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Sample records for alzheimers disease patients

  1. Alzheimer's disease. Physician-patient communication.

    PubMed Central

    Orange, J. B.; Molloy, D. W.; Lever, J. A.; Darzins, P.; Ganesan, C. R.

    1994-01-01

    The number of cognitively impaired elderly in Canada has increased greatly during the past two decades; nearly all have Alzheimer's disease (AD). The memory problems and changes in language and communication of these patients place tremendous strain on physicians who are searching for a differential diagnosis and are trying to communicate with them. Reviewing the salient language and communication features of AD patients leads to strategies for improving effective physician-patient communication. PMID:8019193

  2. Emotional Working Memory in Alzheimer's Disease Patients

    PubMed Central

    Satler, Corina; Tomaz, Carlos

    2011-01-01

    Background Few studies have assessed whether emotional content affects processes supporting working memory in Alzheimer disease (AD) patients. Methods We assessed 22 AD patients and 40 elderly controls (EC) with a delayed matching and non-matching to sample task (DMST/DNMST), and a spatial-delayed recognition span task (SRST; unique/varied) using emotional stimuli. Results AD patients showed decreased performance on both tasks compared with EC. With regard to the valence of the stimuli, we did not observe significant performance differences between groups in the DMST/DNMST. However, both groups remembered a larger number of negative than positive or neutral pictures on unique SRST. Conclusion The results suggest that AD patients show a relative preservation of working memory for emotional information, particularly for negative stimuli. PMID:22163239

  3. About Alzheimer's Disease: Alzheimer's Basics

    MedlinePlus

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Alzheimer's Basics What is Alzheimer's disease? What happens to ... with Alzheimer's disease? What is dementia? What is Alzheimer's disease? Alzheimer’s disease is an irreversible, progressive brain ...

  4. Alzheimer's disease.

    PubMed

    Scheltens, Philip; Blennow, Kaj; Breteler, Monique M B; de Strooper, Bart; Frisoni, Giovanni B; Salloway, Stephen; Van der Flier, Wiesje Maria

    2016-07-30

    Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research. PMID:26921134

  5. Sexual Concerns of Male Spouses of Female Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Litz, Brett T.; And Others

    1990-01-01

    Presents case study which highlights attendant cognitive changes that occur in Alzheimer's patient, presenting caregiver with challenges to couple's sexual functioning. Describes man who reported erectile dysfunction directly stemming from stressful changes that had occurred in his relationship to his wife who had Alzheimer's disease. General…

  6. Alzheimer disease

    MedlinePlus

    Senile dementia - Alzheimer type (SDAT); SDAT; Dementia - Alzheimer ... The exact cause of Alzheimer disease (AD) is not known. Research shows that certain changes in the brain lead to AD. You are more likely ...

  7. Stereological quantification of the cerebellum in patients with Alzheimer's disease.

    PubMed

    Andersen, Kjeld; Andersen, Birgitte Bo; Pakkenberg, Bente

    2012-01-01

    Nonquantitative studies indicate that the cerebellum is neuropathologically affected in Alzheimer's disease; however, no quantitative studies on the subject have yet been conducted. Ten cerebella from elderly female subjects with severe Alzheimer's disease and 10 age- and gender-matched controls were examined. The cerebellum was divided into 5 regions and the Purkinje and granule cell number and density, cortical volume, molecular and granular layer volume and thickness, white matter volume, surface area, and the Purkinje cell gradient were stereologically estimated. There was no significant difference between the groups in Purkinje or granule cell number or density, and no overall difference in Purkinje cell gradient. However, there was a significant 12.7% reduction in total cerebellar volume in the Alzheimer's group and significant localized differences between the groups regarding other parameters. The relative lack of neuropathological changes in the cerebellum of severely demented Alzheimer's patients suggests that neuronal cell bodies on a global scale apparently still are intact. PMID:20728248

  8. Semantic Priming for Coordinate Distant Concepts in Alzheimer's Disease Patients

    ERIC Educational Resources Information Center

    Perri, R.; Zannino, G. D.; Caltagirone, C.; Carlesimo, G. A.

    2011-01-01

    Semantic priming paradigms have been used to investigate semantic knowledge in patients with Alzheimer's disease (AD). While priming effects produced by prime-target pairs with associative relatedness reflect processes at both lexical and semantic levels, priming effects produced by words that are semantically related but not associated should…

  9. Assessing Impact on Family Caregivers to Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Talkington-Boyer, Shannon; Snyder, Douglas K.

    1994-01-01

    Examined impact of caregiving among 110 caregivers to aging family member with Alzheimer's disease. Family caregivers' appraisals along dimensions of subjective burden, negative impact, caregiving satisfaction, and caregiver mastery were correlated with extent of memory and behavior problems of patient and caregivers' coping style, locus of…

  10. Alzheimer disease

    MedlinePlus

    ... of brain function that occurs with certain diseases. Alzheimer disease (AD) is one form of dementia. It affects ... The exact cause of Alzheimer disease (AD) is not known. Research shows that certain changes in the brain lead to AD. You are more likely to ...

  11. Alzheimer's Disease

    MedlinePlus

    Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that ... higher if a family member has had the disease. No treatment can stop the disease. However, some ...

  12. Communicative function in patients with questionable Alzheimer's disease.

    PubMed

    Heller, R B; Dobbs, A R; Rule, B G

    1992-09-01

    The communicative skills of patients with questionable Alzheimer's disease (AD) were examined by having patients describe events shown in a silent video cartoon. As anticipated, questionable AD patients provided fewer clauses in their descriptions than did education- and age-matched controls. This finding was independent of differences in word finding ability. More important, the patients failed to describe as many of the thematically important events as did the controls, a difference that affected the overall informativeness of the communication. Even though the patients were sensitive to event importance, there was no evidence of compensation in their descriptions (i.e., a greater concentration of important events). Several interpretations are presented that focus on possible deficits in the pragmatic or semantic systems of language or both as an early symptom of Alzheimer's disease. PMID:1388860

  13. [Treatment of patients with Alzheimer's disease: a breakthrough or not?].

    PubMed

    van Marum, Rob J

    2015-01-01

    The results of an open-label extension study of the Expedition I and II studies with solanezumab in patients with Alzheimer's disease, neither of which had shown an effect on cognition and functional ability, were recently presented at the Alzheimer's Association International Conference in Toronto. Placebo and intervention patients with mild Alzheimer's disease from both studies were offered the option of continuing with solanezumab for 2 additional years. The data from this group were re-analysed using a new analysis technique, the so-called 'delayed start analysis'. On the basis of the re-analysis it was concluded that solanezumab does show disease-modifying activity and should be considered a promising candidate for treatment of Alzheimer's disease in the near future. This conclusion, however, is poorly supported by the data presented in the study. A more definite positioning of solanezumab will not be possible until data from the ongoing Expedition III study becomes available in 2017 at the earliest. PMID:26271177

  14. [Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs].

