influence body weight?

PubMed Central

Tordoff, Michael G.; Pearson, Jordan A.; Ellis, Hillary T.; Poole, Rachel L.

2016-01-01

Does eating good-tasting food influence body weight? To investigate, we first established some concentrations of sucralose and mineral oil in chow that mice strongly preferred. Then, in Experiment 1, we compared groups of 16 mice fed plain chow (i.e., chow with no additives) to groups fed chow with added (a) sucralose, (b) mineral oil, (c) sucralose and mineral oil, or (d) sucralose on odd days and mineral oil on even days. During a 6-week test, the body weights and body compositions of the five groups never differed. In Experiment 2, we compared groups of 18 mice fed plain chow or plain high-fat diet to groups fed these diets with added sucralose. During a 9-week test, the high-fat diet caused weight gain, but the body weights of mice fed the sucralose-sweetened diets did not differ from those fed the corresponding plain versions. Two-cup choice tests conducted at the end of each experiment showed persisting strong preferences for the diets with added sucralose and/or mineral oil. In concert with earlier work, our results challenge the hypothesis that the orosensory properties of a food influence body weight gain. A good taste can stimulate food intake acutely, and guide selection toward nutrient-dense foods that cause weight gain, but it does not determine how much is eaten chronically. PMID:27988248

Autism and Classical Eyeblink Conditioning: Performance Changes of the Conditioned Response Related to Autism Spectrum Disorder Diagnosis

PubMed Central

Welsh, John P.; Oristaglio, Jeffrey T.

2016-01-01

Changes in the timing performance of conditioned responses (CRs) acquired during trace and delay eyeblink conditioning (EBC) are presented for diagnostic subgroups of children having autism spectrum disorder (ASD) aged 6–15 years. Children diagnosed with autistic disorder (AD) were analyzed separately from children diagnosed with either Asperger’s syndrome or Pervasive developmental disorder (Asp/PDD) not otherwise specified and compared to an age- and IQ-matched group of children who were typically developing (TD). Within-subject and between-groups contrasts in CR performance on sequential exposure to trace and delay EBC were analyzed to determine whether any differences would expose underlying functional heterogeneities of the cerebral and cerebellar systems, in ASD subgroups. The EBC parameters measured were percentage CRs, CR onset latency, and CR peak latency. Neither AD nor Asp/PDD groups were impaired in CR acquisition during trace or delay EBC. Both AD and Asp/PDD altered CR timing, but not always in the same way. Although the AD group showed normal CR timing during trace EBC, the Asp/PDD group showed a significant 27 and 28 ms increase in CR onset and peak latency, respectively, during trace EBC. In contrast, the direction of the timing change was opposite during delay EBC, during which the Asp/PDD group showed a significant 29 ms decrease in CR onset latency and the AD group showed a larger 77 ms decrease in CR onset latency. Only the AD group showed a decrease in CR peak latency during delay EBC, demonstrating another difference between AD and Asp/PDD. The difference in CR onset latency during delay EBC for both AD and Asp/PDD was due to an abnormal prevalence of early onset CRs that were intermixed with CRs having normal timing, as observed both in CR onset histograms and mean CR waveforms. In conclusion, significant heterogeneity in EBC performance was apparent between diagnostic groups, and this may indicate that EBC performance can report the heterogeneity in the neurobiological predispositions for ASD. The findings will inform further explorations with larger cohorts, different sensory modalities, and different EBC paradigms and provide a reference set for future EBC studies of children having ASD and non-human models. PMID:27563293

Parent training for Attention Deficit/Hyperactivity Disorder: is it as effective when delivered as routine rather than as specialist care?

PubMed

Sonuga-Barke, Edmund J S; Thompson, Margaret; Daley, David; Laver-Bradbury, Cathy

2004-11-01

The effectiveness of parent training (PT) when delivered as part of specialist tier-two services for preschool AD/HD children has been recently demonstrated. To assess the effectiveness of the same PT programme when delivered as part of routine primary care by non-specialist nurses. A sample of 89 3-year-old children with preschool AD/HD took part in a controlled trial of an eight-week (one hour a week), health visitor delivered, PT package. Children, allocated randomly to PT (n = 59) and waiting list control (WLC; n = 30) groups, were compared. PT did not reduce AD/HD symptoms. Maternal well-being decreased in both PT and WLC groups. While PT is an effective intervention for preschool AD/HD when delivered in specialized settings, these benefits do not appear to generalize when programme are delivered as part of routine primary care by non-specialist nurses.

Efficacy of prolonged ingestion of Lactobacillus acidophilus L-92 in adult patients with atopic dermatitis.

PubMed

Yamamoto, Kozo; Yokoyama, Kazuhito; Matsukawa, Takehisa; Kato, Sayaka; Kato, Shinji; Yamada, Kazuhisa; Hirota, Tatsuhiko

2016-07-01

To evaluate the safety and efficacy of prolonged ingestion of Lactobacillus acidophilus L-92 (L-92) on skin symptoms in adult atopic dermatitis (AD) patients, a placebo-controlled double-blinded parallel-group comparison study was performed. This included daily administration of heat-killed and dried L-92 or placebo for 24wk in 50 AD patients who were 16yr old or older. The severity of skin symptoms was evaluated at baseline and at 4, 8, 12, 16, 20, and 24wk during the intervention using the investigator global assessment, eczema area and severity index, and scoring atopic dermatitis. Serum cytokine and blood marker levels were also measured at baseline and at 4, 8, 16, and 24wk during the intervention. No adverse events were reported during the study period. Compared with the placebo group, the L-92 group showed significant decreases in investigator global assessment, eczema area and severity index, and scoring atopic dermatitis. Subjective symptoms in adult AD patients were reduced by intake of L-92. Furthermore, it was suggested that sustained ingestion of L-92 resulted in suppression of scratching behavior and maintenance of remission status of skin symptoms. Sixteen weeks after the study commenced, a significant decrease in lactate dehydrogenase and a significant increase in transforming growth factor-β were observed in the L-92 group compared with the placebo group. In the L-92 group, a significant elevation of IL-12 (p70) level at the end of treatment period compared with before the treatment was observed. This study suggested that L-92 suppresses type-2-helper-T-cell-dominant inflammation by activating regulatory T cells and type 1 helper T cells. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Suicidal tendency in a sample of adolescent outpatients with adjustment disorder: gender differences.

PubMed

Ferrer, Laia; Kirchner, Teresa

2014-08-01

Although Adjustment Disorder (AD) is a prevalent diagnosis in adolescent mental health services and linked to suicidal tendency in adolescence, little research exists examining prevalence and gender differences of suicidal symptoms among AD patients using standardized instruments. The present study aims to assess the presence of suicidal tendency in a clinical sample of Spanish adolescents with AD analyzing gender differences. Ninety-seven adolescents with AD were recruited at a public mental health center and included in the AD sample; they were administered the Inventario de Riesgo Suicida para Adolescentes (Suicide Risk Inventory for Adolescents-IRIS) and the Millon Adolescent Clinical Inventory (MACI). Ninety-nine community adolescents were recruited and administered the IRIS inventory. The community sample works as a contrast group. Girls with AD show higher levels of suicidal symptoms than boys on both the IRIS Suicidal Ideation and Intention scale (t=8.15, p<.001) and the MACI Suicidal Tendency scale (t=6.6, p<.001). Girls with AD scored significantly higher than girls from the community contrast group sample in the IRIS Suicidal Ideation and Intention scale, but boys with AD presented no differences with regard to boys form the community contrast group sample. Compared with normative clinical samples of the MACI, no differences in the Suicidal Tendency scale scores were found between AD and normative girls, but AD boys showed significantly lower mean scores than normative boys. Suicidal symptoms were presented by 27% of girls and 18% of boys, although only 6% of the girls and none of the boys presented clear suicidal tendencies. Considering suicidal tendencies in adolescents with Adjustment Disorder is important-especially in girls, who present high suicidal tendencies in relation both to boys and to community peers and the normative clinical population. Copyright © 2014 Elsevier Inc. All rights reserved.

Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

PubMed Central

Davis, Melissa A.; Macko, Antoni R.; Steyn, Leah V.; Anderson, Miranda J.; Limesand, Sean W.

2015-01-01

Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses. PMID:25584967

Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

PubMed

Fuchs, Jonathan D; Bart, Pierre-Alexandre; Frahm, Nicole; Morgan, Cecilia; Gilbert, Peter B; Kochar, Nidhi; DeRosa, Stephen C; Tomaras, Georgia D; Wagner, Theresa M; Baden, Lindsey R; Koblin, Beryl A; Rouphael, Nadine G; Kalams, Spyros A; Keefer, Michael C; Goepfert, Paul A; Sobieszczyk, Magdalena E; Mayer, Kenneth H; Swann, Edith; Liao, Hua-Xin; Haynes, Barton F; Graham, Barney S; McElrath, M Juliana

2015-05-01

Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.

Exercise training for depressed older adults with Alzheimer's disease.

PubMed

Williams, C L; Tappen, R M

2008-01-01

The purpose of this study was to compare the effects of 16 weeks of a comprehensive exercise routine to supervised walking and social conversation on depression in nursing home residents with Alzheimer's disease (AD). This study was a three-group, repeated-measures design with random assignment to treatment group. Forty-five nursing home residents with moderate to severe AD were randomly assigned to a 16-week programme of comprehensive exercise, supervised walking or social conversation. Raters were blinded to treatment group assignment. Major outcome variables were depression measured by the Cornell Scale for Depression in Dementia, mood measured by the Dementia Mood Assessment Scale and the Alzheimer's Mood Scale, and affect measured by the Observed Affect Scale. Depression was reduced in all three groups with some evidence of superior benefit from exercise. Depression is a common problem with serious and costly consequences for nursing home residents with AD. Exercise as a behavioural approach to treatment of depression in nursing home residents with severe AD evidenced a clear benefit to participants in this study. More research is needed to clarify the relative benefits of different types of exercise in conjunction with or without pharmacological intervention.

An automated normative-based fluorodeoxyglucose positron emission tomography image-analysis procedure to aid Alzheimer disease diagnosis using statistical parametric mapping and interactive image display

NASA Astrophysics Data System (ADS)

Chen, Kewei; Ge, Xiaolin; Yao, Li; Bandy, Dan; Alexander, Gene E.; Prouty, Anita; Burns, Christine; Zhao, Xiaojie; Wen, Xiaotong; Korn, Ronald; Lawson, Michael; Reiman, Eric M.

2006-03-01

Having approved fluorodeoxyglucose positron emission tomography (FDG PET) for the diagnosis of Alzheimer's disease (AD) in some patients, the Centers for Medicare and Medicaid Services suggested the need to develop and test analysis techniques to optimize diagnostic accuracy. We developed an automated computer package comparing an individual's FDG PET image to those of a group of normal volunteers. The normal control group includes FDG-PET images from 82 cognitively normal subjects, 61.89+/-5.67 years of age, who were characterized demographically, clinically, neuropsychologically, and by their apolipoprotein E genotype (known to be associated with a differential risk for AD). In addition, AD-affected brain regions functionally defined as based on a previous study (Alexander, et al, Am J Psychiatr, 2002) were also incorporated. Our computer package permits the user to optionally select control subjects, matching the individual patient for gender, age, and educational level. It is fully streamlined to require minimal user intervention. With one mouse click, the program runs automatically, normalizing the individual patient image, setting up a design matrix for comparing the single subject to a group of normal controls, performing the statistics, calculating the glucose reduction overlap index of the patient with the AD-affected brain regions, and displaying the findings in reference to the AD regions. In conclusion, the package automatically contrasts a single patient to a normal subject database using sound statistical procedures. With further validation, this computer package could be a valuable tool to assist physicians in decision making and communicating findings with patients and patient families.

On the Parallel Deterioration of Lexico-Semantic Processes in the Bilinguals' Two Languages: Evidence from Alzheimer's Disease

ERIC Educational Resources Information Center

Costa, Albert; Calabria, Marco; Marne, Paula; Hernandez, Mireia; Juncadella, Montserrat; Gascon-Bayarri, Jordi; Lleo, Alberto; Ortiz-Gil, Jordi; Ugas, Lidia; Blesa, Rafael; Rene, Ramon

2012-01-01

In this article we aimed to assess how Alzheimer's disease (AD), which is neurodegenerative, affects the linguistic performance of early, high-proficient bilinguals in their two languages. To this end, we compared the Picture Naming and Word Translation performances of two groups of AD patients varying in disease progression (Mild and Moderate)…

[Eppendorf Schizophrenia Inventory (ESI) vs. Frankfurt Complaint Questionnaire (FCQ). Direct comparison in a clinical trial].

PubMed

Mass, R

2005-09-01

This study is the first to directly compare two clinical questionnaires which are both aimed at self-experienced cognitive dysfunctions of schizophrenia: Eppendorf Schizophrenia Inventory (ESI) and Frankfurt Complaint Questionnaire (FCQ). Evaluated were (a) diagnostic validity, (b) psychometric properties, (c) scale intercorrelations, and (d) factor analytic stability. Ad (a): schizophrenic subjects (n=36) show highly significant increases in the ESI scales and sum score when compared to other clinical groups (patients with depression, alcohol dependence, or obsessive-compulsive disorder, n>30, respectively); on the other hand, the FCQ yields no systematic group differences. Ad (b): mean of reliability coefficients (Cronbach alpha) of the ESI scales is r(tt)=0.86, mean of reliability coefficients of the FCQ scales is significantly lower. Ad (c): the mean intercorrelation between ESI and FCQ scales amounts to r(xy)=0.56 (minimum 0.29, maximum 0.73), corresponding to an average shared variance of about 31%. Ad (d): factor analysis yielded an ESI factor and a FBF factor; one-way ANOVA with the factor scores confirms the diagnostic validity of the ESI. ESI and FCQ measure essentially different aspects of schizophrenic psychopathology. Regarding reliability and diagnostic validity, the ESI is superior to the FCQ.

Mortality in patients with diabetes mellitus and Addison's disease: a nationwide, matched, observational cohort study.

PubMed

Chantzichristos, Dimitrios; Persson, Anders; Eliasson, Björn; Miftaraj, Mervete; Franzén, Stefan; Bergthorsdottir, Ragnhildur; Gudbjörnsdottir, Soffia; Svensson, Ann-Marie; Johannsson, Gudmundur

2017-01-01

Our hypothesis was that patients with diabetes mellitus obtain an additional risk of death if they develop Addison's disease (AD). Nationwide, matched, observational cohort study cross-referencing the Swedish National Diabetes Register with Inpatient, Cancer and Cause of Death Registers in patients with diabetes (type 1 and 2) and AD and matched controls with diabetes. Clinical characteristics at baseline, overall, and cause-specific mortality were assessed. The relative risk of death was assessed using a Cox proportional hazards regression model. Between January 1996 and December 2012, 226 patients with diabetes and AD were identified and matched with 1129 controls with diabetes. Median (interquartile range) follow-up was 5.9 (2.7-8.6) years. When patients with diabetes were diagnosed with AD, they had an increased frequency of diabetes complications, but both medical history of cancer and coronary heart disease did not differ compared with controls. Sixty-four of the 226 patients with diabetes and AD (28%) died, while 112 of the 1129 controls (10%) died. The estimated relative risk increase (hazard ratio) in overall mortality in the diabetes and AD group was 3.89 (95% confidence interval 2.84-5.32) compared with controls with diabetes. The most common cause of death was cardiovascular in both groups, but patients with diabetes and AD showed an increased death rate from diabetes complications, infectious diseases and unknown causes. Patients with the rare combination of diabetes and AD showed a markedly increased mortality and died more frequently from infections and unknown causes than patients with diabetes alone. Improved strategy for the management of this combination of metabolic disorders is needed. © 2017 European Society of Endocrinology.

Can Salivary Acetylcholinesterase be a Diagnostic Biomarker for Alzheimer?

PubMed

Bakhtiari, Sedigheh; Moghadam, Nahid Beladi; Ehsani, Marjan; Mortazavi, Hamed; Sabour, Siamak; Bakhshi, Mahin

2017-01-01

The loss of brain cholinergic activity is a key phenomenon in the biochemistry of Alzheimer's Disease (AD). Due to the specific biosynthesis of Acetylcholinesterase (AChE) of cholinergic neurons, the enzyme has been proposed as a potential biochemical marker of cholinergic activity. AChE is expressed not only in the Central Nervous System (CNS), Peripheral Nervous System (PNS) and muscles, but also on the surface of blood cells and saliva. This study aimed to measure salivary AChE activity in AD and to determine the feasibility of creating a simple laboratory test for diagnosing such patients. In this cross-sectional study, the recorded data were obtained from 15 Alzheimer's patients on memantine therapy and 15 healthy subjects. Unstimulated whole saliva samples were collected from the participants and salivary levels of AChE activity were determined by using the Ellman colorimetric method. The Mann Whitney U test was used to compare the average (median) of AChE activity between AD and controls. In order to adjust for possible confounding factors, partial correlation coefficient and multivariate linear regressions were used. Although the average of AChE activity in the saliva of people with AD was lower compared to the control group, we found no statistically significant differences using Mann Whitney U test (138 in control group vs. 175 in Alzheimer's patients, p value=0.25). Additionally, no significant differences were observed in the activity of this enzyme in both sexes or with increased age or duration of the disease. After adjusting for age and gender, there was no association between AChE activity and AD (regression coefficient β=0.08; p value= 0.67). Saliva AChE activity was not significantly associated with AD. This study might help in introduce a new diagnostic aid for AD or monitor patients with AD.

Semantic memory and depressive symptoms in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

PubMed

Lehrner, J; Coutinho, G; Mattos, P; Moser, D; Pflüger, M; Gleiss, A; Auff, E; Dal-Bianco, P; Pusswald, G; Stögmann, E

2017-07-01

Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

Sensitivity derivatives for advanced CFD algorithm and viscous modelling parameters via automatic differentiation

NASA Technical Reports Server (NTRS)

Green, Lawrence L.; Newman, Perry A.; Haigler, Kara J.

1993-01-01

The computational technique of automatic differentiation (AD) is applied to a three-dimensional thin-layer Navier-Stokes multigrid flow solver to assess the feasibility and computational impact of obtaining exact sensitivity derivatives typical of those needed for sensitivity analyses. Calculations are performed for an ONERA M6 wing in transonic flow with both the Baldwin-Lomax and Johnson-King turbulence models. The wing lift, drag, and pitching moment coefficients are differentiated with respect to two different groups of input parameters. The first group consists of the second- and fourth-order damping coefficients of the computational algorithm, whereas the second group consists of two parameters in the viscous turbulent flow physics modelling. Results obtained via AD are compared, for both accuracy and computational efficiency with the results obtained with divided differences (DD). The AD results are accurate, extremely simple to obtain, and show significant computational advantage over those obtained by DD for some cases.

Reduced Th22 cell proportion and prevention of atopic dermatitis in infants following maternal probiotic supplementation.

PubMed

Rø, A D B; Simpson, M R; Rø, T B; Storrø, O; Johnsen, R; Videm, V; Øien, T

2017-08-01

In the randomized, controlled study Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT), maternal probiotic supplementation reduced the incidence of atopic dermatitis (AD) in the offspring. In the current study, we hypothesized that the effect was mediated by a shift in the T helper (Th) cells in the children. To examine whether Th cell proportions were affected by maternal probiotic supplementation and thus could mediate the preventive effect of probiotics on AD. A total of 415 pregnant women were randomized to ingest a combination of Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis subsp. lactis Bb-12 (Bb-12) and Lactobacillus acidophilus La-5 (La-5) or placebo, and their offspring were assessed for AD during the first 2 years of life. Peripheral blood collected at 3 months of age was analysed for regulatory T cells (n=140) and Th subsets (n=77) including Th1, Th2, Th9, Th17 and Th22. The proportion of Th22 cells was reduced in children in the probiotic group compared to the placebo group (median 0.038% vs 0.064%, P=.009). The difference between the probiotic and placebo groups was also observed in the children who did not develop AD during the 2-year follow-up. The proportion of Th22 cells was increased in children who developed AD compared to the children who did not develop AD (0.090% vs 0.044%, P<.001). Mediation analysis indicated that the preventive effect of probiotics was partially mediated through the reduction in Th22 cells. Perinatal maternal probiotic supplementation with a combination of LGG, Bb-12 and La-5 reduced the proportion of Th22 cells in 3-month-old children. This may partially explain the preventive effect of probiotics on AD. © 2017 John Wiley & Sons Ltd.

Famous landmark identification in amnestic mild cognitive impairment and Alzheimer's disease.

PubMed

Sheardova, Katerina; Laczó, Jan; Vyhnalek, Martin; Andel, Ross; Mokrisova, Ivana; Vlcek, Kamil; Amlerova, Jana; Hort, Jakub

2014-01-01

Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer's disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored. To determine whether and how are these three specific domains impaired in head to head comparison of patients with amnestic MCI (aMCI) single domain (SD-aMCI) and multiple domain (MD-aMCI). We propose that FLI might be most reliable in differentiating SD-aMCI, which is considered to be an earlier stage of AD pathology spread out, from the controls. A total of 114 patients, 13 with single domain (SD-aMCI) and 30 with multiple domains (MD-aMCI), 29 with mild AD and 42 controls underwent standard neurological and neuropsychological evaluations as well as tests of FLI, FER and FFI. Compared to the control group, AD subjects performed worse on FFI (p = 0.020), FER (p<0.001) and FLI (p<0.001), MD-aMCI group had significantly worse scores only on FLI (p = 0.002) and approached statistical significance on FER (0.053). SD-aMCI group performed significantly worse only on FLI (p = 0.028) compared to controls. Patients with SD-aMCI had an isolated impairment restricted to FLI, while patients with MD-aMCI showed impairment in FLI as well as in FER. Patients with mild dementia due to AD have more extensive impairment of higher visual perception. The results suggest that FLI testing may contribute to identification of patients at risk of AD. We hypothesize that clinical examination of all three domains might reflect the spread of the disease from transentorhinal cortex, over amygdala to fusiform gyrus.

Famous Landmark Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Disease

PubMed Central

Sheardova, Katerina; Laczó, Jan; Vyhnalek, Martin; Andel, Ross; Mokrisova, Ivana; Vlcek, Kamil; Amlerova, Jana; Hort, Jakub

2014-01-01

Background Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer's disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored. Objectives To determine whether and how are these three specific domains impaired in head to head comparison of patients with amnestic MCI (aMCI) single domain (SD-aMCI) and multiple domain (MD-aMCI). We propose that FLI might be most reliable in differentiating SD-aMCI, which is considered to be an earlier stage of AD pathology spread out, from the controls. Patients and Methods A total of 114 patients, 13 with single domain (SD–aMCI) and 30 with multiple domains (MD–aMCI), 29 with mild AD and 42 controls underwent standard neurological and neuropsychological evaluations as well as tests of FLI, FER and FFI. Results Compared to the control group, AD subjects performed worse on FFI (p = 0.020), FER (p<0.001) and FLI (p<0.001), MD-aMCI group had significantly worse scores only on FLI (p = 0.002) and approached statistical significance on FER (0.053). SD-aMCI group performed significantly worse only on FLI (p = 0.028) compared to controls. Conclusions Patients with SD-aMCI had an isolated impairment restricted to FLI, while patients with MD–aMCI showed impairment in FLI as well as in FER. Patients with mild dementia due to AD have more extensive impairment of higher visual perception. The results suggest that FLI testing may contribute to identification of patients at risk of AD. We hypothesize that clinical examination of all three domains might reflect the spread of the disease from transentorhinal cortex, over amygdala to fusiform gyrus. PMID:25144755

Examining spiritual support among African American and Caucasian Alzheimer's caregivers: A risk and resilience study.

PubMed

Wilks, Scott E; Spurlock, Wanda R; Brown, Sandra C; Teegen, Bettina C; Geiger, Jennifer R

2018-05-25

Research shows African Americans at greater risk of developing Alzheimer's disease (AD) compared to the Caucasian population, suggesting African American AD caregivers are rising in numbers at a greater rate than Caucasian counterparts. Over a decade ago, an article in Geriatric Nursing revealed spiritual well-being differences among these caregiver groups. The purpose of this study was a quasi-follow-up, utilizing a larger caregiver sample to test spiritual support as a moderator via a risk-and-resilience framework. Secondary data analysis from a sample of 691 AD caregivers examined data on demographics and standardized measures of spiritual support, caregiver burden, and psychological resilience. One-third of the sample reported as African American. Resilience negatively regressed, though not significantly, on caregiving burden among both groups. Spiritual support positively, significantly impacted resilience among both groups, slightly stronger among African Americans. Spiritual support did not significantly moderate risk with either group. Implications for professional healthcare practice are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Naming and verbal learning in adults with Alzheimer's disease, mild cognitive impairment and in healthy aging, with low educational levels.

PubMed

Hübner, Lilian Cristine; Loureiro, Fernanda; Tessaro, Bruna; Siqueira, Ellen Cristina Gerner; Jerônimo, Gislaine Machado; Gomes, Irênio; Schilling, Lucas Porcello

2018-02-01

Language assessment seems to be an effective tool to differentiate healthy and cognitively impaired aging groups. This article discusses the impact of educational level on a naming task, on a verbal learning with semantic cues task and on the MMSE in healthy aging adults at three educational levels (very low, low and high) as well as comparing two clinical groups of very low (0-3 years) and low education (4-7 years) patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) with healthy controls. The participants comprised 101 healthy controls, 17 patients with MCI and 19 with AD. Comparisons between the healthy groups showed an education effect on the MMSE, but not on naming and verbal learning. However, the clinical groups were differentiated in both the naming and verbal learning assessment. The results support the assumption that the verbal learning with semantic cues task is a valid tool to diagnose MCI and AD patients, with no influence from education.

Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

PubMed

Gotthardt, Juliet D; Verpeut, Jessica L; Yeomans, Bryn L; Yang, Jennifer A; Yasrebi, Ali; Roepke, Troy A; Bello, Nicholas T

2016-02-01

Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%-52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%-13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%-42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%-60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%-32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%-75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.

HOMA-AD in Assessing Insulin Resistance in Lean Noncirrhotic HCV Outpatients.

PubMed

Michalczuk, Matheus Truccolo; Kappel, Camila Rippol; Birkhan, Oscar; Bragança, Ana Carolina; Alvares-da-Silva, Mário Reis

2012-01-01

Introduction. There is an association between HCV and insulin resistance (IR), which is currently assessed by HOMA-IR. There is evidence that HOMA-adiponectin (HOMA-AD) is more accurate, but its role in HCV patients is unknown. The purpose of this study was to evaluate IR in an HCV sample and controls, in order to compare the accuracy of HOMA-IR and HOMA-AD. Methods. Ninety-four HCV outpatients aged <60 years who met the criteria of nondiabetic, nonobese, noncirrhotic, and nonalcohol abusers were included and compared to 29 controls. Fasting glucose, insulin, adiponectin, and lipid profiles were determined. IR was estimated by HOMA-IR and HOMA-AD. Results. The groups were similar regarding sex and BMI, but the HCV patients were older. The median insulin level was higher in the HCV group (8.6 mU/mL (6.5-13.7) versus 6.5 (4.3-10.7), P = 0.004), as was median HOMA-IR (1.94 (1.51 to 3.48) versus 1.40 (1.02 to 2.36), P = 0.002) and the prevalence of IR (38.3% versus 10.3% (P = 0.009)). No differences were found in adiponectin levels (P = 0.294) and HOMA-AD (P = 0.393). Conclusion. IR is highly prevalent even in low-risk HCV outpatients. Adiponectin is not influenced by the presence of HCV. HOMA-AD does not seem to be useful in assessing IR in HCV patients.

Atrophic Patterns of the Frontal-Subcortical Circuits in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

PubMed Central

Zhao, Hui; Li, Xiaoxi; Wu, Wenbo; Li, Zheng; Qian, Lai; Li, ShanShan; Zhang, Bing; Xu, Yun

2015-01-01

Atrophy of the cortical thickness and gray matter volume are regarded as sensitive markers for the early clinical diagnosis of Alzheimer’s disease (AD). This study aimed to investigate differences in atrophy patterns in the frontal-subcortical circuits between MCI and AD, assess whether these differences were essential for the pathologic basis of cognitive impairment. A total of 131 individuals were recruited, including 45 with cognitively normal controls (CN), 46 with MCI, and 40 with AD. FreeSurfer software was used to perform volumetric measurements of the frontal-subcortical circuits from 3.0T magnetic resonance (MR) scans. Data revealed that both MCI and AD subjects had a thinner cortex in the left caudal middle frontal gyrus and the left lateral orbitofrontal gyrus compared with CN individuals. The left lateral orbitofrontal gyrus was also thinner in AD compared with MCI patients. There were no statistically significant differences in the cortical mean curvature among the three groups. Both MCI and AD subjects exhibited smaller bilateral hippocampus volumes compared with CN individuals. The volumes of the bilateral hippocampus and the right putamen were also smaller in AD compared with MCI patients. Logistic regression analyses revealed that the left lateral orbitofrontal gyrus and bilateral hippocampus were risk factors for cognitive impairment. These current results suggest that atrophy was heterogeneous in subregions of the frontal-subcortical circuits in MCI and AD patients. Among these subregions, the reduced thickness of the left lateral orbitofrontal and the smaller volume of the bilateral hippocampus seemed to be markers for predicting cognitive impairment. PMID:26066658

Weight loss in the healthy elderly might be a non-cognitive sign of preclinical Alzheimer's disease.

PubMed

Jimenez, Amanda; Pegueroles, Jordi; Carmona-Iragui, María; Vilaplana, Eduard; Montal, Victor; Alcolea, Daniel; Videla, Laura; Illán-Gala, Ignacio; Pané, Adriana; Casajoana, Anna; Belbin, Olivia; Clarimón, Jordi; Moizé, Violeta; Vidal, Josep; Lleó, Alberto; Fortea, Juan; Blesa, Rafael

2017-12-01

Weight loss has been proposed as a sign of pre-clinical Alzheimer Disease (AD). To test this hypothesis, we have evaluated the association between longitudinal changes in weight trajectories, cognitive performance, AD biomarker profiles and brain structure in 363 healthy controls from the Alzheimer´s Disease Neuroimaging Initiative (mean follow-up 50.5±30.5 months). Subjects were classified according to body weight trajectory into a weight loss group (WLG; relative weight loss ≥ 5%) and a non-weight loss group (non-WLG; relative weight loss < 5%). Linear mixed effects models were used to estimate the effect of body weight changes on ADAS-Cognitive score across time. Baseline CSF tau/AΔ 42 ratio and AV45 PET uptake were compared between WLG and non-WLG by analysis of covariance. Atrophy maps were compared between groups at baseline and longitudinally at a 2-year follow-up using Freesurfer. WLG showed increased baseline levels of cerebrospinal fluid tau/AΔ 42 ratio, increased PET amyloid uptake and diminished cortical thickness at baseline. WLG also showed faster cognitive decline and faster longitudinal atrophy. Our data support weight loss as a non-cognitive manifestation of pre-clinical AD.

Weight loss in the healthy elderly might be a non-cognitive sign of preclinical Alzheimer's disease

PubMed Central

Carmona-Iragui, María; Vilaplana, Eduard; Montal, Victor; Alcolea, Daniel; Videla, Laura; Illán-Gala, Ignacio; Pané, Adriana; Casajoana, Anna; Belbin, Olivia; Clarimón, Jordi; Moizé, Violeta; Vidal, Josep; Lleó, Alberto; Fortea, Juan; Blesa, Rafael

2017-01-01

Weight loss has been proposed as a sign of pre-clinical Alzheimer Disease (AD). To test this hypothesis, we have evaluated the association between longitudinal changes in weight trajectories, cognitive performance, AD biomarker profiles and brain structure in 363 healthy controls from the Alzheimer´s Disease Neuroimaging Initiative (mean follow-up 50.5±30.5 months). Subjects were classified according to body weight trajectory into a weight loss group (WLG; relative weight loss ≥ 5%) and a non-weight loss group (non-WLG; relative weight loss < 5%). Linear mixed effects models were used to estimate the effect of body weight changes on ADAS-Cognitive score across time. Baseline CSF tau/AΔ42 ratio and AV45 PET uptake were compared between WLG and non-WLG by analysis of covariance. Atrophy maps were compared between groups at baseline and longitudinally at a 2-year follow-up using Freesurfer. WLG showed increased baseline levels of cerebrospinal fluid tau/AΔ42 ratio, increased PET amyloid uptake and diminished cortical thickness at baseline. WLG also showed faster cognitive decline and faster longitudinal atrophy. Our data support weight loss as a non-cognitive manifestation of pre-clinical AD. PMID:29285207

Source Memory for Self and Other in Patients With Mild Cognitive Impairment due to Alzheimer’s Disease

PubMed Central

Deason, Rebecca G.; Budson, Andrew E.; Gutchess, Angela H.

2016-01-01

Objectives. The present study examined the role of enactment in source memory in a cognitively impaired population. As seen in healthy older adults, it was predicted that source memory in people with mild cognitive impairment due to Alzheimer’s disease (MCI-AD) would benefit from the self-reference aspect of enactment. Method. Seventeen participants with MCI-AD and 18 controls worked in small groups to pack a picnic basket and suitcase and were later tested for their source memory for each item. Results. For item memory, self-referencing improved corrected recognition scores for both MCI-AD and control participants. The MCI-AD group did not demonstrate the same benefit as controls in correct source memory for self-related items. However, those with MCI-AD were relatively less likely to misattribute new items to the self and more likely to misattribute new items to others when committing errors, compared with controls. Discussion. The enactment effect and self-referencing did not enhance accurate source memory more than other referencing for patients with MCI-AD. However, people with MCI-AD benefited in item memory and source memory, being less likely to falsely claim new items as their own, indicating some self-reference benefit occurs for people with MCI-AD. PMID:24904049

Source Memory for Self and Other in Patients With Mild Cognitive Impairment due to Alzheimer's Disease.

PubMed

Rosa, Nicole M; Deason, Rebecca G; Budson, Andrew E; Gutchess, Angela H

2016-01-01

The present study examined the role of enactment in source memory in a cognitively impaired population. As seen in healthy older adults, it was predicted that source memory in people with mild cognitive impairment due to Alzheimer's disease (MCI-AD) would benefit from the self-reference aspect of enactment. Seventeen participants with MCI-AD and 18 controls worked in small groups to pack a picnic basket and suitcase and were later tested for their source memory for each item. For item memory, self-referencing improved corrected recognition scores for both MCI-AD and control participants. The MCI-AD group did not demonstrate the same benefit as controls in correct source memory for self-related items. However, those with MCI-AD were relatively less likely to misattribute new items to the self and more likely to misattribute new items to others when committing errors, compared with controls. The enactment effect and self-referencing did not enhance accurate source memory more than other referencing for patients with MCI-AD. However, people with MCI-AD benefited in item memory and source memory, being less likely to falsely claim new items as their own, indicating some self-reference benefit occurs for people with MCI-AD. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

Platelet rich fibrin in jaw defects

NASA Astrophysics Data System (ADS)

Nica, Diana; Ianes, Emilia; Pricop, Marius

2016-03-01

Platelet rich fibrin (PRF) is a tissue product of autologous origin abundant in growth factors, widely used in regenerative procedures. Aim of the study: Evaluation of the regenerative effect of PRF added in the bony defects (after tooth removal or after cystectomy) Material and methods: The comparative nonrandomized study included 22 patients divided into 2 groups. The first group (the test group) included 10 patients where the bony defects were treated without any harvesting material. The second group included 12 patients where the bony defects were filled with PRF. The bony defect design was not critical, with one to two walls missing. After the surgeries, a close clinically monitoring was carried out. The selected cases were investigated using both cone beam computer tomography (CBCT) and radiographic techniques after 10 weeks postoperatively. Results: Faster bone regeneration was observed in the bony defects filled with PRF comparing with the not grafted bony defects. Conclusions: PRF added in the bony defects accelerates the bone regeneration. This simplifies the surgical procedures and decreases the economic costs.

Comparison of effectiveness of Transcutaneous Electrical Nerve Stimulation and Kinesio Taping added to exercises in patients with myofascial pain syndrome.

PubMed

Azatcam, Gokmen; Atalay, Nilgun Simsir; Akkaya, Nuray; Sahin, Fusun; Aksoy, Sibel; Zincir, Ozge; Topuz, Oya

2017-01-01

Although there are several studies of Transcutaneous Electrical Nerve Stimulation (TENS) and exercise in myofascial pain syndrome, there are no studies comparing the effectiveness of Kinesio Taping (KT) and TENS in myofascial pain syndrome patients. To compare the early and late effects of TENS and KT on pain, disability and range of motion in myofascial pain syndrome patients. Sixty-nine patients were divided into three groups randomly as TENS+Exercise, KT+Exercise and exercise groups. Visual Analogue Scale (VAS), pain threshold, Neck Disability Index and cervical contralateral lateral flexion were employed in the evaluation of the patients performed before treatment, after treatment and 3rd month after treatment. The VAS, pain threshold, Neck Disability Index and contralateral lateral flexion values were improved in all groups both in after treatment and 3rd month after treatment (p< 0.01). In the comparison of after treatment vs. before treatment evaluations, VAS score was decreased in KT group compared to the TENS and control group (p= 0.001), in the TENS group compared to control group (p= 0.011). In the comparison of 3rd month and before treatment evaluations, VAS score was decreased in the TENS group compared to control group (p= 0.001) and in the KT group compared to the control group (p= 0.001). There was no significant difference between TENS and KT groups. All other parameters did not differ between the groups. TENS and KT added exercises can decrease pain severity and increase pain threshold, function and cervical range of motion in myofascial pain syndrome patients. Addition of TENS or KT to the exercise therapy resulted in more significant improvement compared to exercise therapy alone with a more pronounced improvement in KT group compared to the TENS group in the early period. Because KT was found to be more effective in decreasing the pain and had the advantage of being used in every 3 days, it seems to be beneficial in acute painful periods in myofascial pain syndrome patients.

Is long-term prognosis for pervasive developmental disorder not otherwise specified different from prognosis for autistic disorder? Findings from a 30-year follow-up study.

PubMed

Mordre, Marianne; Groholt, Berit; Knudsen, Ann Kristin; Sponheim, Eili; Mykletun, Arnstein; Myhre, Anne Margrethe

2012-06-01

We followed 74 children with autistic disorder (AD) and 39 children with pervasive developmental disorder not otherwise specified (PDD NOS) for 17-38 years in a record linkage study. Rates of disability pension award, marital status, criminality and mortality were compared between groups. Disability pension award was the only outcome measure that differed significantly between the AD and PDD NOS groups (89% vs. 72%, p < 0.05). The lower rate of disability pension award in the PDD NOS group was predicted by better psychosocial functioning. The lack of substantial differences in prognosis between the groups supports a dimensional description of autism spectrum disorder, in line with proposed DSM-V revision.

Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease

PubMed Central

Dysken, Maurice W.; Sano, Mary; Asthana, Sanjay; Vertrees, Julia E.; Pallaki, Muralidhar; Llorente, Maria; Love, Susan; Schellenberg, Gerard D.; McCarten, J. Riley; Malphurs, Julie; Prieto, Susana; Chen, Peijun; Loreck, David J.; Trapp, George; Bakshi, Rajbir S.; Mintzer, Jacobo E.; Heidebrink, Judith L.; Vidal-Cardona, Ana; Arroyo, Lillian M.; Cruz, Angel R.; Zachariah, Sally; Kowall, Neil W.; Chopra, Mohit P.; Craft, Suzanne; Thielke, Stephen; Turvey, Carolyn L.; Woodman, Catherine; Monnell, Kimberly A.; Gordon, Kimberly; Tomaska, Julie; Segal, Yoav; Peduzzi, Peter N.; Guarino, Peter D.

2014-01-01

Importance Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. Objective To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. Design, Setting, and Participants Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. Interventions Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). Main Outcomes and Measures Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. Results Over the mean (SD) follow-up of 2.27 (1.22) years, participants receiving alpha tocopherol had slower decline than those receiving placebo as measured by the ADCS-ADL. The change translates into a delay in clinical progression of 19% per year compared with placebo (approximately 6.2 months over the follow-up period). Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of “infections or infestations” with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). ADCS-ADL InventoryVitamin E (n = 140)Memantine (n = 142)Vitamin E + Memantine (n = 139)Placebo (n = 140)Baseline score, mean (SD)57.20 (14.38)57.77 (13.78)57.16 (13.59)56.93 (13.61)Least squares mean (SE) change from baseline−13.81 (1.11)−14.98 (1.10)−15.20 (1.11)−16.96 (1.11)Mean change difference compared with placebo (95% CI)3.15 (0.92 to 5.39)1.98 (−0.24 to 4.20)1.76 (−0.48 to 4.00) Conclusions and Relevance Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. Trial Registration clinicaltrials.gov Identifier: NCT00235716 PMID:24381967

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial.

PubMed

Hoffmann, Kristine; Sobol, Nanna A; Frederiksen, Kristian S; Beyer, Nina; Vogel, Asmus; Vestergaard, Karsten; Brændgaard, Hans; Gottrup, Hanne; Lolk, Annette; Wermuth, Lene; Jacobsen, Søren; Laugesen, Lars P; Gergelyffy, Robert G; Høgh, Peter; Bjerregaard, Eva; Andersen, Birgitte B; Siersma, Volkert; Johannsen, Peter; Cotman, Carl W; Waldemar, Gunhild; Hasselbalch, Steen G

2016-01-01

Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent. To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms. The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: -3.5, 95% confidence interval (CI) -5.8 to -1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition. This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.

Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease.

PubMed

Schaffert, Jeff; LoBue, Christian; White, Charles L; Chiang, Hsueh-Sheng; Didehbani, Nyaz; Lacritz, Laura; Rossetti, Heidi; Dieppa, Marisara; Hart, John; Cullum, C Munro

2018-05-01

To evaluate whether a history of traumatic brain injury (TBI) with reported loss of consciousness (LOC) is a risk factor for earlier onset of Alzheimer's disease (AD) in an autopsy-confirmed sample. Data from 2,133 participants with autopsy-confirmed AD (i.e., at least Braak neurofibrillary tangle stages III to VI and CERAD neuritic plaque score moderate to frequent) were obtained from the National Alzheimer's Coordinating Center (NACC). Participants were categorized by presence/absence of self-reported remote (i.e., >1 year prior to their first Alzheimer's Disease Center visit) history of TBI with LOC (TBI+ vs. TBI-). Analyses of Covariance (ANCOVA) controlling for sex, education, and race compared groups on clinician-estimated age of symptom onset and age of diagnosis. Average age of onset was 2.34 years earlier (p = .01) for the TBI+ group (n = 194) versus the TBI- group (n = 1900). Dementia was diagnosed on average 2.83 years earlier (p = .002) in the TBI+ group (n = 197) versus the TBI- group (n = 1936). Using more stringent neuropathological criteria (i.e., Braak stages V-VI and CERAD frequent), both age of AD onset and diagnosis were 3.6 years earlier in the TBI+ group (both p's < .001). History of TBI with reported LOC appears to be a risk factor for earlier AD onset. This is the first study to use autopsy-confirmed cases, supporting previous investigations that used clinical criteria for the diagnosis of AD. Further investigation as to possible underlying mechanisms of association is needed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A Reanalysis of Cognitive-Functional Performance in Older Adults: Investigating the Interaction Between Normal Aging, Mild Cognitive Impairment, Mild Alzheimer's Disease Dementia, and Depression

PubMed Central

de Paula, Jonas J.; Bicalho, Maria A.; Ávila, Rafaela T.; Cintra, Marco T. G.; Diniz, Breno S.; Romano-Silva, Marco A.; Malloy-Diniz, Leandro F.

2016-01-01

Depressive symptoms are associated with cognitive-functional impairment in normal aging older adults (NA). However, less is known about this effect on people with mild Cognitive Impairment (MCI) and mild Alzheimer's disease dementia (AD). We investigated this relationship along with the NA-MCI-AD continuum by reanalyzing a previously published dataset. Participants (N = 274) underwent comprehensive neuropsychological assessment including measures of Executive Function, Language/Semantic Memory, Episodic Memory, Visuospatial Abilities, Activities of Daily Living (ADL), and the Geriatric Depression Scale. MANOVA, logistic regression and chi-square tests were performed to assess the association between depression and cognitive-functional performance in each group. In the NA group, depressed participants had a lower performance compared to non-depressed participants in all cognitive and functional domains. However, the same pattern was not observed in the MCI group or in AD. The results suggest a progressive loss of association between depression and worse cognitive-functional performance along the NA-MCI-AD continuum. PMID:26858666

Subjective cognitive impairment: functional MRI during a divided attention task.

PubMed

Rodda, J; Dannhauser, T; Cutinha, D J; Shergill, S S; Walker, Z

2011-10-01

Individuals with subjective cognitive impairment (SCI) have persistent memory complaints but normal neurocognitive performance. For some, this may represent a pre-mild cognitive impairment (MCI) stage of Alzheimer's disease (AD). Given that attentional deficits and associated brain activation changes are present early in the course of AD, we aimed to determine whether SCI is associated with brain activation changes during attentional processing. Eleven SCI subjects and 10 controls completed a divided attention task during functional magnetic resonance imaging. SCI and control groups did not differ in sociodemographic, neurocognitive or behavioural measures. When group activation during the divided attention task was compared, the SCI group demonstrated increased activation in left medial temporal lobe, bilateral thalamus, posterior cingulate and caudate. This pattern of increased activation is similar to the pattern of decreased activation reported during divided attention in AD and may indicate compensatory changes. These findings suggest the presence of early functional changes in SCI; longitudinal studies will help to further elucidate the relationship between SCI and AD. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis.

PubMed

Struyfs, Hanne; Van Broeck, Bianca; Timmers, Maarten; Fransen, Erik; Sleegers, Kristel; Van Broeckhoven, Christine; De Deyn, Peter P; Streffer, Johannes R; Mercken, Marc; Engelborghs, Sebastiaan

2015-01-01

Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis. To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P). CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD (n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16). Aβ(1-37) and Aβ(1-38) increased accuracy to differentiate AD from FTD or DLB. Aβ(1-37), Aβ(1-38), and Aβ(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ(1-42)/Aβ(1-40) ratio improved diagnostic performance of Aβ(1-42) in most differential diagnostic situations. Aβ(1-42) levels were lower in APOE ε4 carriers compared to non-carriers. Aβ isoforms help to differentiate AD from FTD and DLB. Aβ isoforms increase diagnostic performance of Aβ(1-42). In contrast to Aβ1-42, Aβ isoforms seem to be correlated with disease severity in AD. Adding the Aβ isoforms to the current biomarker panel could enhance diagnostic accuracy.

[Effects of chronic intermittent hypoxia on oxidative stress and inflammatory response and the interventional roles of adiponectin].

PubMed

Pan, Guoyu; Su, Mei; Ding, Wenxiao; Ding, Ning; Huang, Hanpeng; Zhang, Xilong

2015-04-28

To explore the effects of chronic intermittent hypoxia (CIH) on oxidative stress and inflammatory response and the interventional roles of adiponectin (Ad). A total of 45 male Wistar rats were randomly divided into three groups of control group, CIH and CIH+Ad (n = 15 each). The control group breathed room air while the CIH and CIH+Ad groups received CIH 8 h/d for 5 successive weeks. The CIH+Ad group Ad had an injection of 10 µg once a week through tail vein. At the end of experiment (Day 35), comparison was performed among three groups about Ad, tumor necrosis factor α (TNF-α), C-reactive protein (CRP) and interleukin (IL) 6 from serum as well as malondialdehyde, superoxide dismutase (SOD), myeloperoxidase (MPO), reactive oxygen spieces (ROS) and nuclear factor (NF) κB from genioglossus. Serum Ad level in CIH group was lower than those in control and CIH+Ad groups ((4 208 ± 2 239) vs (7 051 ± 2 432) and (6 405 ± 2 384) ng/ml, all P < 0.05) with no statistic difference between control and CIH+Ad groups. Both serum levels of TNF-α and CRP were higher in CIH group than those in control and CIH+Ad groups ((70.87 ± 35.16) vs (26.54 ± 20.32) and (29.50 ± 22.54) pg/ml, as well as (31.84 ± 11.48) vs (22.68 ± 9.63), (25.32 ± 8.34) mg/L, all P < 0.05)with no significant difference between control and CIH+Ad groups. Serum IL-6 levels were all higher in CIH group and CIH+Ad group than that in control group ((30.54 ± 12.25) and (23.04 ± 13.) vs (14.10 ± 8.83) pg/ml, all P < 0.05) with no significant difference between CIH and CIH+Ad groups. Genioglossal malondialdehyde level was significantly elevated in CIH group than those in control and CIH+Ad groups ((8.05 ± 4.53) vs (5.18 ± 3.03) and ((5.74 ± 3.06) nmol/mg, all P < 0.01) with no significant difference between control and CIH+Ad groups. Genioglossal SOD activity was lower in CIH+Ad group than that in CIH group but higher than that in control group ((42.42 ± 23.17) vs (61.77 ± 36.38) and (18.62 ± 11.67) U/mg, all P < 0.05). Genioglossal MPO levels were significantly higher in both CIH and CIH+Ad groups than that in control group ((0.40 ± 0.29) and (0.31 ± 0.17) vs (0.17 ± 0.08) µU/mg, all P < 0.01), with no significance between CIH and CIH+Ad groups. The relative level of total reactive oxygen species (ROS) in genioglossus of CIH+Ad group was significantly lower than that in CIH group but higher than that in control group (1.94 ± 1.01 vs 3.31 ± 1.56 and 1.08 ± 0.38 all P < 0.05). The transcription of NF-κB was significantly higher in CIH group than that in control and CIH+Ad groups (2.24 ± 0.34 vs 0.78 ± 0.21, P < 0.05), but there was no statistical difference with CIH+Ad group (1.04 ± 0.27). CIH may induce oxidative stress and inflammation possibly through NF κB pathway while a supplement of Ad attenuates the above CIH-induced responses.

FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer’s Disease

PubMed Central

Murray, John; Tsui, Wai H.; Li, Yi; McHugh, Pauline; Williams, Schantel; Cummings, Megan; Pirraglia, Elizabeth; Solnes, Lilja; Osorio, Ricardo; Glodzik, Lidia; Vallabhajosula, Shankar; Drzezga, Alexander; Minoshima, Satoshi; de Leon, Mony J.; Mosconi, Lisa

2014-01-01

Having a parent affected by late-onset Alzheimer’s disease (AD) is a major risk factor for cognitively normal (NL) individuals. This study explores the potential of PET with 18F-FDG and the amyloid- β (Aβ) tracer 11C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents. Methods FDG− and PiB-PET was performed in 119 young to late-middle aged NL individuals including 80 NL with positive family history of AD (FH+) and 39 NL with negative family history of any dementia (FH−). The FH+ group included 50 subjects with maternal (FHm) and 30 with paternal family history (FHp). Individual FDG and PiB scans were Z scored on a voxel-wise basis relative to modality-specific reference databases using automated procedures and rated as positive or negative (+/−) for AD-typical abnormalities using predefined criteria. To determine the effect of age, the cohort was separated into younger (49 ± 9 y) and older (68 ± 5 y) groups relative to the median age (60 y). Results Among individuals of age >60 y, as compared to controls, NL FH+ showed a higher frequency of FDG+ scans vs. FH− (53% vs. 6% p < 0.003), and a trend for PiB+ scans (27% vs. 11%; p = 0.19). This effect was observed for both FHm and FHp groups. Among individuals of age ≤60 y, NL FHm showed a higher frequency of FDG+ scans (29%) compared to FH− (5%, p = 0.04) and a trend compared to FHp (11%) (p = 0.07), while the distribution of PiB+ scans was not different between groups. In both age cohorts, FDG+ scans were more frequent than PiB+ scans among NL FH+, especially FHm (p < 0.03). FDG-PET was a significant predictor of FH+ status. Classification according to PiB status was significantly less successful. Conclusions Automated analysis of FDG− and PiB-PET demonstrates higher rates of abnormalities in at-risk FH+ vs FH− subjects, indicating potentially ongoing early AD-pathology in this population. The frequency of metabolic abnormalities was higher than that of Aβ pathology in the younger cohort, suggesting that neuronal dysfunction may precede major aggregated Aβ burden in young NL FH+. Longitudinal follow-up is required to determine if the observed abnormalities predict future AD. PMID:25530915

Dissociable executive functions in behavioral variant frontotemporal and Alzheimer dementias

PubMed Central

Feigenbaum, Dana; Rankin, Katherine P.; Smith, Glenn E.; Boxer, Adam L.; Wood, Kristie; Hanna, Sherrie M.; Miller, Bruce L.; Kramer, Joel H.

2013-01-01

Objective: The objective of this study was to determine which aspects of executive functions are most affected in behavioral variant frontotemporal dementia (bvFTD) and best differentiate this syndrome from Alzheimer disease (AD). Methods: We compared executive functions in 22 patients diagnosed with bvFTD, 26 with AD, and 31 neurologically healthy controls using a conceptually driven and comprehensive battery of executive function tests, the NIH EXAMINER battery (http://examiner.ucsf.edu). Results: The bvFTD and the AD patients were similarly impaired compared with controls on tests of working memory, category fluency, and attention, but the patients with bvFTD showed significantly more severe impairments than the patients with AD on tests of letter fluency, antisaccade accuracy, social decision-making, and social behavior. Discriminant function analysis with jackknifed cross-validation classified the bvFTD and AD patient groups with 73% accuracy. Conclusions: Executive function assessment can support bvFTD diagnosis when measures are carefully selected to emphasize frontally specific functions. PMID:23658382

Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation

PubMed Central

Tamimi, Ehab A.; Pyne, Jeffrey D.; Muli, Dominic K.; Axman, Katelyn F.; Howerton, Stephen J.; Davis, Matthew R.; Girkin, Christopher A.; Vande Geest, Jonathan P.

2017-01-01

Purpose The purpose of this study was to quantify the biomechanical response of human posterior ocular tissues from donors of various racioethnic groups to better understand how differences in these properties may play a role in the racioethnic health disparities known to exist in glaucoma. Methods Sequential digital image correlation (S-DIC) was used to measure the pressure-induced surface deformations of 23 normal human posterior poles from three racioethnic groups: African descent (AD), European descent (ED), and Hispanic ethnicity (HIS). Regional in-plane principal strains were compared across three zones: the optic nerve stump (ONS), the peripapillary (PP) sclera, and non-PP sclera. Results The PP scleral tensile strains were found to be lower for ED eyes compared with AD and HIS eyes at 15 mm Hg (P = 0.024 and 0.039, respectively). The mean compressive strains were significantly higher for AD eyes compared with ED eyes at 15 mm Hg (P = 0.018). We also found that the relationship between tensile strain and pressure was significant for those of ED and HIS eyes (P < 0.001 and P = 0.004, respectively), whereas it was not significant for those of AD (P = 0.392). Conclusions Our results suggest that, assuming glaucomatous nerve loss is caused by mechanical strains in the vicinity of the optic nerve head, the mechanism of increased glaucoma prevalence may be different in those of AD versus HIS. Our ONS strain analysis also suggested that it may be important to account for ONS geometry and material properties in future scleral biomechanical analysis. PMID:28846773

Altered Behavioral and Autonomic Pain Responses in Alzheimer’s Disease Are Associated with Dysfunctional Affective, Self-Reflective and Salience Network Resting-State Connectivity

PubMed Central

Beach, Paul A.; Huck, Jonathan T.; Zhu, David C.; Bozoki, Andrea C.

2017-01-01

While pain behaviors are increased in Alzheimer’s disease (AD) patients compared to healthy seniors (HS) across multiple disease stages, autonomic responses are reduced with advancing AD. To better understand the neural mechanisms underlying these phenomena, we undertook a controlled cross-sectional study examining behavioral (Pain Assessment in Advanced Dementia, PAINAD scores) and autonomic (heart rate, HR) pain responses in 24 HS and 20 AD subjects using acute pressure stimuli. Resting-state fMRI was utilized to investigate how group connectivity differences were related to altered pain responses. Pain behaviors (slope of PAINAD score change and mean PAINAD score) were increased in patients vs. controls. Autonomic measures (HR change intercept and mean HR change) were reduced in severe vs. mildly affected AD patients. Group functional connectivity differences associated with greater pain behavior reactivity in patients included: connectivity within a temporal limbic network (TLN) and between the TLN and ventromedial prefrontal cortex (vmPFC); between default mode network (DMN) subcomponents; between the DMN and ventral salience network (vSN). Reduced HR responses within the AD group were associated with connectivity changes within the DMN and vSN—specifically the precuneus and vmPFC. Discriminant classification indicated HR-related connectivity within the vSN to the vmPFC best distinguished AD severity. Thus, altered behavioral and autonomic pain responses in AD reflects dysfunction of networks and structures subserving affective, self-reflective, salience and autonomic regulation. PMID:28959201

A randomized investigator-blind parallel-group study to assess efficacy and safety of azelaic acid 15% gel vs. adapalene 0.1% gel in the treatment and maintenance treatment of female adult acne.

PubMed

Thielitz, A; Lux, A; Wiede, A; Kropf, S; Papakonstantinou, E; Gollnick, H

2015-04-01

Growing numbers of post-adolescent females are suffering from treatment-resistant or relapsing adult acne forms, therefore requiring the definition of safe and effective treatment options for this burdening disease. To assess the efficacy of azelaic acid 15% gel (AzA) vs. no treatment during maintenance therapy of female adult acne and to compare its efficacy and safety vs. adapalene 0.1% gel (AD) during a 9-month period (3-month treatment and 6-month maintenance treatment). A total of 55 women between 18 and 45 years with adult acne were included in this investigator-blind trial and randomized into three groups receiving AzA gel b.i.d. for 9 months (AzA9M, n = 17) or AzA gel b.i.d. for 3 months followed by a 6-month observational phase (AzA3M, n = 19) or AD gel once daily for 9 months (AD9M, n = 19). Parameters of efficacy, safety and patient-related factors were analysed. The reduction in lesion counts, severity and Dermatology Life Quality Index score was significant (P < 0.05) and comparable between groups during the treatment phase, while dryness and scaling were significantly lower (P < 0.05) in group AzA9M vs. AD9M. During maintenance, AzA9M was superior to AzA3M in the control of inflammatory lesions (P = 0.008) and total lesions (P = 0.014) at week 24. From week 12 to week 36, a mild relative increase in inflammatory lesions could be observed in all groups. In AzA3M, this increase exceeded that of AzA9M by 23.1% (P = 0.109), while the difference of total lesions diverged to 30.8% (P = 0.038). No significant differences could be detected between AzA9M and AD9M. Group AzA9M was non-inferior to AD9M (non-inferiority margin of 50% for the confidence limit for the relative effect) in the control of inflammatory acne lesions. AzA15% gel is a safe and effective treatment and maintenance treatment of female adult acne with non-inferior efficacy to AD 0.1% gel in the control of inflammatory acne. © 2014 European Academy of Dermatology and Venereology.

Probabilistic Cost-Effectiveness Analysis of Vaccination for Mild or Moderate Alzheimer's Disease.

PubMed

Yang, Kuen-Cheh; Chen, Hsiu-Hsi

2016-01-01

Studies on the immunotherapy for Alzheimer's disease (AD) have increasingly gained attention since 1990s. However, there are pros (preventing of AD) and cons (incurred cost and side effects) regarding the administration of immunotherapy. Up to date, there has been lacking of economic evaluation for immunotherapy of AD. We aimed to assess the cost-effectiveness analysis of the vaccination for AD. A meta-analysis of randomized control trials after systemic review was conducted to evaluate the efficacy of the vaccine. A Markov decision model was constructed and applied to a 120,000-Taiwanese cohort aged ≥65 years. Person years and quality-adjusted life years (QALY) were computed between the vaccinated group and the the unvaccinated group. Economic evaluation was performed to calculate the incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve (CEAC). Vaccinated group gained an additional 0.84 life years and 0.56 QALYs over 10-years and an additional 0.35 life years and 0.282 QALYs over 5-years of follow-up. The vaccinated group dominated the unvaccinated group by ICER over 5-years of follow-up. The ICERs of 10-year follow-up for the vaccinated group against the unvaccinated group were $13,850 per QALY and $9,038 per life year gained. Given the threshold of $20,000 of willingness to pay (WTP), the CEAC showed the probability of being cost-effective for vaccination with QALY was 70.7% and 92% for life years gained after 10-years of follow-up. The corresponding figures were 87.3% for QALY and 93.5% for life years gained over 5-years follow-up. The vaccination for AD was cost-effective in gaining QALY and life years compared with no vaccination, under the condition of a reasonable threshold of WTP.

Spatio-temporal and kinematic gait analysis in patients with Frontotemporal dementia and Alzheimer's disease through 3D motion capture.

PubMed

Rucco, Rosaria; Agosti, Valeria; Jacini, Francesca; Sorrentino, Pierpaolo; Varriale, Pasquale; De Stefano, Manuela; Milan, Graziella; Montella, Patrizia; Sorrentino, Giuseppe

2017-02-01

Alzheimer's disease (AD) and behavioral variant of Frontotemporal Dementia (bvFTD) are characterized respectively by atrophy in the medial temporal lobe with memory loss and prefrontal and anterior temporal degeneration with dysexecutive syndrome. In this study, we hypothesized that specific gait patterns are induced by either frontal or temporal degeneration. To test this hypothesis, we studied the gait pattern in bvFTD (23) and AD (22) patients in single and dual task ("motor" and "cognitive") conditions. To detect subtle alterations, we performed motion analysis estimating both spatio-temporal parameters and joint excursions. In the single task condition, the bvFTD group was more unstable and slower compared to healthy subjects, while only two stability parameters were compromised in the AD group. During the motor dual task, both velocity and stability parameters worsened further in the bvFTD group. In the same experimental conditions, AD patients showed a significantly lower speed and stride length than healthy subjects. During the cognitive dual task, a further impairment of velocity and stability parameters was observed in the bvFTD group. Interestingly, during the cognitive dual task, the gait performance of the AD group markedly deteriorated, as documented by the impairment of more indices of velocity and stability. Finally, the kinematic data of thigh, knee, and ankle were more helpful in revealing gait impairment than the spatio-temporal parameters alone. In conclusion, our data showed that the dysexecutive syndrome induces specific gait alterations. Furthermore, our results suggest that the gait worsens in the AD patients when the cognitive resources are stressed. Copyright © 2016 Elsevier B.V. All rights reserved.

Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers

PubMed Central

D’Sa, Carrol; Dileone, Ralph J.; Anderson, George M.; Sinha, Rajita

2013-01-01

Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have been extensively studied in rodents, BDNF levels have rarely been measured in abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group comparisons of serum BDNF levels is difficult due to limited information regarding analytical variance, biological variability, and the relative contribution of platelet and plasma pools to serum BDNF. Analytical variance (intra- and inter-assay coefficients of variation) of the enzyme-linked immunosorbent assay (ELISA) was characterized. Within- and between-subject variability, and group differences in serum and plasma BDNF, was assessed on three separate days in 16, 4-week abstinent AD individuals (7M/9F) and 16 social drinkers (SDs; 8M/8F). Significantly higher mean (±sd) serum BDNF levels were observed for the AD group compared to the SD (p = 0.003). No significant difference in mean baseline plasma BDNF levels was observed between AD and SD groups. The low analytical variance, high day-to-day within-individual stability and the high degree of individuality demonstrates the potential clinical utility of measuring serum BDNF levels. The low correlations that we observed between plasma and serum levels are congruent with their representing separate pools of BDNF. The observation of higher basal serum BDNF in the AD group without a concomitant elevation in plasma BDNF levels indicates that the elevated serum BDNF in AD patients is not due to greater BDNF exposure. Further research is warranted to fully elucidate mechanisms underlying this alteration and determine the utility of serum BDNF as a predictor or surrogate marker of chronic alcohol abuse. PMID:22364688

Effects of oral vitamin E on treatment of atopic dermatitis: A randomized controlled trial.

PubMed

Jaffary, Fariba; Faghihi, Gita; Mokhtarian, Arghavan; Hosseini, Sayed Mohsen

2015-11-01

The pathogenesis of atopic dermatitis (AD) remains to be determined; recently a possible change in the immune system with production of immunoglobulins is proposed. As vitamin E is a potent antioxidant, with the ability to decrease the serum levels of immunoglobulin E (IgE) in atopic patients, we aimed to evaluate the effect of oral vitamin E on treatment of AD. This randomized, double-blind, placebo-controlled trial comprised seventy participants with mild-to-moderate AD, based on the Hanifin and Rajka diagnostic criteria. The patients were randomly selected from teaching skin clinics in Isfahan, Iran. They were randomly assigned to two groups of equal number, receiving vitamin E (400 IU/day) and placebo for four 4 months. Each month, the extent, severity, and subjective symptoms including itch and sleeplessness were measured by SCORAD index. Three months after the end of intervention, the recurrence rate was assessed. The improvement in all symptoms, except sleeplessness, was significantly higher in the group receiving vitamin E than in controls (-1.5 vs. 0.218 in itching, -10.85 vs. -3.54 in extent of lesion, and -11.12 vs. -3.89 in SCORAD index, respectively, P < 0.05). Three months after the end of intervention, the recurrence rate of AD was evaluated. Recurrence rate between all 42 individuals, who remained in the study, was 18.6%. Recurrence ratio of the group receiving vitamin E compared to the placebo group was 1.17, without significant differences between the two groups (P > 0.05). This study suggests that vitamin E can improve the symptoms and the quality of life in patients with AD. As vitamin E has no side effects with a dosage of 400 IU/day, it can be recommended for the treatment of AD.

Neuropsychological mechanisms of Digit Symbol Substitution Test impairment in Asperger Disorder.

PubMed

Yoran-Hegesh, Roni; Kertzman, Semion; Vishne, Tali; Weizman, Abraham; Kotler, Moshe

2009-03-31

Our aim was to investigate the neurocognitive mechanisms recruited by adolescents with Asperger Disorder (AD), in comparison to controls, and to detect the underlying mechanisms during the complex information processing required for the performance of the Digit Symbol Substitution Test (DSST). Male adolescents (n=23; mean age 15.1+/-3.6 years) with a DSM-IV diagnosis of AD were compared with a normal male control group with similar demographic characteristics (n=43; mean age: 15.1+/-3.6 years). A computerized neurocognitive battery was administered and included: Inspection Time (IT), Finger Tapping Test (FTT), Simple Reaction Time (SRT), Choice Reaction Time (CRT), Digit Running task (DRT), Stroop test and Digit Symbol Substitution Test (DSST). Adolescents with AD performed significantly worse than controls on the DSST. This impaired DSST performance was related to cognitive mechanisms different from those employed by normal controls. Motor slowness and inability to deal with increased amounts of information affected the performance of the AD group, while shifting of attention was the limiting factor in the controls. Both groups were similarly dependent on response selection. This study demonstrated differences in performance in complex cognitive tasks between adolescents with AD and normal controls that may be related to differences in neurocognitive mechanisms underlying information processing. Future neuroimaging studies are needed to clarify the neural network involved in the differences in cognitive performance between AD subjects and normal controls.

Gene Therapy for Liver Transplantation Using Adenoviral Vectors: CD40–CD154 Blockade by Gene Transfer of CD40Ig Protects Rat Livers from Cold Ischemia and Reperfusion Injury

PubMed Central

Ke, Bibo; Shen, Xiu-Da; Gao, Feng; Busuttil, Ronald W.; Löwenstein, Pedro R.; Castro, Maria G.; Kupiec-Weglinski, Jerzy W.

2010-01-01

Liver injury induced by ischemia/reperfusion (I/R) is the prime factor in delayed or loss graft function following transplantation. CD4+ T lymphocytes are key cellular mediators of antigen-independent inflammatory response triggered by I/R. We attempted to modulate rat liver I/R injury by targeted gene therapy with CD40Ig, which blocks the CD40–CD154 costimulation pathway. One hundred percent of Ad-CD40Ig-pretreated orthotopic liver transplants (OLTs) subjected to 24 h of cold (4°C) ischemia survived >14 days (vs 50% in untreated/Ad-β-gal groups). Ad-CD40Ig treatment decreased sGOT levels and depressed neutrophil infiltration, compared with controls. These functional data correlated with histological Suzuki’s grading of hepatic injury, which in untreated/Ad-β-gal groups showed severe necrosis (>60%) and moderate to severe sinusoidal congestion; the Ad-CD40Ig-pretreated group revealed minimal sinusoidal congestion/necrosis. Unlike in controls, OLT expression of mRNA coding for IL-2/IFN-γ remained depressed, whereas that of IL-4/IL-13 reciprocally increased in the Ad-CD40Ig group. Ad-CD40Ig reduced frequency of TUNEL+ cells and proapoptotic Caspase-3, but enhanced antioxidant HO-1 and antiapoptotic Bcl-2/Bcl-xl expression. Thus, prolonged blockade of CD40–CD154 by CD40Ig exerts potent cytoprotection against hepatic I/R injury. These results provide the rationale for a novel gene therapy approach to maximize the organ donor pool through the safer use of liver transplants exposed to prolonged cold ischemia. PMID:14741776

Application of advanced machine learning methods on resting-state fMRI network for identification of mild cognitive impairment and Alzheimer's disease.

PubMed

Khazaee, Ali; Ebrahimzadeh, Ata; Babajani-Feremi, Abbas

2016-09-01

The study of brain networks by resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for identifying patients with dementia from healthy controls (HC). Using graph theory, different aspects of the brain network can be efficiently characterized by calculating measures of integration and segregation. In this study, we combined a graph theoretical approach with advanced machine learning methods to study the brain network in 89 patients with mild cognitive impairment (MCI), 34 patients with Alzheimer's disease (AD), and 45 age-matched HC. The rs-fMRI connectivity matrix was constructed using a brain parcellation based on a 264 putative functional areas. Using the optimal features extracted from the graph measures, we were able to accurately classify three groups (i.e., HC, MCI, and AD) with accuracy of 88.4 %. We also investigated performance of our proposed method for a binary classification of a group (e.g., MCI) from two other groups (e.g., HC and AD). The classification accuracies for identifying HC from AD and MCI, AD from HC and MCI, and MCI from HC and AD, were 87.3, 97.5, and 72.0 %, respectively. In addition, results based on the parcellation of 264 regions were compared to that of the automated anatomical labeling atlas (AAL), consisted of 90 regions. The accuracy of classification of three groups using AAL was degraded to 83.2 %. Our results show that combining the graph measures with the machine learning approach, on the basis of the rs-fMRI connectivity analysis, may assist in diagnosis of AD and MCI.

Effect of chlorhexidine pretreatment on bond strength durability of caries-affected dentin over 2-year aging in artificial saliva and under simulated intrapulpal pressure.

PubMed

Mobarak, E H

2011-01-01

To evaluate the influence of 2% and 5% chlorhexidine (CHX) pretreatment on bond durability of a self-etching adhesive to normal (ND) and caries-affected (AD) dentin after 2-years of aging in artificial saliva and under simulated intrapulpal pressure (IPP). One hundred twenty freshly extracted carious teeth were ground to expose ND and AD. Specimens were distributed into three equal groups (n=40) according to whether the dentin substrates were pretreated with 2% or 5% CHX or with water (control). Clearfil SE Bond (Kuraray) was applied to both substrates and composite cylinders (0.9 mm diameter and 0.7 mm height) were formed. Pretreatment and bonding were done while the specimens were subjected to 15 mm Hg IPP. After curing, specimens were aged in artificial saliva at 37°C and under IPP at 20 mm Hg until being tested after 24 hours or 2 years (n=20/group). Microshear bond strength was evaluated. Failure modes were determined using a scanning electron microscope (SEM) at 400× magnification. Data were statistically analyzed using three-way analysis of variance (ANOVA); one-way ANOVA tests, and t-test (p<0.05). Additional specimens (n=5/group) were prepared to evaluate interfacial silver precipitation. For the 24-hour groups, there were no significant differences among the ND groups and AD groups. For ND aged specimens, the 5% CHX group had the highest value followed by the 2% CHX and control groups, although the difference was statistically insignificant. For AD aged specimens, the 5% CHX group revealed statistically higher bond values compared to the 2% CHX and control groups. Fracture modes were predominately adhesive and mixed. Different interfacial silver depositions were recorded. Two percent or 5% CHX pretreatment has no adverse effect on the 24-hour bonding to ND and AD. Five percent CHX was able to diminish the loss in bonding to AD after 2years of aging in artificial saliva and under simulated IPP.

PSEN1 and PSEN2 gene expression in Alzheimer's disease brain: a new approach.

PubMed

Delabio, Roger; Rasmussen, Lucas; Mizumoto, Igor; Viani, Gustavo-Arruda; Chen, Elizabeth; Villares, João; Costa, Isabela-Bazzo; Turecki, Gustavo; Linde, Sandra Aparecido; Smith, Marilia Cardoso; Payão, Spencer-Luiz

2014-01-01

Presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes encode the major component of y-secretase, which is responsible for sequential proteolytic cleavages of amyloid precursor proteins and the subsequent formation of amyloid-β peptides. 150 RNA samples from the entorhinal cortex, auditory cortex and hippocampal regions of individuals with Alzheimer's disease (AD) and controls elderly subjects were analyzed with using real-time rtPCR. There were no differences between groups for PSEN1 expression. PSEN2 was significantly downregulated in the auditory cortex of AD patients when compared to controls and when compared to other brain regions of the patients. Alteration in PSEN2 expression may be a risk factor for AD.

Structural Connectivity Changes Underlying Altered Working Memory Networks in Mild Cognitive Impairment: A Three-Way Image Fusion Analysis.

PubMed

Teipel, Stefan; Ehlers, Inga; Erbe, Anna; Holzmann, Carsten; Lau, Esther; Hauenstein, Karlheinz; Berger, Christoph

2015-01-01

Working memory impairment is among the earliest signs of cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We aimed to study the functional and structural substrate of working memory impairment in early AD dementia and MCI. We studied a group of 12 MCI and AD subjects compared to 12 age- and gender-matched healthy elderly controls using diffusion tensor imaging (DTI), and functional magnetic resonance imaging (fMRI) during a 2-back versus 1-back letter recognition task. We performed a three-way image fusion analysis with joint independent component analysis of cortical activation during working memory, and DTI derived measures of fractional anisotropy (FA) and the mode of anisotropy. We found significant hypoactivation in posterior brain areas and relative hyperactivation in anterior brain areas during working memory in AD/MCI subjects compared to controls. Corresponding independent components from DTI data revealed reduced FA and reduced mode of anisotropy in intracortical projecting fiber tracts with posterior predominance and increased FA and increased mode along the corticospinal tract in AD/MCI compared to controls. Our findings suggest that impairments of structural fiber tract integrity accompany breakdown of posterior and relatively preserved anterior cortical activation during working memory performance in MCI/AD subjects. Copyright © 2014 by the American Society of Neuroimaging.

Quantitative EEG and LORETA: valuable tools in discerning FTD from AD?

PubMed

Caso, Francesca; Cursi, Marco; Magnani, Giuseppe; Fanelli, Giovanna; Falautano, Monica; Comi, Giancarlo; Leocani, Letizia; Minicucci, Fabio

2012-10-01

Drawing a clinical distinction between frontotemporal dementia (FTD) and Alzheimer's disease (AD) is tricky, particularly at the early stages of disease. This study evaluates the possibility in differentiating 39 FTD, 39 AD, and 39 controls (CTR) by means of power spectral analysis and standardized low resolution brain electromagnetic tomography (sLORETA) within delta, theta, alpha 1 and 2, beta 1, 2, and 3 frequency bands. Both analyses revealed in AD patients, relative to CTR, higher expression of diffuse delta/theta and lower central/posterior fast frequency (from alpha1 to beta2) bands. FTD patients showed diffuse increased theta power compared with CTR and lower delta relative to AD patients. Compared with FTD, AD patients showed diffuse higher theta power at spectral analysis and, at sLORETA, decreased alpha2 and beta1 values in central/temporal regions. Spectral analysis and sLORETA provided complementary information that might help characterizing different patterns of electroencephalogram (EEG) oscillatory activity in AD and FTD. Nevertheless, this differentiation was possible only at the group level because single patients could not be discerned with sufficient accuracy. Copyright © 2012 Elsevier Inc. All rights reserved.

Factors Associated with a Depressive Disorder in Alzheimer's Disease Are Different from Those Found for Other Dementia Disorders

PubMed Central

Barca, Maria Lage; Engedal, Knut; Laks, Jerson; Selbaek, Geir

2012-01-01

Background This study explores factors associated with depression in Alzheimer's disease (AD) compared with mild cognitive impairment (MCI) and other dementia disorders. Method In a prospective study we included 195 patients: 31 with MCI, 112 with AD and 52 with other dementias. Results According to the ICD-10 and the DSM-IV criteria, 88 (44.1%) and 59 (30.3%), respectively, had a depressive disorder. An adjusted multiple regression analysis showed that previous depression (p < 0.05) was significantly associated with depression in AD patients. Severity of dementia (p < 0.05) was significantly associated with a depressive disorder in a group of patients with frontotemporal dementia, vascular dementia, or dementia due to Lewy Body disease or Parkinson's disease. Conclusion We found different factors associated with a depressive disorder in AD compared to those found for other dementia disorders. PMID:22479262

Factors associated with a depressive disorder in Alzheimer's disease are different from those found for other dementia disorders.

PubMed

Barca, Maria Lage; Engedal, Knut; Laks, Jerson; Selbaek, Geir

2012-01-01

This study explores factors associated with depression in Alzheimer's disease (AD) compared with mild cognitive impairment (MCI) and other dementia disorders. In a prospective study we included 195 patients: 31 with MCI, 112 with AD and 52 with other dementias. According to the ICD-10 and the DSM-IV criteria, 88 (44.1%) and 59 (30.3%), respectively, had a depressive disorder. An adjusted multiple regression analysis showed that previous depression (p < 0.05) was significantly associated with depression in AD patients. Severity of dementia (p < 0.05) was significantly associated with a depressive disorder in a group of patients with frontotemporal dementia, vascular dementia, or dementia due to Lewy Body disease or Parkinson's disease. We found different factors associated with a depressive disorder in AD compared to those found for other dementia disorders.