    PubMed

    Zamarrón Cassinello, Ma Dolores; Tárraga Mestre, Luis; Fernández-Ballesteros, Rocío

    2008-08-01

    The main purpose of this article is to examine whether cognitive plasticity increases after cognitive training in Alzheimer's disease patients. Twenty six patients participated in this study, all of them diagnosed with mild Alzheimer's disease, 17 of them received a cognitive training program during 6 months, and the other 9 were assigned to the control group. Participants were assigned to experimental or control conditions for clinical reasons. In order to assess cognitive plasticity, all patients were assessed before and after treatment with three subtests from the "Bateria de Evaluación de Potencial de Aprendizaje en Demencias" [Assessment Battery of Learning Potential in Dementia] (BEPAD). After treatment, Alzheimer's disease patients improved their performance in all the tasks assessing cognitive plasticity: viso-spatial memory, audio-verbal memory and verbal fluency. However, the cognitive plasticity scores of the patients in the control group decreased. In conclusion, this study showed that cognitive stimulation programs can improve cognitive functioning in mildly demented patients, and patients who do not receive any cognitive interventions may reduce their cognitive functioning. PMID:18674439

  15. Positron emission tomography in patients with clinically diagnosed Alzheimer's disease.

    PubMed Central

    McGeer, P L; Kamo, H; Harrop, R; Li, D K; Tuokko, H; McGeer, E G; Adam, M J; Ammann, W; Beattie, B L; Calne, D B

    1986-01-01

    Fourteen patients who had clinically diagnosed Alzheimer's disease with mild to severe dementia (mean age 69.1 years) were evaluated by calculation of local cerebral metabolic rate for glucose (LCMR-gl) based on uptake of 18F-2-fluoro-2-deoxyglucose (FDG) detected with positron emission tomography (PET). PET scanning showed that the patients had significantly lower LCMR-gl values than 11 age-matched neurologically normal volunteers (mean age 66.3 years). The differences were most marked in the temporal cortex, followed by the frontal, parietal and occipital cortex. In each case the LCMR-gl value was below the lowest control value in at least one cortical area and usually in several; the reduction in LCMR-gl and the number of regions involved in the patients increased with the severity of the dementia. Deficits noted in neuropsychologic testing generally correlated with those predicted from loss of regional cortical metabolism. The patients with Alzheimer's disease were also examined with magnetic resonance imaging, computed tomography or both; the degree of atrophy found showed only a poor correlation with the neuropsychologic deficit. Significant atrophy was also noted in some of the controls. A detailed analysis of LCMR-gl values in selected cerebral regions of various sizes refuted the hypothesis that the reduction in cortical glucose metabolism in Alzheimer's disease is due to the filling by metabolically inert cerebrospinal fluid of space created by tissue atrophy. Images Fig. 2 Fig. 3 Fig. 4 Fig. 7 Fig. 8 Fig. 9 PMID:3512063

  16. Mitochondrial DNA sequence analysis of four Alzheimer`s and Parkinson`s disease patients

    SciTech Connect

    Brown, M.D.; Shoffner, J.M.; Wallace, D.C.

    1996-01-22

    The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with Alzheimer`s disease (AD) exhibiting AD plus Parkinson`s disease (PD) neuropathologic changes and one patient with PD. Patient mtDNA sequences were compared to the standard Cambridge sequence to identify base changes. In the first AD + PD patient, 2 of the 15 nucleotide substitutions may contribute to the neuropathology, a nucleotide pair (np) 4336 transition in the tRNA{sup Gln} gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients or 905 controls. In the second AD + PD patient, 27 nucleotide substitutions were detected, including an np 3397 transition in the ND1 gene which converts a conserved methionine to a valine. In the third AD + PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber`s hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene. For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonstrate a casual role for these base substitutions in neurodegenerative disease. 68 refs., 2 tabs.

  17. Functional assessment staging (FAST) in Korean patients with Alzheimer's disease.

    PubMed

    Na, Hae-Ri; Kim, Sang-Yun; Chang, Young-Hee; Park, Moon-Ho; Cho, Sung-Tae; Han, Il-Woo; Kim, Tae-You; Hwang, Sul-A

    2010-01-01

    Functional Assessment Staging (FAST) was devised to meet the need for a more brief patient-derived rating scale for evaluating changes in functional performance and activities of daily living skills in all the stages of Alzheimer's disease (AD). FAST was administered to 464 patients with probable AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The patients were also evaluated using the Korean version of the Mini-Mental Status Examination (K-MMSE), the Clinical Dementia Rating (CDR), the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Global Deterioration Scale (GDS), the Barthel Activities of Daily Living (B-ADL), and the Seoul-Instrumental Activities of Daily Living (S-IADL). For patients with moderate to severe dementia, the Korean versions of the Severe Impairment Battery (SIB-Ko) and Baylor profound mental status examination (BPMSE-Ko) were also administered. There were significant correlations between the FAST and the K-MMSE scores (r= - 0.71, p< 0.001), between the FAST and the SIB-Ko scores (r= - 0.54, p< 0.001) and between the FAST and the BPMSE-Ko scores (r=- 0.46, p< 0.001). The FAST was also correlated with the CDR, the CDR-SB, the B-ADL, and the S-IADL (p< 0.001). Ultimately, FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the disease course. Moreover, the findings of the present study suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD in Korean AD patients with dementia. PMID:20847407

  18. Alzheimer's Disease Medications

    MedlinePlus

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer's Disease Medications Fact Sheet Treatment for Mild to ...

  19. Understanding Alzheimer's Disease

    MedlinePlus

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... National Alzheimer's Project Act (NAPA) About ADEAR Understanding Alzheimer's Disease: What You Need to Know Introduction Many ...

  20. Cerebrospinal fluid carnitine levels in patients with Alzheimer's disease.

    PubMed

    Rubio, J C; de Bustos, F; Molina, J A; Jiménez-Jiménez, F J; Benito-León, J; Martín, M A; Campos, Y; Ortí-Pareja, M; Cabrera-Valdivia, F; Arenas, J

    1998-03-01

    We assessed free carnitine (FC) and acylcarnitine esters (AC) in both cerebrospinal fluid (CSF) and plasma from 24 patients with diagnostic criteria for Alzheimer's disease (AD), and from 28 healthy matched-controls. We found no significant correlation between FC and AC levels in CSF. FC and AC levels in CSF did not differ significantly between AD patients and controls, but plasma FC levels were significantly lower in AD patients. CSF and plasma FC and AC levels did not correlate with age, age at onset of AD, duration of AD, and scores of the Minimental State Examination of Folstein. Although these results suggest that CSF carnitine levels are apparently unrelated with the risk for AD, the trend of the FC/AC ratio to be higher in AD patients might suggest the possibility of a lower carnitine acetyltransferase activity in AD, as previously reported in some brain areas. PMID:9562266

  1. Circadian Rhythm Disturbances in Patients with Alzheimer's Disease: A Review

    PubMed Central

    Weldemichael, Dawit A.; Grossberg, George T.