Lower limb motor restlessness in Asperger's disorder, measured using actometry.

PubMed

Tuisku, Katinka; Tani, Pekka; Nieminen-von Wendt, Taina; von Wendt, Lennart; Holi, Matti Mikael; Porkka-Heiskanen, Tarja; Lauerma, Hannu; Lindberg, Nina; Appelberg, Björn; Wahlbeck, Kristian

2004-08-30

The movement disturbances and brain imaging findings in Asperger's disorder (AD) suggest a dopaminergic deficit in movement regulation. Movement disorders of different etiologies have been quantified and specified with actometry. We compared 10 AD patients with 10 healthy controls, measuring their rest-activities by actometry. The lower limb motor activity was significantly higher in the AD group. They also displayed a rhythmic, periodic movement pattern similar to akathisia. These findings suggest a hypothesis of idiopathic akathisia and a special sensitivity to adverse effects of neuroleptic drugs.

C145 as a short-latency electrophysiological index of cognitive compensation in Alzheimer's disease

PubMed Central

Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; DeGrush, Elizabeth; Reilly, Lindsey A.

2012-01-01

Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimer's disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency ERP component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage Alzheimer's disease (AD). Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (Controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using Principal Components Analysis. C145 amplitudes and spatial distributions were compared among Controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, Control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals. PMID:22886016

Adrenomedullin and angiopoietin-1 additively restore erectile function in diabetic rats: comparison with the combination therapy of vascular endothelial growth factor and angiopoietin-1.

PubMed

Nishimatsu, Hiroaki; Suzuki, Etsu; Nomiya, Akira; Niimi, Aya; Suzuki, Motofumi; Fujimura, Tetsuya; Fukuhara, Hiroshi; Homma, Yukio

2013-07-01

Erectile dysfunction (ED) is a major health problem. We have shown that adrenomedullin (AM) restores erectile function in diabetic rats. The aim of this study is to explore a better treatment for ED, we examined whether combination of AM and angiopoietin-1 (Ang-1) was more effective to treat ED than treatment with AM alone or Ang-1 alone. We also compared the effect of the combination therapy with that of treatment with vascular endothelial growth factor-A (VEGF-A). Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. Adenoviruses expressing AM (AdAM), Ang-1 (AdAng-1), and VEGF-A (AdVEGF-A) were injected into the penis 6 weeks after STZ administration. Erectile function, penile histology, and protein expression were analyzed 4 weeks after the injection of the adenoviruses. Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. The morphology of the penis was analyzed by Elastica van Gieson stain and immunohistochemistry. The expression of α-smooth muscle actin (SMA), VE-cadherin and type I collagen was assessed by Western blot analysis. Infection with AdAM plus AdAng-1 more effectively restored erectile function than infection with AdAM alone or AdAng-1 alone. This combination therapy restored erectile function to a level similar to that observed in the age-matched Wistar rats. Expression of SMA and VE-cadherin increased more significantly in the AdAM plus AdAng-1-treated group than in the AdAM- or AdAng-1-treated group. Although AdVEGF-A infection restored erectile function significantly, it also caused enlargement of the trabeculae of the cavernous body, aberrant angiogenesis, and overproduction of type I collagen. These results suggested that combination therapy with AM and Ang-1 potently restored erectile function and normal morphology of the cavernous body compared with VEGF-A administration. This combination therapy will be useful to treat ED patients with a severely damaged cavernous body. © 2013 International Society for Sexual Medicine.

[Effect of substance P on the potassium and calcium currents of colonic smooth muscle cells].

PubMed

Tang, Qincai; Luo, Hesheng; Quan, Xiaojing; Fan, Han; Yu, Guang

2015-08-11

To investigate the effect of substance P(SP) on the spontaneous contractile activity of smooth muscle cells,the large-conductance calcium-activated potassium channel currents (IBKCa) and the L-type calcium channel currents (ICaL) in rat smooth muscle cells of the proximal colon. A total of 24 healthy male Wista rats were used in this test. The change of smooth muscle strips spontaneous contraction of rat proximal colon after adding SP was recorded by a physiological signal stystem (RM6240). The IBKCa and ICaL were measured via the whole cell patch-clamp technique. The longitudinal muscle contraction was obviously increased concentration-dependently after adding different concentrations of SP (10(-7)-10(-6) mol/L), so as the circular muscle while adding SP(10(-8)-10(-6) mol/L) (all P<0.05). Compared with the control group, IBKCa was decreased after adding SP(10(-6) mol/L). Under the stimulating voltage of 60 mV, the IBKCa current density was (11.71±1.65) pA/pF, which was significantly lower compared with the control group (14.42±2.89) pA/pF (P<0.05). The ICaL) was apparently increased. Under the stimulating voltage of 0 mV, the ICaL) currents density was (-5.04±0.67) pA/pF, compared with the control group (-4.25±0.46) pA/pF, which was significantly increased (P<0.01). SP can promote the spontaneous contractile activity of colon smooth muscle of rats in vitro.And SP decrease IBKCa representatively while apparently increase ICaL). That is probably one of the mechanism SP regulate the gastrointestinal motility.

Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary Report.

PubMed

Weiner, Michael W; Harvey, Danielle; Hayes, Jacqueline; Landau, Susan M; Aisen, Paul S; Petersen, Ronald C; Tosun, Duygu; Veitch, Dallas P; Jack, Clifford R; Decarli, Charles; Saykin, Andrew J; Grafman, Jordan; Neylanthe, Thomas C

2017-06-01

Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. Potential subjects identified by Veterans Administration records underwent an initial telephone screen. Consented subjects underwent clinical evaluation, lumbar puncture, structural MRI and amyloid PET scans. We observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global cognitive functioning in the PTSD group, lower superior parietal volume in the TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not increased in the PTSD and/or TBI groups. Preliminary results do not indicate that TBI or PTSD increase the risk for AD measured by amyloid PET. Additional recruitment, longitudinal follow-up, and tau PET scans will provide more information in the future.

Hemispheric Differences in White Matter Microstructure between Two Profiles of Children with High Intelligence Quotient vs. Controls: A Tract-Based Spatial Statistics Study

PubMed Central

Nusbaum, Fanny; Hannoun, Salem; Kocevar, Gabriel; Stamile, Claudio; Fourneret, Pierre; Revol, Olivier; Sappey-Marinier, Dominique

2017-01-01

Objectives: The main goal of this study was to investigate and compare the neural substrate of two children's profiles of high intelligence quotient (HIQ). Methods: Two groups of HIQ children were included with either a homogeneous (Hom-HIQ: n = 20) or a heterogeneous IQ profile (Het-HIQ: n = 24) as defined by a significant difference between verbal comprehension index and perceptual reasoning index. Diffusion tensor imaging was used to assess white matter (WM) microstructure while tract-based spatial statistics (TBSS) analysis was performed to detect and localize WM regional differences in fractional anisotropy (FA), mean diffusivity, axial (AD), and radial diffusivities. Quantitative measurements were performed on 48 regions and 21 fiber-bundles of WM. Results: Hom-HIQ children presented higher FA than Het-HIQ children in widespread WM regions including central structures, and associative intra-hemispheric WM fasciculi. AD was also greater in numerous WM regions of Total-HIQ, Hom-HIQ, and Het-HIQ groups when compared to the Control group. Hom-HIQ and Het-HIQ groups also differed by their hemispheric lateralization in AD differences compared to Controls. Het-HIQ and Hom-HIQ groups showed a lateralization ratio (left/right) of 1.38 and 0.78, respectively. Conclusions: These findings suggest that both inter- and intra-hemispheric WM integrity are enhanced in HIQ children and that neural substrate differs between Hom-HIQ and Het-HIQ. The left hemispheric lateralization of Het-HIQ children is concordant with their higher verbal index while the relative right hemispheric lateralization of Hom-HIQ children is concordant with their global brain processing and adaptation capacities as evidenced by their homogeneous IQ. PMID:28420955

Addition of pimecrolimus cream 1% to a topical corticosteroid treatment regimen in paediatric patients with severe atopic dermatitis: a randomized, double-blind trial.

PubMed

Meurer, Michael; Eichenfield, Lawrence F; Ho, Vincent; Potter, Paul C; Werfel, Thomas; Hultsch, Thomas

2010-05-01

Pimecrolimus and topical corticosteroids (TCS) combination therapy may provide an alternative treatment for patients with severe atopic dermatitis (AD), with faster clearance of disease flares, consequently reducing the duration of TCS treatment. To assess the safety profile of pimecrolimus cream 1% combined with fluticasone versus fluticasone alone in paediatric patients with severe AD. Patients (n = 376) were randomized to a combination of pimecrolimus cream 1% with fluticasone or vehicle plus fluticasone for 4 weeks. The primary outcome measure was the frequency of clinically relevant pre-defined adverse events (AEs) associated with the topical use of corticosteroids in patients with severe AD. Erythematous rash was the only AE, occurring more frequently in the combination group, while there were no noticeable differences in the frequency of other AEs of clinical interest between treatment groups. Efficacy variables were comparable between the two groups. A trend for greater time to relapse was observed for the combination of pimecrolimus cream 1% with fluticasone in patients who were clear at the end of treatment, with a marked improvement in facial AD. In paediatric patients with severe AD the overall safety profile of pimecrolimus cream 1% combined with fluticasone was similar to that of fluticasone alone.

Oral infections and orofacial pain in Alzheimer's disease: a case-control study.

PubMed

de Souza Rolim, Thaís; Fabri, Gisele Maria Campos; Nitrini, Ricardo; Anghinah, Renato; Teixeira, Manoel Jacobsen; de Siqueira, José Tadeu T; Cestari, José Augusto Ferrari; de Siqueira, Silvia Regina Dowgan T

2014-01-01

Dental infections are frequent and have recently been implicated as a possible risk factor for Alzheimer's disease (AD). Despite a lack of studies investigating orofacial pain in this patient group, dental conditions are known to be a potential cause of pain and to affect quality of life and disease progression. To evaluate oral status, mandibular function and orofacial pain in patients with mild AD versus healthy subjects matched for age and gender. Twenty-nine patients and 30 control subjects were evaluated. The protocol comprised a clinical questionnaire and dental exam, research diagnostic criteria for temporomandibular disorders, the McGill Pain Questionnaire, the decayed, missing, and filled teeth index, and included a full periodontal evaluation. AD signs and symptoms as well as associated factors were evaluated by a trained neurologist. A higher prevalence of orofacial pain (20.7%, p < 0.001), articular abnormalities in temporomandibular joints (p < 0.05), and periodontal infections (p = 0.002) was observed in the study group compared to the control group. Orofacial pain and periodontal infections were more frequent in patients with mild AD than in healthy subjects. Orofacial pain screening and dental and oral exams should be routinely performed in AD patients in order to identify pathological conditions that need treatment thus improving quality of life compromised due to dementia.

Low-cost composited accelerants for anaerobic digestion of dairy manure: Focusing on methane yield, digestate utilization and energy evaluation.

PubMed

Zhang, Chen; Yun, Sining; Li, Xue; Wang, Ziqi; Xu, Hongfei; Du, Tingting

2018-05-11

To improve the methane yield and digestate utilization of anaerobic digestion (AD), low-cost composited accelerants consisting of urea (0.2-0.5%), bentonite (0.5-0.8%), active carbon (0.6-0.9%), and plant ash (0.01-0.3%) were designed and tested in batch experiments. Total biogas yield (485.7-681.9 mL/g VS) and methane content (63.0-66.6%) were remarkably enhanced in AD systems by adding accelerants compared to those of control group (361.9 mL/g VS, 59.4%). Composited accelerant addition led to the highest methane yield (454.1 mL/g VS), more than double that of control group. The TS, VS, and CODt removal rates (29.7-55.3%, 50.9-63.0%, and 46.8-69.1%) for AD with accelerants were much higher than control group (26.2%, 37.1%, and 39.6%). The improved digestate stability and enhanced fertilizer nutrient content (4.95-5.66%) confirmed that the digestate of AD systems with composited accelerants could safely serve as a potential component of bioorganic fertilizer. These findings open innovative avenues in composited accelerant development and application. Copyright © 2018 Elsevier Ltd. All rights reserved.

Progressive aphasia secondary to Alzheimer disease pathology: A clinicopathologic and MRI study

PubMed Central

Josephs, Keith A.; Whitwell, Jennifer L.; Duffy, Joseph R.; Vanvoorst, Wendy A.; Strand, Edyth A.; Hu, William T.; Boeve, Bradley F.; Graff-Radford, Neill R.; Parisi, Joseph E.; Knopman, David S.; Dickson, Dennis W.; Jack, Clifford R.; Petersen, Ronald C.

2009-01-01

Background The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive-inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD). Objective To compare clinicopathological and MRI features of subjects with progressive aphasia and AD pathology, to subjects with aphasia and FTLD-U pathology, and subjects with typical AD. Methods We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathological re-analysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared to a normal control group. Results All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed grey matter atrophy predominantly in the temporoparietal cortices with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy. Conclusions A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying AD pathology rather than FTLD-U. PMID:18166704

Driving Simulator Performance in Patients with Possible and Probable Alzheimer’s Disease

PubMed Central

Stein, Anthony C.; Dubinsky, Richard M.

2011-01-01

Drivers with more advanced stages of Alzheimer’s disease (AD) have been previously associated with an increased rate of motor vehicle accidents. Drivers suffering from early AD are also involved in, and may even cause motor vehicle accidents with greater frequency than “normal” drivers. Consequently there is considerable public concern regarding traffic safety issues for those with AD and subsequently for society, but there has been little research in understanding whether deterioration in driving ability is progressive, or has a sudden onset once the disease has reached a certain severity. The purpose of this study was to identify possible degradation in simulated driving performance that may occur at the earliest stages of AD, and compare these decrements to a control group of normal drivers. Using a single blind design, seventeen AD subjects, eight at a Clinical Dementia Rating (CDR) of 0.5 (possible AD) and nine at a CDR of 1 (probable AD), were compared to 63 cognitively normal, elderly controls. All subjects were trained to drive a computerized interactive driving simulator and then tested on a 19.3 km (12 mile) test course. The AD subjects demonstrated impaired driving performance when compared to the controls. The simulated driving performance of the CDR 1 AD subjects was so degraded that it would be regarded as unsafe by standard assessment criteria. The CDR 0.5 subjects made similar errors, suggesting that driving impairment may occur at the earliest stages of the disease. Further work will be necessary to determine the significance of these findings. PMID:22105407

Recall and recognition of verbal paired associates in early Alzheimer's disease.

PubMed

Lowndes, G J; Saling, M M; Ames, D; Chiu, E; Gonzalez, L M; Savage, G R

2008-07-01

The primary impairment in early Alzheimer's disease (AD) is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. AD patients perform poorly on cued-recall paired associate learning (PAL) tasks, which assess the ability of the MTLs to encode relational memory. Since encoding and retrieval processes are confounded within performance indexes on cued-recall PAL, its specificity for AD is limited. Recognition paradigms tend to show good specificity for AD, and are well tolerated, but are typically less sensitive than recall tasks. Associate-recognition is a novel PAL task requiring a combination of recall and recognition processes. We administered a verbal associate-recognition test and cued-recall analogue to 22 early AD patients and 55 elderly controls to compare their ability to discriminate these groups. Both paradigms used eight arbitrarily related word pairs (e.g., pool-teeth) with varying degrees of imageability. Associate-recognition was equally effective as the cued-recall analogue in discriminating the groups, and logistic regression demonstrated classification rates by both tasks were equivalent. These preliminary findings provide support for the clinical value of this recognition tool. Conceptually it has potential for greater specificity in informing neuropsychological diagnosis of AD in clinical samples but this requires further empirical support.

Alzheimer's disease and the law: positive and negative consequences of structural stigma and labeling in the legal system.

PubMed

Werner, Perla; Doron, Israel Issi

2017-11-01

To explore the meaning and consequences of labeling on structural stigma in the context of Alzheimer's disease (AD) in the legal system. This qualitative study was made up of three focus groups including social workers and lawyers (n = 26). Participants were asked to report their experience in circumstances in which persons with AD and their family members engage with the legal system. Thematic analysis using the constant comparative method was used. The discussions in the focus groups raised two overall themes. (1) The significance of the medical diagnostic labeling of AD in the legal system and (2) the consequences of labeling of AD within the legal system. This last theme included four sub-themes: (a) negative consequences of labeling; (b) reasons associated with negative consequences of labeling; (c) positive consequences of labeling; and (d) reasons associated with positive consequences of labeling. Findings of the study provide a first foundation for future research on the meaning and consequences of labeling in legal cases involving persons with AD. They suggest that increasing judges' knowledge about AD and reforming the existing 'status-based' legal capacity legislation might benefit by limiting the legal weight given today to the medical diagnosis.

Balance and gait of adults with very mild Alzheimer’s disease

PubMed Central

Gras, LZ; Kanaan, SF; McDowd, JM; Colgrove, YM; Burns, J; Pohl, PS

2015-01-01

Background and Purpose Studies have shown that adults with Alzheimer’s disease (AD) have gait and balance deficits, however the focus has been on those with mild to severe disease. The purpose of this study was to determine if balance and gait deficits are present in those with very mild AD. Methods Thirteen adults (72.9 ± 4.7 years old) with very mild AD and thirteen age (72.6 ± 4.6 years old) and gender-matched (10 males, 3 females) participants in a control group without AD performed balance and gait tests. All participants were living in the community and independent in community ambulation. Results Participants with very mild AD had shorter times in the sharpened Romberg tests with eyes open (p<0.001) and with eyes closed (p=0.007) compared to participants in the control group. Those with AD also took longer to complete the Timed “Up & Go” Test (TUG), (p< 0.001). Gait deficits were found for those with AD as demonstrated by slower velocities in the 10-meter walk at a comfortable pace (p=0.029) and on an instrumented walkway (p<0.001). Stance times were longer for those with AD (p<0.001) and step length was shorter (p=0.001). There were no group differences in the 10-meter walk at a fast pace. The gait velocity of participants in the control group was faster on the instrumented walkway than in the 10-meter walk at a comfortable pace (p=0.031). In contrast, the gait velocity of those with AD was significantly slower on the instrumented walkway than in the 10-meter walk at a comfortable pace, (p=0.024). Discussion Balance and gait deficits may be present in those in the very early stages of AD. Novel surfaces may affect gait speed in those with very mild AD. Identifying mobility deficits early in the progression of AD may provide an opportunity for early physical therapy intervention, thus promoting continued functional independence. Conclusions Adults in the very early stages of AD may show signs of balance and gait deficits. Recognition of these problems early with subsequent physical therapy may slow the progression of further balance and gait dysfunction. PMID:24755691

The effect of stimulation therapy and donepezil on cognitive function in Alzheimer's disease. A community based RCT with a two-by-two factorial design.

PubMed

Andersen, Fred; Viitanen, Matti; Halvorsen, Dag S; Straume, Bjørn; Wilsgaard, Tom; Engstad, Torgeir A

2012-07-19

Progressive neurodegeneration in Alzheimer's disease (AD) induces cognitive deterioration, and there is controversy regarding the optimal treatment strategy in early AD. Stimulation therapy, including physical exercise and cholinesterase inhibitors are both reported to postpone cognitive deterioration in separate studies. We aimed to study the effect of stimulation therapy and the additional effect of donepezil on cognitive function in early AD. A two-by-two factorial trial comprising stimulation therapy for one year compared to standard care to which a randomized double-blinded placebo controlled trial with donepezil was added. Nine rural municipalities in Northern Norway. 187 participants 65 years and older with a recent diagnosis of mild or moderate AD were included in the study of which 146 completed a one-year follow-up. In five municipalities the participants received stimulation therapy whereas participants in four received standard care. All participants were randomised double-blindly to donepezil or placebo and tested with three different cognitive tests four times during the one-year study period. Changes in MMSE sum score.Secondary outcome: Changes in ADAS-Cog and Clock Drawing Test. MMSE scores remained unchanged amongst AD participants receiving stimulation therapy and those receiving standard care. The results were consistent for ADAS-Cog and Clock Drawing Test. No time trend differences were found during one-year follow-up between groups receiving stimulation therapy versus standard care or between donepezil versus placebo. In rural AD patients non-pharmacological and pharmacological therapy did not improve outcome compared with standard care but all groups retained cognitive function during one year follow-up. Other studies are needed to confirm these results. ClinicalTrials.gov (Identifier: NCT00443014). EudraCT database (no 2004-002613-37).

Head motion parameters in fMRI differ between patients with mild cognitive impairment and Alzheimer disease versus elderly control subjects.

PubMed

Haller, Sven; Monsch, Andreas U; Richiardi, Jonas; Barkhof, Frederik; Kressig, Reto W; Radue, Ernst W

2014-11-01

Motion artifacts are a well-known and frequent limitation during neuroimaging workup of cognitive decline. While head motion typically deteriorates image quality, we test the hypothesis that head motion differs systematically between healthy controls (HC), amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD) and consequently might contain diagnostic information. This prospective study was approved by the local ethics committee and includes 28 HC (age 71.0 ± 6.9 years, 18 females), 15 aMCI (age 67.7 ± 10.9 years, 9 females) and 20 AD (age 73.4 ± 6.8 years, 10 females). Functional magnetic resonance imaging (fMRI) at 3T included a 9 min echo-planar imaging sequence with 180 repetitions. Cumulative average head rotation and translation was estimated based on standard fMRI preprocessing and compared between groups using receiver operating characteristic statistics. Global cumulative head rotation discriminated aMCI from controls [p < 0.01, area under curve (AUC) 0.74] and AD from controls (p < 0.01, AUC 0.73). The ratio of rotation z versus y discriminated AD from controls (p < 0.05, AUC 0.71) and AD from aMCI (p < 0.05, AUC of 0.75). Head motion systematically differs between aMCI/AD and controls. Since motion is not random but convoluted with diagnosis, the higher amount of motion in aMCI and AD as compared to controls might be a potential confounding factor for fMRI group comparisons. Additionally, head motion not only deteriorates image quality, yet also contains useful discriminatory information and is available for free as a "side product" of fMRI data preprocessing.

Socioeconomic factors, rather than diabetes mellitus per se, contribute to an excessive use of antidepressants among young adults with childhood onset type 1 diabetes mellitus: a register-based study.

PubMed

Lind, T; Waernbaum, I; Berhan, Y; Dahlquist, G

2012-03-01

Mood disorders, including depression, are suggested to be prevalent in persons with type 1 diabetes and may negatively affect self-management and glycaemic control and increase the risk of diabetic complications. The aim of this study was to analyse the prevalence of antidepressant (AD) use in adults with childhood onset type 1 diabetes and to compare risk determinants for AD prescription among diabetic patients and a group of matched controls. Young adults ≥ 18 years on 1 January 2006 with type 1 diabetes (n = 7,411) were retrieved from the population-based Swedish Childhood Diabetes Registry (SCDR) and compared with 30,043 age- and community-matched controls. Individual level data were collected from the Swedish National Drug Register (NDR), the Hospital Discharge Register (HDR) and the Labor Market Research database (LMR). ADs were prescribed to 9.5% and 6.8% of the type 1 diabetes and control subjects, respectively. Female sex, having received economic or other social support, or having a disability pension were the factors with the strongest association with AD prescription in both groups. Type 1 diabetes was associated with a 44% (OR 1.44, 95% CI 1.32, 1.58) higher risk of being prescribed ADs in crude analysis. When adjusting for potential confounders including sex, age and various socioeconomic risk factors, this risk increase was statistically non-significant (OR 1.11, 95% CI 0.99, 1.21). The risk factor patterns for AD use are similar among type 1 diabetic patients and controls, and socioeconomic risk factors, rather than the diabetes per se, contribute to the increased risk of AD use in young adults with type 1 diabetes.

The influence of different types of brackets and efficacy of two chlorhexidine mouthwashes on oral hygiene and the incidence of white spot lesions in adolescents during the orthodontic therapy.

PubMed

Jurišić, Sanja; Kozomara, Davorin; Jurić, Hrvoje; Verzak, Željko; Jurišić, Gordan

2016-12-01

To detect the effect of two different types of brackets (ceramic and stainless steel) and investigate the effectiveness of two chlorhexidine mouthwashes 0.2% (CHX) on oral hygiene status and incidence of white spot lesions (WSLs) in adolescents wearing fixed orthodontic appliance. One hundred and twenty subjects (aged 11 to 18 years, mean age 14.5 years) were divided into six equal groups according to brackets type and to different mouthwashes: Group 1: metal brackets and conventional CHX, Group 2: metal brackets and CHX with anti-discoloration system (CHX-ADS), Group 3: ceramic brackets and conventional CHX, Group 4: ceramic brackets and CHX-ADS, Group 5: metal brackets and water correction flavors mouthwash (placebo), Group 6: ceramic brackets and placebo. Four weeks after the placement of fixed orthodontic appliance the subjects were provided with three different mouthwashes for use during the next two weeks. Assessment was carried out according to oral hygiene index-simplified (OHI-S) and WSL index performed: prior to placement of the appliance (baseline), four weeks, six weeks, eighteen weeks, and thirty weeks after the placement. The data were then subjected to statistical analysis. Group 4 showed reduction in the OHI-S scores when compared to the Group 5 (in the 6 th week), and Group 6 (in the 6 th and 18 th week), which was statistically significant, P<0.05. Group 4 showed decrease in the WSLs scores when compared to the Group 1 (in the 4 th , 6 th , 18 th and 30 th week), Group 5 (in the 18 th and 30 th week) and Group 6 (in the 6 th , 18 th and 30 th week), which was statistically significant, P<0.05. The ceramic brackets and the usage of CHX-ADS resulted in better oral hygiene status and lower incidence of WSLs.

Could Alkali Production Be Considered an Approach for Caries Control?

PubMed Central

Gordan, V.V.; Garvan, C.W.; Ottenga, M.E.; Schulte, R.; Harris, P.A.; McEdward, D.; Magnusson, I.

2011-01-01

This study investigated the relationship of arginine deiminase (ADS) and urease activities with dental caries through a case-control study. ADS and urease activities were measured in dental smooth-surface supragingival plaque and whole saliva samples from 93 subjects, who were in three different groups: caries-free (n = 31), caries-active (n = 30), and caries-experienced (n = 32). ADS activity was measured by quantification of the ammonia generated from the incubation of plaque and saliva samples in a mixture containing 50 mM arginine-HCl and 50 mM Tris-maleate buffer, pH 6.0. ADS-specific activity was defined as nanomoles of ammonia generated per minute per milligram of protein. Urease activity was determined by quantification of ammonia produced from 50 mM urea. For bacterial identification and enumeration real-time qPCR analysis was used. Groups were compared using Kruskal-Wallis tests. Spearman correlations were used to analyze plaque metabolic activity and bacterial relationships. The results revealed significantly higher ammonia production from arginine in saliva (1.06 vs. 0.18; p < 0.0001) and plaque samples (1.74 vs. 0.58; p < 0.0001) from caries-free subjects compared to caries-active subjects. Urease levels were about 3-fold higher in the plaque of caries-free subjects (p < 0.0001). Although higher urease activity in saliva of caries-experienced and caries-free subjects was evident, no significant difference was found between the groups. PMID:21071940

Perception of emotion in frontotemporal dementia and Alzheimer disease.

PubMed

Lavenu, I; Pasquier, F; Lebert, F; Petit, H; Van der Linden, M

1999-01-01

Frontotemporal dementia (FTD) is the second cause of degenerative dementia. Behavioral changes occur before the cognitive decline and remain the major feature. A poor perception of emotion could account for some behavioral symptoms. The aim of this study was to assess the perception of emotion in patients with FTD and to compare it with that of patients with Alzheimer disease (AD). Fifty subjects performed the tests: 20 patients with probable AD, 18 patients with FTD, and 12 matched controls. The two patient groups did not differ in age, sex, severity of dementia, duration of the disease, and language tests. Subjects had to recognize and point out the name of one of seven basic emotions (anger, disgust, happiness, fear, sadness, surprise, and contempt) on a set of 28 faces presented on slides. The three groups were equally able to distinguish a face displaying affect from one not displaying affect. Naming of emotion was worse in patients with FTD than in patients with AD (correct answers 46% vs. 62%; p = 0.0006) who did not differ significantly from controls (72%). Anger, sadness, and disgust were less recognized in FTD than in AD patients who did not differ from controls, whereas fear and contempt were poorly recognized in both groups of patients compared with controls. These findings argue for different neural substrates underlying the recognition of various basic emotions. Behavioral disorders in FTD may be partly due to an impaired interpretation of the emotional environment.

An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice

PubMed Central

Sheline, Yvette I.; West, Tim; Yarasheski, Kevin; Swarm, Robert; Jasielec, Mateusz S.; Fisher, Jonathan R.; Ficker, Whitney D.; Yan, Ping; Xiong, Chengjie; Frederiksen, Christine; Grzelak, Monica V.; Chott, Robert; Bateman, Randall J.; Morris, John C.; Mintun, Mark A.; Lee, Jin-Moo; Cirrito, John R.

2014-01-01

Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer’s disease (AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor (SSRI), decreased Aβ in brain interstitial fluid (ISF) in a dose-dependent manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram. Citalopram arrested the growth of pre-existing plaques and reduced the appearance of new plaques by 78%. In healthy human volunteers, citalopram’s effects on Aβ production and Aβ concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable-isotope labeling kinetics (SILK), with CSF sampling during acute dosing of citalopram. Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo. This change was associated with a 38% decrease in total CSF Aβ concentrations in the drug-treated group. The ability to safely decrease Aβ concentrations is potentially important as a preventive strategy for AD. This study demonstrates key target engagement for future AD prevention trials. PMID:24828079

Non-Ceruloplasmin Copper Distincts Subtypes in Alzheimer's Disease: a Genetic Study of ATP7B Frequency.

PubMed

Squitti, Rosanna; Ventriglia, Mariacarla; Gennarelli, Massimo; Colabufo, Nicola A; El Idrissi, Imane Ghafir; Bucossi, Serena; Mariani, Stefania; Rongioletti, Mauro; Zanetti, Orazio; Congiu, Chiara; Rossini, Paolo M; Bonvicini, Cristian

2017-01-01

Meta-analyses show that serum copper non-bound-to-ceruloplasmin (non-Cp-Cu) is higher in patients with Alzheimer's disease (AD). ATP7B gene variants associate with AD, modulating the size of non-Cp-Cu pool. However, a dedicated genetic study comparing AD patients after stratification for a copper biomarker to demonstrate the existence of a copper subtype of AD has not yet been carried out. An independent patient sample of 287 AD patients was assessed for non-Cp-Cu serum concentrations, rs1801243, rs1061472, and rs732774 ATP7B genetic variants and the APOE4 genotype. Patients were stratified into two groups based on a non-Cp-Cu cutoff (1.9 μM). Single-locus and haplotype-group analyses were performed to define their frequencies in dependence of the non-Cp-Cu group. The two AD subgroups did not differ regarding age, sex, MMSE score, or APOE4 frequency allele, while they did differ regarding non-Cp-Cu concentrations in serum, allele, genotype, and haplotype frequencies of rs1061472 A > G and rs732774 C > T after multiple testing corrections. AD patients with a GG genotype had a 1.76-fold higher risk of having a non-Cp-Cu higher than 1.9 μmol/L (p = 0.029), and those with a TT genotype for rs732774 C > T of 1.8-fold (p = 0.018). After 100,000 permutations for multiple testing corrections, the haplotype containing the AC alleles appeared more frequently in AD patients with normal non-Cp-Cu [43 vs. 33 %; Pm = 0.03], while the haplotype containing the GT risk alleles appeared more frequently in the higher non-Cp-Cu AD (66 vs. 55 %; Pm = 0.01). Genetic heterogeneity sustains a copper AD metabolic subtype; non-Cp-Cu is a marker of this copper AD.

MicroRNA Profile in Patients with Alzheimer's Disease: Analysis of miR-9-5p and miR-598 in Raw and Exosome Enriched Cerebrospinal Fluid Samples.

PubMed

Riancho, Javier; Vázquez-Higuera, José Luis; Pozueta, Ana; Lage, Carmen; Kazimierczak, Martha; Bravo, María; Calero, Miguel; Gonalezález, Andrea; Rodríguez, Eloy; Lleó, Alberto; Sánchez-Juan, Pascual

2017-01-01

MicroRNAs have been postulated as potential biomarkers for Alzheimer's disease (AD). Exosomes are nanovesicles which transport microRNAs, proteins, and other cargos. It has been hypothesized that the exosome traffic might be increased in neurodegenerative disorders. i) To assess the cerebrospinal fluid (CSF) microRNA profile in a group of AD patients and control subjects and to validate a group of microRNAs previously reported by other authors. ii) To compare microRNA levels in whole CSF and in the exosome-enriched fraction in AD patients. A panel of 760 microRNAs was analyzed in the CSF of 10 AD patients and 10 healthy subjects. Among microRNAs differently expressed, we selected those that had been previously reported by other authors. Candidates were validated in a larger group by individual qPCR assays. MicroRNA expression was also evaluated in exosome-enriched CSF samples of patients with AD and controls. Fifteen microRNAs were differently expressed in AD. MiR-9-5p, miR-134, and miR-598 were selected as candidates for further analysis. MiR-9-5p and miR-598 were detected in 50 and 75% of control CSF samples, respectively, while they were not detected in any AD CSF samples. We observed an opposite pattern when we evaluated the microRNA expression in the exosome-enriched CSF AD samples. No pattern variations were noted among healthy subjects. These data propose miR-9-5p and miR-598 as potential biomarkers for AD. Further studies in plasma and other body fluids will confirm their potential role as easily accessible biomarkers. In addition, our data suggest that exosome trafficking is different between AD and control subjects raising the need to take this phenomenon into consideration in future studies of AD biomarkers.

Alzheimer's disease can spare local metacognition despite global anosognosia: revisiting the confidence-accuracy relationship in episodic memory.

PubMed

Gallo, David A; Cramer, Stefanie J; Wong, Jessica T; Bennett, David A

2012-07-01

Alzheimer's disease (AD) can impair metacognition in addition to more basic cognitive functions like memory. However, while global metacognitive inaccuracies are well documented (i.e., low deficit awareness, or anosognosia), the evidence is mixed regarding the effects of AD on local or task-based metacognitive judgments. Here we investigated local metacognition with respect to the confidence-accuracy relationship in episodic memory (i.e., metamemory). AD and control participants studied pictures of common objects and their verbal labels, and then took forced-choice picture recollection tests using the verbal labels as retrieval cues. We found that item-based confidence judgments discriminated between accurate and inaccurate recollection responses in both groups, implicating relatively spared metamemory in AD. By contrast, there was evidence for global metacognitive deficiencies, as AD participants underestimated the severity of their everyday problems compared to an informant's assessment. Within the AD group, individual differences in global metacognition were related to recollection accuracy, and global metacognition for everyday memory problems was related to task-based metacognitive accuracy. These findings suggest that AD can spare the confidence-accuracy relationship in recollection tasks, and that global and local metacognition measures tap overlapping neuropsychological processes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Adenoviral Mediated Gene Transfer of IGF-1 Enhances Wound Healing and Induces Angiogenesis

PubMed Central

Balaji, S.; LeSaint, M.; Bhattacharya, S. S.; Moles, C.; Dhamija, Y.; Kidd, M.; Le, L.D.; King, A.; Shaaban, A.; Crombleholme, T. M.; Bollyky, P.; Keswani, S. G.

2014-01-01

Background Chronic wounds are characterized by a wound healing and neovascularization deficit. Strategies to increase neovascularization can significantly improve chronic wound healing. Insulin like growth factor (IGF-1) is reported to be a keratinocyte mitogen and is believed to induce angiogenesis via a vascular endothelial growth factor (VEGF) dependent pathway. Using a novel ex vivo human dermal wound model and a diabetic impaired wound healing murine model, we hypothesized that adenoviral over expression of IGF-1 (Ad-IGF-1) will enhance wound healing and induce angiogenesis through a VEGF dependent pathway. Methods Ex vivo: 6 mm full thickness punch biopsies were obtained from normal human skin, and 3 mm full thickness wounds were created at the center. Skin explants were maintained at air liquid interface. Db/db murine model: 8 mm full thickness dorsal wounds in diabetic (db/db) mice were created. Treatment groups in both human ex vivo and in vivo db/db wound models include 1×108 PFU of Ad-IGF-1 or Ad-LacZ, and PBS (n=4–5/group). Cytotoxicity (LDH) was quantified at days 3, 5 and 7 for the human ex vivo wound model. Epithelial gap closure (H&E; Trichrome), VEGF expression (ELISA) and capillary density (CD 31+ CAPS/HPF) were analyzed at day 7. Results In the human ex vivo organ culture, the adenoviral vectors did not demonstrate any significant difference in cytotoxicity compared to PBS. Ad-IGF-1 over expression significantly increases basal keratinocyte migration, with no significant effect on epithelial gap closure. There was a significant increase in capillary density in the Ad-IGF-1 wounds. However, there was no effect on VEGF levels in Ad-IGF-1 samples compared to controls. In db/db wounds, Ad-IGF-1 over expression significantly improves epithelial gap closure and granulation tissue with a dense cellular infiltrate compared to controls. Ad-IGF-1 also increases capillary density, again with no significant difference in VEGF levels in the wounds compared to control treatments. Conclusions In two different models, our data demonstrates that adenoviral mediated gene transfer of IGF-1 results in enhanced wound healing and induces angiogenesis via a VEGF-independent pathway. Understanding the underlying mechanisms of IGF-1 effects on angiogenesis may help produce novel therapeutics for chronic wounds or diseases characterized by a deficit in neovascularization. PMID:24725678

Dexmedetomidine in a surgically inserted catheter for transversus abdominis plane block in donor hepatectomy: A prospective randomized controlled study.

PubMed

Aboelela, Mohamed Adel; Kandeel, Al-Refaey; Elsayed, Usama; Elmorshedi, Mohamed; Elsarraf, Waleed; Elsayed, Eman; Elgawalby, Ahmed; Sultan, Ahmed Mohamed; Wahab, Mohamed Abdel; Yassen, Amr

2018-01-01

Transversus abdominis plane (TAP) block is a promising technique for analgesia after abdominal surgery. This prospective, randomized controlled trial assessed the effect of adding dexmedetomidine to bupivacaine in TAP block for donor hepatectomy. We hypothesized that this would improve postoperative morphine consumption and reduce analgesia related complication and inflammation. A total of 50 donor hepatectomy were enrolled in this study. Patients divided into two equal groups according to drugs used for TAP block. Group (B) received 20 ml of bupivacaine hydrochloride 0.25%, Group (BD) received 20 ml of bupivacaine hydrochloride 0.25% and 0.3 μg/kg dexmedetomidine, on both sides at the end of surgery and every 8 h for 48 h at right side only through inserted catheter. Primary outcome objective was morphine consumption at first 72 h. Secondary outcome objectives were morphine requirement, numbers of intake, time to first intake, pain score numerical analog scale (NAS), postoperative analgesia related complications, recovery of intestinal motility, and inflammatory markers. Data were analyzed, rescue morphine analgesia was significantly lower in (BD) group compared with (B) groups as considering total morphine consumption (B 4 ± 1.9, BD 1.5 ± 0.5, P = 0.03), numbers of morphine intake ( P = 0.04), morphine requirement ( P = 0.03), and first time of analgesia intake ( P = 0.04). NAS was significantly lower in group (BD) compared with group (B) group in the first 12 h (NAS 0 - P = 0.001, NAS 1 - P = 0.03). Adding dexmedetomidine improved gut motility, first oral intake without detectable anti-inflammatory effect. Adding dexmedetomidine to bupivacine in a surgically inserted catheter for TAP block in donor hepatectomy reduced morphine consumption without detectable anti-inflammatory effect.

Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial.

PubMed

Henderson, Victor W; Ala, Tom; Sainani, Kristin L; Bernstein, Allan L; Stephenson, B Sue; Rosen, Allyson C; Farlow, Martin R

2015-12-01

To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect. This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog). Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68-84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval -0.39 to 0.44, 2-tailed p = 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. Results on the primary outcome showed no cognitive benefits in the raloxifene-treated group. This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect. © 2015 American Academy of Neurology.

Raloxifene for women with Alzheimer disease

PubMed Central

Ala, Tom; Sainani, Kristin L.; Bernstein, Allan L.; Stephenson, B. Sue; Rosen, Allyson C.; Farlow, Martin R.

2015-01-01

Objective: To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect. Methods: This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog). Results: Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68–84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval −0.39 to 0.44, 2-tailed p = 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. Conclusions: Results on the primary outcome showed no cognitive benefits in the raloxifene-treated group. Classification of evidence: This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect. PMID:26537053

[The effect of edaravone on MAPKs signal pathway associated with Abeta(25-35) treatment in PC12 cells].

PubMed

Zhang, Gui-lian; Guo, Ying-ying; Zhang, Lei; Li, Ting-ting; Du, Yun; Yao, Li; Zhang, Wang-gang; Wu, Hai-qin; Ma, Zhu-lin

2015-03-01

To explore whether edaravone protects cells damage via mitogen-activated protein kinases (MAPKs) signal pathway, and which procedure of p38 be affected so as to add theories for AD pathogenesis and treatments. According to different drugs treated, PC12 cells in vitro were divided into four groups. Negative control group: cells were treated with media alone. AD model group: cells were treated with 30 pmol/L Abeta(25-35). Inhibitor control group: cells were treated with 10 micromol/L SB203580 Cp38 mitogen-activated protein kinase (p38) inhibitor], 10 micromol/L SP600125 [c-Jun NH2 terminal kinase (JNK) inhibitor], or 10 micromol/L PD98059 extracelular signal regulated kinase (ERK) inhibitor]. Low-dose, middle-dose and high-dose edaravone group: cells plated for 24 hours treated with 30 micromol/L Abeta(25-35) and co-treated with 20, 40, 80 micromol/L edaravone 3 hours, respectively. The morphology of the treated cells were observed, the p-p38, p-JNK and p-ERK proteins in each group were tested by the Western blot. The p38 mRNA were tested in each group above (only add SB203580 10 micromol/L in third group) by the real time PCR. (1) The p-p38 protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-p38 protein in the inhibitor group and edaravone groups was decreased significantly (P<0.05) when compared with that in model control group. The p-p38 proteins were significantly increased in the three edaravone groups compared with that in inhibiter control group (P<0.05). The p-p38 protein in middle-dose edaravone group was decreased compared with that in low-dose edaravone group (P<0.05). There was no relationship in dose-dependent manner about edaravone. Compared with three edaravone groups, the p-p38 protein was lower than it in high-dose edaravone & inhibiter group (P<0.05). (2) The p-JNK protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-JNK protein in the inhibitor group was decreased compared with that in model control group (P<0.05). (3) No significantly difference of p-ERK protein concentration was observed in other groups when compared with that in negative control group (P>0.05 each). (4) Compared with negative control group, the p38 mRNA in model control group was significantly increased, and it was significantly decreased in inhibitor control group (P<0.05 each). In 40 micromol/L and 80 micromol/L edaravone groups, the p38 mRNA was significantly decreased compared with that in model control group, and it still was decreased compared with that in inhibitor control group (P<0.05). The p38 mRNA in 40 micromol/L edaravone group was the lowest among three edaravone groups, and it was obviously different from that in 20 micromol/L and 80 micromol/L edaravone groups (P<0.05). Abeta(25-35) could increase the p-p38 and p-JNK protein expression in cultured PC12 cells, but there was no obviously expression of p-ERK protein. These indicated that Abeta(25-35) might activate MAPKs signal pathway, especially p38 and JNK, and lead to PC12 cell damage. Edaravone could decrease p38 mRNA induced-Abeta(25-35), which indicated edaravone could protect PC12 cell damage via blocking p38 signal pathway in mRNA stage and protein stage simultaneously. Hence, it is promising that edaravone would be a new medicine for AD.

Technology-enabled academic detailing: computer-mediated education between pharmacists and physicians for evidence-based prescribing.

PubMed

Ho, Kendall; Nguyen, Anne; Jarvis-Selinger, Sandra; Novak Lauscher, Helen; Cressman, Céline; Zibrik, Lindsay

2013-09-01

Academic detailing (AD) is the practice of specially trained pharmacists with detailed medication knowledge meeting with physicians to share best practices of prescribing. AD has demonstrated efficacy in positively influencing physicians' prescribing behavior. Nevertheless, a key challenge has been that physicians in rural and remote locations, or physicians who are time challenged, have limited ability to participate in face-to-face meetings with academic detailers, as these specially trained academic detailers are primarily urban-based and limited in numbers. To determine the feasibility of using information technologies to facilitate communication between academic detailers and physicians (known as Technology-Enabled Academic Detailing or TEAD) through a comparison to traditional face-to-face academic detailing (AD). Specifically, TEAD is compared to AD in terms of the ability to aid physicians in acquiring evidence-informed prescribing information on diabetes-related medications, measured in terms of time efficiency, satisfaction of both physicians and pharmacists, and quality of knowledge exchange. General Practitioner Physicians (n=105) and pharmacists (n=12) were recruited from across British Columbia. Pharmacists were trained to be academic detailers on diabetes medication usage. Physicians were assigned to one of four intervention groups to receive four academic detailing sessions from trained pharmacists. Intervention groups included: (1) AD only, (2) TEAD only, (3) TEAD crossed over to AD at midpoint, and (4) AD crossed over to TEAD at midpoint. Evaluation included physician-completed surveys before and after each session, pharmacist logs after each detailing session, interviews and focus groups with physicians and pharmacists at study completion, as well as a technical support log to record all phone calls and emails from physicians and pharmacists regarding any technical challenges during the TEAD sessions, or usage of the web portal. Because recruitment was very low for the cross over groups, we analyzed the results in two groups instead: AD only and TEAD only. 354 sessions were conducted (AD=161, TEAD=193). Of these, complete data were available for 300 sessions, which were included in analysis (AD=133, TEAD=167). On average, TEAD sessions were 49min long, and AD sessions 81min long. Overall, physicians enjoyed both modalities of academic detailing (AD and TEAD) because they received information that both reinforced their existing diabetes knowledge and also provided new prescribing insights and approaches. The results suggest that TEAD is an acceptable alternative to AD for providing physicians advice about prescribing. TEAD is more time efficient, facilitates effective knowledge exchange and interprofessional collaboration, and can reach those physicians virtually where face-to-face AD is not possible or practical. Due to logistics, physicians were allocated, rather than randomized, to receive AD and/or TEAD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effects of combined fine motor skill and cognitive therapy to cognition, degree of dementia, depression, and activities of daily living in the elderly with Alzheimer's disease.

PubMed

Lee, Jin; Lee, ByoungHee; Park, YuHyung; Kim, Yumi

2015-10-01

[Purpose] This study evaluated the effects of combined fine motor skill and cognitive therapies on cognition, depression, and activities of daily living in elderly patients with Alzheimer's disease (AD). [Subjects and Methods] Twenty-six participants comprised 2 groups. The experimental group (n=13) received combined fine motor skill and cognitive therapy, and the control group (n=13) received only general medical care. [Results] The experimental group showed improvements in cognition, degree of dementia, depression, and activities of daily living compared to the control group. However, there were no significant differences between the two groups. [Conclusion] These results suggest that combined fine motor skill and cognitive therapy improves cognition, degree of dementia, depression, and daily living in elderly patients with AD. These therapies would therefore be effective as general medical care strategies.

An Investigation of Stimulant Effects on the EEG of Children With Attention-Deficit/Hyperactivity Disorder.

PubMed

Clarke, Adam R; Barry, Robert J; Baker, Iris E; McCarthy, Rory; Selikowitz, Mark

2017-07-01

Stimulant medications are the most commonly prescribed treatment for Attention-Deficit/Hyperactivity Disorder (AD/HD). These medications result in a normalization of the EEG. However, past research has found that complete normalization of the EEG is not always achieved. One reason for this may be that studies have used different medications interchangeably, or groups of subjects on different stimulants. This study investigated whether methylphenidate and dexamphetamine produce different levels of normalization of the EEG in children with AD/HD. Three groups of 20 boys participated in this study. There were 2 groups with a diagnosis of AD/HD; one group, good responders to methylphenidate, and the second, good responders to dexamphetamine. The third group was a normal control group. Baseline EEGs were recorded using an eyes-closed resting condition, and analyzed for total power and relative delta, theta, alpha, and beta. Subjects were placed on a 6-month trial of methylphenidate or dexamphetamine, after which a second EEG was recorded. At baseline, the children with AD/HD had elevated relative theta, less relative alpha and beta compared with controls. Baseline differences were found between the two medication groups, with the dexamphetamine group having greater EEG abnormalities than the methylphenidate group. The results indicate that good responders to methylphenidate and dexamphetamine have different EEG profiles when assessed before medication, and these differences may represent different underlying central nervous system deficits. The 2 medications were found to result in substantial normalization of the EEG, with no significant differences in EEG changes occurring between the 2 medications. This indicates that the degree of pretreatment EEG abnormality was the major factor contributing to the degree of normalization of the EEG. As good responders to the 2 medications appear to have different central nervous system abnormalities, it is recommended that stimulant medications be treated independently and not used interchangeably in research and treatment of AD/HD.

Validity of a semantically cued recall procedure for the mini-mental state examination.

PubMed

Yuspeh, R L; Vanderploeg, R D; Kershaw, D A

1998-10-01

The validity of supplementing the three-item recall portion of the Mini-Mental State Examination (MMSE) with a cued recall procedure to help specify the nature of patients' memory problems was examined. Subjects were 247 individuals representing three diagnostic groups: Alzheimer's disease (AD), subcortical vascular ischemic dementia (SVaD), and normal controls. Individuals were administered a battery of neuropsychological tests, including the MMSE, as part of a comprehensive evaluation for the presence of dementia or other neurologic disorder. MMSE performance differed among groups. The three-item free recall performance also differed among groups, with post hoc analyses revealing the AD and SVaD groups were more impaired than controls but did not differ significantly from each other. Following a cued recall procedure of the MMSE three-items, groups differed, with post hoc analyses showing that AD patients failed to benefit from cues, whereas SVaD patients performed significantly better and comparable to control subjects. Significant correlations between the MMSE three-item cued recall performance and other memory measures demonstrated concurrent validity. Consistent with previous research indicating that SVaD is associated with memory encoding and retrieval deficits, whereas AD is associated with consolidation and storage problems, the present study supported the validity of the cued recall procedure of the three items on the MMSE in helping to distinguish between patients with AD and those with a vascular dementia with primarily subcortical pathology; however, despite these findings, a more extensive battery of neuropsychological measures is still recommended to consistently assess subtle diagnostic differences in these memory processes.

Examining the Screen for Child Anxiety-Related Emotional Disorder-71 as an Assessment Tool for Anxiety in Children with High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

van Steensel, Francisca J. A.; Deutschman, Amber A. C. G.; Bögels, Susan M.

2013-01-01

The psychometric properties of a questionnaire developed to assess symptoms of anxiety disorders (SCARED-71) were compared between two groups of children: children with high-functioning autism spectrum disorder and comorbid anxiety disorders (ASD-group; "n" = 115), and children with anxiety disorders (AD-group; "n" = 122).…

Cerebral White Matter Changes on Therapeutic Response to Rivastigmine in Alzheimer's Disease.

PubMed

Ho, Bo-Lin; Kao, Yi-Hui; Chou, Mei-Chuan; Yang, Yuan-Han

2016-08-10

Rivastigmine has been approved in the treatment of Alzheimer's disease (AD) patients as it can inhibit acetyl- and butyryl-cholinesterase and provide neuroprotective effects involving the synapses. White matter changes (WMCs) are frequently observed in AD, and clinical-pathological correlations imply their possible impacts on cognitive function by interference with cortical and subcortical neuronal pathways. To evaluate the therapeutic effects of rivastigmine in AD patients with cerebral WMCs. Clinically diagnosed AD patients from Kaohsiung Municipal Ta-Tung hospital were recruited together with their cranial magnetic resonance imaging and a series of annual psychometric tests, including Mini-Mental State Examination (MMSE) and sum of boxes of clinical dementia rating scale (CDR-SB). WMCs were rated through the modified Fazekas scale for the periventricular and deep WMCs. In total, 87 AD patients treated with rivastigmine were enrolled. Patients at severe stage of WMCs, compared to mild stage ones, had significant improvement evaluated by MMSE (periventricular WMCs, p = 0.025; deep WMCs, p = 0.030), but not CDR-SB. Compared to the worsening group, the clinically improving group had a significant higher ratio of pre-existing hypertension in terms of cognitive performance [p = 0.016, odds ratio (OR) = 3.48, 95% CI = 1.25-10.34], while having younger age (p = 0.043, OR = 0.11, 95% CI = 0.01-1.12) in terms of global status. Rivastigmine may provide better benefits in cognitive function, but not global status, for AD patients with more advanced WMCs. The detailed mechanisms still have to be determined in future studies.

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials

PubMed Central

Ma, Jiantao; Karlsen, Micaela C.; Chung, Mei; Jacques, Paul F.; Saltzman, Edward; Smith, Caren E.; Fox, Caroline S.

2016-01-01

Context: The effect of added sugar intake on ectopic fat accumulation is a subject of debate. Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. Data Sources: MEDLINE, CAB Abstracts, CAB Global Health, and EBM (Evidence-Based Medicine) Reviews – Cochrane Central Register of Controlled Trials databases were searched for studies published from 1973 to September 2014. Data Extraction: RCTs with a minimum of 6 days’ duration of added sugar exposure in the intervention group were selected. The dosage of added sugar intake as a percentage of total energy was extracted or calculated. Means and standard deviations of pre- and post-test measurements or changes in ectopic fat depots were collected. Data Synthesis: Fourteen RCTs were included. Most of the studies had a medium to high risk of bias. Meta-analysis showed that, compared with eucaloric controls, subjects who consumed added sugar under hypercaloric conditions likely increased ectopic fat, particularly in the liver (pooled standardized mean difference = 0.9 [95%CI, 0.6–1.2], n = 6) and muscles (pooled SMD = 0.6 [95%CI, 0.2–1.0], n = 4). No significant difference was observed in liver fat, visceral adipose tissue, or muscle fat when isocaloric intakes of different sources of added sugars were compared. Conclusions: Data from a limited number of RCTs suggest that excess added sugar intake under hypercaloric diet conditions likely increases ectopic fat depots, particularly in the liver and in muscle fat. There are insufficient data to compare the effect of different sources of added sugars on ectopic fat deposition or to compare intake of added sugar with intakes of other macronutrients. Future well-designed RCTs with sufficient power and duration are needed to address the role of sugars on ectopic fat deposition. PMID:26518034

Brazilian Pediatric Reference Data for Quantitative Ultrasound of Phalanges According to Gender, Age, Height and Weight

PubMed Central

de Carvalho, Wellington Roberto Gomes; de Moraes, Anderson Marques; Roman, Everton Paulo; Santos, Keila Donassolo; Medaets, Pedro Augusto Rodrigues; Veiga-Junior, Nélio Neves; Coelho, Adrielle Caroline Lace de Moraes; Krahenbühl, Tathyane; Sewaybricker, Leticia Esposito; Barros-Filho, Antonio de Azevedo; Morcillo, Andre Moreno; Guerra-Júnior, Gil

2015-01-01

Aims To establish normative data for phalangeal quantitative ultrasound (QUS) measures in Brazilian students. Methods The sample was composed of 6870 students (3688 females and 3182 males), aged 6 to 17 years. The bone status parameter, Amplitude Dependent Speed of Sound (AD-SoS) was assessed by QUS of the phalanges using DBM Sonic BP (IGEA, Carpi, Italy) equipment. Skin color was obtained by self-evaluation. The LMS method was used to derive smoothed percentiles reference charts for AD-SoS according to sex, age, height and weight and to generate the L, M, and S parameters. Results Girls showed higher AD-SoS values than boys in the age groups 7–16 (p<0.001). There were no differences on AD-SoS Z-scores according to skin color. In both sexes, the obese group showed lower values of AD-SoS Z-scores compared with subjects classified as thin or normal weight. Age (r2 = 0.48) and height (r2 = 0.35) were independent predictors of AD-SoS in females and males, respectively. Conclusion AD-SoS values in Brazilian children and adolescents were influenced by sex, age and weight status, but not by skin color. Our normative data could be used for monitoring AD-SoS in children or adolescents aged 6–17 years. PMID:26043082

Gene Therapy With Extracellular Superoxide Dismutase Protects Conscious Rabbits Against Myocardial Infarction

PubMed Central

Li, Qianhong; Bolli, Roberto; Qiu, Yumin; Tang, Xian-Liang; Guo, Yiru; French, Brent A.

2013-01-01

Background Extracellular superoxide dismutase (Ec-SOD) may protect the heart against myocardial infarction (MI) because of its extended half-life and capacity to bind heparan sulfate proteoglycans on cellular surfaces. Accordingly, we used direct gene transfer to increase systemic levels of Ec-SOD and determined whether this gene therapy could protect against MI. Methods and Results The cDNA for human Ec-SOD was incorporated into a replication-deficient adenovirus (Ad5/CMV/Ec-SOD). Injection of this virus produced a high level of Ec-SOD in the liver, which was redistributed to the heart and other organs by injection of heparin. Untreated rabbits (group I) underwent a 30-minute coronary occlusion and 3 days of reperfusion. For comparison, preconditioned rabbits (group II) underwent a sequence of six 4-minute-occlusion/4-minute-reperfusion cycles 24 hours before the 30-minute occlusion. Control-treated rabbits (group III) were injected intravenously with Ad5/CMV/nls-LacZ, and gene-therapy rabbits (group IV) were injected with Ad5/CMV/Ec-SOD 3 days before the 30-minute occlusion. Both groups treated with Ad5 received intravenous heparin 2 hours before the 30-minute occlusion. Infarct size (percent risk area) was similar in groups I (57±6%) and III (58±5%). Ec-SOD gene therapy markedly reduced infarct size to 25±4% (P<0.01, group IV versus group III), a protection comparable to that of the late phase of ischemic preconditioning (29±3%, P<0.01 group II versus group I). Conclusions Direct gene transfer of the cDNA encoding membrane-bound Ec-SOD affords powerful cardioprotection, providing proof of principle for the effectiveness of antioxidant gene therapy against MI. PMID:11294809

Imaging correlates of pathology in corticobasal syndrome(Podcast)

PubMed Central

Whitwell, J.L.; Jack, C.R.; Boeve, B.F.; Parisi, J.E.; Ahlskog, J.E.; Drubach, D.A.; Senjem, M.L.; Knopman, D.S.; Petersen, R.C.; Dickson, D.W.; Josephs, K.A.

2010-01-01

Background: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS. Methods: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls. Results: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD. Conclusions: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology. GLOSSARY AAL = automated anatomic labeling; AD = Alzheimer disease; CBD = corticobasal degeneration; CBS = corticobasal syndrome; CDR-SB = Clinical Dementia Rating sum of boxes; FDR = false discovery rate; FTLD = frontotemporal lobar degeneration; MMSE = Mini-Mental State Examination; PSP = progressive supranuclear palsy; ROI = region of interest; SMA = supplemental motor area; TDP = TDP-43 immunoreactivity; TIV = total intracranial volume; VBM = voxel-based morphometry. PMID:21098403

Neuropsychological Testing in Pathologically Verified Alzheimer Disease and Frontotemporal Dementia: How Well Do the Uniform Data Set Measures Differentiate Between Diseases?

PubMed

Ritter, Aaron R; Leger, Gabriel C; Miller, Justin B; Banks, Sarah J

2017-01-01

Differences in cognition between frontotemporal dementia (FTD) and Alzheimer disease (AD) are well described in clinical cohorts, but have rarely been confirmed in studies with pathologic verification. For emerging therapeutics to succeed, determining underlying pathology early in the disease course is increasingly important. Neuropsychological evaluation is an important component of the diagnostic workup for AD and FTD. Patients with FTD are thought to have greater deficits in language and executive function while patients with AD are more likely to have deficits in memory. To determine if performance on initial cognitive testing can reliably distinguish between patients with frontotemporal lobar degeneration (FTLD) and AD neuropathology. In addition, are there other factors of the neuropsychological assessment that can be used to enhance the accuracy of underlying pathology? Using a logistic regression we retrospectively compared neurocognitive performance on initial evaluation of 106 patients with pathologically verified FTLD (pvFTLD), with 558 pathologically verified AD (pvAD) patients from the National Alzheimer's Coordinating Center using data from the Uniform Data Set (UDS) and the neuropathology data set. As expected, pvFTLD patients were younger, demonstrated better memory performance, and had more neuropsychiatric symptoms than pvAD patients. Other results were less predictable: pvFTLD patients performed better on one test of executive function (trail making test part B) but worse on another (digit span backward). Performance on language testing did not strongly distinguish the 2 groups. To determine what factors led to a misdiagnosis of AD in patients with FTLD, we further analyzed a small group of pvFTLD patients. These patients demonstrated older age and lower Neuropsychiatric Inventory Questionnaire counts compared with accurately diagnosed cases. Other than memory, numerical scores of neurocognitive performance on the UDS are of limited value in differentiating FTLD from AD at the initial visit. These results highlight the difficulty of obtaining an accurate early diagnosis of FTLD and argue for adding supplemental tests to those included in the UDS to assess cognition in FTD and AD patients.

[Comparative Study on Bowel Preparation Efficacy of Ascorbic Acid Containing Polyethylene Glycol by Adding Either Simethicone or 1 L of Water in Health Medical Examination Patients: A Prospective Randomized Controlled Study].

PubMed

Yeo, Se Hwan; Kwak, Jae Hoon; Kim, Yeo Un; Kwon, Tae Ho; Park, Jeong Bae; Park, Jun Hyung; Lee, Yong Kook; Lim, Yun Jeong; Yang, Chang Heon

2016-04-25

There are no studies that looked into the bubble eliminating efficacy of polyethylene glycol with ascorbic acid (PEGA), which has been one of the shortcomings of polyethylene glycol (PEG). In this study, we compared newly introduced PEGA regimen by adding either simethicone or 1 L of water. A prospective randomized controlled study was carried out at Dongguk Universtiy Gyeongju Hospital from July 2014 to September 2014. A total of 90 patients were randomly assigned to 3 groups; PEGA group (n=30) which served as control, simethicone addition group (n=30) to which simethicone 400 mg was additionally prescribed, and water addition group (n=30) to whom additional 1 L of water was given. Cleansing effectiveness, gas elimination efficacy, side effects, and patient satisfaction were compared between the groups. PEGA group demonstrated the highest cleansing effectiveness, but there was no statistically significant difference among the groups. Simethicone addition group showed significantly lesser amount of bubbles than the other groups (2.57±2.05 vs. 1.10±1.83 vs. 2.60±2.84, p=0.017). The rates of side effects in each group were 20.00% vs. 16.77% vs. 53.33%. Water addition group had significantly more side effects than the PEGA group and the simethicone addition group (p=0.003). The patient satisfaction score of each group was 3.37±0.85 vs. 3.73±0.74 vs. 3.20±0.66 with simethicone addition group showing significantly higher satisfaction than water addition group (p=0.020). PEGA bowel preparation agent showed satisfactory bowel cleansing despite the decrease in dosage, and addition of simethicone resulted in better bubble elimination.

Increased expression of aquaporin-1 on the pleura of rats with a tuberculous pleural effusion.

PubMed

Du, Hongchun; Xie, Canmao; He, Qiao; Deng, Xiaohua

2007-12-01

The purpose of this study was to investigate whether the expression of AQP-1 on the pleura is altered in a rat model with a tuberculous pleural effusion (TPE) and to study its function. A TPE model was established by intrapleural inoculation with 0.03 mg (2 ml) standard tuberculosis bacillus (H(37)Rv). The rats with TPE were sacrificed at different time points (day 1, 3, or 5) after inoculation. The control group received a 2-ml intrapleural injection of saline. The visceral and parietal pleural tissues were harvested and processed for real-time RT-PCR, Western blot, immunohistochemistry, and determination of tissue AQP-1 levels. Recombinant adenovirus Ad-rAQP-1 containing full-length cDNA of AQP-1 was constructed. Six groups of seven Wistar rats were assigned to receive the following treatments: group 1: intrapleural administration of normal saline; group 2: intrapleural administration of tuberculosis bacilli (TB); group 3: intrapleural inoculation with TB at day 7 following intrapleural administration of Ad-rAQP-1 vector; group 4: intrapleural inoculation with 0.03 mg TB at day 7 following intrapleural administration of control Ad-GFP vector; group 5: intrapleural administration of Ad-rAQP-1; group 6: intrapleural administration of control Ad-GFP vector. The expression of AQP-l on the pleural tissue was detected by immunohistochemistry and Western blot analysis. Histopathologic changes of the pleura and the volume of pleural fluid were examined on day 7 following gene intervention or on day 3 following TB inoculation. Bilateral pleural effusions appeared within 5 days in all rats who received an intrapleural inoculation with TB. The peak amount of pleural fluid occurred on day 3. The AQP-1 expression at protein and mRNA was increased in the early phase of TPE. The expression of AQP-1 was increased in the Ad-rAQP-1 gene transfer group, indicating successful adenovirus gene transfer. The volume of pleural fluid in group 3 (6.1 +/- 0.7 ml) was significantly increased compared with that in group 2 (3.8 +/- 1.0 ml) and group 4 (4.0 +/- 1.1 ml). These findings suggested that AQP-1 was increased in TPE and it may be involved in the formation of TPE.

Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Navesh K.; Li Tianyu; Chen, David Y.

Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dosemore » was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.« less

Brain Differences in Infants at Differential Genetic Risk for Late-Onset Alzheimer Disease A Cross-sectional Imaging Study

PubMed Central

Dean, Douglas C.; Jerskey, Beth A.; Chen, Kewei; Protas, Hillary; Thiyyagura, Pradeep; Roontiva, Auttawat; O’Muircheartaigh, Jonathan; Dirks, Holly; Waskiewicz, Nicole; Lehman, Katie; Siniard, Ashley L.; Turk, Mari N.; Hua, Xue; Madsen, Sarah K.; Thompson, Paul M.; Fleisher, Adam S.; Huentelman, Matthew J.; Deoni, Sean C. L.; Reiman, Eric M.

2014-01-01

IMPORTANCE Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. OBJECTIVE To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD. DESIGN, SETTING, AND PARTICIPANTS Quiet magnetic resonance imaging was performed at an academic research imaging center on 162 healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders. Cross-sectional measurements were compared in the APOE ε4 carrier and noncarrier groups. White matter MWF was compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60 ε4 carriers and 102 noncarriers). Gray matter volume was compared in a subset of fifty-nine 6- to 25-month-old infants (23 ε4 carriers and 36 noncarriers), who remained asleep during the scanning session. The carrier and noncarrier groups were matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. MAIN OUTCOMES AND MEASURES Automated algorithms compared regional white matter MWF and GMV in the carrier and noncarrier groups and characterized their associations with age. RESULTS Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05, after correction for multiple comparisons; GMV differences, P < .001, uncorrected for multiple comparisons). Infant ε4 carriers also exhibited an attenuated relationship between MWF and age in posterior white matter regions. CONCLUSIONS AND RELEVANCE While our findings should be considered preliminary, this study demonstrates some of the earliest brain changes associated with the genetic predisposition to AD. It raises new questions about the role of APOE in normal human brain development, the extent to which these processes are related to subsequent AD pathology, and whether they could be targeted by AD prevention therapies. PMID:24276092

Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study.

PubMed

Dean, Douglas C; Jerskey, Beth A; Chen, Kewei; Protas, Hillary; Thiyyagura, Pradeep; Roontiva, Auttawat; O'Muircheartaigh, Jonathan; Dirks, Holly; Waskiewicz, Nicole; Lehman, Katie; Siniard, Ashley L; Turk, Mari N; Hua, Xue; Madsen, Sarah K; Thompson, Paul M; Fleisher, Adam S; Huentelman, Matthew J; Deoni, Sean C L; Reiman, Eric M

2014-01-01

Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD. Quiet magnetic resonance imaging was performed at an academic research imaging center on 162 healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders. Cross-sectional measurements were compared in the APOE ε4 carrier and noncarrier groups. White matter MWF was compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60 ε4 carriers and 102 noncarriers). Gray matter volume was compared in a subset of fifty-nine 6- to 25-month-old infants (23 ε4 carriers and 36 noncarriers), who remained asleep during the scanning session. The carrier and noncarrier groups were matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. Automated algorithms compared regional white matter MWF and GMV in the carrier and noncarrier groups and characterized their associations with age. Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05, after correction for multiple comparisons; GMV differences, P < .001, uncorrected for multiple comparisons). Infant ε4 carriers also exhibited an attenuated relationship between MWF and age in posterior white matter regions. While our findings should be considered preliminary, this study demonstrates some of the earliest brain changes associated with the genetic predisposition to AD. It raises new questions about the role of APOE in normal human brain development, the extent to which these processes are related to subsequent AD pathology, and whether they could be targeted by AD prevention therapies.

Lactobacillus plantarum IS-10506 supplementation reduced SCORAD in children with atopic dermatitis.

PubMed

Prakoeswa, C R S; Herwanto, N; Prameswari, R; Astari, L; Sawitri, S; Hidayati, A N; Indramaya, D M; Kusumowidagdo, E R; Surono, I S

2017-10-13

Lactobacillus plantarum IS-10506 is a novel probiotic isolated from dadih, an Indonesian traditional fermented buffalo milk. It's in vitro and in vivo probiotic properties have been assessed. Probiotic function has been shown in vivo by the suppression of allergic reactions in BALB/c mice through the action of T-regulatory cells cytokines by balancing Th1 and Th2 immune response. Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease characterised by the imbalance of Th1 and Th2. The aim of the study was to assess the probiotic function of L. plantarum IS-10506 in children with mild and moderate AD. A randomised double-blind placebo-controlled trial comparing microencapsulated L. plantarum IS-10506 (10 10 cfu/day) and placebo (skim milk-Avicel) twice daily for 12 weeks was conducted in an outpatient clinic on children with mild and moderate AD. The trial included 22 AD children divided into intervention and control groups of n=12 and n=10 patients, respectively. Scoring Atopic Dermatitis Index (SCORAD) and serum immunoglobulin E (IgE), interleukin (IL)-4, interferon gamma (IFN-γ), forkhead box P3 (Foxp3+)/IL-10, and IL-17 levels were assessed. Demographic and baseline characteristics were not significantly different between the two groups. SCORAD and levels of IL-4, IFN-γ, and IL-17 were significantly lower in the probiotic group than those in the placebo group, while the IgE levels were not significantly changed. The ratio of Foxp3+ to IL-10 was significantly higher in the probiotic group than that in placebo group. Supplementation with the probiotic L. plantarum IS-10506 offered a potential treatment for children with AD. Further long-term studies with a larger sample size are required to confirm the therapeutic efficacy of L. plantarum IS-10506 in AD.

Chemical and neuropathological analyses of an Alzheimer’s disease patient treated with solanezumab

PubMed Central

Roher, Alex E; Maarouf, Chera L; Kokjohn, Tyler A; Belden, Christine; Serrano, Geidy; Sabbagh, Marwan S; Beach, Thomas G

2016-01-01

Introduction: Based on the amyloid cascade hypothesis of Alzheimer’s disease (AD) pathogenesis, a series of clinical trials involving immunotherapies have been undertaken including infusion with the IgG1 monoclonal anti-Aβ antibody solanezumab directed against the middle of the soluble Aβ peptide. In this report, we give an account of the clinical history, psychometric testing, gross and microscopic neuropathology as well as immunochemical quantitation of soluble and insoluble Aβ peptides and other proteins of interest related to AD pathophysiology in a patient treated with solanezumab. Materials and Methods: The solanezumab-treated AD case (SOLA-AD) was compared to non-demented control (NDC, n = 5) and non-immunized AD (NI-AD, n = 5) subjects. Brain sections were stained with H&E, Thioflavine-S, Campbell-Switzer and Gallyas methods. ELISA and Western blots were used for quantification of proteins of interest. Results: The SOLA-AD subject’s neuropathology and biochemistry differed sharply from the NDC and NI-AD groups. The SOLA-AD case had copious numbers of amyloid laden blood vessels in all areas of the cerebral cortex, from leptomeningeal perforating arteries to arteriolar deposits which attained the cerebral amyloid angiopathy (CAA) maximum score of 12. In contrast, the maximum CAA for the NI-AD cases averaged a total of 3.6, while the NDC cases only reached 0.75. The SOLA-AD subject had 4.4-fold more soluble Aβ40 and 5.6-fold more insoluble Aβ40 in the frontal lobe compared to NI-AD cases. In the temporal lobe of the SOLA-AD case, the soluble Aβ40 was 80-fold increased, and the insoluble Aβ40 was 13-fold more abundant compared to the non-immunized AD cases. Both soluble and insoluble Aβ42 levels were not dramatically different between the SOLA-AD and NI-AD cohort. Discussion: Solanezumab immunotherapy provided no apparent relief in the clinical evolution of dementia in this particular AD patient, since there was a continuous cognitive deterioration and full expression of amyloid deposition and neuropathology. PMID:27725918

Behavioral phenomenology in Alzheimer's disease, frontotemporal dementia, and late-life depression: a retrospective analysis.

PubMed

Swartz, J R; Miller, B L; Lesser, I M; Booth, R; Darby, A; Wohl, M; Benson, D F

1997-04-01

Often patients in the early stages of Alzheimer's disease (AD), frontotemporal dementia (FTD), and late-life depression can be difficult to differentiate clinically. Although subtle cognitive distinctions exist between these disorders, noncognitive behavioral phenomenology may provide additional discriminating power. In 19 subjects with AD, 19 with FTD, 16 with late-life psychotic depression (LLPD), and 19 with late-life nonpsychotic depression (LLNPD), noncognitive behavioral symptoms were quantified retrospectively using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and compared using both a one-way ANOVA and a multivariate stepwise discriminant analysis, which utilized a jackknife procedure. The FTD group showed the highest mean total SCAN score, while the AD group showed the lowest. ANOVA showed significant differences in the mean total SCAN scores between the four diagnostic groups (P < .0001). With the discriminant analysis, the four disorders demonstrated different clusters of behavioral abnormalities and were differentiated by these symptoms (P < .0001). A subset of 14 SCAN item group symptoms was identified that collectively classified the following percentages of subjects in each diagnostic category: AD 94.7%, FTD 100%, LLPD 87.5%, and LLNPD 100%. These results indicate that AD, FTD, LLPD, and LLNPD were distinguished retrospectively by the SCAN without using cognitive data. Better definition of the longitudinal course of noncognitive behavioral symptoms in different dementias and psychiatric disorders will be valuable both for diagnosis and to help define behavioral syndromes that are associated with selective neuroanatomic and neurochemical brain pathology.

Effect of timed bright light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease.

PubMed

Dowling, Glenna A; Mastick, Judy; Hubbard, Erin M; Luxenberg, Jay S; Burr, Robert L

2005-08-01

Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to entrain the circadian clock to the 24-hour day. The purpose of this randomized clinical trial was to test the effectiveness of timed bright light therapy in reducing rest-activity (circadian) disruption in institutionalized patients with AD. The experimental groups received either morning (9.30-10.30 am) or afternoon (3.30-4.30 pm) bright light exposure ( > or = 2500 lux in gaze direction) Monday through Friday for 10 weeks. The control group received usual indoor light (150-200 lux). Nighttime sleep, daytime wake, and rest-activity parameters were determined by actigraphy. Repeated measures analysis of variance was employed to test the primary study hypotheses. Seventy institutionalized subjects with AD (mean age 84) completed the study. No significant differences in actigraphy-based measures of nighttime sleep or daytime wake were found between groups. Subjects in either experimental light condition evidenced a significantly (p < 0.01) more stable rest-activity rhythm acrophase over the 10-week treatment period compared to the control subjects whose rhythm phase delayed by over two hours. One hour of bright light, administered to subjects with AD either in the morning or afternoon, did not improve nighttime sleep or daytime wake compared to a control group of similar subjects. However, exposure to one-hour of bright light in either the morning or afternoon may provide sufficient additional input to the circadian pacemaker to facilitate entrainment to the 24-hour day. (c) 2005 John Wiley & Sons, Ltd.

Effect of timed bright light treatment for rest-activity disruption in institutionalized patients with Alzheimer’s disease

PubMed Central

Dowling, Glenna A.; Mastick, Judy; Hubbard, Erin M.; Luxenberg, Jay S.; Burr, Robert L.