    2010-01-01

    Circadian Rhythm Disturbances (CRDs) affect as many as a quarter of Alzheimer's disease (AD) patients during some stage of their illness. Alterations in the suprachiasmatic nucleus and melatonin secretion are the major factors linked with the cause of CRDs. As a result, the normal physiology of sleep, the biological clock, and core body temperature are affected. This paper systematically discusses some of the causative factors, typical symptoms, and treatment options for CRDs in patients with AD. This paper also emphasizes the implementation of behavioral and environmental therapies before embarking on medications to treat CRDs. Pharmacotherapeutic options are summarized to provide symptomatic benefits for the patient and relieve stress on their families and professional care providers. As of today, there are few studies relative to CRDs in AD. Large randomized trials are warranted to evaluate the effects of treatments such as bright light therapy and engaging activities in the reduction of CRDs in AD patients. PMID:20862344

  2. Treatments for Alzheimer's Disease

    MedlinePlus

    ... 3900 Find your chapter: search by state Home > Alzheimer's Disease > Treatments Overview What Is Dementia? What Is Alzheimer's? ... and move closer to a cure. Treatments for Alzheimer's disease Currently, there is no cure for Alzheimer's. But ...

  3. Endostatin level in cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Salza, Romain; Oudart, Jean-Baptiste; Ramont, Laurent; Maquart, François-Xavier; Bakchine, Serge; Thoannès, Henri; Ricard-Blum, Sylvie

    2015-01-01

    The aim of this study was to measure the level of endostatin, a fragment of collagen XVIII that accumulates in the brain of patients with Alzheimer's disease (AD), in the cerebrospinal fluids (CSF) of patients with neurodegenerative diseases. The concentrations of total protein, endostatin, amyloid-β1-42 peptide, tau, and hyperphosphorylated tau proteins were measured by enzyme-linked immunosorbent assay in CSF of patients with AD (n = 57), behavioral frontotemporal dementia (bvFTD, n = 22), non AD and non FTD dementia (nAD/nFTD, n = 84), and 45 subjects without neurodegenerative diseases. The statistical significance of the results was assessed by Mann-Whitney and Kruskal and Wallis tests, and by ROC analysis. The concentration of endostatin in CSF was higher than the levels of the three markers of AD both in control subjects and in patients with neurodegenerative diseases. The endostatin/amyloid-β1-42 ratio was significantly increased in patients with AD (257%, p < 0.0001) and nAD/nFTD (140%, p < 0.0001) compared to controls. The endostatin/tau protein ratio was significantly decreased in patients with AD (-49%, p < 0.0001) but was increased in bvFTD patients (89%, p < 0.0001) compared to controls. In the same way, the endostatin/hyperphosphorylated tau protein ratio was decreased in patients with AD (-21%, p = 0.0002) but increased in patients with bvFTD (81%, p = 0.0026), compared to controls. The measurement of endostatin in CSF and the calculation of its ratio relative to well-established AD markers improve the diagnosis of bvFTD patients and the discrimination of patients with AD from those with bvFTD and nAD/nFTD. PMID:25408220

  4. Delusions in Patients with Alzheimer's Disease: A Multidimensional Approach.

    PubMed

    D'Onofrio, Grazia; Panza, Francesco; Sancarlo, Daniele; Paris, Francesco F; Cascavilla, Leandro; Mangiacotti, Antonio; Lauriola, Michele; Paroni, Giulia H; Seripa, Davide; Greco, Antonio

    2016-01-01

    In Alzheimer's disease (AD) patients with delusions, clinical outcomes and mortality result from a combination of psychological, biological, functional, and environmental factors. We determined the effect of delusions on mortality risk, clinical outcomes linked to comprehensive geriatric assessment (CGA), cognitive, depressive, and neuropsychiatric symptoms (NPS) in 380 consecutive AD patients with Mini-Mental State Examination, Clinical Dementia Rating scale, 15-item Geriatric Depression Scale, and Neuropsychiatric Inventory (NPI), assessing one-year mortality risk using the Multidimensional Prognostic Index (MPI). We included 121 AD patients with delusions (AD-D) and 259 AD patients without delusions (AD-noD). AD-D patients were significantly older, with higher age at onset and cognitive impairment, a more severe stage of dementia, and more depressive symptoms than AD-noD patients. Disease duration was slightly higher in AD-D patients than in those without delusions, although this difference was not statistically significant. At CGA, AD-D patients showed a higher grade of disability in basic and instrumental activities of daily living, and an increased risk of malnutrition and bedsores. The two groups of patients significantly differed in MPI score (AD-D: 0.65 versus AD-noD: 0.51, p <  0.0001) and MPI grade. AD-D patients showed also a significant higher score in NPI of the following NPS than AD-noD patients: hallucinations, agitation/aggression, depression mood, apathy, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. Therefore, AD-D patients showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and several neuropsychiatric domains than AD-noD patients, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality. PMID:26890768

  5. Galantamine: additional benefits to patients with Alzheimer's disease.

    PubMed

    Lilienfeld, S; Parys, W

    2000-09-01

    Galantamine, a novel treatment for Alzheimer's disease (AD), has a dual mechanism of action, combining allosteric modulation of nicotinic acetylcholine receptors with reversible, competitive inhibition of acetylcholinesterase. In the Phase III clinical trial programme, over 3,000 patients with mild-to-moderate AD were enrolled in one of five randomized, controlled, double-blind studies. Using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) to assess memory and other cognitive functions, galantamine was found to be significantly superior to placebo in all five studies at doses of 16, 24 and 32 mg/day. In all studies, galantamine-treated patients maintained their cognitive function, whereas the placebo-treated patients experienced a significant deterioration in ADAS-cog scores. The 32-mg/day dose was not associated with any additional cognitive benefit. Pooled data from two 6-month studies (n = 1,269), which were of identical design, show that the therapeutic benefits of galantamine are sustained for the duration of treatment. The treatment effect (galantamine-placebo difference on ADAS-cog) for the pooled data was approximately 4 points. Clinical benefit was seen in all levels of disease severity, with a 7-point advantage over placebo on ADAS-cog for patients with moderately severe disease. Galantamine was well tolerated, with most patients completing the 6-month studies. The long-term effects of galantamine have been evaluated in a 12-month study. Patients who completed one of the pivotal 6-month studies (n = 353) were entered into a 6-month open-label extension. Cognitive and daily function were maintained throughout the 12 months in patients who received galantamine 24 mg/day. This sustained level of benefit may reflect galantamine's dual effect on the cholinergic system. Data from a 5-month, placebo-controlled study have also shown that galantamine produces significant benefits on behavioural symptoms. The persistence and range of

  6. Analysis of Retinal Peripapillary Segmentation in Early Alzheimer's Disease Patients

    PubMed Central

    Salobrar-Garcia, Elena; Hoyas, Irene; Leal, Mercedes; de Hoz, Rosa; Rojas, Blanca; Ramirez, Ana I.; Salazar, Juan J.; Yubero, Raquel; Gil, Pedro; Triviño, Alberto; Ramirez, José M.

    2015-01-01

    Decreased thickness of the retinal nerve fiber layer (RNFL) may reflect retinal neuronal-ganglion cell death. A decrease in the RNFL has been demonstrated in Alzheimer's disease (AD) in addition to aging by optical coherence tomography (OCT). Twenty-three mild-AD patients and 28 age-matched control subjects with mean Mini-Mental State Examination 23.3 and 28.2, respectively, with no ocular disease or systemic disorders affecting vision, were considered for study. OCT peripapillary and macular segmentation thickness were examined in the right eye of each patient. Compared to controls, eyes of patients with mild-AD patients showed no statistical difference in peripapillary RNFL thickness (P > 0.05); however, sectors 2, 3, 4, 8, 9, and 11 of the papilla showed thinning, while in sectors 1, 5, 6, 7, and 10 there was thickening. Total macular volume and RNFL thickness of the fovea in all four inner quadrants and in the outer temporal quadrants proved to be significantly decreased (P < 0.01). Despite the fact that peripapillary RNFL thickness did not statistically differ in comparison to control eyes, the increase in peripapillary thickness in our mild-AD patients could correspond to an early neurodegeneration stage and may entail the existence of an inflammatory process that could lead to progressive peripapillary fiber damage. PMID:26557684

  7. Vaccination against Alzheimer disease

    PubMed Central

    Fettelschoss, Antonia; Zabel, Franziska; Bachmann, Martin F

    2014-01-01

    Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer. PMID:24535580

  8. Memory for emotional stimuli in patients with Alzheimer's disease.

    PubMed

    Fleming, Kirsten; Kim, Susan H; Doo, Michael; Maguire, Gerald; Potkin, Steven G

    2003-01-01

    Although a hallmark of Alzheimer's disease (AD) is memory impairment, there is speculation that recall may be enhanced when an emotional component is associated with an event. The current study aims to assess whether patients with AD would recall emotionally laden material better than neutral stimuli. DSM-IV-diagnosed AD patients with mild to moderate dementia, as well as groups of young and elderly healthy controls, participated in this study. All subjects were administered three word lists for three trials each. The words were positive, negative, or neutral in valence and matched for concreteness, emotionality, and pleasantness. As expected, the controls performed significantly better than the AD patients. Importantly, the pattern of recall for the emotions was different, such that both control groups recalled all emotions equally, whereas the AD patients recalled significantly more negative words than positive or neutral. These findings of improved immediate memory for emotional material in AD lends support to the notion that mnemonic functions are differentially affected in the disease. PMID:14682081

  9. [Alzheimer and the discovery of Alzheimer's disease].

    PubMed

    Zhagn, Lili; Li, Zhiping

    2014-09-01

    Alzheimer was born in Germany in 1864. In 1887, Alzheimer graduated with a medical doctor degree at the University of Würzburg. In 1888, Alzheimer began to work in the Community Hospital for Mental and Epileptic Patients in Frankfurt am Main for 14 years. During this time, Alzheimer published the six-volume Histologic and Histopathologic Studies of the Cerebral Cortex, with co-author Franz Nissl. In 1903, Alzheimer came to work in the Royal Psychiatric Clinic of the University of Munich. One year later, he published his postdoctoral paper of Histological Studies about the Differential Diagnosis of Progressive Paralysis in 1904. In 1912, Alzheimer was provided the chair of psychiatry at the University of Breslau. On the way to Breslau, Alzheimer got sick, and eventually died in 1915. In 1906, Alzheimer found numerous amyloid plaques and neurofibrillary tangles in the brain of a patient called Auguste under the microscope. In November of the same year, Alzheimer gave a lecture about Auguste's case at the 37(th) Conference of South-West German Psychiatrists in Tübingen, which received little attention. In 1910, Kraepelin mentioned "Alzheimer's disease" for the first time to name the disease of what Auguste got in the 8th edition of Handbook of Psychiatry. Therefore, Alzheimer achieved worldwide recognition. PMID:25579215

  10. Factors Associated with Caregiver Burden in Patients with Alzheimer's Disease

    PubMed Central

    Kang, Hyo Shin; Myung, Woojae; Na, Duk L.; Kim, Seong Yoon; Lee, Jae-Hong; Han, Seol-Heui; Choi, Seong Hye; Kim, SangYun; Kim, Seonwoo

    2014-01-01

    Objective Caregivers for patients with Alzheimer's disease (AD) suffer from psychological and financial burdens. However, the results of the relationship between burden and cognitive function, performance of activities of daily living, and depressive symptoms have remained inconsistent. Therefore, the aim of this study was to examine which factors are more significant predictors of heightened burden, cognitive impairment or functional decline, besides neuropsychiatric symptoms. Methods A cross-sectional study was conducted in a sample comprised of 1,164 pairs of patients with AD and caregivers from the Clinical Research of Dementia of South Korea study cohorts. The cognitive function of each sub-domain, functional impairments, depressive symptoms, and caregiver burden were assessed using the dementia version of Seoul Neuropsychological Screening Battery (SNSB-D), Barthel Index for Daily Living Activities (ADL), Seoul-Instrumental Activities of Daily Living (S-IADL), the Clinical Dementia Rating Sum of Box (CDR-SB), the Global Deterioration Scale (GDS), the Korean version of the Neuropsychiatric Inventory (K-NPI), and the 15-item Geriatric Depression Scale. Results We found that higher severity (higher CDR-SB and GDS scores) and more functional impairment (lower ADL and higher S-IADL scores) were significantly associated with higher caregiver burden. In addition, depressive symptoms of patients (higher Geriatric Depression Scale scores) were associated with higher caregiver burden. Conclusion Therefore, interventions to help maintain activities of daily living in patients with AD may alleviate caregiver burden and improve caregiver well-being. PMID:24843370

  11. Analysis of electroencephalograms in Alzheimer's disease patients with multiscale entropy.

    PubMed

    Escudero, J; Abásolo, D; Hornero, R; Espino, P; López, M

    2006-11-01

    The aim of this study was to analyse the electroencephalogram (EEG) background activity of Alzheimer's disease (AD) patients using multiscale entropy (MSE). MSE is a recently developed method that quantifies the regularity of a signal on different time scales. These time scales are inspected by means of several coarse-grained sequences formed from the analysed signals. We recorded the EEGs from 19 scalp electrodes in 11 AD patients and 11 age-matched controls and estimated the MSE profile for each epoch of the EEG recordings. The shape of the MSE profiles reveals the EEG complexity, and it suggests that the EEG contains information in deeper scales than the smallest one. Moreover, the results showed that the EEG background activity is less complex in AD patients than control subjects. We found significant differences between both subject groups at electrodes F3, F7, Fp1, Fp2, T5, T6, P3, P4, O1 and O2 (p-value < 0.01, Student's t-test). These findings indicate that the EEG complexity analysis performed on deeper time scales by MSE may be a useful tool in order to increase our knowledge of AD. PMID:17028404

  12. Special Units for Alzheimer's Disease Patients: A Critical Look.

    ERIC Educational Resources Information Center

    Ohta, Russell; Ohta, Brenda M.