2008-01-01

SUMMARY Background Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer’s disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to entrain the circadian clock to the 24-hour day. Method The purpose of this randomized clinical trial was to test the effectiveness of timed bright light therapy in reducing rest-activity (circadian) disruption in institutionalized patients with AD. The experimental groups received either morning (9.30–10.30 am) or afternoon (3.30–4.30 pm) bright light exposure (≥ 2500 lux in gaze direction) Monday through Friday for 10 weeks. The control group received usual indoor light (150–200 lux). Nighttime sleep, daytime wake, and rest-activity parameters were determined by actigraphy. Repeated measures analysis of variance was employed to test the primary study hypotheses. Results Seventy institutionalized subjects with AD (mean age 84) completed the study. No significant differences in actigraphy-based measures of nighttime sleep or daytime wake were found between groups. Subjects in either experimental light condition evidenced a significantly (p < 0.01) more stable rest-activity rhythm acrophase over the 10-week treatment period compared to the control subjects whose rhythm phase delayed by over two hours. Conclusions One hour of bright light, administered to subjects with AD either in the morning or afternoon, did not improve nighttime sleep or daytime wake compared to a control group of similar subjects. However, exposure to one-hour of bright light in either the morning or afternoon may provide sufficient additional input to the circadian pacemaker to facilitate entrainment to the 24-hour day. PMID:16035127

Association between Plasma Ceramides and Phosphatidylcholines and Hippocampal Brain Volume in Late Onset Alzheimer’s Disease

PubMed Central

Kim, Min; Nevado-Holgado, Alejo; Whiley, Luke; Snowden, Stuart G.; Soininen, Hilkka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Thambisetty, Madhav; Dobson, Richard J.B.; Powell, John F.; Lupton, Michelle K.; Simmons, Andy; Velayudhan, Latha; Lovestone, Simon; Proitsi, Petroula; Legido-Quigley, Cristina

2016-01-01

Lipids such as ceramides and phosphatidylcholines (PC) have been found altered in the plasma of Alzheimer’s disease (AD) patients in a number of discovery studies. For this reason, the levels of 6 ceramides and 3 PCs, with different fatty acid length and saturation levels, were measured in the plasma from 412 participants (AD n = 205, Control n = 207) using mass spectrometry coupled with ultra-performance liquid chromatography. After this, associations with AD status, brain atrophy, and age-related effects were studied. In the plasma of AD participants, cross-sectional analysis revealed elevated levels of three ceramides (Cer16:0 p < 0.01, Cer18:0 p < 0.01, Cer24:1 p < 0.05). In addition, two PCs in AD plasma (PC36:5 p < 0.05, PC38:6 p < 0.05) were found to be depleted compared to the control group, with PC36:5 also associating with hippocampal atrophy (p < 0.01). Age-specific analysis further revealed that levels of Cer16:0, Cer18:0, and Cer20:0 were associated with hippocampal atrophy only in younger participants (age < 75, p < 0.05), while all 3 PCs did so in the older participants (age > 75, p < 0.05). PC36:5 was associated with AD status in the younger group (p < 0.01), while PC38:6 and 40:6 did so in the older group (p < 0.05). In this study, elevated ceramides and depleted PCs were found in the plasma from 205 AD volunteers. Our findings also suggest that dysregulation in PC and ceramide metabolism could be occurring in different stages of AD progression. PMID:27911300

On the global existence of hairy black holes and solitons in anti-de Sitter Einstein-Yang-Mills theories with compact semisimple gauge groups

NASA Astrophysics Data System (ADS)

Baxter, J. Erik

2016-10-01

We investigate the existence of black hole and soliton solutions to four dimensional, anti-de Sitter (adS), Einstein-Yang-Mills theories with general semisimple connected and simply connected gauge groups, concentrating on the so-called regular case. We here generalise results for the asymptotically flat case, and compare our system with similar results from the well-researched adS {mathfrak {su}}(N) system. We find the analysis differs from the asymptotically flat case in some important ways: the biggest difference is that for Λ <0, solutions are much less constrained as r→ infty , making it possible to prove the existence of global solutions to the field equations in some neighbourhood of existing trivial solutions, and in the limit of |Λ |→ infty . In particular, we can identify non-trivial solutions where the gauge field functions have no zeroes, which in the {mathfrak {su}}(N) case proved important to stability.

Immunostimulatory activities of dendritic cells loaded with adenovirus vector carrying HBcAg/HBsAg

PubMed Central

Jia, Hongyu; Li, Chunling; Zhang, Yimin; Yu, Liang; Xiang, Dairong; Liu, Jun; Chen, Fengzhe; Han, Xiaochun

2015-01-01

Objective: This study is to investigate the immunostimulatory activities of dendritic cells (DCs) transfected with HBcAg and/or HBsAg recombinant adenovirus (rAd). Methods: DCs were transfected with rAd (DC/Ad-C+Ad-S, DC/Ad-C, and DC/Ad-S), or pulsed with HBcAg antigen (DC/HBcAg). Flow cytometry was used to detect the phenotype of DCs and the cytokine production of T lymphocytes. Mice were vaccinated with DCs transfected with rAd or pulsed with antigen, and DNA vaccine. Mixed lymphocyte reaction (MLR) was used to evaluate the T-cell stimulatory capacity, and HBcAg-specific cytotoxic T lymphocyte (CTL) activity was assessed. Results: Phenotypic analysis showed that DCs transfected with rAd or pulsed with HBcAg antigen exhibited mature phenotypes. MLR indicated no significant differences in stimulating T-cell proliferation between the DC/rAd and DC/HBcAg groups. When mixed with DCs, Th and Tc cells mainly secreted IFN-γ, indicating type I immune responses. In vaccinated mice, DCs transduced with rAd and pulsed with HBcAg induced significantly more IFN-γ secretion from Th cells, compared with DNA vaccine, indicating stronger Th1 response. Moreover, DCs transduced with rAd stimulated Tc cells to produce more IFN-γ, indicating stronger Tc1 response. In vaccinated mice, HBcAg-specific CTL activities were decreased in the following order: the DC/Ad-C+Ad-S, DC/Ad-C, DC/Ad-S, DC/HBcAg, and DNA vaccine groups. Conclusion: DCs transfected with rAd induce stronger Th1/Tc1 (type I) cell immune responses and specific CTL response than HBcAg-pulsed DCs or DNA vaccine. Our findings suggest that DCs transfected with rAd-C/rAd-S might provide an effective approach in the treatment of persistent hepatitis B virus infection. PMID:26064236

Structural Alteration of the Dorsal Visual Network in DLB Patients with Visual Hallucinations: A Cortical Thickness MRI Study

PubMed Central

Delli Pizzi, Stefano; Franciotti, Raffaella; Tartaro, Armando; Caulo, Massimo; Thomas, Astrid; Onofrj, Marco; Bonanni, Laura

2014-01-01

Visual hallucinations (VH) represent one of the core features in discriminating dementia with Lewy bodies (DLB) from Alzheimer’s Disease (AD). Previous studies reported that in DLB patients functional alterations of the parieto-occipital regions were correlated with the presence of VH. The aim of our study was to assess whether morphological changes in specific cortical regions of DLB could be related to the presence and severity of VH. We performed a cortical thickness analysis on magnetic resonance imaging data in a cohort including 18 DLB patients, 15 AD patients and 14 healthy control subjects. Relatively to DLB group, correlation analysis between the cortical thickness and the Neuropsychiatric Inventory (NPI) hallucination item scores was also performed. Cortical thickness was reduced bilaterally in DLB compared to controls in the pericalcarine and lingual gyri, cuneus, precuneus, superior parietal gyrus. Cortical thinning was found bilaterally in AD compared to controls in temporal cortex including the superior and middle temporal gyrus, part of inferior temporal cortex, temporal pole and insula. Inferior parietal and supramarginal gyri were also affected bilaterally in AD as compared to controls. The comparison between DLB and AD evidenced cortical thinning in DLB group in the right posterior regions including superior parietal gyrus, precuneus, cuneus, pericalcarine and lingual gyri. Furthermore, the correlation analysis between cortical thickness and NPI hallucination item scores showed that the structural alteration in the dorsal visual regions including superior parietal gyrus and precuneus closely correlated with the occurrence and severity of VH. We suggest that structural changes in key regions of the dorsal visual network may play a crucial role in the physiopathology of VH in DLB patients. PMID:24466177

Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease

PubMed Central

Swerdlow, Russell H.; Vidoni, Eric D.; Burns, Jeffrey M.

2011-01-01

Objective: Beyond age, having a family history is the most significant risk factor for Alzheimer disease (AD). This longitudinal brain imaging study examines whether there are differential patterns of regional gray matter atrophy in cognitively healthy elderly subjects with (FH+) and without (FH−) a family history of late-onset AD. Methods: As part of the KU Brain Aging Project, cognitively intact individuals with a maternal history (FHm, n = 11), paternal history (FHp, n = 10), or no parental history of AD (FH−, n = 32) similar in age, gender, education, and Mini-Mental State Examination (MMSE) score received MRI at baseline and 2-year follow-up. A custom voxel-based morphometry processing stream was used to examine regional differences in atrophy between FH groups, controlling for age, gender, and APOE ϵ4 (APOE4) status. We also analyzed APOE4-related atrophy. Results: Cognitively normal FH+ individuals had significantly increased whole-brain gray matter atrophy and CSF expansion compared to FH−. When FH+ groups were split, only FHm was associated with longitudinal measures of brain change. Moreover, our voxel-based analysis revealed that FHm subjects had significantly greater atrophy in the precuneus and parahippocampus/hippocampus regions compared to FH− and FHp subjects, independent of APOE4 status, gender, and age. Individuals with an ε4 allele had more regional atrophy in the frontal cortex compared to ε4 noncarriers. Conclusions: We conclude that FHm individuals without dementia have progressive gray matter volume reductions in select AD-vulnerable brain regions, specifically the precuneus and parahippocampal gyrus. These data complement and extend reports of regional cerebral metabolic differences and increases in amyloid-β burden in FHm subjects, which may be related to a higher risk for developing AD. PMID:21357834

Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats.

PubMed

Atta, Hussein; El-Rehany, Mahmoud; Roeb, Elke; Abdel-Ghany, Hend; Ramzy, Maggie; Gaber, Shereen

2016-02-01

Postoperative peritoneal adhesions continue to be a major source of morbidity and occasional mortality. Studies have shown that matrix metalloproteinase-9 (MMP-9) levels are decreased postoperatively which may limits matrix degradation and participate in the development of peritoneal adhesions. In this proof-of-principle study, we evaluated the effect of gene therapy with catalytically inactive mutant MMP-9 on postoperative peritoneal adhesions in rats. Adenovirus encoding mutant MMP-9 (Ad-mMMP-9) or saline was instilled in the peritoneal cavity after cecal and parietal peritoneal injury in rats. Expression of mutant MMP-9 transcript was verified by sequencing. Adenovirus E4 gene expression, adhesion scores, MMP-9, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) expression were evaluated at sacrifice one week after treatment. Both mutant MMP-9 transcripts and adenovirus E4 gene were expressed in Ad-mMMP-9 treated adhesions. Adhesions severity decreased significantly (p = 0.036) in the Ad-mMMP-9-treated compared with saline-treated adhesions. Expression of MMP-9 mRNA and protein were elevated (p = 0.001 and p = 0.029, respectively) in the Ad-mMMP-9-treated adhesions compared with saline-treated adhesions. While tPA levels were increased (p = 0.02) in Ad-mMMP-9 treated adhesions compared with saline-treated adhesions, TGF-β1 and PAI-1 levels were decreased (p = 0.017 and p = 0.042, respectively). No difference in mortality were found between groups (p = 0.64). Mutant MMP-9 gene therapy effectively transduced peritoneal adhesions resulting in reduction of severity of primary peritoneal adhesions. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Effects of bilingualism on the age of onset and progression of MCI and AD: evidence from executive function tests.

PubMed

Bialystok, Ellen; Craik, Fergus I M; Binns, Malcolm A; Ossher, Lynn; Freedman, Morris

2014-03-01

Previous articles have reported that bilingualism is associated with a substantial delay in the onset of both Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). The present study reports results from 74 MCI patients and 75 AD patients; approximately half of the patients in each group were bilingual. All patients were interviewed to obtain details of their language use, onset of their condition, and lifestyle habits. Patients performed three executive function (EF) tests from the D-KEFS battery (Trails, Color-Word Interference, Verbal Fluency) on 3 occasions over a period of approximately 1 year. Results replicated the finding that bilingual patients are several years older than comparable monolinguals at both age of symptom onset and date of first clinic visit. This result could not be attributed to language group differences in such lifestyle variables as diet, smoking, alcohol consumption, physical activity, or social activity. On the first testing occasion, performance on the EF tasks was generally comparable between the language groups, contesting arguments that bilinguals wait longer before attending the clinic. Finally, EF performance tended to decline over the 3 sessions, but no differences were found between monolinguals and bilinguals in the rate of decline. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Obsessive-compulsive disorders and anxiety disorders: A comparison of personality and emotionality patterns.

PubMed

Pelissolo, Antoine; Moukheiber, Albert; Mallet, Luc

2015-10-30

Even though obsessive-compulsive disorders (OCD) and anxiety disorders (AD) have been separated in the taxonomy adopted by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, many issues remain concerning the physiopathological similarities and differences between those categories. Our objective was therefore to explore and compare their personality and emotional features, with the assumption that the distinction of two independent spectrums should imply the existence of two partially distinct temperamental profiles. We used the Temperament and Character Inventory (TCI-R) and the Positive and Negative Emotionality (PNE) scale to compare two groups of patients with OCD (n=227) or AD (n=827). The latter group included patients with social anxiety disorder, panic disorder, agoraphobia, and generalized anxiety disorder. Most temperament, character and emotionality measures showed no significant differences between both groups. In the personality measures results, only the self-directedness score (TCI-R) was significantly lower in OCD patients but this difference was not significant when the comparison was adjusted for the depressive scale score and age. Only lower PNE positive affects scores were obtained in OCD patients in the adjusted comparisons. These findings suggest that OCD and AD are not really distinguishable from the point of view of associated personality traits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Serum macrophage-derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis

PubMed Central

KAKINUMA, T; NAKAMURA, K; WAKUGAWA, M; MITSUI, H; TADA, Y; SAEKI, H; TORII, H; KOMINE, M; ASAHINA, A; TAMAKI, K

2002-01-01

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, macrophage-derived chemokine (MDC)/CCL22, a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)-expressing cells, in addition to thymus and activation-regulated chemokine (TARC). We have previously reported that serum TARC levels correlate with the severity of AD. In this report, we investigated the participation of MDC in AD. First, we measured serum MDC levels in 45 patients with AD, 25 patients with psoriasis vulgaris and 25 healthy controls. Serum MDC levels in AD patients were significantly higher than those in healthy controls and psoriasis patients. Furthermore, the increases in serum MDC levels in AD patients were greater in the severely affected group than in the moderate or mild groups. We compared serum MDC levels in 11 AD patients, before and after treatment, and observed a significant decrease after treatment. Moreover, the serum MDC levels significantly correlated with the Scoring AD (SCORAD) index, serum soluble (s) E-selectin levels, serum soluble interleukin-2 receptor (sIL-2R) levels, serum TARC levels and eosinophil numbers in peripheral blood. Our study strongly suggests that serum MDC levels have a notable correlation with disease activity and that MDC, as well as the CC chemokine TARC, may be involved in the pathogenesis of AD. PMID:11876749

ApoE -491A/T promoter polymorphism is not an independent risk factor, but associated with the epsilon4 allele in Hungarian Alzheimer's dementia population.

PubMed

Juhász, Anna; Palotás, András; Janka, Zoltán; Rimanóczy, Agnes; Palotás, Miklós; Bódi, Nikoletta; Boda, Krisztina; Zana, Marianna; Vincze, Gábor; Kálmán, János

2005-05-01

Apolipoprotein E gene (Apo(epsilon)) has three common alleles (epsilon2, epsilon3, and epsilon4), of which epsilon4 has been shown to be associated with an increased risk for Alzheimer's disease (AD). Possible additional genetic factors, like the -491A variant of ApoE promoter may modify the development of AD, independently of the ApoE allele status. The objective of this study was to investigate whether A/T allelic polymorphism at site-491 of the ApoE promoter is associated with AD in a Hungarian population. The genomic DNA isolated from peripheral blood lymphocytes of 52 late-onset AD and 53 control individuals was used as a template for the two examined polymorphisms and PCR assay was applied. The epsilon4 allele was significantly over-represented in the AD group (28%) as compared with the control population (7%). No significant differences have been found between the control and the AD populations regarding the occurrence of the promoter A allele frequencies (control: 77%, AD: 70%). However, the AA genotype was more frequent in the AD group (48%) than in the control (10%) when the presence of epsilon4 allele was also considered. It is unlikely therefore that the -491A variant of the ApoE promoter gene is an independent risk factor in the Hungarian AD population, but a linkage disequilibrium exists between the two examined mutations.

Identifying psychological responses of stigmatized groups to referendums.

PubMed

Flores, Andrew R; Hatzenbuehler, Mark L; Gates, Gary J

2018-04-10

Public votes and referendums on the rights of marginalized communities are utilized in 27 states and occur with some regularity. However, research has only recently begun to examine the psychological consequences of these voter referendums for members of stigmatized groups, and a number of important questions remain regarding the internal validity and generalizability of the existing evidence. The current study advances this literature by combining survey data from a large probability-based sample conducted in 2012 [lesbian, gay, bisexual, and/or transgender (LGBT) n = 939; non-LGBT n = 31,067] with media market ad-buy data in states where marriage equality was on the ballot. Television media markets cross state boundaries, ensuring that there was an unintended group of people in 12 states who were exposed to the same-sex marriage discourse but who did not live in states with the voter referendum ("media market spillovers"). We take advantage of this unique data structure by comparing LGBT people in the media market spillovers to those residing in the same state but in nonspillover markets with no ad exposure. LGBT people are emotionally affected by these campaigns, and non-LGBT people are unaffected. LGBT people in markets with a cumulative total of 400 ads have a 34.0% greater probability of reporting stress than LGBT people not exposed to ads. Additionally, while the negative ads evoked sadness, positive ads evoked enjoyment and happiness. Thus, public votes on minority rights represent both a source of minority stress and resilience.

The CERAD Neuropsychologic Battery Total Score and the progression of Alzheimer disease.

PubMed

Rossetti, Heidi C; Munro Cullum, C; Hynan, Linda S; Lacritz, Laura H

2010-01-01

To establish the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychologic battery as a valid measure of cognitive progression in Alzheimer disease (AD) by deriving annualized CERAD Total Change Scores and corresponding confidence intervals in AD and controls from which to define clinically meaningful change. Subjects included 383 normal control (NC) and 655 AD subjects with serial data from the CERAD registry database. Annualized CERAD Total Change Scores were derived and Reliable Change Indexes (RCIs) calculated to establish statistically reliable change values. CERAD Change Scores were compared with annualized change scores from the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR) Sum of Boxes, and Blessed Dementia Rating Scale (BDRS). For the CERAD Total Score, the AD sample showed significantly greater decline than the NC sample over the 4-year interval, with AD subjects declining an average of 22.2 points compared with the NCs' improving an average 2.8 points from baseline to last visit [Group x Time interaction [F(4,1031)=246.08, P<0.001)]. By Visit 3, the majority of AD subjects (65.2%) showed a degree of cognitive decline that fell outside the RCI. CERAD Change Scores significantly correlated (P<0.001) with MMSE (r=-0.66), CDR (r=-0.42), and BDRS (r=-0.38) change scores. Results support the utility of the CERAD Total Score as a measure of AD progression and provide comparative data for annualized change in CERAD Total Score and other summary measures.

Voice Onset Time Production in Speakers with Alzheimer's Disease

ERIC Educational Resources Information Center

Baker, Julie; Ryalls, Jack; Brice, Alejandro; Whiteside, Janet

2007-01-01

In the present study, voice onset time (VOT) measurements were compared between a group of individuals with moderate Alzheimer's disease (AD) and a group of healthy age- and gender-matched peers. Participants read a list of consonant-vowel-consonant (CVC) words, which included the six stop consonants. The VOT measurements were made from…

Sense of coherence, depression, and anger among adults with atopic dermatitis.

PubMed

Takaki, Hiroko; Ishii, Yasutomo

2013-01-01

The prevalence of atopic disease (AD) in adults has significantly increased in industrialized countries. Psychological traits and lack of skills to cope with stress could be maintaining factors of AD. The first aim of the present study was to compare sense of coherence (SOC), depression, and anger among adult patients with AD, adults with remission from AD, and adults without AD. The second aim was to explore whether depression and anger have significant impacts on SOC. A cross-sectional survey was carried out from May to September of 2007. In total, 43 adult patients with AD, 32 adults with remission from AD, and 63 adults without AD participated. A one-way analysis of variance showed that adult patients with AD have significantly higher levels of depression than adults with remission from AD and adults without AD. Furthermore, structural equation modeling indicated a significant impact of depression on SOC across the three groups, along with a significant impact of anger suppression on depression, particularly in adult patients with AD. The findings of this study suggest that psychological traits have a negative impact on skills for coping with stress, and that this relationship might be a contributory factor for maintenance of AD.

Comparison of odor identification among amnestic and non-amnestic mild cognitive impairment, subjective cognitive decline, and early Alzheimer's dementia.

PubMed

Park, Sung-Jin; Lee, Jee-Eun; Lee, Kwang-Soo; Kim, Joong-Seok

2018-03-01

Olfactory impairment might be an important clinical marker and predictor of Alzheimer's disease (AD). In the present study, we aimed to compare the degree of olfactory identification impairment in each mild cognitive impairment (MCI) subtype, subjective memory impairment, and early AD dementia and assessed the relationship between olfactory identification and cognitive performance. We consecutively included 50 patients with amnestic MCI, 28 patients with non-amnestic MCI, 20 patients with mild AD, and 17 patients with subjective memory impairment (SMI). All patients underwent clinical and neuropsychological assessments. A multiple choice olfactory identification cross-cultural smell identification test was also utilized. Controlling for age and gender, olfactory impairment was significantly more severe in patients with AD and amnestic MCI compared with the results from the non-amnestic MCI and SMI groups. Higher scores on MMSE, verbal and non-verbal memory, and frontal executive function tests were significantly related to olfactory identification ability. In conclusion, olfactory identification is impaired in amnestic MCI and AD. These findings are consistent with previous studies. In amnestic MCI patients, this dysfunction is considered to be caused by underlying AD pathology.

Effects of phentermine and phenformin on biomarkers of aging in rats.

PubMed

Anisimov, Vladimir N; Ukraintseva, Svetlana V; Anikin, Ivan V; Popovich, Irina G; Zabezhinski, Mark A; Bertsein, Lev M; Arutjunyan, Alexander V; Ingram, Donald K; Lane, Mark A; Roth, George S

2005-01-01

Caloric restriction (CR) is the only treatment known to substantially prolong both average and maximal life span in experimental animals. Interventions that mimic certain effects of CR could be potential anti-aging treatments in humans. Drugs which reduce appetite (anorexiants) represent one class of candidate treatments. Agents that reduce the glucose utilization by the organism could also represent another class of candidate CR mimetics. In our study, we addressed the following questions: (1) Does treatment with an anorexiant reduce caloric intake and body weight of experimental animals comparable to that caused by CR? (2) Does treatment with an antidiabetic agent influence caloric intake and body weight? (3) Does treatment with any of these drugs affect metabolic parameters of an organism in the way similar to that observed with CR? One hundred and twenty 6-month-old female Wistar-derived LIO rats were randomly subdivided into four groups and exposed to: (1) ad libitum feeding with placebo (controls); (2) the antidiabetic drug phenformin (2 mg/kg); (3) the anorectic drug phentermine (1 mg/kg), and (4) the same amount of food as the group with the least food intake during the previous week (pair-fed controls). Food and water intake, body weight, and rectal temperature were measured weekly during 16 weeks. At the end of the 16th week of the experiment, serum levels of glucose, total beta-lipoprotein and pre-beta-lipoprotein fractions, cholesterol, triglycerides, insulin, total triiodothyronine, and free thyroxine were estimated. The contents of diene conjugates and Schiff's bases, total antioxidant activity, the activities of Cu/Zn superoxide dismutase, glutathione S-transferase, and glutathione peroxidase, and the generation of reactive oxygen species (ROS) were studied in brain and liver homogenates and in the serum. The controls exposed to pair feeding had a significantly reduced food consumption (about 20%) as compared with the ad libitum fed controls and thus exhibited a moderate CR. Treatment with phentermine reduced the caloric intake by about 12% as compared with the ad libitum fed controls. Body weight and water intake in this group were only slightly decreased (by about 2 and 5%, respectively) as compared with the controls. The mean rectal temperature in the phentermine group (38 degrees C) was significantly higher than in the ad libitum fed (37.8 degrees C) and pair-fed (37.6 degrees C) controls. Treatment with phentermine also resulted in significantly reduced ROS levels in all tissues studied, while the highest ROS production was found in ad libitum (blood serum) and pair-fed (brain) controls. Treatment with phenformin did not significantly influence food and water consumption, body weight, and temperature when compared with the ad libitum fed controls. Rats treated with this antidiabetic drug showed intermediate values of ROS generation. Differences among the groups in total antioxidant activity were not obvious. Treatment with phentermine reduces caloric intake slightly less than is commonly observed in CR studies. CR due to forcibly reduced feeding and CR due to substance-suppressed appetite appear to act through different metabolic mechanisms and thus may affect aging and longevity in different ways. Copyright (c) 2005 S. Karger AG, Basel

The Effect of Hearing Loss on Novel Word Learning in Infant- and Adult-Directed Speech.

PubMed

Robertson, V Susie; von Hapsburg, Deborah; Hay, Jessica S

Relatively little is known about how young children with hearing impairment (HI) learn novel words in infant- and adult-directed speech (ADS). Infant-directed speech (IDS) supports word learning in typically developing infants relative to ADS. This study examined how children with normal hearing (NH) and children with HI learn novel words in IDS and ADS. It was predicted that IDS would support novel word learning in both groups of children. In addition, children with HI were expected to be less proficient word learners as compared with their NH peers. A looking-while-listening paradigm was used to measure novel word learning in 16 children with sensorineural HI (age range 23.2 to 42.1 months) who wore either bilateral hearing aids (n = 10) or bilateral cochlear implants (n = 6) and 16 children with NH (age range 23.1 to 42.1 months) who were matched for gender, chronological age, and maternal education level. Two measures of word learning were assessed (accuracy and reaction time). Each child participated in two experiments approximately 1 week apart, one in IDS and one in ADS. Both groups successfully learned the novel words in both speech type conditions, as evidenced by children looking at the correct picture significantly above chance. As a group, children with NH outperformed children with HI in the novel word learning task; however, there were no significant differences between performance on IDS versus ADS. More fine-grained time course analyses revealed that children with HI, and particularly children who use hearing aids, had more difficulty learning novel words in ADS, compared with children with NH. The pattern of results observed in the children with HI suggests that they may need extended support from clinicians and caregivers, through the use of IDS, during novel word learning. Future research should continue to focus on understanding the factors (e.g., device type and use, age of intervention, audibility, acoustic characteristics of input, etc.) that may influence word learning in children with HI in both IDS and ADS.

Cardiopulmonary exercise testing is well tolerated in people with Alzheimer-related cognitive impairment.

PubMed

Billinger, Sandra A; Vidoni, Eric D; Greer, Colby S; Graves, Rasinio S; Mattlage, Anna E; Burns, Jeffrey M

2014-09-01

To retrospectively assess whether cardiopulmonary exercise testing would be well tolerated in individuals with Alzheimer disease (AD) compared with a nondemented peer group. We retrospectively reviewed 575 cardiopulmonary exercise tests (CPETs) in individuals with and without cognitive impairment caused by AD. University medical center. Exercise tests (N=575) were reviewed for nondemented individuals (n=340) and those with AD-related cognitive impairment (n=235). Not applicable. The main outcome measure for this study was reporting the reason for CPET termination. The hypothesis reported was formulated after data collection. We found that in cognitively impaired individuals, CPETs were terminated because of fall risk more often, but that overall test termination was infrequent-5.5% versus 2.1% (P=.04) in peers without cognitive impairment. We recorded 6 cardiovascular and 7 fall risk events in those with AD, compared with 7 cardiovascular and 0 fall risk events in those without cognitive impairment. Our findings support using CPETs to assess peak oxygen consumption in older adults with cognitive impairment caused by AD. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer disease.

PubMed

Brown, Patrick J; Devanand, D P; Liu, Xinhua; Caccappolo, Elise

2011-06-01

The original mild cognitive impairment (MCI) criteria exclude substantial functional deficits, but recent reports suggest otherwise. Identifying the extent, severity, type, and correlates of functional deficits that occur in MCI and mild Alzheimer disease (AD) can aid in early detection of incipient dementia and can identify potential mechanistic pathways to disrupted instrumental activities of daily living (IADLs). To examine the number, type, and severity of functional impairments and to identify the clinical characteristics associated with functional impairment across patients with amnestic MCI (aMCI) and those with mild AD. Study using baseline data from the Alzheimer's Disease Neuroimaging Initiative. Multiple research sites in the United States and Canada. Patients Samples included 229 control individuals, 394 patients with aMCI, and 193 patients with AD. The 10-item Pfeffer Functional Activities Questionnaire (FAQ) assessed function. Informant-reported FAQ deficits were common in patients with aMCI (72.3%) and AD (97.4%) but were rarely self-reported by controls (7.9%). The average severity per FAQ deficit did not differ between patients with aMCI and controls; both were less impaired than patients with AD (P < .001). Two FAQ items (remembering appointments, family occasions, holidays, and medications and assembling tax records, business affairs, or other papers) were specific (specificity estimate, 0.95) in differentiating the control group from the combined aMCI and AD groups (only 34.0% of patients with aMCI and 3.6% of patients with AD had no difficulty with these 2 items). The severity of FAQ deficits in the combined aMCI and AD group was associated with worse Trail Making Test, part A scores and smaller hippocampal volumes (P < .001 for both). Within the aMCI group, functionally intact individuals had greater hippocampal volumes and better Auditory Verbal Learning Test 30-minute delay and Trail Making Test, part A (P < .001 for each) scores compared with individuals with moderate or severe FAQ deficits. Patients with a high number of deficits were more likely to express the apolipoprotein ε4 allele (63.8%) compared with patients with no (46.8%) or few (48.4%) functional deficits. Mild IADL deficits are common in individuals with aMCI and should be incorporated into MCI criteria. Two IADLs--remembering appointments, family occasions, holidays, and medications and assembling tax records, business affairs, or other papers--appear to be characteristic of clinically significant cognitive impairment. In patients with aMCI, impairment in memory and processing speed and greater medial temporal atrophy were associated with greater IADL deficits.

A comparative study of the impairment of quality of life in Czech children with atopic dermatitis of different age groups and their families.

PubMed

Jiráková, Anna; Vojáčková, Naděžda; Göpfertová, Dana; Hercogová, Jana

2012-06-01

Atopic dermatitis (AD) still remains one of the most common childhood inflammatory skin diseases. As a chronic disease, it can have a physical and psychological effect on social functioning of the affected child as well as their family. The objective of this study was to evaluate the quality of life of children with AD of different age groups and their families. A total of 203 children with a diagnosis of AD from newborn to 18 years of age and 202 of their parents took part in our study (as one parent did not return the questionnaire). All participants, according to their age, completed the following questionnaires: Infants' Dermatitis Quality of Life Index (IDQOL); Children's Dermatology Life Quality Index (CDLQI) - text and cartoon version; and Dermatitis Family Impact questionnaire (DFI). The mean total IDQOL score in our study was 8.18 (SD = 5.84, n = 120). The mean total CDLQI scores in the groups of children from 7 to 13 and from 14 to 18 years were 8.58 (SD = 4.98, n = 48) and 9.89 (SD = 5.26, n = 35). There was also a proven influence of the child's AD on the quality of life of his parents with the mean score: 7.98 (SD = 6.41, n = 202). The study demonstrated and confirmed that AD significantly impairs the children's quality of life in all age groups and also quality of life of their families. Such data give us patient-oriented information that is of great importance for understanding the situation of individuals with AD and its influence on members of their family. © 2012 The International Society of Dermatology.

Disorders of "taste cognition" are associated with insular involvement in patients with Alzheimer's disease and vascular dementia: "memory of food is impaired in dementia and responsible for poor diet".

PubMed

Suto, Teiko; Meguro, Kenichi; Nakatsuka, Masahiro; Kato, Yuriko; Tezuka, Kimihiro; Yamaguchi, Satoshi; Tashiro, Manabu

2014-07-01

In dementia patients, dietary intake problems may occur despite the absence of swallowing problems. We investigated cognitive functions on food and taste in Alzheimer's disease (AD) and vascular dementia (VaD) patients. Participants included 15 healthy controls (HC), 30 AD and 20 VaD patients. Food Cognition Test: Replicas of three popular foods in Japan with no odors were presented visually to each participant, with the instruction to respond with the name of each food. Replicas of food materials were subsequently presented to ask whether they were included in these foods. Taste Cognition Test: Replicas of 12 kinds of foods were presented to describe their expected tastes. The AD/VaD groups exhibited significantly lower scores on Food/Taste Cognition Tests compared with the HC group. These scores correlated inversely with Mini-Mental State Examination (MMSE) scores in the AD group. Decreased dietary intake was observed in 12 of the 50 patients; 8 of the 12 exhibited decreased Taste Cognition Test scores, higher than that of the normal-intake patients. There was no difference in the filter paper taste disc test between HC/AD/VaD groups. To test the hypothesis that the insula is associated with taste cognition, two MMSE-matched AD subgroups (n = 10 vs. 10) underwent positron emission tomography. Glucose metabolism in the right insula was lower in the low taste cognition subgroup. The VaD patients with insular lesions exhibited impaired Taste Cognition Test findings. It is important to consider the cognitive aspect of dietary intake when we care for dementia patients.

Regional functional synchronizations in dementia with Lewy bodies and Alzheimer's disease.

PubMed

Peraza, Luis R; Colloby, Sean J; Deboys, Liam; O'Brien, John T; Kaiser, Marcus; Taylor, John-Paul

2016-07-01

Dementia with Lewy bodies (DLB) is a common cause of dementia in the elderly population after Alzheimer's disease (AD), and at early stages differential diagnosis between DLB and AD might be difficult due to their symptomatic overlap, e.g. cognitive and memory impairments. We aimed to investigate functional brain differences between both diseases in patients recently diagnosed. We investigated regional functional synchronizations using regional homogeneity (ReHo) in patients clinically diagnosed with DLB (n = 19) and AD (n = 18), and for comparisons we also included healthy controls (HC, n = 16). Patient groups were matched by age, education, and by the level of cognitive impairment (MMSE p-value = 0.36). Additionally, correlations between ReHo values and clinical scores were investigated. The DLB group showed lower ReHo in sensory-motor cortices and higher ReHo in left middle temporal gyrus when compared with HCs (p-value < 0.001 uncorrected). The AD group demonstrated lower ReHo in the cerebellum and higher ReHo in the left/right lingual gyri, precuneus cortex, and other occipital and parietal regions (p-value < 0.001 uncorrected). Our results agree with previous ReHo investigations in Parkinson's disease (PD), suggesting that functional alterations in motor-related regions might be a characteristic of the Lewy body disease spectrum. However, our results in AD contradict previously reported findings for this disease and ReHo, which we speculate are a reflection of compensatory brain responses at early disease stages. ReHo differences between patient groups were at regions related to the default mode and sensory-motor resting state networks which might reflect the aetiological divergences in the underlying disease processes between AD and DLB.

Differential Risk of Incident Alzheimer's Disease Dementia in Stable Versus Unstable Patterns of Subjective Cognitive Decline.

PubMed

Wolfsgruber, Steffen; Kleineidam, Luca; Wagner, Michael; Mösch, Edelgard; Bickel, Horst; Lϋhmann, Dagmar; Ernst, Annette; Wiese, Birgitt; Steinmann, Susanne; König, Hans-Helmut; Brettschneider, Christian; Luck, Tobias; Stein, Janine; Weyerer, Siegfried; Werle, Jochen; Pentzek, Michael; Fuchs, Angela; Maier, Wolfgang; Scherer, Martin; Riedel-Heller, Steffi G; Jessen, Frank

2016-10-04

It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimer's disease (AD) dementia. We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study. We assessed SCD with/without associated worries both at baseline and first follow-up 18 months later. Participants were then classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n = 613), (b) inconsistent SCD (with SCD reported only at baseline or at follow-up 1, n = 637), (c) consistent SCD but without/or with inconsistent worries (n = 610) or (d) consistent SCD with worries (n = 130). We estimated incident AD dementia risk over up to 6 years for each group with Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status, and depression. Compared to CO, inconsistent SCD was not associated with increased risk of incident AD dementia. In contrast, risk was doubled in the group of consistent SCD without/ with inconsistent worries, and almost 4-fold in the group of consistent SCD with worries. These results could be replicated when using follow-up 1 to follow-up 2 response patterns for group definition. These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.

Optimal load for the peak power and maximal strength of the upper body in Brazilian Jiu-Jitsu athletes.

PubMed

da Silva, Bruno Victor C; Simim, Mário A de Moura; Marocolo, Moacir; Franchini, Emerson; da Mota, Gustavo R

2015-06-01

We determined the optimal load for the peak power output (PPO) during the bench press throw (BPT) in Brazilian Jiu-Jitsu (BJJ) athletes and compared the PPO and maximal strength between advanced (AD) and nonadvanced (NA) athletes. Twenty-eight BJJ athletes (24.8 ± 5.7 years) performed the BPT at loads of 30, 40, 50, and 60% of their 1 repetition maximum (RM) in a randomized order (5-minute rest between BPTs). The PPO was determined by measuring the barbell displacement by an accelerometer (Myotest). The absolute (F = 7.25; p < 0.001; effect size [ES] = 0.21) and relative intensities were different (F = 7.11; p < 0.001; ES = 0.21) between the AD and NA. There was also a group and intensity interaction effect (F = 2.79; p = 0.046; ES = 0.10), but the differences were centered around the AD group, which achieved higher values using 40% (p = 0.001) and 50% of the 1RM (p < 0.001) than the PPO with 60% of 1RM. The AD athletes presented with higher 1RM than NA (p ≤ 0.05; ES = 1.0), but there was no difference (p > 0.05) in the PPO (30-60% 1RM). A polynomial adjustment indicated that the optimal load was ∼42% of 1RM for all groups and subgroups (R from 0.82 to 0.99). Our results suggest that there can be (1RM) differences between AD and NA BJJ athletes; however, there is no difference in the muscle power between the AD and NA groups. Additionally, ∼42% of 1RM seems to be the optimal load for developing maximal power using the BPT for the BJJ athletes.

Effect of vanadium on colonic aberrant crypt foci induced in rats by 1,2 Dimethyl hydrazine

PubMed Central

Kanna, P Suresh; Mahendrakumar, CB; Chakraborty, T; Hemalatha, P; Banerjee, Pratik; Chatterjee, M

2003-01-01

AIM: To investigate the chemo preventive effects of vanadium on rat colorectal carcinogenesis induced by 1,2-dimethylhydrazine (DMH). METHODS: Male Sprague-Dawley Rats were randomly divided into four groups. Rats in Group A received saline vehicle alone for 16 weeks. Rats in Group B were given DMH injection once a week intraperitoneally for 16 weeks; rats in Group C, with the same DMH treatment as in the Group B, but received 0.5-ppm vanadium in the form ammonium monovanadate ad libitum in drinking water. Rats in the Group D received vanadium alone as in the Group C without DMH injection. RESULTS: Aberrant crypt foci (ACF) were formed in animals in DMH-treated groups at the end of week 16. Compared to DMH group, vanadium treated group had less ACF (P < 0.001). At the end of week 32, all rats in DMH group developed large intestinal tumors. Rats treated with vanadium contained significantly few colonic adenomas and carcinomas (P < 0.05) compared to rats administered DMH only. In addition, a significant reduction (P < 0.05) in colon tumor burden (sum of tumor sizes per animal) was also evident in animals of Group C when compared to those in rats of carcinogen control Group B. The results also showed that vanadium significantly lowered PCNA index in ACF (P < 0.005). Furthermore, vanadium supplementation also elevated liver GST and Cyt P-450 activities (P < 0.001 and P < 0.02, respectively). CONCLUSION: Vanadium in the form of ammonium monovanadate supplemented in drinking water ad libitum has been found to be highly effective in reducing tumor incidence and preneoplastic foci on DMH-induced colorectal carcinogenesis. These findings suggest that vanadium administration can suppress colon carcinogenesis in rats. PMID:12717849

An Island of Stability: Art Images and Natural Scenes - but Not Natural Faces - Show Consistent Esthetic Response in Alzheimer's-Related Dementia.