    1988-01-01

    Examined special nursing home units for patients with Senile Dementia of the Alzheimer's Type using published and unpublished reports, as well as policy manuals, and personal observations. Identified critical dimensions on which these units can differ. Discusses heterogeneity of these units. (Author/ABL)

  13. Family History of Alzheimer's Disease and Cortical Thickness in Patients With Dementia.

    PubMed

    Ganske, Steffi; Haussmann, Robert; Gruschwitz, Antonia; Werner, Annett; Osterrath, Antje; Baumgaertel, Johanna; Lange, Jan; Donix, Katharina L; Linn, Jennifer; Donix, Markus

    2016-08-01

    A first-degree family history of Alzheimer's disease reflects genetic risks for the neurodegenerative disorder. Recent imaging data suggest localized effects of genetic risks on brain structure in healthy people. It is unknown whether this association can also be found in patients who already have dementia. Our aim was to investigate whether family history risk modulates regional medial temporal lobe cortical thickness in patients with Alzheimer's disease. We performed high-resolution magnetic resonance imaging and cortical unfolding data analysis on 54 patients and 53 nondemented individuals. A first-degree family history of Alzheimer's disease was associated with left hemispheric cortical thinning in the subiculum among patients and controls. The contribution of Alzheimer's disease family history to regional brain anatomy changes independent of cognitive impairment may reflect genetic risks that modulate onset and clinical course of the disease. PMID:27303063

  14. Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease.

    PubMed Central

    Etcheberrigaray, R; Ito, E; Oka, K; Tofel-Grehl, B; Gibson, G E; Alkon, D L

    1993-01-01

    Since memory loss is characteristic of Alzheimer disease (AD), and since K+ channels change during acquisition of memory in both molluscs and mammals, we investigated K+ channel function as a possible site of AD pathology and, therefore, as a possible diagnostic index as well. A 113-pS tetraethylammonium (TEA)-sensitive K+ channel was consistently absent from AD fibroblasts, while it was often present in young and aged control fibroblasts. A second (166-pS) K+ channel was present in all three groups. Elevated external potassium raised intracellular Ca2+ in all cases. TEA depolarized and caused intracellular Ca2+ elevation in young and aged control fibroblasts but not AD fibroblasts. The invariable absence of a 113-pS TEA-sensitive K+ channel and TEA-induced Ca2+ signal indicate K+ channel dysfunction in AD fibroblasts. These results suggest the possibility of a laboratory method that would diagnostically distinguish AD patients, with or without a family history of AD, from normal age-matched controls and also from patients with non-AD neurological and psychiatric disorders. PMID:8367484

  15. Music as a memory enhancer in patients with Alzheimer's disease.

    PubMed

    Simmons-Stern, Nicholas R; Budson, Andrew E; Ally, Brandon A

    2010-08-01

    Musical mnemonics have a long and diverse history of popular use. In addition, music processing in general is often considered spared by the neurodegenerative effects of Alzheimer's disease (AD). Research examining these two phenomena is limited, and no work to our knowledge has explored the effectiveness of musical mnemonics in AD. The present study sought to investigate the effect of music at encoding on the subsequent recognition of associated verbal information. Lyrics of unfamiliar children's songs were presented bimodally at encoding, and visual stimuli were accompanied by either a sung or a spoken recording. Patients with AD demonstrated better recognition accuracy for the sung lyrics than the spoken lyrics, while healthy older adults showed no significant difference between the two conditions. We propose two possible explanations for these findings: first, that the brain areas subserving music processing may be preferentially spared by AD, allowing a more holistic encoding that facilitates recognition, and second, that music heightens arousal in patients with AD, allowing better attention and improved memory. PMID:20452365

  16. From here to epilepsy: the risk of seizure in patients with Alzheimer's disease.

    PubMed

    Nicastro, Nicolas; Assal, Frédéric; Seeck, Margitta

    2016-03-01

    To describe the association between Alzheimer's disease and seizures by reviewing epidemiological data from available literature and to assess the putative pathophysiological links between neurodegeneration and altered cortical excitability. We also discuss specific antiepileptic treatment strategies in patients with Alzheimer's disease, as well as transient epileptic amnesia as a possible crossroads between degeneration and epilepsy. Regarding epidemiology, we searched publications in Pubmed, Medline, Scopus and Web of Science (until September 2015) using the keywords "incidence", "prevalence" and "frequency", as well as "Alzheimer's disease" and "seizures". In addition, therapeutic aspects for seizures in Alzheimer's disease were searched using the key words "antiepileptic drugs", "seizure treatment" and "Alzheimer". The prevalence and incidence rates of seizures were found to be increased 2 to 6-fold in patients with Alzheimer's disease compared to age-adjusted control patients. Treatment strategies have mainly been extrapolated from elderly patients without dementia, except for one single randomised trial, in which levetiracetam, lamotrigine and phenobarbital efficacy and tolerance were investigated in patients with Alzheimer's disease. Mouse models appear to show a major role of amyloid precursor protein and its cleavage products in the generation of cortical hyperexcitability. A link between Alzheimer's disease and epilepsy has long been described and recent cohort studies have more clearly delineated risk factors associated with the genesis of seizures, such as early onset and possibly severity of dementia. As genetic forms of Alzheimer's disease and experimental mouse models suggest, beta-amyloid may play a prominent role in the propagation of synchronised abnormal discharges, perhaps more via an excitatory mode than a direct neurodegenerative effect. PMID:26907471

  17. Naming ability in patients with mild to moderate Alzheimer's disease: what changes occur with the evolution of the disease?

    PubMed Central

    Silagi, Marcela Lima; Bertolucci, Paulo Henrique Ferreira; Ortiz, Karin Zazo

    2015-01-01

    OBJECTIVES: Naming deficit is a linguistic symptom that appears in the initial phase of Alzheimer's disease, but the types of naming errors and the ways in which this deficit changes over the course of the disease are unclear. We analyzed the performance of patients with Alzheimer's disease on naming tasks during the mild and moderate phases and verified how this linguistic skill deteriorates over the course of the disease. METHODS: A reduced version of the Boston Naming Test was administered to 30 patients with mild Alzheimer's disease, 30 patients with moderate Alzheimer's disease and 30 healthy controls. Errors were classified as verbal semantic paraphasia, verbal phonemic paraphasia, no response (pure anomia), circumlocution, unrelated verbal paraphasia, visual errors or intrusion errors. RESULTS: The patients with moderate Alzheimer's disease had significantly fewer correct answers than did both the control group and the group with mild Alzheimer's disease. With regard to the pattern of errors, verbal semantic paraphasia errors were the most frequent errors in all three groups. Additionally, as the disease severity increased, there was an increase in the number of no-response errors (pure anomia). The group with moderate Alzheimer's disease demonstrated a greater incidence of visual errors and unrelated verbal paraphasias compared with the other two groups and presented a more variable pattern of errors. CONCLUSIONS: Performance on nominative tasks worsened as the disease progressed in terms of both the quantity and the type of errors encountered. This result reflects impairment at different levels of linguistic processing. PMID:26106961