PubMed

Graham, Daniel J; Stockinger, Simone; Leder, Helmut

2013-01-01

Alzheimer's disease (AD) causes severe impairments in cognitive function but there is evidence that aspects of esthetic perception are somewhat spared, at least in early stages of the disease. People with early Alzheimer's-related dementia have been found to show similar degrees of stability over time in esthetic judgment of paintings compared to controls, despite poor explicit memory for the images. Here we expand on this line of inquiry to investigate the types of perceptual judgments involved, and to test whether people in later stages of the disease also show evidence of preserved esthetic judgment. Our results confirm that, compared to healthy controls, there is similar esthetic stability in early stage AD in the absence of explicit memory, and we report here that people with later stages of the disease also show similar stability compared to controls. However, while we find that stability for portrait paintings, landscape paintings, and landscape photographs is not different compared to control group performance, stability for face photographs - which were matched for identity with the portrait paintings - was significantly impaired in the AD group. We suggest that partially spared face-processing systems interfere with esthetic processing of natural faces in ways that are not found for artistic images and landscape photographs. Thus, our work provides a novel form of evidence regarding face-processing in healthy and diseased aging. Our work also gives insights into general theories of esthetics, since people with AD are not encumbered by many of the semantic and emotional factors that otherwise color esthetic judgment. We conclude that, for people with AD, basic esthetic judgment of artistic images represents an "island of stability" in a condition that in most other respects causes profound cognitive disruption. As such, esthetic response could be a promising route to future therapies.

An Island of Stability: Art Images and Natural Scenes – but Not Natural Faces – Show Consistent Esthetic Response in Alzheimer’s-Related Dementia

PubMed Central

Graham, Daniel J.; Stockinger, Simone; Leder, Helmut

2013-01-01

Alzheimer’s disease (AD) causes severe impairments in cognitive function but there is evidence that aspects of esthetic perception are somewhat spared, at least in early stages of the disease. People with early Alzheimer’s-related dementia have been found to show similar degrees of stability over time in esthetic judgment of paintings compared to controls, despite poor explicit memory for the images. Here we expand on this line of inquiry to investigate the types of perceptual judgments involved, and to test whether people in later stages of the disease also show evidence of preserved esthetic judgment. Our results confirm that, compared to healthy controls, there is similar esthetic stability in early stage AD in the absence of explicit memory, and we report here that people with later stages of the disease also show similar stability compared to controls. However, while we find that stability for portrait paintings, landscape paintings, and landscape photographs is not different compared to control group performance, stability for face photographs – which were matched for identity with the portrait paintings – was significantly impaired in the AD group. We suggest that partially spared face-processing systems interfere with esthetic processing of natural faces in ways that are not found for artistic images and landscape photographs. Thus, our work provides a novel form of evidence regarding face-processing in healthy and diseased aging. Our work also gives insights into general theories of esthetics, since people with AD are not encumbered by many of the semantic and emotional factors that otherwise color esthetic judgment. We conclude that, for people with AD, basic esthetic judgment of artistic images represents an “island of stability” in a condition that in most other respects causes profound cognitive disruption. As such, esthetic response could be a promising route to future therapies. PMID:23471005

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.

PubMed

Kennedy, Stephen B; Bolay, Fatorma; Kieh, Mark; Grandits, Greg; Badio, Moses; Ballou, Ripley; Eckes, Risa; Feinberg, Mark; Follmann, Dean; Grund, Birgit; Gupta, Swati; Hensley, Lisa; Higgs, Elizabeth; Janosko, Krisztina; Johnson, Melvin; Kateh, Francis; Logue, James; Marchand, Jonathan; Monath, Thomas; Nason, Martha; Nyenswah, Tolbert; Roman, François; Stavale, Eric; Wolfson, Julian; Neaton, James D; Lane, H Clifford

2017-10-12

The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSV∆G-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSV∆G-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSV∆G-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407 .).

[Different patterns of brain activation between patients of Alzheimer's disease with and without depression: a functional MRI study during emotion Stroop task].

PubMed

Wang, Hai-tao; Jia, Jian-ping

2007-04-03

To examine whether emotional factor influences the depression onset in Alzheimer's disease (AD). Twenty mild AD patients conforming to the of DSM-IV criteria with a clinical dementia rating score of 1.0 were divided into 2 groups: 11 patients without depression (AD group), and 9 patients with depression confirming to the National Institute of Mental Health-dAD criteria with a Cornell scale for depression in dementia score>12 (dAD group), without significant differences in age, gender, educational level, onset duration, and MMSE scores between these 2 groups. Ten age-and gender ratio-matched healthy elderly subjects were used as controls. Emotion Stroop task was performed to these 3 groups: emotion Stroop task images were presented with colored positive or negative emotion words (such as HAPPY or SUICIDE, etc.) at the left part of the image to induce emotional responses and with pure color at the right part of the image. The subjects were asked to press the right button when the ink color of the emotion word was congruent with the color at the right part, and press the left button when the ink color of the word was not congruent with the color at the right part. Neutral words were used in the test of general word task. The reaction time, false ratio, and missing ratio were recorded. Functional MRI (fMRI) was conducted. The behavioral data were analyzed with SPSS 11.0 software and the fMRI data were analyzed with SPM2 software. The emotion Stroop task showed that the reaction time of the normal control group was 848 ms+/-320 ms, significantly shorter than those of the dAD and AD groups (1528 ms+/-302 ms and 1173 ms+/-237 ms respectively, both P<0.01), and the reaction time of the AD group was significantly shorter than that of the dAD group too (P=0.04). The false ratio of the normal control group was 0.5%, significantly lower than those of the AD and dAD groups (7.6% and 9.7% respectively, both P<0.01), and there was not a significant difference between the latter 2 groups (P=0.22). The missing ratio of the normal control group was 0, significantly lower than those of the AD and dAD groups (3.1% and 2.5% respectively, both P<0.01), and there was not a significant difference between the latter 2 groups (P=0.29). The fMRI results showed that the bilateral amygdala, left parietal lobe, and left prefrontal lobe were activated in the normal control group, bilateral parietal lobe were activated in the AD group; and bilateral prefrontal cortex in dAD group. The subtraction of the results of emotion Stroop task and general word task showed the brain function area activation images as follows simple emotion factors activated the right amygdala, left parietal lobe, and bilateral prefrontal cortices and occipital lobes in the normal control group; bilateral parietal lobes and left dorsal lateral frontal cortex in the AD group; and bilateral prefrontal cortices in the dAD group; With quite different brain activation pattern, the dAD patients are more susceptible to the influence of emotional factors than AD patients. Impaired emotional neurocircus and emotional reaction may play an important role in the depression onset in AD.

Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures in Ovis aries.

PubMed

Hernandez-Hurtado, Adelina A; Borrego-Soto, Gissela; Marino-Martinez, Ivan A; Lara-Arias, Jorge; Romero-Diaz, Viktor J; Abrego-Guerra, Adalberto; Vilchez-Cavazos, Jose F; Elizondo-Riojas, Guillermo; Martinez-Rodriguez, Herminia G; Espinoza-Juarez, Marcela A; Lopez-Romero, Gloria C; Robles-Zamora, Alejandro; Mendoza Lemus, Oscar F; Ortiz-Lopez, Rocio; Rojas-Martinez, Augusto

2016-01-01

Adipose-derived mesenchymal stem cells (ADMSCs) are inducible to an osteogenic phenotype by the bone morphogenetic proteins (BMPs). This facilitates the generation of implants for bone tissue regeneration. This study evaluated the in vitro osteogenic differentiation of ADMSCs transduced individually and in combination with adenoviral vectors expressing BMP2 and BMP7. Moreover, the effectiveness of the implant containing ADMSCs transduced with the adenoviral vectors AdBMP2/AdBMP7 and embedded in demineralized bone matrix (DBM) was tested in a model of tibial fracture in sheep. This graft was compared to ewes implanted with untransduced ADMSCs embedded in the same matrix and with injured but untreated animals. In vivo results showed accelerated osteogenesis in the group treated with the AdBMP2/AdBMP7 transduced ADMSC graft, which also showed improved restoration of the normal bone morphology.

Blood type gene locus has no influence on ACE association with Alzheimer's disease.

PubMed

Braae, Anne; Medway, Christopher; Carrasquillo, Minerva; Younkin, Steven; Kehoe, Patrick G; Morgan, Kevin

2015-04-01

The ABO blood group locus was recently found to contribute independently and via interactions with angiotensin-converting enzyme (ACE) gene variation to plasma levels of ACE. Variation in ACE has previously been not only implicated as individually conferring susceptibility for Alzheimer's disease (AD) but also proposed to confer risk via interactions with other as yet unknown genes. More recently, larger studies have not supported ACE as a risk factor for AD, whereas the role of ACE pathway in AD has come under increased levels of scrutiny with respect to various aspects of AD pathology and possible therapies. We explored the potential combined involvement of ABO and ACE variations in the genetic susceptibility of 2067 AD cases compared with 1376 nondemented elderly. Including the effects of ABO haplotype did not provide any evidence for the genetic association of ACE with AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Innovative neurophysiological methods in itch research: long-latency evoked potentials after electrical and thermal stimulation in patients with atopic dermatitis.

PubMed

Yudina, Marina M; Toropina, Galina G; Lvov, Andrey; Gieler, Uwe

2011-10-01

The aim of this study was to examine the findings of innovative neurophysiological methods of itch research. Short-latency and pain-related somatosensory-evoked potentials after electrical stimulation, as well as long-latency evoked potentials after thermal stimulation were studied in 38 patients with atopic dermatitis (AD) and 26 healthy volunteers. Quantitative Sensory Testing of thermal perception was performed in 22 patients with AD from the main AD group and in 15 healthy volunteers. Brain hyperactivity to electrical stimuli, delayed thermal-evoked potentials and elevated thermal thresholds were revealed in patients with AD compared with healthy controls. The data indicate small nerve fibre dysfunction in patients with AD, which may contribute to the pathogenesis of AD and chronic itch. The study demonstrates objective approaches to assess the function of small nerve fibres in patients with chronic itch.

Adherence to dietary recommendations for Swedish adults across categories of greenhouse gas emissions from food.

PubMed

Sjörs, Camilla; Hedenus, Fredrik; Sjölander, Arvid; Tillander, Annika; Bälter, Katarina

2017-12-01

To explore associations between diet-related greenhouse gas emissions (GHGE), nutrient intakes and adherence to the Nordic Nutrition Recommendations among Swedish adults. Diet was assessed by 4d food records in the Swedish National Dietary Survey. GHGE was estimated by linking all foods to carbon dioxide equivalents, using data from life cycle assessment studies. Participants were categorized into quartiles of energy-adjusted GHGE and differences between GHGE groups regarding nutrient intakes and adherence to nutrient recommendations were explored. Sweden. Women (n 840) and men (n 627) aged 18-80 years. Differences in nutrient intakes and adherence to nutrient recommendations between GHGE groups were generally small. The dietary intake of participants with the lowest emissions was more in line with recommendations regarding protein, carbohydrates, dietary fibre and vitamin D, but further from recommendations regarding added sugar, compared with the highest GHGE group. The overall adherence to recommendations was found to be better among participants with lower emissions compared with higher emissions. Among women, 27 % in the lowest GHGE group adhered to at least twenty-three recommendations compared with only 12 % in the highest emission group. For men, the corresponding figures were 17 and 10 %, respectively. The study compared nutrient intakes as well as adherence to dietary recommendations for diets with different levels of GHGE from a national dietary survey. We found that participants with low-emission diets, despite higher intake of added sugar, adhered to a larger number of dietary recommendations than those with high emissions.

Biomarker validation of a cued recall memory deficit in prodromal Alzheimer disease.

PubMed

Wagner, M; Wolf, S; Reischies, F M; Daerr, M; Wolfsgruber, S; Jessen, F; Popp, J; Maier, W; Hüll, M; Frölich, L; Hampel, H; Perneczky, R; Peters, O; Jahn, H; Luckhaus, C; Gertz, H-J; Schröder, J; Pantel, J; Lewczuk, P; Kornhuber, J; Wiltfang, J

2012-02-07

To compare cued recall measures with other memory and nonmemory tests regarding their association with a biomarker profile indicative of Alzheimer disease (AD) in CSF among patients with mild cognitive impairment (MCI). Data were obtained by the German Dementia Competence Network. A total of 185 memory clinic patients fulfilling broad criteria for MCI (1 SD deficit in memory tests or in nonmemory tests) were assessed with an extended neuropsychological battery, which included the Free and Cued Selective Reminding Test (FCSRT), the word list learning task from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NP), and the Logical Memory (LM) paragraph recall test from the Wechsler Memory Scale-Revised. CSF was obtained from all patients. A total of 74 out of 185 subjects with MCI (40%) had a CSF profile consistent with AD (Aβ(1-42)/tau ratio; CSF AD+ group). FCSRT measures reflecting both free and cued recall discriminated best between CSF AD+ and CSF AD- patients, and significantly improved CSF AD classification accuracy, as compared with CERAD delayed recall and LM delayed recall. Cued recall deficits are most closely associated with CSF biomarkers indicative of AD in subjects with MCI. This novel finding complements results from prospective clinical studies and provides further empirical support for cued recall as a specific indicator of prodromal AD, in line with recently proposed research criteria.

The incremental validity of a computerised assessment added to clinical rating scales to differentiate adult ADHD from autism spectrum disorder.

PubMed

Groom, Madeleine J; Young, Zoe; Hall, Charlotte L; Gillott, Alinda; Hollis, Chris

2016-09-30

There is a clinical need for objective evidence-based measures that are sensitive and specific to ADHD when compared with other neurodevelopmental disorders. This study evaluated the incremental validity of adding an objective measure of activity and computerised cognitive assessment to clinical rating scales to differentiate adult ADHD from Autism spectrum disorders (ASD). Adults with ADHD (n=33) or ASD (n=25) performed the QbTest, comprising a Continuous Performance Test with motion-tracker to record physical activity. QbTest parameters measuring inattention, impulsivity and hyperactivity were combined to provide a summary score ('QbTotal'). Binary stepwise logistic regression measured the probability of assignment to the ADHD or ASD group based on scores on the Conners Adult ADHD Rating Scale-subscale E (CAARS-E) and Autism Quotient (AQ10) in the first step and then QbTotal added in the second step. The model fit was significant at step 1 (CAARS-E, AQ10) with good group classification accuracy. These predictors were retained and QbTotal was added, resulting in a significant improvement in model fit and group classification accuracy. All predictors were significant. ROC curves indicated superior specificity of QbTotal. The findings present preliminary evidence that adding QbTest to clinical rating scales may improve the differentiation of ADHD and ASD in adults. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice

PubMed Central

Gotthardt, Juliet D.; Verpeut, Jessica L.; Yeomans, Bryn L.; Yang, Jennifer A.; Yasrebi, Ali; Bello, Nicholas T.

2016-01-01

Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%–52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%–13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%–42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%–60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%–32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%–75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy. PMID:26653760

Human Cerebrospinal Fluid Fatty Acid Levels Differ between Supernatant Fluid and Brain-Derived Nanoparticle Fractions, and Are Altered in Alzheimer's Disease

PubMed Central

Fonteh, Alfred N.; Cipolla, Matthew; Chiang, Jiarong; Arakaki, Xianghong; Harrington, Michael G.

2014-01-01

Background Although saturated (SAFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids are important structural components of neuronal membranes and precursors of signaling molecules, knowledge of their metabolism in Alzheimer's disease (AD) is limited. Based on recent discovery that lipids in cerebrospinal fluid (CSF) are distributed in both brain-derived nanoparticles (NP) and supernatant fluid (SF), we hypothesized that fatty acid (FA) abundance and distribution into these compartments is altered in early AD pathology. Methodology and Findings We assayed the FA composition and abundance in CSF fractions from cognitively healthy (CH), mild cognitive impairment (MCI), and AD study participants using gas chromatography - mass spectrometry. In the SF fraction, concentration of docosahexaenoic acid [DHA, (C22:6n-3)] was less in AD compared with CH, while alpha linolenic acid [α-LNA, (C18:3n-3)] was lower in MCI compared with CH. In the NP fraction, levels of SAFAs (C15:0, C16:0) and a MUFA (C15:1) differentiated CH from MCI, while two MUFAs (C15:1, C19:1) and four PUFAs (C20:2n-6, C20:3n-3, C22:4n-6, C22:5n-3) were higher in AD compared with CH. Levels of even-chain free SAFA and total free FA levels were higher in AD, levels of odd-chain free SAFAs, MUFAs, n-3 PUFAs, and total PUFA, were lower in AD compared with CH. Free n-6 PUFA levels were similar in all three groups. Conclusions and Significance FA metabolism is compartmentalized differently in NP versus SF fractions of CSF, and altered FA levels reflect the importance of abnormal metabolism and oxidative pathways in AD. Depleted DHA in CSF fractions in AD is consistent with the importance of n-3 PUFAs in cognitive function, and suggests that disturbed PUFA metabolism contributes to AD pathology. This study of FA levels in CSF fractions from different cognitive stages shows potential AD biomarkers, and provides further insight into cell membrane dysfunctions, including mechanisms leading to amyloid production. PMID:24956173

Reducing safety risk among underserved caregivers with an Alzheimer's home safety program.

PubMed

Levy-Storms, Lené; Cherry, Debra L; Lee, Linda J; Wolf, Sheldon M

2017-09-01

Older adults living with Alzheimer's disease (AD) experience more of the types of accidents and injuries prevalent among older adults. Relatively few studies specifically on safety risks have included older adults of color and tested interventions. This pilot study tested the feasibility and evaluability of educating Hispanic and African American caregivers of patients living with AD about reducing safety risks in their homes. This outpatient memory clinic-based intervention study included a pre-/post-test survey design with two nonequivalent groups and predominately serves Hispanic and African Americans. Of 60 eligible caregivers, 67% participated in a tailored, safety training class with an optional follow-up call. The results indicate a reduction in some safety risks compared to baseline and/or a no intervention group, respectively, including leaving patients at home alone part-time (p < .01 and p < .01), getting lost (p < .05 and p < .05), going outdoors alone less often (p < .05 and p < .01), and giving themselves medicine (p < .05 and p < .01). At post-test, 47 clinically significant instances occurred, in which caregivers who participated in the intervention self-reported patients living with AD to be 'completely safe' in one or more of the safety risk items compared to 8 instances among those who did not. This pilot pre/post design with non-equivalent groups study needs refinement in a future randomized control trial. Despite limitations, this pilot study demonstrates the first feasible and evaluable intervention with both statistically and clinically significant results that suggest potential for reducing safety risks among at-risk minority patients living with AD in future research.

Changes in connectivity of the posterior default network node during visual processing in mild cognitive impairment: staged decline between normal aging and Alzheimer's disease.

PubMed

Krajcovicova, Lenka; Barton, Marek; Elfmarkova-Nemcova, Nela; Mikl, Michal; Marecek, Radek; Rektorova, Irena

2017-12-01

Visual processing difficulties are often present in Alzheimer's disease (AD), even in its pre-dementia phase (i.e. in mild cognitive impairment, MCI). The default mode network (DMN) modulates the brain connectivity depending on the specific cognitive demand, including visual processes. The aim of the present study was to analyze specific changes in connectivity of the posterior DMN node (i.e. the posterior cingulate cortex and precuneus, PCC/P) associated with visual processing in 17 MCI patients and 15 AD patients as compared to 18 healthy controls (HC) using functional magnetic resonance imaging. We used psychophysiological interaction (PPI) analysis to detect specific alterations in PCC connectivity associated with visual processing while controlling for brain atrophy. In the HC group, we observed physiological changes in PCC connectivity in ventral visual stream areas and with PCC/P during the visual task, reflecting the successful involvement of these regions in visual processing. In the MCI group, the PCC connectivity changes were disturbed and remained significant only with the anterior precuneus. In between-group comparison, we observed significant PPI effects in the right superior temporal gyrus in both MCI and AD as compared to HC. This change in connectivity may reflect ineffective "compensatory" mechanism present in the early pre-dementia stages of AD or abnormal modulation of brain connectivity due to the disease pathology. With the disease progression, these changes become more evident but less efficient in terms of compensation. This approach can separate the MCI from HC with 77% sensitivity and 89% specificity.

Safety and efficacy of early intervention with pimecrolimus cream 1% combined with corticosteroids for major flares in infants and children with atopic dermatitis.

PubMed

Siegfried, Elaine; Korman, Neil; Molina, Carmen; Kianifard, Farid; Abrams, Ken

2006-01-01

To assess early intervention with pimecrolimus combined with corticosteroid (CS) for major flares in patients with severe atopic dermatitis (AD). In this 6-month, double-blind, multicenter, randomized, vehicle-controlled, parallel-group in 35 US centers, 275 children aged 3 months to 11 years with mild to severe AD applied the study medication twice daily at first signs/symptoms of AD. For major flares not controlled with study medication, a mid-potency CS cream replaced the evening study drug for up to 3 weeks. The percentage of subjects with no major flares was the main outcome measure. Pimecrolimus reduced the major flare incidence and prolonged flare-free intervals. Significantly more pimecrolimus subjects (52%) had no major flares compared with vehicle subjects (34%; p = 0.007). Pimecrolimus significantly delayed the first flare (median, 53 days vs 13 days; p<0.001), and increased the time between flares (median, 31 days vs 15 days). Additionally, there was earlier pruritus improvement (median, day 3 vs day 6; p = 0.034) in the pimecrolimus group, as well as a reduced need for CS by 37% (p = 0.020) [corrected] Adverse events (AEs) incidence and type were comparable between groups. Combination therapy with pimecrolimus used at half the recommended dose did not shorten the mean flare duration or alter the AE profile. Early treatment of signs/symptoms of AD with pimecrolimus cream 1% provided an effective steroid-sparing option that reduced the incidence of major flares.

Error behaviors associated with loss of competency in Alzheimer's disease.

PubMed

Marson, D C; Annis, S M; McInturff, B; Bartolucci, A; Harrell, L E

1999-12-10

To investigate qualitative behavioral changes associated with declining medical decision-making capacity (competency) in patients with AD. Qualitative measures can yield clinical information about functional changes in neurologic disease not available through quantitative measures. Normal older controls (n = 21) and patients with mild and moderate probable AD (n = 72) were compared using a standardized competency measure and neuropsychological measures. A system of 16 qualitative error scores representing conceptual domains of language, executive dysfunction, affective dysfunction, and compensatory responses was used to analyze errors produced on the competency measure. Patterns of errors were examined across groups. Relationships between error behaviors and competency performance were determined, and neurocognitive correlates of specific error behaviors were identified. AD patients demonstrated more miscomprehension, factual confusion, intrusions, incoherent responses, nonresponsive answers, loss of task, and delegation than controls. Errors in the executive domain (loss of task, nonresponsive answer, and loss of detachment) were key predictors of declining competency performance by AD patients. Neuropsychological analyses in the AD group generally confirmed the conceptual domain assignments of the qualitative scores. Loss of task, nonresponsive answers, and loss of detachment were key behavioral changes associated with declining competency of AD patients and with neurocognitive measures of executive dysfunction. These findings support the growing linkage between executive dysfunction and competency loss.

Impaired Processing of Serial Order Determines Working Memory Impairments in Alzheimer's Disease.

PubMed

De Belder, Maya; Santens, Patrick; Sieben, Anne; Fias, Wim

2017-01-01

Working memory (WM) problems are commonly observed in Alzheimer's disease (AD), but the affected mechanisms leading to impaired WM are still insufficiently understood. The ability to efficiently process serial order in WM has been demonstrated to be fundamental to fluent daily life functioning. The decreased capability to mentally process serial position in WM has been put forward as the underlying explanation for generally compromised WM performance. Determine which mechanisms, such as order processing, are responsible for deficient WM functioning in AD. A group of AD patients (n = 32) and their partners (n = 25), assigned to the control group, were submitted to an extensive battery of neuropsychological and experimental tasks, assessing general cognitive state and functioning of several aspects related to serial order WM. The results revealed an impaired ability to bind item information to serial position within WM in AD patients compared to controls. It was additionally observed that AD patients experienced specific difficulties with directing spatial attention when searching for item information stored in WM. The processing of serial order and the allocation of attentional resources are both disrupted, explaining the generally reduced WM functioning in AD patients. Further studies should now clarify whether this observation could explain disease-related problems for other cognitive functions such as verbal expression, auditory comprehension, or planning.

Formulaic Language in Alzheimer’s Disease

PubMed Central

Bridges, Kelly Ann; Van Lancker Sidtis, Diana

2013-01-01

Background Studies of productive language in Alzheimer’s disease (AD) have focused on formal testing of syntax and semantics but have directed less attention to naturalistic discourse and formulaic language. Clinical observations suggest that individuals with AD retain the ability to produce formulaic language long after other cognitive abilities have deteriorated. Aims This study quantifies production of formulaic expressions in the spontaneous speech of individuals with AD. Persons with early- and late-onset forms of the disease were compared. Methods & Procedures Conversational language samples of individuals with early- (n = 5) and late-onset (n = 6) AD and healthy controls (n = 5) were analyzed to determine whether formulaic language, as measured by the number of words in formulaic expressions, differs between groups. Outcomes & Results Results indicate that individuals with AD, regardless of age of onset, used significantly more formulaic expressions than healthy controls. The early- and late-onset AD groups did not differ on formulaic language measures. Conclusions These findings contribute to a dual process model of cerebral function, which proposes differing processing principles for formulaic and novel expressions. In this model, subcortical areas, which remain intact into late in the progression of Alzheimer’s disease, play an important role in the production of formulaic language. Applications to clinical practice include identifying preserved formulaic language and providing informed counseling to patient and family. PMID:24187417

Multilevel Deficiency of White Matter Connectivity Networks in Alzheimer's Disease: A Diffusion MRI Study with DTI and HARDI Models.

PubMed

Wang, Tao; Shi, Feng; Jin, Yan; Yap, Pew-Thian; Wee, Chong-Yaw; Zhang, Jianye; Yang, Cece; Li, Xia; Xiao, Shifu; Shen, Dinggang

2016-01-01

Alzheimer's disease (AD) is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI) to detect abnormal topological organization of white matter (WM) structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC) elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI) model and the high angular resolution diffusion imaging (HARDI) model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels.

Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain.

PubMed

Kobayashi, Eiji; Nakano, Masako; Kubota, Kenta; Himuro, Nobuaki; Mizoguchi, Shougo; Chikenji, Takako; Otani, Miho; Mizue, Yuka; Nagaishi, Kanna; Fujimiya, Mineko

2018-01-26

Although the cognitive impairment in Alzheimer's disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.

Cognitive Rehabilitation in Alzheimer's Disease: A Controlled Intervention Trial.

PubMed

Brueggen, Katharina; Kasper, Elisabeth; Ochmann, Sina; Pfaff, Henrike; Webel, Steffi; Schneider, Wolfgang; Teipel, Stefan

2017-01-01

Cognitive Rehabilitation for Alzheimer's disease (AD) is an integrative multimodal intervention. It aims to maintain autonomy and quality of life by enhancing the patients' abilities to compensate for decreased cognitive functioning. We evaluated the feasibility of a group-based Cognitive Rehabilitation approach in mild AD dementia and assessed its effect on activities of daily living (ADL). We included 16 patients with AD dementia in a controlled partial-randomized design. We adapted the manual-guided Cognitive Rehabilitation program (CORDIAL) to a group setting. Over the course of three months, one group received the Cognitive Rehabilitation intervention (n = 8), while the other group received a standardized Cognitive Training as an active control condition (n = 8). ADL-competence was measured as primary outcome. The secondary outcome parameters included cognitive abilities related to daily living, functional cognitive state, and non-cognitive domains, e.g., quality of life. For each scale, we assessed the interaction effect 'intervention by time', i.e., from pre-to post-intervention. We found no significant interaction effect of intervention by time on the primary outcome ADL-competence. The interaction effect was significant for quality of life (Cohen's d: -1.43), showing an increase in the intervention group compared with the control group. Our study demonstrates the feasibility of a group-based Cognitive Rehabilitation program for patients with mild AD dementia. The Cognitive Rehabilitation showed no significant effect on ADL, possibly reflecting a lack of transfer between the therapy setting and real life. However, the group setting enhanced communication skills and coping mechanisms. Effects on ADL may not have reached statistical significance due to a limited sample size. Furthermore, future studies might use an extended duration of the intervention and integrate caregivers to a greater extent to increase transfer to activities of daily living.

DSM-IV-TR “pain disorder associated with psychological factors” as a nonhysterical form of somatization

PubMed Central

Aragona, Massimiliano; Tarsitani, Lorenzo; De Nitto, Serena; Inghilleri, Maurizio

2008-01-01

BACKGROUND: Elevated Minnesota Multiphasic Personality Inventory (MMPI) scores on the hysteria (Hy) scale are reported in several forms of pain. Previous results were possibly biased by diagnostic heterogeneity (psychogenic, somatic and mixed pain syndromes included in the same index sample) or Hy heterogeneity (failure to differentiate Hy scores into clinically meaningful sub-scales, such as admission of symptoms [Ad] and denial of symptoms [Dn]). METHODS: To overcome this drawback, 48 patients diagnosed as having a Diagnostic and Statistical Manual of Mental Disorders, 4th edn, Text Revision (DSM-IV-TR) diagnosis of “pain disorder associated with psychological factors” were compared with 48 patients experiencing somatic pain excluding psychological factors, and 42 somatic controls without pain. RESULTS: MMPI Hy and hypochondriasis (Hs) scores were significantly higher in the pain disorder group than in control groups, who scored similarly. MMPI correction (K) scores and Dn scores were similar in the three groups, whereas Ad was significantly higher in the pain disorder group and lower and similar in the two control groups, respectively. In the pain disorder group, Ad and Dn were negatively correlated, whereas in control groups they were unrelated. CONCLUSIONS: These findings suggest that whereas a pattern of high Hs and Hy scores together with a normal K score might characterize patients with a pain disorder associated with psychological factors, elevated Hy scores per se do not indicate hysterical traits. In the pain disorder group, elevated Hy scores reflected the Ad subscale alone, indicating a strikingly high frequency of distressing somatic symptoms. They tend not to repress or deny the emotional malaise linked to symptoms, as the hysterical construct expects. The pain disorder designation should be considered a nonhysterical form of somatization. PMID:18301811

DSM-IV-TR "pain disorder associated with psychological factors" as a nonhysterical form of somatization.

PubMed

Aragona, Massimiliano; Tarsitani, Lorenzo; De Nitto, Serena; Inghilleri, Maurizio

2008-01-01

Elevated Minnesota Multiphasic Personality Inventory (MMPI) scores on the hysteria (Hy) scale are reported in several forms of pain. Previous results were possibly biased by diagnostic heterogeneity (psychogenic, somatic and mixed pain syndromes included in the same index sample) or Hy heterogeneity (failure to differentiate Hy scores into clinically meaningful subscales, such as admission of symptoms [Ad] and denial of symptoms [Dn]). To overcome this drawback, 48 patients diagnosed as having a Diagnostic and Statistical Manual of Mental Disorders, 4th edn, Text Revision (DSM-IV-TR) diagnosis of "pain disorder associated with psychological factors" were compared with 48 patients experiencing somatic pain excluding psychological factors, and 42 somatic controls without pain. MMPI Hy and hypochondriasis (Hs) scores were significantly higher in the pain disorder group than in control groups, who scored similarly. MMPI correction (K) scores and Dn scores were similar in the three groups, whereas Ad was significantly higher in the pain disorder group and lower and similar in the two control groups, respectively. In the pain disorder group, Ad and Dn were negatively correlated, whereas in control groups they were unrelated. These findings suggest that whereas a pattern of high Hs and Hy scores together with a normal K score might characterize patients with a pain disorder associated with psychological factors, elevated Hy scores per se do not indicate hysterical traits. In the pain disorder group, elevated Hy scores reflected the Ad subscale alone, indicating a strikingly high frequency of distressing somatic symptoms. They tend not to repress or deny the emotional malaise linked to symptoms, as the hysterical construct expects. The pain disorder designation should be considered a nonhysterical form of somatization.

Plasma testosterone levels in Alzheimer and Parkinson diseases.

PubMed

Okun, M S; DeLong, M R; Hanfelt, J; Gearing, M; Levey, A

2004-02-10

Testosterone deficiency, a treatable condition commonly seen in aging men, has been linked to Parkinson disease (PD) and Alzheimer disease (AD). In normal subjects, low testosterone levels are associated with cognitive and neuropsychiatric symptoms, yet the relationship between testosterone levels and cognitive function in PD and AD remains unclear. To examine the relationship of testosterone levels to age and cognitive function in PD and AD. Plasma testosterone levels were determined in men enrolled in a clinical registry of subjects with PD and AD, and neuropsychological testing was performed on subjects who consented. Testosterone levels in men with PD were compared with those in men with AD. In both groups, the relationship between testosterone levels and neuropsychological test scores was analyzed, adjusting for age and education. Linear regression analysis revealed that testosterone levels decreased with age in male PD patients (p < 0.03) and male AD patients (p < 0.07). The rate of decline was similar for the two groups. In PD patients, lower testosterone levels were associated with poorer performance on Trails B Seconds (p < 0.02). There is a similar age-related decline in plasma testosterone levels in men with either PD or AD. Previously described associations between low testosterone levels and frontal lobe dysfunction in normal aged men, together with these results, suggest that the hormonal deficiency may act as a "second hit" to impair cognitive function in neurodegenerative disease.

Depth of word processing in Alzheimer patients and normal controls: a magnetoencephalographic (MEG) study.

PubMed

Walla, P; Püregger, E; Lehrner, J; Mayer, D; Deecke, L; Dal Bianco, P

2005-05-01

Effects related to depth of verbal information processing were investigated in probable Alzheimer's disease patients (AD) and age matched controls. During word encoding sessions 10 patients and 10 controls had either to decide whether the letter "s" appeared in visually presented words (alphabetical decision, shallow encoding), or whether the meaning of each presented word was animate or inanimate (lexical decision, deep encoding). These encoding sessions were followed by test sessions during which all previously encoded words were presented again together with the same number of new words. The task was then to discriminate between repeated and new words. Magnetic field changes related to brain activity were recorded with a whole cortex MEG.5 probable AD patients showed recognition performances above chance level related to both depths of information processing. Those patients and 5 age matched controls were then further analysed. Recognition performance was poorer in probable AD patients compared to controls for both levels of processing. However, in both groups deep encoding led to a higher recognition performance than shallow encoding. We therefore conclude that the performance reduction in the patient group was independent of depth of processing. Reaction times related to false alarms differed between patients and controls after deep encoding which perhaps could already be used for supporting an early diagnosis. The analysis of the physiological data revealed significant differences between correctly recognised repetitions and correctly classified new words (old/new-effect) in the control group which were missing in the patient group after deep encoding. The lack of such an effect in the patient group is interpreted as being due to the respective neuropathology related to probable AD. The present results demonstrate that magnetic field recordings represent a useful tool to physiologically distinguish between probable AD and age matched controls.

Functional mobility in a divided attention task in older adults with cognitive impairment.

PubMed

Borges, Sheila de Melo; Radanovic, Márcia; Forlenza, Orestes Vicente

2015-01-01

Motor disorders may occur in mild cognitive impairment (MCI) and at early stages of Alzheimer's disease (AD), particularly under divided attention conditions. We examined functional mobility in 104 older adults (42 with MCI, 26 with mild AD, and 36 cognitively healthy) using the Timed Up and Go test (TUG) under 4 experimental conditions: TUG single task, TUG plus a cognitive task, TUG plus a manual task, and TUG plus a cognitive and a manual task. Statistically significant differences in mean time of execution were found in all four experimental conditions when comparing MCI and controls (p < .001), and when comparing MCI and AD patients (p < .05). Receiver-operating characteristic curve analyses showed that all four testing conditions could differentiate the three groups (area under the curve > .8, p < .001 for MCI vs. controls; area under the curve > .7, p < .001 for MCI vs. AD). The authors conclude that functional motor deficits occurring in MCI can be assessed by the TUG test, in single or dual task modality.

Yogurt protects against growth retardation in weanling rats fed diets high in phytic acid

PubMed Central

Gaetke, Lisa M.; McClain, Craig J.; Toleman, C. Jean; Stuart, Mary A.

2010-01-01

The purpose of this study was to determine the affects of adding yogurt to animal diets which were high in phytic acid (PA) and adequate in zinc (38 μg Zn/g). The PA:Zn molar ratio was 60:1. Zinc status was determined by documenting growth and measuring the zinc concentration in bone (tibia) and plasma. For 25 days, 6 groups (n=6) of Sprague-Dawley weanling rats were fed one of the following AIN-76 diets. Half of the diets contained PA. Four of the diets contained yogurt with either active or heat-treated (inactive) cultures added at 25% of the diet. Diets: (without PA) 1) AIN, 2) AIN with active yogurt, 3) AIN and inactive yogurt; and (with PA) 4) AIN with PA, 5) AIN with PA plus active yogurt, and 6) AIN with PA plus inactive yogurt. Body weight, weight gain, and zinc concentration in bone and plasma were measured, and feed efficiency ratio (FER) was calculated. Rats fed diets with PA and yogurt had normal growth compared to the control group. Growth retardation was evident in the group fed the diet with PA and no yogurt. This group had significantly lower body weight compared to all other groups (p<0.05). Rats fed diets with PA, with or without yogurt, had significantly lower zinc concentration in bone and plasma (p<0.05). Adding yogurt to diets high in PA resulted in normal growth in weanling rats, however, zinc concentration in bone and plasma was still sub-optimal. PMID:19269152

Time-dependent enhancement of lymphocyte activation by mitogens after exposure to isolation or water scheduling.

PubMed

Jessop, J J; Gale, K; Bayer, B M

1988-01-01

The effects of isolation and water scheduling on mitogen induced lymphocyte proliferation were investigated. Isolated rats were animals which had been raised in group-housed conditions and then transferred to individual cages with ad lib access to water for a 1 or 2 week period. Water scheduled rats were maintained in group housing (5 rats per cage) with ad lib access to food but with access to water for a single 30 minute session each day. Responses of these groups were compared to those of animals which had been continuously group-housed with ad lib access to food and water. No differences in lymphocyte responses to phytohemagglutinin (PHA) were found 1 week after exposure to isolation. However, after 2 weeks, splenic and blood T lymphocytes from isolated animals demonstrated an increased proliferative response to suboptimum and maximum concentrations of PHA. Splenic B lymphocyte responses to lipopolysaccharide (LPS) from isolated animals were also increased by 2- to 3-fold compared to group-housed controls. Two weeks of exposure of animals to daily water scheduling similarly increased the splenic lymphocyte proliferation. This increased responsiveness to PHA was not accompanied by a significant change in the sensitivity of the lymphocytes to PHA, in the total number of white blood cells, or the proportion of splenic T or T helper lymphocytes. Our results show that the increase in lymphocyte proliferation is time-dependent, requires greater than 1 week of exposure to isolation and is due to factors other than changes in sensitivity to mitogen or T lymphocyte number.