  18. Treatment of Alzheimer disease.

    PubMed

    Winslow, Bradford T; Onysko, Mary K; Stob, Christian M; Hazlewood, Kathleen A

    2011-06-15

    Alzheimer disease is the most common form of dementia, affecting nearly one-half [corrected] of Americans older than 85 years. It is characterized by progressive memory loss and cognitive decline. Amyloid plaque accumulation, neurofibrillary tau tangles, and depletion of acetylcholine are among the pathologic manifestations of Alzheimer disease. Although there are no proven modalities for preventing Alzheimer disease, hypertension treatment, omega-3 fatty acid supplementation, physical activity, and cognitive engagement demonstrate modest potential. Acetylcholinesterase inhibitors are first-line medications for the treatment of Alzheimer disease, and are associated with mild improvements in cognitive function, behavior, and activities of daily living; however, the clinical relevance of these effects is unclear. The most common adverse effects of acetylcholinesterase inhibitors are nausea, vomiting, diarrhea, dizziness, confusion, and cardiac arrhythmias. Short-term use of the N-methyl-D-aspartate receptor antagonist memantine can modestly improve measures of cognition, behavior, and activities of daily living in patients with moderate to severe Alzheimer disease. Memantine can also be used in combination with acetylcholinesterase inhibitors. Memantine is generally well tolerated, but whether its benefits produce clinically meaningful improvement is controversial. Although N-methyl-D-aspartate receptor antagonists and acetylcholinesterase inhibitors can slow the progression of Alzheimer disease, no pharmacologic agents can reverse the progression. Atypical antipsychotics can improve some behavioral symptoms, but have been associated with increased mortality rates in older patients with dementia. There is conflicting evidence about the benefit of selegiline, testosterone, and ginkgo for the treatment of Alzheimer disease. There is no evidence supporting the beneficial effects of vitamin E, estrogen, or nonsteroidal anti-inflammatory drug therapy. PMID:21671540

  19. Neuropathology of Alzheimer's Disease

    PubMed Central

    Perl, Daniel P.

    2010-01-01

    Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer's disease are the neurofibrillary tangle and the senile plaque. The neurofibrillary tangle consists of abnormal accumulations of abnormally phosphorylated tau within the perikaryal cytoplasm of certain neurons. The senile plaque consists of a central core of beta-amyloid, a 4-kD peptide, surrounded by abnormally configured neuronal processes or neurites. Other neuropathological lesions are encountered in cases of Alzheimer's disease, but the disease is defined and recognized by these 2 cardinal lesions. Other lesions include poorly understood changes such as granulovacuolar degeneration and eosinophilic rod-like bodies (Hirano bodies). The loss of synaptic components is a change that clearly has a significant impact on cognitive function and represents another important morphological alteration. It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age. It is also noted that instances of pure forms of Alzheimer's disease, in the absence of other coexistent brain disease processes, such as infarctions or Parkinson's disease–related lesions, are relatively uncommon, and this must be taken into account by researchers who employ postmortem brain tissues for research. PMID:20101720

  20. The Missing Link between Faces and Names: Evidence from Alzheimer's Disease Patients

    ERIC Educational Resources Information Center

    Calabria, Marco; Sabio, Alicia; Martin, Clara; Hernandez, Mireia; Juncadella, Montserrat; Gascon-Bayarri, Jordi; Rene, Ramon; Ortiz-Gil, Jordi; Ugas, Lidia; Costa, Albert

    2012-01-01

    Retrieval of proper names is a cause of concern and complaint among elderly adults and it is an early symptom of patients suffering from neurodegenerative diseases such as Alzheimer's disease (AD). While it is well established that AD patients have deficits of proper name retrieval, the nature of such impairment is not yet fully understood.…

  1. Genetics Home Reference: Alzheimer disease

    MedlinePlus

    ... and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center MalaCards: alzheimer disease MalaCards: alzheimer disease risk factor Merck Manual Consumer Version: Alzheimer Disease Quick Facts ...

  2. [Socio- and psychotherapy in patients with Alzheimer disease].

    PubMed

    Hirsch, R D

    2001-04-01

    Symptoms presented by patients with Alzheimer-type dementia do not only reflect organic disturbances only but require a holistic and person-oriented view. Affective and behavioral disturbances are not necessarily secondary to cognitive impairment. Guidelines are presented for a multidimensional treatment involving the significant other. Socio- and psychotherapy are essential for this treatment. Their approaches have greatly increased in number and diversity in the past few years. Sociotherapy is based on milieu therapy and includes different training- and group activities. Several psychosocial treatment modalities are available, including validation, dementia care mapping, reminiscence therapy, cognitive training and psychoeducational group work. Psychotherapeutic approaches include relaxation techniques, and psychodynamic oriented- and behavioral modalities. The indication for a specific modality is based on an assessment of the disturbances present and available resources. Of special importance are also services to family carers, including counseling, psychotherapy, as well as support and modification of the care-setting. Even though there are only limited empirical data available on the effects of socio- and psychotherapy for patients with Alzheimer-type dementia, the available evidence is indicative of a positive influence on symptoms of this illness. Diversity of symptoms and individualized, variable course of the illness may point to the importance of psychological and social factors in this illness, by far larger than presently recognized. PMID:11393010

  3. Assessing subtle structural changes in Alzheimer's disease patients.

    PubMed

    Whitwell, Jennifer L; Vemuri, Prashanthi

    2011-01-01

    Magnetic resonance imaging (MRI) allows the assessment of structural changes in subjects with Alzheimer's disease (AD). Early studies used visual assessments of MRI or manual measurements of structures of interest, although these methods were limited by inter-rater variability. Techniques have now been developed which allow automated analysis of both cross-sectional and longitudinal MRI data and have provided valuable information concerning the patterns and progression of atrophy in subjects with AD. It is also now possible using machine learning-based techniques to provide individual-level diagnostic information from MRI scans. Various analysis techniques have been applied to validate the use of MRI to capture subtle structural changes due to atrophy in AD and its usefulness in providing diagnostic and prognostic information, as well as tracking the disease progression in AD. PMID:21279621

  4. About Alzheimer's Disease: Caregiving

    MedlinePlus

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Caregiving On this page: Caregiving Tip Sheets and ... Care Caregiving News Caring for a person with Alzheimer’s disease can have high physical, emotional, and financial costs. ...

  5. Selective Loss of Cholinergic Neurons in the Ventral Striatum of Patients with Alzheimer Disease

    NASA Astrophysics Data System (ADS)

    Lehericy, Stephane; Hirsch, Etienne C.; Cervera, Pascale; Hersh, Louis B.; Hauw, Jean-Jacques; Ruberg, Merle; Agid, Yves

    1989-11-01

    Cholinergic neurons were studied by immunohistochemistry with an antiserum against human choline acetyltransferase in the caudate nucleus, putamen, and ventral striatum (including the nucleus accumbens) of three patients with Alzheimer disease and three control subjects. Immunoreactive cell bodies were mapped and counted. In the ventral striatum of patients with Alzheimer disease, a 60% decrease in the number of cholinergic neurons was observed, whereas in the caudate nucleus and putamen values for control subjects and patients were similar. To determine whether all neurons in the ventral striatum were affected, neuropeptide Y-containing neurons were also immunostained, mapped, and counted. The number of these neurons was the same in control subjects and patients with Alzheimer disease, indicating that neuronal loss is not generalized in the ventral striatum and may be specific to the cholinergic population.

  6. The Effects of Aerobic Exercise on Cognitive Function of Alzheimer's Disease Patients.

    PubMed

    Yang, Si-Yu; Shan, Chun-Lei; Qing, He; Wang, Wei; Zhu, Yi; Yin, Meng-Mei; Machado, Sergio; Yuan, Ti-Fei; Wu, Ting

    2015-01-01

    To evaluate the effect of moderate intensity of aerobic exercise on elderly people with mild Alzheimer's disease, we recruited fifty volunteers aged 50 years to 80 years with cognitive impairment. They were randomized into two groups: aerobic group (n=25) or control group (n=25). The aerobic group was treated with cycling training at 70% of maximal intensity for 40 min/d, 3 d/wk for 3 months. The control group was only treated with heath education. Both groups were received cognitive evaluation, laboratory examination before and after 3 months. The results showed that the Minimum Mental State Examination score, Quality of Life Alzheimer's Disease score and the plasma Apo-a1 level was significantly increased (P<0.05), the Alzheimer's Disease Assessment Scale-cognition score, Neuropsychiatric Inventory Questionnaire score was significantly decreased.(P<0.05) in aerobic group before and after 3 months in aerobic group. For the control group, there was no significant difference in scores of Alzheimer's Disease Assessment Scale-cognition, Neuropsychiatric Inventory Questionnaire, Quality of Life Alzheimer's Disease, Apo-a1 (P>0.05), while Minimum Mental State Examination scores decreased significantly after 3 months (P<0.05). In conclusion, moderate intensity of aerobic exercise can improve cognitive function in patients with mild Alzheimer's disease. PMID:26556080

  7. [Neuropsychological study of decline of attention and drug therapy of patients with Alzheimer's disease].

    PubMed

    Tecce, J J; Cattanach, L; Boehner-Davis, M B; Branconnier, R J; Cole, J O

    1983-12-29

    The present study provided a neuropsychological assessment of impaired attention in Alzheimer's patients (57-89 years of age). Three control groups were evaluated: young normals (ages 18-32 years of age), an older group (55-69 years of age), and an elderly group (70-85 years of age). Alzheimer's patients showed an absence of CNV rebound and impairment in attention performance. They also showed significantly less facilitation in speed of response by a preparatory signal than the non-patient groups. These findings suggested a possible discontinuity between normal aging and Alzheimer's disease. On the other hand, a comparison of young, normal elderly, and Alzheimer's groups indicated a pattern of systematic decrease in CNV rebound, lowered short-term memory performance, and slowing of reaction time during divided-attention, a finding that suggests normal aging and senile dementia to represent quantitative differences on a continuum of gradual age-related deterioration. Alzheimer's patients showed elevated levels of basal heart rate and eyeblink rate and increased oculomotor responsiveness in divided-attention conditions. This finding was interpreted as compelling evidence against the concept of hypoactivity in senile dementia and as support for a distraction-arousal interpretation of impaired attention in Alzheimer's patients, although decreased basal myogenic activity and lowered heart rate levels during divided attention in the patients indicated selectively dampened psycho-physiological functioning. Distraction-arousal processes appeared to be curtailed in the patient group after Hydergine treatment. PMID:6228933

  8. Prediabetes and Alzheimer's Disease

    PubMed Central

    Bitra, V. R.; Rapaka, Deepthi; Akula, Annapurna

    2015-01-01

    Aging patients with diabetes are at higher risk of developing Alzheimer's disease. Emerging evidences demonstrate the role of brain insulin resistance, which is a key mediator in prediabetes and diabetes mellitus that may lead to Alzheimer's disease. Insulin and insulin-like growth factors regulate many biological processes such as axonal growth, protein synthesis, cell growth, gene expression, proliferation, differentiation, and development. Among these, the energy metabolism and synaptic plasticity are the major transduction processes regulated by insulin, which are the core objectives for learning and memory. It was also proposed that hyper insulinemia induced insulin resistance results in injury to the central nervous system by the activation of glycogen synthase kinase 3β which is the key ailment in the cognitive decline. Hence, the endogenous brain specific insulin impairments and signaling account for the majority of Alzheimer's abnormalities. PMID:26798163

  9. Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients

    SciTech Connect

    Shoffner, J.M.; Brown, M.D.; Torroni, A.; Lott, M.T.; Cabell, M.F.; Mirra, S.S.; Yang, C.C.; Gearing, M.; Salvo, R. ); Beal, M.F. )

    1993-07-01

    Mitochondrial DNA (mtDNA) variants associated with Alzheimer disease (AD) and Parkinson disease (PD) were sought by restriction endonuclease analysis in a cohort of 71 late-onset Caucasian patients. A tRNA[sup Gln] gene variant at nucleotide pair (np) 4336 that altered a moderately conserved nucleotide was present in 9/173 (5.2%) of the patients surveyed but in only 0.7% of the general Caucasian controls. One of these patients harbored an additional novel 12S rRNA 5-nucleotide insertion at np 956-965, while a second had a missense variant at np 3397 that converted a highly conserved methionine to a valine. This latter mutation was also found in an independent AD + PD patient, as was a heteroplasmic 16S rRNA variant at np 3196. Additional studies will be required to determine the significance, if any, of these mutations. 122 refs., 4 figs., 2 tabs.

  10. Do Alzheimer's Disease Patients Want to Participate in a Treatment Decision, and Would Their Caregivers Let Them?

    ERIC Educational Resources Information Center

    Hirschman, Karen B.; Joyce, Colette M.; James, Bryan D.; Xie, Sharon X.; Karlawish, Jason H.T.

    2005-01-01

    Purpose: This study was designed to examine the factors associated with the preferences of Alzheimer's disease patients to participate in a decision to use an Alzheimer's disease-slowing medication and how involved their caregivers would let them be in this decision. Design and Methods: Interviews were conducted with 48 patients in the…

  11. [Dissociation of structural and functional parameters of the retina and optic nerve in a patient with Alzheimer's disease (clinical case)].

    PubMed

    Erichev, V P; Panyushkina, L A; Ronzina, I A

    2015-01-01

    Visual impairment is often one of the earliest sings of Alzheimer's disease. This article reports a clinical case of a female patient diagnosed with mild dementia due to Alzheimer's disease. As revealed by a comprehensive examination, her visual fields and visual evoked potentials were markedly changed, while morphometric parameters of the retina and optic nerve appeared normal. Such a significant dissociation of structural and functional parameters may indicate a more proximal involvement of visual pathways in Alzheimer's disease. PMID:26080589

  12. [Alzheimer's disease and depression].