COMPARISON OF LAPAROSCOPIC SKILLS PERFORMANCE USING SINGLE-SITE ACCESS (SSA) DEVICES VS. AN INDEPENDENT-PORT SSA APPROACH

PubMed Central

Schill, Matthew R.; Varela, J. Esteban; Frisella, Margaret M.; Brunt, L. Michael

2015-01-01

Background We compared performance of validated laparoscopic tasks on four commercially available single site access (SSA) access devices (AD) versus an independent port (IP) SSA set-up. Methods A prospective, randomized comparison of laparoscopic skills performance on four AD (GelPOINT™, SILS™ Port, SSL Access System™, TriPort™) and one IP SSA set-up was conducted. Eighteen medical students (2nd–4th year), four surgical residents, and five attending surgeons were trained to proficiency in multi-port laparoscopy using four laparoscopic drills (peg transfer, bean drop, pattern cutting, extracorporeal suturing) in a laparoscopic trainer box. Drills were then performed in random order on each IP-SSA and AD-SSA set-up using straight laparoscopic instruments. Repetitions were timed and errors recorded. Data are mean ± SD, and statistical analysis was by two-way ANOVA with Tukey HSD post-hoc tests. Results Attending surgeons had significantly faster total task times than residents or students (p< 0.001), but the difference between residents and students was NS. Pair-wise comparisons revealed significantly faster total task times for the IP-SSA set-up compared to all four AD-SSA’s within the student group only (p<0.05). Total task times for residents and attending surgeons showed a similar profile, but the differences were NS. When data for the three groups was combined, the total task time was less for the IP-SSA set-up than for each of the four AD-SSA set-ups (p < 0.001). Similarly,, the IP-SSA set-up was significantly faster than 3 of 4 AD-SSA set-ups for peg transfer, 3 of 4 for pattern cutting, and 2 of 4 for suturing. No significant differences in error rates between IP-SSA and AD-SSA set-ups were detected. Conclusions When compared to an IP-SSA laparoscopic set-up, single site access devices are associated with longer task performance times in a trainer box model, independent of level of training. Task performance was similar across different SSA devices. PMID:21993938

Quantitative sensory testing and pain tolerance in patients with mild to moderate Alzheimer disease compared to healthy control subjects.

PubMed

Jensen-Dahm, Christina; Werner, Mads U; Dahl, Jørgen B; Jensen, Troels Staehelin; Ballegaard, Martin; Hejl, Anne-Mette; Waldemar, Gunhild

2014-08-01

Patients with Alzheimer disease (AD) report pain less frequently than their cognitively intact peers. It has been hypothesized that pain processing is altered in AD. The aim of this study was to investigate agreement and reliability of 3 pain sensitivity tests and to examine pain threshold and tolerance in patients with AD. We examined 29 patients with mild to moderate AD and 29 age- and gender-matched healthy control subjects with quantitative sensory testing, ie, assessments of detection threshold (warmth detection threshold [WDT]) and pain threshold (heat pain threshold [HPT], pressure algometry, cold pressor test), and assessments of tolerance (pressure algometry, cold pressor test). All procedures were done twice on day 1, 1 hour apart, and repeated on day 2. We found no difference between groups for WDT (patient vs control subjects: mean [95% confidence interval]: 35.5°C [33.4°C to 37.6°C] vs 35.4°C [34.3°C to 36.5°C], P=.8) or HPT (41.2°C [40.0°C to 42.4°C] vs 42.3°C [41.1°C to 43.5°C], P=.24). We observed comparable thresholds for pressure algometry (median [25% to 75% interquartile range]: 120 kPa [100 to 142 kPa] vs 131 kPa [113 to 192 kPa], P=.10), but significantly lower tolerance in AD patients (213 kPa [188 to 306 kPa] vs 289 kPa [262 to 360 kPa], P=.008). No differences were found for the cold pressor test. The study demonstrated good replicability of the sensory testing data with comparable data variability, for both groups, which supports the use of these methods in studies of patients with mild to moderate AD. Contrary to previous studies, we observed a reduced pain tolerance in patients with mild to moderate AD, which suggests that the reduced report of pain cannot be explained by reduced processing of painful stimuli. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Effect of changes in an FFQ: comparing data from two national dietary survey instruments among 2-year-olds.

PubMed

Kristiansen, A L; Lillegaard, I T L; Lande, B; Andersen, L F

2013-01-28

In the interpretation of dietary trends, it is important to consider the potential effect of modifications in the dietary assessment method. Therefore, our objective was to explore the comparability of data obtained at two time points by a semi-quantitative FFQ (SFFQ) which has had slight modifications over time. In the national dietary surveys among Norwegian 2-year-olds, diet was assessed by an SFFQ which underwent modifications between the 1999 survey and the 2007 survey. In the present study, fifty-nine families with a 2-year-old child participated by completing both the SFFQ in a crossover design within a month's time. With regard to the reported intake of energy and nutrients, the largest significant differences observed between the two questionnaires were for carbohydrates and added sugar. According to intake of food groups, significant differences were observed for five out of sixteen food groups. Spearman's correlation coefficients for energy, nutrients and food groups ranged from 0.43 (Ca) to 0.85 (soft drinks). Most Bland-Altman plots indicated broad limits of agreement. The differences between the two questionnaires can be explained by changes in the questionnaires, changes in the food composition databases used and random variation. Comparing differences between the questionnaires by maternal educational level, number of children and type of day care revealed minor differences. In conclusion, this study showed that at the group level there was reasonable comparability between the two questionnaires, except for carbohydrates, added sugar and some food groups. Moreover, there were moderate to high correlations for energy, nutrients and food groups.

Osteoporosis in adult patients with atopic dermatitis: A nationwide population-based study

PubMed Central

Lu, Chun-Ching; Su, Yu-Feng; Tsai, Tai-Hsin; Wu, Chieh-Hsin

2017-01-01

The aim of this study was to investigate osteoporosis risk in atopic dermatitis (AD) patients. This study included patients in the Taiwan National Health Insurance Research dataset. The population-based study included all patients aged 20–49 years who had been diagnosed with AD during 1996–2010. In total, 35,229 age and gender-matched patients without AD in a 1:1 ratio were randomly selected as the non-AD group. Cox proportional-hazards regression and Kaplan–Meier analyses were used to measure the hazard ratios and the cumulative incidences of osteoporosis, respectively. During the follow-up period, 360(1.02%) AD patients and 127(0.36%) non-AD patients developed osteoporosis. The overall incidence of osteoporosis was4.72-fold greater in the AD patients compared to the non-AD patients (1.82 vs. 0.24 per 1,000 person-years, respectively) after adjusting for potential confounding factors. Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression and use of corticosteroids. The dataset analysis showed that AD was significantly associated with subsequent risk of osteoporosis. PMID:28207767

Childrearing style in families of anxiety-disordered children: between-family and within-family differences.

PubMed

Lindhout, Ingeborg E; Markus, Monica Th; Borst, Sophie R; Hoogendijk, Thea H G; Dingemans, Peter M A J; Boer, Frits

2009-06-01

This study examined whether (1) parents of anxiety-disordered (AD) children differed from those of non-clinical controls in their childrearing style, and whether (2) the child-rearing style of parents towards AD children is different from that towards their siblings. A clinical sample of 25 AD children, age range 8-13 years, was compared with 25 siblings and a non-clinical control group (n = 25). Childrearing was assessed by means of parental self-report, child report and through an expressed emotion interview measure. AD children perceived more parental rejection than non-clinical control children or the AD children's siblings. High-expressed emotion was scored significantly more often towards AD children than non-clinical control children, or their siblings. On [Symbol: see text]care' and [Symbol: see text]control' parental self-report showed some differences regarding AD children on the one hand and non-clinical control children or siblings of AD children on the other. These results suggest that the rearing of AD children differs significantly both from the rearing of their siblings and that of non-clinical control children.

Detecting navigational deficits in cognitive aging and Alzheimer disease using virtual reality.

PubMed

Cushman, Laura A; Stein, Karen; Duffy, Charles J

2008-09-16

Older adults get lost, in many cases because of recognized or incipient Alzheimer disease (AD). In either case, getting lost can be a threat to individual and public safety, as well as to personal autonomy and quality of life. Here we compare our previously described real-world navigation test with a virtual reality (VR) version simulating the same navigational environment. Quantifying real-world navigational performance is difficult and time-consuming. VR testing is a promising alternative, but it has not been compared with closely corresponding real-world testing in aging and AD. We have studied navigation using both real-world and virtual environments in the same subjects: young normal controls (YNCs, n = 35), older normal controls (ONCs, n = 26), patients with mild cognitive impairment (MCI, n = 12), and patients with early AD (EAD, n = 14). We found close correlations between real-world and virtual navigational deficits that increased across groups from YNC to ONC, to MCI, and to EAD. Analyses of subtest performance showed similar profiles of impairment in real-world and virtual testing in all four subject groups. The ONC, MCI, and EAD subjects all showed greatest difficulty in self-orientation and scene localization tests. MCI and EAD patients also showed impaired verbal recall about both test environments. Virtual environment testing provides a valid assessment of navigational skills. Aging and Alzheimer disease (AD) share the same patterns of difficulty in associating visual scenes and locations, which is complicated in AD by the accompanying loss of verbally mediated navigational capacities. We conclude that virtual navigation testing reveals deficits in aging and AD that are associated with potentially grave risks to our patients and the community.

Behavioral and Electrophysiological Correlates of Memory Binding Deficits in Patients at Different Risk Levels for Alzheimer's Disease.

PubMed

Pietto, Marcos; Parra, Mario A; Trujillo, Natalia; Flores, Facundo; García, Adolfo M; Bustin, Julian; Richly, Pablo; Manes, Facundo; Lopera, Francisco; Ibáñez, Agustín; Baez, Sandra

2016-06-30

Deficits in visual short-term memory (VSTM) binding have been proposed as an early and specific marker for Alzheimer's disease (AD). However, no studies have explored the neural correlates of this domain in clinical categories involving prodromal stages with different risk levels of conversion to AD. We assessed underlying electrophysiological modulations in patients with mild cognitive impairment (MCI), patients in the MCI stages of familial AD carrying the mutation E280A of the presenilin-1 gene (MCI-FAD), and healthy controls. Moreover, we compared the behavioral performance and neural correlates of both patient groups. Participants completed a change-detection VSTM task assessing recognition of changes between shapes or shape-color bindings, presented in two consecutive arrays (i.e., study and test) while event related potentials (ERPs) were recorded. Changes always occurred in the test array and consisted of new features replacing studied features (shape-only) or features swapping across items (shape-color binding). Both MCI and MCI-FAD patients performed worse than controls in the shape-color binding condition. Early electrophysiological activity (100-250 ms) was significantly reduced in both clinical groups, particularly over fronto-central and parieto-occipital regions. However, shape-color binding performance and their reduced neural correlates were similar between MCI and MCI-FAD. Our results support the validity of the VSTM binding test and their neural correlates in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion. The combined analysis of behavioral and ERP data gleaned with the VSTM binding task can offer a valuable memory biomarker for AD.

Post-stroke dementia: the contribution of thalamus and basal ganglia changes.

PubMed

Lopes, Marcos Antonio; Firbank, Michael J; Widdrington, Michelle; Blamire, Andrew M; Kalaria, Raj N; O'Brien, John T

2012-04-01

The neurobiological basis of increased risk of dementia in stroke patients is unclear, though there are several related pathological changes, including white matter hyperintensities (WMH), and medial temporal atrophy. Subcortical gray matter structures have also been implicated in dementia resulting from vascular pathology, particularly vascular dementia. This study aimed to investigate the contribution of changes in subcortical gray matter structures to post-stroke dementia (PSD). T1- and T2-weighted images and T2-weighted fluid-attenuated inversion recovery (FLAIR) images were obtained on a 3-Tesla magnetic resonance (MR) system, in four groups aged over 75 years: post-stroke with dementia (PSD; 8), post-stroke no dementia (PSnoD; 33), Alzheimer's disease (AD; 26) and controls (30). Automated software was used to measure the volume of thalamus, putamen, caudate nucleus, and hippocampus as well as total WMH volume. The number of subcortical lacunes was also counted. The number of caudate lacunes was higher in the PSnoD group, compared with AD (p = 0.029) and controls (p = 0.019). The putamen volume was smaller in the stroke and AD groups, when compared with controls. In the whole stroke group, putamen lacunes were correlated with impairment in memory (Rey test; ρ = -0.365; p = 0.031), while WMH and hippocampal volume both correlated with global dysfunction. Our findings implicate a variety of neurobiological substrates of dementia, such as small vessel disease and Alzheimer pathology, which develop after stroke in an old older population, with a contribution from subcortical brain structures.

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

PubMed

Frejo, L; Martin-Sanz, E; Teggi, R; Trinidad, G; Soto-Varela, A; Santos-Perez, S; Manrique, R; Perez, N; Aran, I; Almeida-Branco, M S; Batuecas-Caletrio, A; Fraile, J; Espinosa-Sanchez, J M; Perez-Guillen, V; Perez-Garrigues, H; Oliva-Dominguez, M; Aleman, O; Benitez, J; Perez, P; Lopez-Escamez, J A

2017-12-01

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. © 2017 John Wiley & Sons Ltd.

Effect of parental family history of Alzheimer's disease on serial position profiles.

PubMed

La Rue, Asenath; Hermann, Bruce; Jones, Jana E; Johnson, Sterling; Asthana, Sanjay; Sager, Mark A

2008-07-01

An exaggerated recency effect (ie, disproportionate recall of last-presented items) has been consistently observed in the word list learning of patients with Alzheimer's disease (AD). Our study sought to determine whether there were similar alterations in serial position learning among asymptomatic persons at risk for AD as a result of parental family history. Subjects included 623 asymptomatic middle-aged children of patients with AD (median, 53 years) and 157 control participants whose parents survived to at least age 70 without AD or other memory disorders. All participants were administered the Rey Auditory Verbal Learning Test, which requires learning and recall of 15 unrelated nouns. There was no significant difference in total words recalled between the AD children and control groups. However, compared with controls, AD children exhibited a significantly greater tendency to recall words from the end (recency) versus beginning (primacy) of the list. Serial position effects were unrelated to apolipoprotein allele epsilon 4 or depressive symptoms. Asymptomatic persons at risk for AD by virtue of family history do not show a difference in total words recalled compared with controls, but they exhibit a distinctly different serial position curve, suggesting greater reliance on immediate as opposed to episodic memory. This is the same serial position pattern observed in mild AD, seen here in reduced severity. Longitudinal follow-up is planned to determine whether changes in serial position patterns are a meaningful marker for preclinical detection of AD.

Increased vitamin D receptor gene expression and rs11568820 and rs4516035 promoter polymorphisms in autistic disorder.

PubMed

Balta, Burhan; Gumus, Hakan; Bayramov, Ruslan; Korkmaz Bayramov, Keziban; Erdogan, Murat; Oztop, Didem Behice; Dogan, Muhammet Ensar; Taheri, Serpil; Dundar, Munis

2018-05-18

Although there are a large number of sequence variants of different genes and copy number variations at various loci identified in autistic disorder (AD) patients, the pathogenesis of AD has not been elucidated completely. Recently, in AD patients, a large number of expression array and transcriptome studies have shown an increase in the expression of genes especially related to innate immune response. Antimicrobial effects of vitamin D and VDR are exerted through Toll-Like-Receptors (TLR) which have an important role in the innate immune response, are expressed by antigen presenting cells and recognize foreign microorganisms. In this study, age and gender matched 30 patients diagnosed with AD and 30 healthy controls were included in the study. Comparatively whole blood VDR gene expression and rs11568820 and rs4516035 SNP profile of the promoter region of the VDR gene were investigated by real time PCR. Whole blood VDR gene expression was significantly higher in the AD group compared to control subjects (p < 0.0001). There were no significant differences among allele and genotype distribution of rs11568820 and rs4516035 polymorphisms between AD patients and controls. The increase of VDR gene expression in patients with AD may be in accordance with an increase in the innate immune response in patients with AD. Furthermore, this study will stimulate new studies in order to clarify the relationship among AD, vitamin D, VDR, and innate immunity.

Principal component analysis of PiB distribution in Parkinson and Alzheimer diseases

PubMed Central

Markham, Joanne; Flores, Hubert; Hartlein, Johanna M.; Goate, Alison M.; Cairns, Nigel J.; Videen, Tom O.; Perlmutter, Joel S.

2013-01-01

Objective: To use principal component analyses (PCA) of Pittsburgh compound B (PiB) PET imaging to determine whether the pattern of in vivo β-amyloid (Aβ) in Parkinson disease (PD) with cognitive impairment is similar to the pattern found in symptomatic Alzheimer disease (AD). Methods: PiB PET scans were obtained from participants with PD with cognitive impairment (n = 53), participants with symptomatic AD (n = 35), and age-matched controls (n = 67). All were assessed using the Clinical Dementia Rating and APOE genotype was determined in 137 participants. PCA was used to 1) determine the PiB binding pattern in AD, 2) determine a possible unique PD pattern, and 3) directly compare the PiB binding patterns in PD and AD groups. Results: The first 2 principal components (PC1 and PC2) significantly separated the AD and control participants (p < 0.001). Participants with PD with cognitive impairment also were significantly different from participants with symptomatic AD on both components (p < 0.001). However, there was no difference between PD and controls on either component. Even those participants with PD with elevated mean cortical binding potentials were significantly different from participants with AD on both components. Conclusion: Using PCA, we demonstrated that participants with PD with cognitive impairment do not exhibit the same PiB binding pattern as participants with AD. These data suggest that Aβ deposition may play a different pathophysiologic role in the cognitive impairment of PD compared to that in AD. PMID:23825179

Attenuated heart rate responses to public speaking in individuals with alcohol dependence.

PubMed

Panknin, Tera L; Dickensheets, Stacey L; Nixon, Sara J; Lovallo, William R

2002-06-01

Because individuals with alcohol dependence (AD) have shown blunted cortisol responses to psychological stress, we assessed whether they also show attenuated cardiovascular responses. This study examined the cardiovascular responses of people meeting DSM-IV criteria for AD to orthostasis and public speaking. Heart rate (HR), stroke volume, cardiac output, total peripheral resistance, mean arterial pressure, systolic blood pressure, and diastolic blood pressure during orthostasis and public speaking were assessed by use of impedance cardiography and Dinamap blood pressure monitoring in 20 AD subjects abstinent for 21 to 28 days and in 10 age-matched controls. Orthostasis consisted of standing, whereas public speaking involved preparing and presenting two speeches. Self-reported mood state was also assessed during the tasks. AD subjects had significantly lower resting BP compared with controls. Cardiovascular responses to orthostasis were similar between groups. AD subjects had attenuated HR during public speaking but reported similar anxiety responses to controls. Comparable cardiovascular responses to orthostasis in controls and AD subjects suggest intact reflex control of circulation. AD subjects had blunted HR responses to public speaking; this is consistent with the attenuated cortisol responses observed in this sample and in previous studies. This suggests a possible alteration in limbic system regulation of hypothalamic and brainstem responses to psychological stress. Cardiovascular responses of AD subjects that are inconsistent with subjective accounts of tension and anxiety suggest a disconnection between perception of threat and resulting physiologic responses in AD subjects.

Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase.

PubMed

Burbaeva, G Sh; Boksha, I S; Tereshkina, E B; Savushkina, O K; Prokhorova, T A; Vorobyeva, E A

2014-10-01

Enzymes of glutamate and GABA metabolism in postmortem cerebellum from patients with Alzheimer's disease (AD) have not been comprehensively studied. The present work reports results of original comparative study on levels of phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase isoenzymes (GAD65/67) in autopsied cerebellum samples from AD patients and matched controls (13 cases in each group) as well as summarizes published evidence for altered levels of PAG and GAD65/67 in AD brain. Altered (decreased) levels of these enzymes and changes in links between amounts of these enzymes and other glutamate-metabolizing enzymes (such as glutamate dehydrogenase and glutamine synthetase-like protein) in AD cerebella suggest significantly impaired glutamate and GABA metabolism in this brain region, which was previously regarded as not substantially involved in AD pathogenesis.

Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type.

PubMed

Lee, Min-Jung; Kang, Mi-Jin; Lee, So-Yeon; Lee, Eun; Kim, Kangjin; Won, Sungho; Suh, Dong In; Kim, Kyung Won; Sheen, Youn Ho; Ahn, Kangmo; Kim, Bong-Soo; Hong, Soo-Jong

2018-04-01

Perturbations of the infant gut microbiota can shape development of the immune system and link to the risk of allergic diseases. We sought to understand the role of the gut microbiome in patients with atopic dermatitis (AD). The metagenome of the infant gut microbiome was analyzed according to feeding types. Composition of the gut microbiota was analyzed in fecal samples from 129 infants (6 months old) by using pyrosequencing, including 66 healthy infants and 63 infants with AD. The functional profile of the gut microbiome was analyzed by means of whole-metagenome sequencing (20 control subjects and 20 patients with AD). In addition, the total number of bacteria in the feces was determined by using real-time PCR. The gut microbiome of 6-month-old infants was different based on feeding types, and 2 microbiota groups (Bifidobacterium species-dominated and Escherichia/Veillonella species-dominated groups) were found in breast-fed and mixed-fed infants. Bacterial cell amounts in the feces were lower in infants with AD than in control infants. Although no specific taxa directly correlated with AD in 16S rRNA gene results, whole-metagenome analysis revealed differences in functional genes related to immune development. The reduction in genes for oxidative phosphorylation, phosphatidylinositol 3-kinase-Akt signaling, estrogen signaling, nucleotide-binding domain-like receptor signaling, and antigen processing and presentation induced by reduced colonization of mucin-degrading bacteria (Akkermansia muciniphila, Ruminococcus gnavus, and Lachnospiraceae bacterium 2_1_58FAA) was significantly associated with stunted immune development in the AD group compared with the control group (P < .05). Alterations in the gut microbiome can be associated with AD because of different bacterial genes that can modulate host immune cell function. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Protective effects of melatonin against thioacetamide-induced liver fibrosis in rats.

PubMed

Czechowska, G; Celinski, K; Korolczuk, A; Wojcicka, G; Dudka, J; Bojarska, A; Reiter, R J

2015-08-01

The aim of this study was to determine the effect of melatonin on thioacetamide (TAA) induced liver fibrosis in rats. The antifibrotic effects of melatonin were assessed by determining activity indirect markers of fibrosis: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and proinflammatory cytokines: interleukin 6 (IL-6), interleukin-1beta (IL-1β), tumour necrosis factor alpha (TNF-α), transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF). Parameters of oxidative stress: oxidised glutathione (GSSG), reduced glutathione (GSH) and presaged activity of paraoxonase 1 (PON-1), an antioxidative enzyme were determined. Inflammatory changes and fibrosis extent were evaluated histologically. Experiments were carried out in Wistar rats. Animals were divided into 4 groups: I - controls, water ad libitum for 12 weeks, group II - TAA, 300 mg/L ad libitum for 12 weeks, III - melatonin, 10 mg/kg b.w. intraperitoneally (i.p.) daily for 4 weeks, IV - TAA, 300 mg/L ad libitum for 12 weeks followed by melatonin, 10 mg/kg/b.w. i.p. daily for 4 weeks. Results of serum determinations demonstrated significantly lower activity of AST, ALT and AP in the group receiving TAA followed by melatonin compared to the group receiving only TAA. Immunoenzymatic findings on effect of melatonin on concentration of proinflammatory cytokines confirmed these data. Biochemical examinations in liver homogenates revealed statistically significant improvement (concentration of GSH increases and concentration of GSSG decreases) in animals with TAA-induced liver damage receiving melatonin. Moreover, the activity of PON-1 toward phenyl acetate and paraoxon was increased in liver homogenates and serum in the group receiving TAA followed by melatonin compared to the TAA group without melatonin treatment. Microscopic evaluation disclosed inhibitory effects of melatonin on inflammatory changes and extent of liver fibrosis.

Effect of vitamin D on stress-induced hyperglycaemia and insulin resistance in critically ill patients.

PubMed

Alizadeh, N; Khalili, H; Mohammadi, M; Abdollahi, A; Ala, S

2016-05-01

Effects of vitamin D supplementation on the glycaemic indices and insulin resistance in diabetic and non-diabetic patients were studied. In this study, effects of vitamin D supplementation on stress-induced hyperglycaemia and insulin resistance were evaluated in non-diabetic surgical critically ill patients. Adult surgical patients with stress-induced hyperglycaemia within the first 24 h of admission to the ICU were recruited. The patients randomly assigned to receive either vitamin D or placebo. Patients in the vitamin D group received a single dose of 600,000 IU vitamin D3 as intramuscular injection at time of recruitment. Besides demographic and clinical characteristics of the patients, plasma glucose, insulin, 25(OH) D and adiponectin levels were measured at the time of ICU admission and day 7. Homoeostasis model assessment for insulin resistance (HOMA-IR) and homestasis model assessment adiponectin (HOMA-AD) ratio were considered at the times of assessment. Comparing with the baseline, plasma 25(OH) D level significantly increased in the subjects who received vitamin D (p = 0.04). Improvement in fasting plasma glucose levels was detected in day 7 of the study compared with the baseline status in both groups. HOMA-IR showed a decrement pattern in vitamin D group (p = 0.09). Fasting plasma adiponectin levels increased significantly in the vitamin D group (p = 0.007), but not in the placebo group (p = 0.38). Finally, changes in HOMA-AD ratio were not significant in the both groups. Vitamin D supplementation showed positive effect on plasma adiponectin level, as a biomarker of insulin sensitivity in surgical critically ill patients with stress-induced hyperglycaemia. However, effects of vitamin D supplementation on HOMA-IR and HOMA-AD as indicators of insulin resistance were not significant. © 2016 John Wiley & Sons Ltd.

Assessment of Fecal Microbiota and Fecal Metabolome in Symptomatic Uncomplicated Diverticular Disease of the Colon.

PubMed

Tursi, Antonio; Mastromarino, Paola; Capobianco, Daniela; Elisei, Walter; Miccheli, Alfredo; Capuani, Giorgio; Tomassini, Alberta; Campagna, Giuseppe; Picchio, Marcello; Giorgetti, GianMarco; Fabiocchi, Federica; Brandimarte, Giovanni

2016-10-01

The aim of this study was to assess fecal microbiota and metabolome in a population with symptomatic uncomplicated diverticular disease (SUDD). Whether intestinal microbiota and metabolic profiling may be altered in patients with SUDD is unknown. Stool samples from 44 consecutive women [15 patients with SUDD, 13 with asymptomatic diverticulosis (AD), and 16 healthy controls (HCs)] were analyzed. Real-time polymerase chain reaction was used to quantify targeted microorganisms. High-resolution proton nuclear magnetic resonance spectroscopy associated with multivariate analysis with partial least-square discriminant analysis (PLS-DA) was applied on the metabolite data set. The overall bacterial quantity did not differ among the 3 groups (P=0.449), with no difference in Bacteroides/Prevotella, Clostridium coccoides, Bifidobacterium, Lactobacillus, and Escherichia coli subgroups. The amount of Akkermansia muciniphila species was significantly different between HC, AD, and SUDD subjects (P=0.017). PLS-DA analysis of nuclear magnetic resonance -based metabolomics associated with microbiological data showed significant discrimination between HCs and AD patients (R=0.733; Q=0.383; P<0.05, LV=2). PLS analysis showed lower N-acetyl compound and isovalerate levels in AD, associated with higher levels of A. municiphila, as compared with the HC group. PLS-DA applied on AD and SUDD samples showed a good discrimination between these 2 groups (R=0.69; Q=0.35; LV=2). SUDD patients were characterized by low levels of valerate, butyrate, and choline and by high levels of N-acetyl derivatives and U1. SUDD and AD do not show colonic bacterial overgrowth, but a significant difference in the levels of fecal A. muciniphila was observed. Moreover, increasing expression of some metabolites as expression of different AD and SUDD metabolic activity was found.

False Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease-Disinhibition or Amnesia?

PubMed

Flanagan, Emma C; Wong, Stephanie; Dutt, Aparna; Tu, Sicong; Bertoux, Maxime; Irish, Muireann; Piguet, Olivier; Rao, Sulakshana; Hodges, John R; Ghosh, Amitabha; Hornberger, Michael

2016-01-01

Episodic memory recall processes in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39 bvFTD, 77 AD and 61 control participants from two centers (India, Australia), as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits-false-positives). Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients.

Combined Socio-Behavioral Evaluation Improves the Differential Diagnosis Between the Behavioral Variant of Frontotemporal Dementia and Alzheimer's Disease: In Search of Neuropsychological Markers.

PubMed

Dodich, Alessandra; Cerami, Chiara; Cappa, Stefano F; Marcone, Alessandra; Golzi, Valeria; Zamboni, Michele; Giusti, Maria Cristina; Iannaccone, Sandro

2018-01-01

Current diagnostic criteria for behavioral variant of frontotemporal dementia (bvFTD) and typical Alzheimer's disease (AD) include a differential pattern of neuropsychological impairments (episodic memory deficit in typical AD and dysexecutive syndrome in bvFTD). There is, however, large evidence of a frequent overlap in neuropsychological features, making the differential diagnosis extremely difficult. In this retrospective study, we evaluated the diagnostic value of different cognitive and neurobehavioral markers in bvFTD and AD patient groups. We included 95 dementia patients with a clinical and biomarker evidence of bvFTD (n = 48) or typical AD (n = 47) pathology. A clinical 2-year follow-up confirmed clinical classification. Performances at basic cognitive tasks (memory, executive functions, visuo-spatial, language) as well as social cognition skills and neurobehavioral profiles have been recorded. A stepwise logistic regression model compared the neuropsychological profiles between groups and assessed the accuracy of cognitive and neurobehavioral markers in discriminating bvFTD from AD. Statistical comparison between patient groups proved social cognition and episodic memory impairments as main cognitive signatures of bvFTD and AD neuropsychological profiles, respectively. Only half of bvFTD patients showed attentive/executive deficits, questioning their role as cognitive marker of bvFTD. Notably, the large majority of bvFTD sample (i.e., 70%) poorly performed at delayed recall tasks. Logistic regression analysis identified social cognition performances, Frontal Behavioral Inventory and Mini-Mental State Examination scores as the best combination in distinguishing bvFTD from AD. Social cognition tasks and socio-behavioral questionnaires are recommended in clinical settings to improve the accuracy of early diagnosis of bvFTD.

Decreased melatonin secretion is associated with increased intestinal permeability and marker of endotoxemia in alcoholics

PubMed Central

Gorenz, Annika; Shaikh, Maliha; Desai, Vishal; Forsyth, Christopher; Fogg, Louis; Burgess, Helen J.; Keshavarzian, Ali

2015-01-01

Chronic heavy alcohol use is known to cause gut leakiness and alcoholic liver disease (ALD), but only 30% of heavy drinkers develop increased intestinal permeability and ALD. The hypothesis of this study was that disruption of circadian rhythms is a potential risk factor in actively drinking alcoholics for gut leakiness and endotoxemia. We studied 20 subjects with alcohol use disorder (AD) and 17 healthy controls (HC, 6 day workers, 11 night workers). Subjects wore a wrist actiwatch for 7 days and underwent a 24-h dim light phase assessment and urine collection for intestinal permeability. The AD group had significantly less total sleep time and increased fragmentation of sleep (P < 0.05). AD also had significantly lower plasma melatonin levels compared with the HC [mean area under the curve (AUC) 322.78 ± 228.21 vs. 568.75 ± 304.26 pg/ml, P = 0.03]. In the AD group, AUC of melatonin was inversely correlated with small bowel and colonic intestinal permeability (lactulose-to-mannitol ratio, r = −0.39, P = 0.03; urinary sucralose, r = −0.47, P = 0.01). Cosinor analysis of lipopolysaccharide-binding protein (marker of endotoxemia) and lipopolysaccharide every 4 h for 24 h in HC and AD subjects had a midline estimating statistic of rhythm of 5,026.15 ± 409.56 vs. 6,818.02 ± 628.78 ng/ml (P < 0.01) and 0.09 ± 0.03 vs. 0.15 ± 0.19 EU/ml (P < 0.05), respectively. We found plasma melatonin was significantly lower in the AD group, and lower melatonin levels correlated with increased intestinal permeability and a marker of endotoxemia. Our study suggests the suppression of melatonin in AD may promote gut leakiness and endotoxemia. PMID:25907689

Discerning mild cognitive impairment and Alzheimer Disease from normal aging: morphologic characterization based on univariate and multivariate models.

PubMed

Liao, Weiqi; Long, Xiaojing; Jiang, Chunxiang; Diao, Yanjun; Liu, Xin; Zheng, Hairong; Zhang, Lijuan

2014-05-01

Differentiating mild cognitive impairment (MCI) and Alzheimer Disease (AD) from healthy aging remains challenging. This study aimed to explore the cerebral structural alterations of subjects with MCI or AD as compared to healthy elderly based on the individual and collective effects of cerebral morphologic indices using univariate and multivariate analyses. T1-weighted images (T1WIs) were retrieved from Alzheimer Disease Neuroimaging Initiative database for 116 subjects who were categorized into groups of healthy aging, MCI, and AD. Analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) were performed to explore the intergroup morphologic alterations indexed by surface area, curvature index, cortical thickness, and subjacent white matter volume with age and sex controlled as covariates, in 34 parcellated gyri regions of interest (ROIs) for both cerebral hemispheres based on the T1WI. Statistical parameters were mapped on the anatomic images to facilitate visual inspection. Global rather than region-specific structural alterations were revealed in groups of MCI and AD relative to healthy elderly using MANCOVA. ANCOVA revealed that the cortical thickness decreased more prominently in entorhinal, temporal, and cingulate cortices and was positively correlated with patients' cognitive performance in AD group but not in MCI. The temporal lobe features marked atrophy of white matter during the disease dynamics. Significant intercorrelations were observed among the morphologic indices with univariate analysis for given ROIs. Significant global structural alterations were identified in MCI and AD based on MANCOVA model with improved sensitivity. The intercorrelation among the morphologic indices may dampen the use of individual morphological parameter in featuring cerebral structural alterations. Decrease in cortical thickness is not reflective of the cognitive performance at the early stage of AD. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

[Dracorhodin perchlorate inhibit high glucose induce serum and glucocorticoid induced protein kinase 1 and fibronectin expression in human mesangial cells].

PubMed

Xie, Yifeng; Wang, Quansheng; Liu, Jianguo; Xie, Jiwen; Xue, Kaming; Tang, Qing

2010-08-01

To investigate the effect of dracorhodin perchlorate (DP) on inhibiting high glucose-induced serum and glucocorticoid induced protein kinase 1 (SGK1) and fibronectin (FN) expression in human mesangial cells (HMC), and its mechanism of prevention and treatment on renal fibrosis in diabetic nephropathy (DN) . The HMC were divided into normal glucose group (NG group, 5.5 mmol x L(-1) D-glucose), normal glucose +low DP group (NG + LDP group, 5.5 mmol x L(-1) D-glucose +7.5 micromol x L(-1) DP), normal glucose +high DP group (NG + HDP group, 5.5 mmol x L(-1) D-glucose + 15 micromol x L(-1) DP), high glucose group (HG group,25 mmol x L(-1) D-glucose), high glucose +low DP group (HG + LDP group, 25 mmol x L(-1) D-glucose + 7.5 micromol x L(-1) DP)and high glucose +high DP group (HG +HDP group, 25 mmol x L(-1) D-glucose + 15 micromol x L(-1) DP). Each group was examined at 24 hours. The levels of SGK1 and FN mRNA was detected by real-time fluorescence quantitative PCR,and the expression of SGK1 and FN protein was detected by Western blot or indirect immunofluorescence. A basal level of SGK1 and FN in HMC were detected in NG group, and the level of SGK1 and FN mRNA and protein were not evidently different compared to that of NG group adding 7.5 micromol x L(-1) DP for 24 hours. On the other hand, the levels of SGK1 and FN mRNA and protein were obviously decreased by adding 15 micromol x L(-1) DP for 24 hours. Compared to NG group, the levels of SGK1 and FN mRNA and protein were increased in HG group after stimulating for 24 hours (P < 0.01). Compared to HG group, the level of SGK1 and FN mRNA and protein were evidently reduced in HG + LDP and HG + HDP groups by adding 7.5 micromol x L(-1) DP and 15 micromol x L(-1) DP for 24 hours (P < 0.01). Dracorhodin perchlorate can inhibit high glucose-induced serum and glucocorticoid induced protein kinase 1 (SGK1) and fibronectin(FN) expression in human mesangial cells, and this may be part of the mechanism of preventing and treating renal fibrosis of DN.

Analysis of macrolinguistic aspects of narratives from individuals with Alzheimer's disease, mild cognitive impairment, and no cognitive impairment.

PubMed

Toledo, Cíntia Matsuda; Aluísio, Sandra Maria; Dos Santos, Leandro Borges; Brucki, Sonia Maria Dozzi; Trés, Eduardo Sturzeneker; de Oliveira, Maira Okada; Mansur, Letícia Lessa

2018-01-01

The depiction of features in discourse production promotes accurate diagnosis and helps to establish the therapeutic intervention in cognitive impairment and dementia. We aimed to identify alterations in the macrolinguistic aspects of discourse using a new computational tool. Sixty individuals, aged 60 years and older, were distributed in three different groups: mild Alzheimer's disease (mAD), amnestic mild cognitive impairment, and healthy controls. A narrative created by individuals was analyzed through the Coh-Metrix-Dementia program, extracting the features of interest automatically. mAD showed worse overall performance compared to the other groups: less informative discourse, greater impairment in global coherence, greater modalization, and inferior narrative structure. It was not possible to discriminate between amnestic mild cognitive impairment and healthy controls. Our results are in line with the literature, verifying a pathological change in the macrostructure of discourse in mAD.

Levels of Nonphosphorylated and Phosphorylated Tau in Cerebrospinal Fluid of Alzheimer’s Disease Patients

PubMed Central

Hu, Yuan Yuan; He, Shan Shu; Wang, Xiaochuan; Duan, Qiu Hong; Grundke-Iqbal, Inge; Iqbal, Khalid; Wang, Jianzhi

2002-01-01

We have developed an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay for the measurement of Alzheimer’s disease (AD) abnormally hyperphosphorylated tau in cerebrospinal fluid (CSF). The assay, which recognizes attomolar amounts of tau, is ∼400 and ∼1300 times more sensitive than conventional enzyme-linked immunosorbent assay in determining the hyperphosphorylated tau and total tau, respectively. With this method, we measured both total tau and tau phosphorylated at Ser-396/Ser-404 in lumbar CSFs from AD and control patients. We found that the total tau was 215 ± 77 pg/ml in cognitively normal control (n = 56), 234 ± 92 pg/ml in non-AD neurological (n = 37), 304 ± 126 pg/ml in vascular dementia (n = 46), and 486 ± 168 pg/ml (n = 52) in AD patients, respectively. However, a remarkably elevated level in phosphorylated tau was only found in AD (187 ± 84 pg/ml), as compared with normal controls (54 ± 33 pg/ml), non-AD (63 ± 34 pg/ml), and vascular dementia (72 ± 33 pg/ml) groups. If we used the ratio of hyperphosphorylated tau to total tau of ≥0.33 as cutoff for AD diagnosis, we could confirm the diagnosis in 96% of the clinically diagnosed patients with a specificity of 95%, 86%, 100%, and 94% against nonneurological, non-AD neurological, vascular dementia, and all of the three control groups combined, respectively. It is suggested that the CSF level of tau phosphorylated at Ser-396/Ser-404 is a promising diagnostic marker of AD. PMID:11943712

Effects of a stable prostacyclin analog on experimental ischemic acute renal failure.

PubMed Central

Tobimatsu, M; Ueda, Y; Saito, S; Tsumagari, T; Konomi, K

1988-01-01

The effect of OP-41483, a stable prostacyclin (PGI2) analog, on ischemic acute renal failure (ARF) was investigated in dogs. Administration of OP-41483 for three days after ischemia significantly increased renal cortical blood flow (RCBF) when compared with dogs treated with the saline vehicle. In the OP-41483-treated group, serum creatinine levels remained relatively low during postoperative days 1-3 and mean survival time was prolonged. Injection of a silicone rubber vascular casting compound (Microfil) revealed increased numbers of visible renal cortical glomeruli and microvessels compared to the saline vehicle group. Histologic sections showed only very limited tubular necrosis, whereas sections of kidneys treated with saline showed extensive tubular necrosis. In conclusion, this stable prostacyclin analog provided a significant degree of protection for the kidneys from ischemic injury and may be useful in a clinical setting. Images Figs. 3A-D. Figs. 4A-D. PMID:3291800

ERP C250 Shows the Elderly (Cognitively Normal, Alzheimer’s Disease) Store More Stimuli in Short-Term Memory than Young Adults Do

PubMed Central

Chapman, Robert M.; Gardner, Margaret N.; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P.; Dupree, Haley M.; Antonsdottir, Inga M.; Kamalyan, Lily

2016-01-01

Objective To determine how aging and dementia affect the brain’s initial storing of task-relevant and irrelevant information in short-term memory. Methods We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. Results In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in intratrial parts 1–3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Conclusions Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. Significance C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. PMID:27178862

APOEε2 is associated with milder clinical and pathological Alzheimer's disease

PubMed Central

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E.; Betensky, Rebecca A.; Hyman, Bradley T.

2015-01-01

Objective The Alzheimer disease (AD) APOEε4 risk allele associates with an earlier age of onset and increased amyloid-β deposition, whereas the protective APOEε2 allele delays the onset and appears to prevent amyloid-β deposition. Yet the clinical and pathological effects of APOEε2 remain uncertain because of its relative rarity. We investigated the effects of APOE ε2 and ε4 alleles on AD pathology and cognition in a large US dataset of well characterized AD patients. Methods We studied individuals from the National Alzheimer's Coordinating Center (NACC) autopsy cohort across the entire clinico-pathological continuum of AD. Multivariable models were built to examine the associations between APOE alleles and AD neuropathological changes, using the APOEε3/ε3 group as comparator. Mediation analysis was used to estimate the direct and indirect effects of APOE alleles on AD pathology and cognition (CDR-SOB and MMSE). Results Compared to APOEε3/ε3, APOEε2 is independently associated with lower Braak NFT stages and, possibly, fewer neuritic plaques, but has no direct effect on CAA severity, whereas APOEε4 is associated with more neuritic plaques and CAA, but has no independent effect on Braak NFT stage. Unadjusted analyses showed marked differences among APOE genotypes with respect to cognitive performance (ε2>ε3>ε4). Mediation analysis suggests that this is largely explained through effects on pathology. Interpretation Even when adjusted for age of onset, symptom duration and other demographic variables, APOEε2 is associated with milder AD pathology and less severe antemortem cognitive impairment compared to APOE ε3 and ε4 alleles, suggesting a relative neuroprotective effect of APOEε2 in AD. PMID:25623662

The Analgesic Effect of Obturator Nerve Block Added to a Femoral Triangle Block After Total Knee Arthroplasty: A Randomized Controlled Trial.

PubMed

Runge, Charlotte; Børglum, Jens; Jensen, Jan Mick; Kobborg, Tina; Pedersen, Anette; Sandberg, Jon; Mikkelsen, Lone Ramer; Vase, Morten; Bendtsen, Thomas Fichtner

2016-01-01

Total knee arthroplasty (TKA) is associated with severe pain, and effective analgesia is essential for the quality of postoperative care and ambulation. The analgesic effects of adding an obturator nerve block (ONB) to a femoral triangle block (FTB) after TKA have not been tested previously. We hypothesized that combined ONB and FTB will reduce opioid consumption and pain compared with those of a single FTB or local infiltration analgesia (LIA). Seventy-eight patients were randomized to combined ONB and FTB, single FTB, or LIA after primary unilateral TKA. The primary outcome was morphine consumption during the first 24 postoperative hours. Secondary outcomes included morphine consumption during the first 48 postoperative hours, pain at rest and passive knee flexion, nausea and vomiting, cumulated ambulation score, and Timed Up and Go test. Seventy-five patients were included in the analysis. The total intravenous morphine consumption during the first 24 postoperative hours was 2 mg (interquartile range [IQR], 0-15) in the combined ONB and FTB group, 20 mg (IQR, 10-26) in the FTB group (P = 0.0007), and 17 mg (IQR, 10-36) in the LIA group (P = 0.002). The combined ONB and FTB group displayed reduced pain, nausea, and vomiting compared with the other groups. The ambulation tests showed no statistically significant differences between the groups. Addition of ONB to FTB significantly reduced opioid consumption and pain after TKA compared with a single FTB or LIA, without impaired ambulation.

Effects of Growth Hormone and Nutritional Therapy in Boys with Constitutional Growth Delay: A Randomized Controlled Trial

PubMed Central

Han, Joan C.; Damaso, Ligeia; Welch, Susan; Balagopal, Prabhakaran; Hossain, Jobayer; Mauras, Nelly

2010-01-01

Objective To examine whether supplemental nutrition augments the anabolic actions of growth hormone (GH) in boys with constitutional delay of growth and maturation (CDGM). Study design We conducted a randomized, controlled trial at an outpatient clinical research center. Subjects were 20 prepubertal boys (age 9.3±1.3y) with CDGM (height-SDS -2.0±0.5, bone age delay 1.8±0.8y, BMI-SDS -1.2±1.0, peak stimulated GH 15.7±7.7ng/mL), who were randomized (N=10/group) to 6 months observation or daily nutritional supplementation, followed by additional daily GH therapy in all for another 12 months. T-tests and repeated measures ANOVAs compared energy intake, total energy expenditure (TEE), growth, hormones and nutrition markers. Results Energy intake was increased at 6 months within the Nutrition (p=0.04) but not the Observation group, and TEE was not statistically different within either group at 6 months. Addition of 6 months GH resulted in higher energy intake and TEE in the GH/Nutrition group at 12 months (p<0.01), but not in the GH group vs. baseline. Height, weight, lean body mass, hormones and nutrition markers increased comparably in both groups throughout 18 months. Conclusions Boys with CDGM utilize energy at an accelerated rate, an imbalance not overcome with added nutrition. GH therapy increases growth comparably with or without added nutrition in these patients. PMID:20961566

[Effects of adenoviral vector containing human angiotensin II type 1 receptor antisense cDNA on biological action of human pulmonary artery smooth muscle cells].

PubMed

Tu, Ming-li; Wang, Han-qin; Lei, Huai-ding; Luo, Guo-shi; Liu, Xian-jun; Liu, Wei-shun; Xiong, Chang; Liu, Yu-quan; Ren, Si-qun

2005-04-01

To investigate the effect of human angiotensin II (AngII) type 1 receptor (AT(1)R) antisense cDNA (ahAT(1)) on migration, proliferation, and apoptosis of cultured human pulmonary artery smooth muscle cells (PASMC). Two recombinant adenoviral vectors, AdCMVahAT(1) containing full length antisense cDNA targeting to human AT(1)R mRNA, and AdCMVLacZ containing LacZ, were constructed by orientation clone technology and homologous recombination. The PASMC was divided into 3 groups (DMEM, AdCMVLacZ, AdCMVahAT(1)) and different interventions were given to different groups. AT(1)R expression was detected by RT-PCR and immunohistochemistry method; migration of PASMC was measured by Boyden's Chamer method. Other PASMC was divided into 4 groups (DMEM, AngII, AdCMVLacZ + AngII and AdCMVahAT(1) + AngII), and only the last 2 groups were respectively transfected with AdCMVLacZ and AdCMVahAT(1) before administration of AngII. From 6 h to 96 h after stimulation by AngII (10(-7) mol/L), proliferation index (PI) and apoptosis of PASMC were determined by flow cytometry. At the 48 h the level of AT(1)R mRNA was significantly less in PASMC transfected AdCMVahAT(1) than that in group DMEM and in group AdCMVLacZ. The protein level showed a same difference (P < 0.01). At 24 h the migration distance of PASMC also was significantly less in group AdCMVahAT(1) than that in group DMEM and Group AdCMVLacZ (P < 0.01). Stimulated by AngII for 48 h, in group AngII the PI of PASMC markedly increased (P < 0.01 vs group DMEM). But in Group AdCMVahAT(1) + AngII PI of PASMC clearly decreased (P < 0.01 vs group AngII and group DMEM respectively). There was no statistic difference of PI between group AdCMVLacZ + AngII and group AngII. Moreover, apoptosis peak emerged only in group AdCMVahAT(1) + AngII. The rate of apoptosis in those PASMC used AdCMVahAT(1) and AngII was 24.70 +/- 4.04 (P < 0.01 vs the other 3 groups respectively). These results indicate that AngII stimulates proliferation via AT(1) receptors in human PASMC, and antisense cDNA targeting to human AT(1)R transfection mediated by adenoviral vector has powerful inhibitory effects on AngII-induced migration and proliferation of human PASMC by attenuating AT(1)R mRNA and protein expression. Also, it can promote apoptosis of human PASMC. That demonstrate that AT(1)R antisense cDNA is a potent inhibitors of the actions of AngII on PASMC. Antisense inhibition targeting to AT(1)R has therapeutic potential for the treatment of pulmonary vascular diseases.

Evaluation of intraepidermal nerve fibres in the skin of normal and atopic dogs.

PubMed

Laprais, Aurore; Dunston, Stanley M; Torres, Sheila M F; Favrot, Claude; Olivry, Thierry

2017-08-01

Interest in intraepidermal nerve fibres (IENFs) is rising in human medicine, because variations in fibre density occur in some diseases and these neurites might contribute to disease pathogenesis. An increase in IENF density is seen in human atopic dermatitis (AD); there are no such data in atopic dogs. To compare the prevalence of IENFs in normal and atopic canine skin. Eight millimetre skin punch biopsies were taken from six sites of 25 healthy dogs without dermatitis and compared to lesional and nonlesional skin samples of dogs with AD (23 and 14 dogs, respectively). Thirty micrometre-thick paraffin-embedded sections were stained by indirect immunofluorescence for neuronal beta-3 tubulin. Only sections with detectable dermal nerves were then screened for the presence of IENFs. IENFs were identified in all 25 normal nasal planum sections, but in only one biopsy collected from each of the normal canine haired skin (NCHS) sites. As there was no significant difference in IENF prevalence between NCHS areas, they were grouped together. The rate of detection of IENFs was significantly higher (one-tailed Fisher's test, P = 0.004) in lesional AD specimens (18 of 23; 78%) than in nonlesional AD (four of 14; 29%) and NCHS specimens (four of 111; 4%, P < 0.0001). The prevalence of IENF detection in nonlesional AD samples was significantly higher than in normal canine skin (P = 0.006). IENFs are detected more commonly in canine AD than in normal haired skin; these results are comparable to those seen for human AD. © 2017 ESVD and ACVD.

Daily intake of probiotics with high IFN-γ/IL-10 ratio increases the cytotoxicity of human natural killer cells: a personalized probiotic approach.

PubMed

Ho, Yu-Hsuan; Lu, Yu-Chiu; Chang, Hung-Cheng; Lee, Shin-Yi; Tsai, Min-Fen; Huang, Yu-Ting; Hsu, Ting-Yuan

2014-01-01

A personalized probiotic microfluidic chip system has been established and used to screen the probiotics which had the highest value of IFN-γ/IL-10 or IL-10/IFN-γ among six probiotics, including L. paracasei BRAP01, L. acidophilus AD300, B. longum BA100, E. faecium BR0085, L. rhamnosus AD500, and L. reuteri BR101. One hundred volunteers were included and their PBMCs were collected and stimulated by the six probiotics. People who belonged to the IFN-γ group took the probiotics that exerted the highest ratio of IFN-γ/IL-10 and vice versa in IL-10 group. A significant increase in NK cytotoxicity of 69 volunteers in the IFN-γ group was observed compared to the IL-10 group (n = 21) and control group (n = 10). The result also showed that L. paracasei BRAP01 and L. acidophilus AD300 were the two dominant inducers in IFN-γ group which yielded higher value of IFN-γ/IL-10 than the other 4 probiotics, while L. reuteri BR101 was the most effective agent on the ratio of IL-10/IFN-γ in the IL-10 group. Our finding highlighted the concept of personalized probiotics and also provided a good foundation to investigate the probiotics with NK activity.

Efficacy and safety of teneligliptin added to canagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: A multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group comparative study

PubMed Central

Kadowaki, Takashi; Inagaki, Nobuya; Kondo, Kazuoki; Nishimura, Kenichi; Kaneko, Genki; Maruyama, Nobuko; Nakanishi, Nobuhiro; Gouda, Maki; Iijima, Hiroaki

2017-01-01

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors and sodium glucose co‐transporter 2 (SGLT2) inhibitors are frequently used in combination for the treatment of type 2 diabetes mellitus (T2DM). We examined the efficacy and safety of teneligliptin (a DPP‐4 inhibitor) added to canagliflozin (an SGLT2 inhibitor) monotherapy in Japanese patients with poorly controlled T2DM as part of the development of a fixed‐dose combination of teneligliptin and canagliflozin. Japanese patients treated with canagliflozin (100 mg) for ≥12 weeks were randomized to receive add‐on teneligliptin (20 mg; C + T group) or placebo (C + P group) for 24 weeks. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to Week 24. The between‐group differences in reductions from baseline to Week 24 were significantly greater in the C + T group for HbA1c (−0.94%; P < .001). The incidence of adverse events was similar in both groups (55.8% and 49.4% in the C + T and C + P groups, respectively). No episodes of hypoglycaemia were reported. Teneligliptin added to ongoing canagliflozin monotherapy improved glycaemic control and was well tolerated in Japanese patients with inadequately controlled T2DM. PMID:28786530

Cost effectiveness of a manual based coping strategy programme in promoting the mental health of family carers of people with dementia (the START (STrAtegies for RelaTives) study): a pragmatic randomised controlled trial.

PubMed

Knapp, Martin; King, Derek; Romeo, Renee; Schehl, Barbara; Barber, Julie; Griffin, Mark; Rapaport, Penny; Livingston, Debbie; Mummery, Cath; Walker, Zuzana; Hoe, Juanita; Sampson, Elizabeth L; Cooper, Claudia; Livingston, Gill

2013-10-25

To assess whether the START (STrAtegies for RelatTives) intervention added to treatment as usual is cost effective compared with usual treatment alone. Cost effectiveness analysis nested within a pragmatic randomised controlled trial. Three mental health and one neurological outpatient dementia service in London and Essex, UK. Family carers of people with dementia. Eight session, manual based, coping intervention delivered by supervised psychology graduates to family carers of people with dementia added to usual treatment, compared with usual treatment alone. Costs measured from a health and social care perspective were analysed alongside the Hospital Anxiety and Depression Scale total score (HADS-T) of affective symptoms and quality adjusted life years (QALYs) in cost effectiveness analyses over eight months from baseline. Of the 260 participants recruited to the study, 173 were randomised to the START intervention, and 87 to usual treatment alone. Mean HADS-T scores were lower in the intervention group than the usual treatment group over the 8 month evaluation period (mean difference -1.79 (95% CI -3.32 to -0.33)), indicating better outcomes associated with the START intervention. There was a small improvement in health related quality of life as measured by QALYs (0.03 (-0.01 to 0.08)). Costs were no different between the intervention and usual treatment groups (£252 (-28 to 565) higher for START group). The cost effectiveness calculations suggested that START had a greater than 99% chance of being cost effective compared with usual treatment alone at a willingness to pay threshold of £30,000 per QALY gained, and a high probability of cost effectiveness on the HADS-T measure. The manual based coping intervention START, when added to treatment as usual, was cost effective compared with treatment as usual alone by reference to both outcome measures (affective symptoms for family carers, and carer based QALYs). ISCTRN 70017938.

Comparison of behavioral and psychological symptoms of Alzheimer's disease among institution residents and memory clinic outpatients.

PubMed

Cheng, Ting-Wen; Chen, Ta-Fu; Yip, Ping-Keung; Hua, Mau-Sun; Yang, Chi-Cheng; Chiu, Ming-Jang

2009-12-01

Behavioral and psychological symptoms of dementia (BPSD) cause caregiver distress and earlier institutionalization. We compared the prevalence and characteristics of BPSD between institution residents and memory clinic outpatients with Alzheimer's disease (AD) to test the hypothesis that there is more BPSD among institution residents than among their outpatient counterparts. We assessed BPSD by interviewing the patients' principal caregivers, either family or professionals, using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Data from 138 patients with probable AD from the memory clinic and 173 residents with possible AD living in the long-term care facilities were collected. The diagnoses followed the NINCDS-ADRDA criteria. BPSD profiles of the two groups were similar but not identical. The prevalence of at least one BPSD was high in both groups (community 81.9%, institution 74.9%). Activity disturbance was the most frequently reported BPSD in both groups (community 52.2%, institution 38.7%). Delusions, hallucinations, anxiety and aggressiveness were seen more frequently in memory clinic outpatients. The outpatients also had higher scores of BEHAVE-AD subscales in delusion/paranoid ideation, affective disturbance, and global rating of severity. With the increase of disease severity there were significantly more activity disturbance, psychosis, and aggressiveness in patients with AD. Caregiver factor and institution effect were two possible reasons for the higher prevalence and the greater severity of BPSD in community patients. BPSD caused more distress to family caregivers than the professional caregivers. High levels of psychotropic prescriptions for patients living in the long-term care facilities may also play a role.

Can overeating induce conditioned taste avoidance in previously food restricted rats?

PubMed

Hertel, Amanda; Eikelboom, Roelof

2010-03-30

While feeding is rewarding, the feeling of satiation has been theorized to have a mixed affect. Using a food restriction model of overeating we examined whether bingeing was capable of supporting conditioned taste avoidance (CTA). Adult male Sprague-Dawley rats were maintained on either an ad lib (n=8) or restricted (50% of regular consumption; n=24) food access for 20 days. On Days 9, 14, and 19 all rats were given access to a novel saccharin solution in place of water, and two groups of food restricted rats were given access to either 100% of regular food consumption or ad lib food. Ad lib access in the restricted rats induced significant overeating on all three exposures. After all rats were returned to ad lib feeding, a 24h two-bottle saccharin/water choice test displayed significantly reduced saccharin consumption in the overeating rats, compared to those in the other 3 groups. To determine whether this avoidance was due to a learned association, a second experiment used a latent inhibition paradigm, familiarizing half the rats with the saccharin for 8 days prior to pairing it with overeating. Using the design of Experiment 1, with only the continuously ad lib and the restricted to ad lib feeding groups, it was found that the overeating-induced saccharin avoidance was attenuated by the pre-exposure. These results suggest that self-induced overeating is capable of supporting a learned avoidance of a novel solution suggestive of a conditioned satiety or taste avoidance. (c) 2009 Elsevier Inc. All rights reserved.

[Effects-of combined calories restriction and polyunsaturated fatty acids on colitis in rats].

PubMed

Qian, Yan; Zhang, Ying; Liu, Hui; Wang, Lei; Li, Xiuhua; Qiu, Fubin

2014-09-01

To explore the effect of n-6 and n-3 polyunsaturated fatty acids combined with calorie restriction( CR) in DSS induced ulcerative colitis rats. Forty female rats were randomly divided into five groups, control group, model group, CR group, 5:1 PUFA ad libitum group, 5: 1 PUFA CR group. CR groups provided with a limited daily food allotment of 60% of that eaten by the ad libitum animals for 14 weeks. Ulcerative colitis model in rats were given 5. 0% dextran sulfate sodium in their drinking water for 7 days. 5:1 PUFA CR group significantly decreased body weight, disease activity index, macroscopic and histological score compared to model group. In addition, administration of 5: 1 PUFA CR effectively inhibited MPO activity. The levels of TNF-α and IL-6 in the serum with colitis were decreased by 5: 1 PUFA CR (P <0. 05). These results suggest that combination of calories restriction and n-6/n-3 =5:1 PUFA may be more beneficial in attenuating the progression of DSS induced ulcerative colitis.

Which rivastigmine formula is better for heart in elderly patients with Alzheimer's disease: oral or patch?

PubMed

Isik, Ahmet Turan; Soysal, Pinar; Yay, Adnan

2014-12-01

Rivastigmine is commonly used for the treatment of Alzheimer's disease (AD). All cholinesterase inhibitors, including rivastigmine, may cause cardiac side effects. The aim of this study is to compare the electrocardiographic (ECG) and hypotensive effects of formulations of rivastigmine. Eighty-five newly diagnosed patients with AD who were treated with rivastigmine were retrospectively evaluated. The ECG records were reviewed at baseline and at administration of either 12 mg of oral rivastigmine or 10 cm(2) transdermal rivastigmine. When compared with the baseline, there were no changes in any of the ECG parameters in all of the patients (P > .05). Moreover, when compared with the mean change from baseline for each treatment group, there were no changes, except heart rate (P = .035). It was demonstrated that rivastigmine formulations were not associated with increased arrhythmogenic or hypotensive effects in elderly patients with AD and was not superior to each other. © The Author(s) 2014.

Pronounced impairment of everyday skills and self-care in posterior cortical atrophy.

PubMed

Shakespeare, Timothy J; Yong, Keir X X; Foxe, David; Hodges, John; Crutch, Sebastian J

2015-01-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and self-care while the tAD group showed greater impairment in aspects of memory and orientation, and motivation. We suggest that PCA poses specific challenges for those caring for people affected by the condition.

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials.

PubMed

Ma, Jiantao; Karlsen, Micaela C; Chung, Mei; Jacques, Paul F; Saltzman, Edward; Smith, Caren E; Fox, Caroline S; McKeown, Nicola M

2016-01-01

The effect of added sugar intake on ectopic fat accumulation is a subject of debate. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. MEDLINE, CAB Abstracts, CAB Global Health, and EBM (Evidence-Based Medicine) Reviews - Cochrane Central Register of Controlled Trials databases were searched for studies published from 1973 to September 2014. RCTs with a minimum of 6 days' duration of added sugar exposure in the intervention group were selected. The dosage of added sugar intake as a percentage of total energy was extracted or calculated. Means and standard deviations of pre- and post-test measurements or changes in ectopic fat depots were collected. Fourteen RCTs were included. Most of the studies had a medium to high risk of bias. Meta-analysis showed that, compared with eucaloric controls, subjects who consumed added sugar under hypercaloric conditions likely increased ectopic fat, particularly in the liver (pooled standardized mean difference = 0.9 [95%CI, 0.6-1.2], n = 6) and muscles (pooled SMD = 0.6 [95%CI, 0.2-1.0], n = 4). No significant difference was observed in liver fat, visceral adipose tissue, or muscle fat when isocaloric intakes of different sources of added sugars were compared. Data from a limited number of RCTs suggest that excess added sugar intake under hypercaloric diet conditions likely increases ectopic fat depots, particularly in the liver and in muscle fat. There are insufficient data to compare the effect of different sources of added sugars on ectopic fat deposition or to compare intake of added sugar with intakes of other macronutrients. Future well-designed RCTs with sufficient power and duration are needed to address the role of sugars on ectopic fat deposition. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Plasma long non-coding RNA BACE1 as a novel biomarker for diagnosis of Alzheimer disease.

PubMed

Feng, Liang; Liao, Yu-Ting; He, Jin-Cai; Xie, Cheng-Long; Chen, Si-Yan; Fan, Hui-Hui; Su, Zhi-Peng; Wang, Zhen

2018-01-09

Long non-coding RNA (LncRNA) have been reported to be involved in the pathogenesis of neurodegenerative diseases, but whether it can serve as a biomarker for Alzheimer disease (AD) is not yet known. The present study selected four specific LncRNA (17A, 51A, BACE1 and BC200) as possible AD biomarker. RT-qPCR was performed to validate the LncRNA. Receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were applied to study the potential of LncRNA as a biomarker in a population of 88 AD patients and 72 control individuals. We found that the plasma LncRNA BACE1 level of AD patients was significantly higher than that of healthy controls (p = 0.006). Plasma level of LncRNA 17A, 51A and BC200 did not show a significant difference between two groups (p = 0.098, p = 0.204 and p = 0.232, respectively). ROC curve analysis showed that LncRNA BACE1 was the best candidate of these LncRNA (95% CI: 0.553-0.781, p = 0.003). In addition, no correlation was found for expression of these LncRNA in both control and AD groups with age or MMSE scale (p > 0.05). Our present study compared the plasma level of four LncRNA between AD and non-AD patients, and found that the level of the BACE1 is increased in the plasma of AD patients and have a high specificity (88%) for AD, indicating BACE1 may be a potential candidate biomarker to predict AD.

Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: An analysis using the National Health and Wellness Survey.

PubMed

Eckert, Laurent; Gupta, Shaloo; Amand, Caroline; Gadkari, Abhijit; Mahajan, Puneet; Gelfand, Joel M

2017-08-01

Given its public health impact, there is need for broad and representative data on the humanistic burden of atopic dermatitis (AD). To establish the humanistic burden of AD in US adults. Data were from the 2013 US National Health and Wellness Survey; AD self-reports were propensity-matched with non-AD controls and with psoriasis controls. Bivariate analyses were conducted on burden outcomes between the AD and control groups. Demographics and baseline characteristics were comparable between matched groups. Subjects with AD (n = 349) versus non-AD controls (n = 698) had significantly higher rates of anxiety, depression, and sleep disorders (29.8%, 31.2%, and 33.2% vs 16.1%, 17.3%, and 19.2%, respectively [all P < .001]); a lower Short Form-36 v2 mental component summary score (44.5 vs 48.0, respectively [P < .001]); a lower physical component summary score (47.6 vs 49.5, respectively [P = .004]), and lower health utilities (0.67 vs 0.72, respectively [P < .001]) in addition to a higher work absenteeism rate (9.9% vs 3.6%, respectively [P < .001]) and activity impairment rate (33.6% vs 25.2%, respectively [P < .001]). Subjects with AD and psoriasis controls (n = 260 each) showed similar impairment in health-related quality of life and productivity. Data were self-reported. AD is associated with a substantial humanistic burden that is similar in magnitude to that of psoriasis, which is also recognized for its debilitating symptoms, indicating the need for more effective treatments for AD. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Continuous positive airway pressure deepens sleep in patients with Alzheimer's disease and obstructive sleep apnea

PubMed Central

Cooke, Jana R.; Ancoli-Israel, Sonia; Liu, Lianqi; Loredo, Jose S.; Natarajan, Loki; Palmer, Barton S.; He, Feng; Corey-Bloom, Jody

2009-01-01

Objective Patients with Alzheimer's disease (AD) and obstructive sleep apnea (OSA) experience disrupted sleep. This study examined the effect of continuous positive airway pressure (CPAP) on sleep parameters in AD patients with OSA. Methods A randomized placebo-controlled trial of 3 weeks of therapeutic CPAP (tCPAP) vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. Polysomnography data from screening after one night and after three weeks of treatment were analyzed. Records were scored for percent of each sleep stage, total sleep time (TST), sleep efficiency (SE), sleep period (SP), time in bed (TIB), sleep onset (SO), wake time after sleep onset (WASO), and arousals. A randomized design comparing one night of pCPAP to tCPAP and a paired analysis combining 3 weeks of tCPAP were performed. Results Fifty-two participants (mean age=77.8 years, SD=7.3) with AD and OSA were included. After one treatment night, the tCPAP group had significantly less % Stage 1 (p=0.04) and more % Stage 2 sleep (p=0.02) when compared to the pCPAP group. In the paired analysis, 3-weeks of tCPAP resulted in significant decreases in WASO (p=0.005), % Stage 1 (p=0.001), arousals (p=0.005), and in an increase in % Stage 3 (p=0.006). Conclusion In mild to moderate AD patients with OSA, the use of tCPAP resulted in deeper sleep after just one night, with improvements maintained for three weeks. PMID:19699148

Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

PubMed Central

Martínez-Montes, Eduardo

2013-01-01

This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

Evaluation of micronuclear frequencies in both circulating lymphocytes and buccal epithelial cells of patients with oral lichen planus and oral lichenoid contact reactions.

PubMed

Saruhanoğlu, A; Ergun, S; Kaya, M; Warnakulasuriya, S; Erbağcı, M; Öztürk, Ş; Deniz, E; Özel, S; Çefle, K; Palanduz, Ş; Tanyeri, H

2014-07-01

The aim of this study was to evaluate the frequency of micronuclei (MNs) in both circulating lymphocytes and buccal epithelial cells of patients with oral lichenoid contact reactions (OLCRs) or with oral lichen planus (OLP) and compare their MN scores with those of healthy controls (HCs). The study group included 21 patients (mean age 51.3 ± 12.4; 6 males, 15 females) with OLCRs and 22 patients (mean age 47.6 ± 14.4; 4 males, 18 females) with OLP who were clinically diagnosed and histopathologically confirmed according to WHO diagnostic criteria (WHO Collaborating Centre for Oral Precancerous Lesions, 1978). All patients with OLCR demonstrated contact allergy to tested dental materials when evaluated by skin patch testing according to International Contact Dermatitis Research Group (ICDRG), while all OLP patients tested negative to patch testing. Seventeen individuals with no oral mucosal disorders (mean age 51.7 ± 11.3; 8 males, 9 females) were recruited to constitute the healthy control group. [Correction added on 30 May 2014, after first online publication: the term, 'mean age' has been added to the text in parenthesis throughout the Material and Methods section.] Clinical features including type of OLP, location, disease severity, presence of skin lesions, presence of systemic disease including any allergies and dental (periodontal) status were recorded. MN analyses were performed on peripheral blood lymphocytes and on smears of buccal epithelial cells of all three study groups. Most OLP and OLCR lesions were of reticular type (83%), and OLP lesions were distributed bilaterally on the buccal mucosa (90.5%). The medians of MN frequencies in buccal epithelial cells in OLP and OLCR groups were significantly higher when compared with HC group (P < 0.001). [Correction added on 30 May 2014, after first online publication: in the results, 2nd sentence, the word 'lymphocytes' has been removed.] There was no significant difference between OLP group (14.5 range 3-95) and OLCR group (16.0 range 3-93) in terms of median MN frequencies in buccal epithelial cells (P = 0.724) nor in peripheral lymphocytes between OLP group (2.0 range 0-7) and OLCR group (1.0 range 0-6) (P = 0.92). [Correction added on 30 May 2014, after first online publication: (P = 0.92) was wrongly placed after 'peripheral lymphocytes' and has now been shifted to the end of the last sentence.] Micronuclei scores do not distinguish OLP from OLCR when using buccal smears. OLP and OLCR both demonstrated significantly higher MN frequencies in buccal cells, compared with healthy controls. MN assessment in both buccal epithelial cells and circulating lymphocytes may serve as a potential biomarker tool for evaluating any cancer risk in OLP and OLCR. [Correction added on 30 May 2014, after first online publication: the first and second sentences in the conclusions have been slightly changed.]. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease☆

PubMed Central

Dukart, Juergen; Mueller, Karsten; Villringer, Arno; Kherif, Ferath; Draganski, Bogdan; Frackowiak, Richard; Schroeter, Matthias L.

2013-01-01

The early diagnostic value of glucose hypometabolism and atrophy as potential neuroimaging biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been extensively explored using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI). The vast majority of previous imaging studies neglected the effects of single factors, such as age, symptom severity or time to conversion in MCI thus limiting generalisability of results across studies. Here, we investigated the impact of these factors on metabolic and structural differences. FDG-PET and MRI data from AD patients (n = 80), MCI converters (n = 65) and MCI non-converters (n = 64) were compared to data of healthy subjects (n = 79). All patient groups were split into subgroups by age, time to conversion (for MCI), or symptom severity and compared to the control group. AD patients showed a strongly age-dependent pattern, with younger patients showing significantly more extensive reductions in gray matter volume and glucose utilisation. In the MCI converter group, the amount of glucose utilisation reduction was linked to the time to conversion but not to atrophy. Our findings indicate that FDG-PET might be more closely linked to future cognitive decline whilst MRI being more closely related to the current cognitive state reflects potentially irreversible damage. PMID:24179852

Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein.

PubMed Central

Stevenson, S C; Rollence, M; Marshall-Neff, J; McClelland, A

1997-01-01

The adenovirus fiber protein is responsible for attachment of the virion to unidentified cell surface receptors. There are at least two distinct adenovirus fiber receptors which interact with the group B (Ad3) and group C (Ad5) adenoviruses. We have previously shown by using expressed adenovirus fiber proteins that it is possible to change the specificity of the fiber protein by exchanging the head domain with another serotype which recognizes a different receptor (S. C. Stevenson et al., J. Virol. 69:2850-2857, 1995). A chimeric fiber cDNA containing the Ad3 fiber head domain fused to the Ad5 fiber tail and shaft was incorporated into the genome of an adenovirus vector with E1 and E3 deleted encoding beta-galactosidase to generate Av9LacZ4, an adenovirus particle which contains a chimeric fiber protein. Western blot analysis of the chimeric fiber vector confirmed expression of the chimeric fiber protein and its association with the adenovirus capsid. Transduction experiments with fiber protein competitors demonstrated the altered receptor tropism of the chimeric fiber vector compared to that of the parental Av1LacZ4 vector. Transduction of a panel of human cell lines with the chimeric and parental vectors provided evidence for a different cellular distribution of the Ad5 and Ad3 receptors. Three cell lines (THP-1, MRC-5, and FaDu) were more efficiently transduced by the vector containing the Ad3 fiber head than by the Ad5 fiber vector. In contrast, human coronary artery endothelial cells were transduced more readily with the vector containing the Ad5 fiber than with the chimeric fiber vector. HeLa and human umbilical vein endothelial cells were transduced at equivalent levels compared with human diploid fibroblasts, which were refractory to transduction with both vectors. These results provide evidence for the differential expression of the Ad5 and Ad3 receptors on human cell lines derived from clinically relevant target tissues. Furthermore, we show that exchange of the fiber head domain is a viable approach to the production of adenovirus vectors with cell-type-selective transduction properties. It may be possible to extend this approach to the use of ligands for a range of different cellular receptors in order to target gene transfer to specific cell types at the level of transduction. PMID:9151872

Cholinergic and dopaminergic activities in senile dementia of Lewy body type.

PubMed

Perry, E K; Marshall, E; Perry, R H; Irving, D; Smith, C J; Blessed, G; Fairbairn, A F

1990-01-01

Analyses of brain tissue in a recently identified group of elderly demented patients suggest a neurochemical basis for some of the clinical features. Senile dementia of the Lewy body type (SDLT) can be distinguished from classical Alzheimer disease (AD) clinically by its acute presentation with confusion frequently accompanied by visual hallucinations, and neuropathologically by the presence of Lewy bodies and senile plaques (but not generally neurofibrillary tangles) in the cerebral cortex. Reductions in the cortical cholinergic enzyme choline acetyltransferase were more pronounced in individuals with (80%) compared to those without (50%) hallucinations and correlated strongly with mental test scores in the group as a whole. In the caudate nucleus, dopamine levels were related to the number of neurons in the substantia nigra, there being a 40-60% loss of both in SDLT--probably accounting for mild extrapyramidal features in some of these cases--compared with an 80% loss in Parkinson disease and no change in AD. The cholinergic correlates of mental impairment in SDLT together with the relative absence of cortical neurofibrillary tangles and evidence for postsynaptic cholinergic receptor compensation raise the question of whether this type of dementia may be more amenable to cholinotherapy than classical AD.

Women have farther to fall: gender differences between normal elderly and Alzheimer's disease in verbal memory engender better detection of Alzheimer's disease in women.

PubMed

Chapman, Robert M; Mapstone, Mark; Gardner, Margaret N; Sandoval, Tiffany C; McCrary, John W; Guillily, Maria D; Reilly, Lindsey A; DeGrush, Elizabeth

2011-07-01

We analyzed verbal episodic memory learning and recall using the Logical Memory (LM) subtest of the Wechsler Memory Scale-III to determine how gender differences in AD compare to those seen in normal elderly and whether or not these differences impact assessment of AD. We administered the LM to both an AD and a Control group, each comprised of 21 men and 21 women, and found a large drop in performance from normal elders to AD. Of interest was a gender interaction whereby the women's scores dropped 1.6 times more than the men's did. Control women on average outperformed Control men on every aspect of the test, including immediate recall, delayed recall, and learning. Conversely, AD women tended to perform worse than AD men. Additionally, the LM achieved perfect diagnostic accuracy in discriminant analysis of AD versus Control women, a statistically significantly higher result than for men. The results indicate the LM is a more powerful and reliable tool in detecting AD in women than in men.

Intrusions in story recall: when over-learned information interferes with episodic memory recall. Evidence from Alzheimer's disease.

PubMed

De Anna, Francesca; Attali, Eve; Freynet, Laurence; Foubert, Lucie; Laurent, Aurore; Dubois, Bruno; Dalla Barba, Gianfranco

2008-03-01

Patients with Alzheimer's disease (AD) suffer from distortions of memory. Among such distortions, intrusions in memory tests are frequently observed. In this study we describe the performance of a group of mild AD patients and a group of normal controls on the recall of three different types of stories: a previously unknown story, a well-known fairy-tale (Cinderella), and a modified well-known fairy-tale (Little Red Riding Hood is not eaten by the wolf). The aim of our study was to test the hypothesis that in patients who tend to produce intrusions, over-learned information interferes with episodic recall, i.e., the retrieval of specific, unique past episodes. AD patients produced significantly more intrusions in the recall of the modified fairy-tale compared to the recall of the two other stories. Intrusions in the recall of the modified fairy-tale always consisted of elements of the original version of the story. We suggest that in AD patients intrusions may be traced back to the interference of strongly represented, over-learned information in episodic memory recall.