    PubMed

    Gallarda, T

    1999-11-01

    Alzheimer's disease is the most frequent cause of dementia (60% of all dementias) and affects nearly 300,000 people in France. Alzheimer's disease is a disease of the elderly which generally begins after 60 years and whose prevalence increases markedly after age 75 years. The elderly population is increasing in all Western countries. Alzheimer's disease thus constitutes a veritable emergent public health problem. The rapid inflation of the epidemiological and etiopathogenetic data have contributed to enhanced nosographic definition and finer semiological characterization of the disease. Thus, the classic concept of senile dementia has been totally abandoned. In contrast, the concept of depressive pseudodementia as defined by Kiloh (1961) remains present in the "psychiatric culture". The concept refers to rare clinical situations in which the controversial concept of "test therapy" with antidepressants retains, in the author's opinion, some utility. Depressive or psychobehavioral signs and symptoms frequently inaugurate Alzheimer's disease giving rise to first-line psychiatric management. The use of multidimensional evaluation instruments such as the neuropsychiatric inventory (NPI) has enabled demonstration of the signs and symptoms and their quantification through the course of the disease. In the dementia stage, the psychobehavioral symptoms are related to the patient's awareness of the degradation in his intellectual functions and the loss of independence and to specific neuropathological lesions responsible for "frontal deafferentation". Certain clinical forms of depression of late onset are also characterized by symptoms reflecting hypofrontal signs (blunted affect, apathy, defective initiative, etc.) and severe cognitive disorders. Those depressions are associated with risk factors shared with Alzheimer's disease (sex, age, vascular function, APOE 4) and constitute a risk factor for progression to dementia, requiring regular clinical and neuropsychological

  13. [Immunotherapy for Alzheimer's disease].

    PubMed

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers

    2016-01-18

    Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD. Solanezumab and new monoclonal antibodies are being tested in patients with prodromal and preclinical AD in search for a disease-modifying treatment. PMID:26815584

  14. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

    SciTech Connect

    van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.

    1987-08-01

    Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related ..beta..-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approx. 4000 and its partial amino acid sequence to position 21 showed homology to the ..beta..-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of ..beta..-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.

  15. Platelet dysfunction in hypercholesterolemia mice, two Alzheimer's disease mouse models and in human patients with Alzheimer's disease.

    PubMed

    Plagg, Barbara; Marksteiner, Josef; Kniewallner, Kathrin M; Humpel, Christian

    2015-08-01

    Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized mainly by accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic and neuronal loss. Blood platelets contain the neurotransmitter serotonin and amyloid-precursor protein (APP), and may thus be useful as a peripheral biomarker for AD. The aim of the present study was to functionally characterize platelets by FACS, to examine alterations in APP expression and secretion, and to measure serotonin levels in hypercholesterolemia mice with AD-like pathology and in two AD mouse models, the triple transgenic AD model (3xTg) and the APP overexpressing AD model with the Swedish-Dutch-Iowa mutations (APP_SweDI). These data are supplemented with epidermal growth factor (EGF) levels and compared with changes observed in platelets of patients with AD. We observed decreased platelet APP isoforms in 3xTg mice and patients with AD when analysed by means of Western blot. In patients, a significant increase of APP levels was observed when assessed by ELISA. Secreted APPβ proved to be altered amongst all three animal models of AD at different time points and in human patients with AD. Serotonin levels were only reduced in 7 and 14 month old 3xTg mice. Moreover, we found significantly lower EGF levels in human AD patients and could thereby reproduce previous findings. Taken together, our data confirm that platelets are dysfunctional in AD, however, results from AD animal models do not coincide in all aspects, and markedly differ when compared to AD patients. We support previous data that APP, as well as EGF, could become putative biomarkers for diagnosing AD in human platelets. PMID:25947203

  16. [Approach of the sexuality of Alzheimer's disease patients according to caregivers' guides approach].

    PubMed

    Ostrowski, Madeleine; Mietkiewicz, Marie-Claude

    2015-12-01

    If sexual behavior disorders are not a major symptom of Alzheimer's disease, they might be a source for suffering and hardship to the patient's entourage, especially since it is usually not easy to address sexuality. Guides for relatives have been devoted to improve their knowledge about the disease and to help providing best care for the patient. Thirty of the forty-six guides make references to sexual behavior disorders in Alzheimer's disease patients, sometimes in a few lines, sometimes in a few paragraphs illustrated by clinical vignettes. All these guides report two types of sexual disorders, loss of interest and decreased sexual activity, or inappropriate sexual behavior, and give advices to help relatives, spouses and children, managing the patient's sexual disorders without blaming the patients. PMID:26707561

  17. Preserved Metamemorial Ability in Patients with Mild Alzheimer's Disease: Shifting Response Bias

    ERIC Educational Resources Information Center

    Waring, Jill D.; Chong, Hyemi; Wolk, David A.; Budson, Andrew E.

    2008-01-01

    Patients with mild Alzheimer's disease (AD) display a greater tendency to endorse unstudied items as "old" on memory tests than healthy older adults. This liberal response bias may result in mistaken beliefs about the completion of common tasks. This research attempted to determine whether it was possible to shift the response bias of mild AD…

  18. The Use of Errorless Learning Strategies for Patients with Alzheimer's Disease: A Literature Review

    ERIC Educational Resources Information Center

    Li, Ruijie; Liu, Karen P. Y.

    2012-01-01

    The aim of this article was to review the evidence of errorless learning on learning outcomes in patients with early-stage Alzheimer's disease. A computer-aided literature search from 1999 to 2011 was carried out using MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and PsycArticles. Keywords included…

  19. Simple Method for Evaluation of Planum Temporale Pyramidal Neurons Shrinkage in Postmortem Tissue of Alzheimer Disease Patients

    PubMed Central

    Kutová, Martina; Mrzílková, Jana; Kirdajová, Denisa; Řípová, Daniela; Zach, Petr

    2014-01-01

    We measured the length of the pyramidal neurons in the cortical layer III in four subregions of the planum temporale (transitions into superior temporal gyrus, Heschl's gyrus, insular cortex, and Sylvian fissure) in control group and Alzheimer disease patients. Our hypothesis was that overall length of the pyramidal neurons would be smaller in the Alzheimer disease group compared to controls and also there would be right-left asymmetry in both the control and Alzheimer disease groups. We found pyramidal neuron length asymmetry only in controls—in the transition into the Sylvian fissure—and the rest of the subregions in the control group and Alzheimer disease patients did not show size difference. However, control-Alzheimer disease group pyramidal neuron length comparison revealed (a) no length difference in superior temporal gyrus transition area, (b) reversal of asymmetry in the insular transition area with left insular transition significantly shorter in the Alzheimer disease group compared to the control group, (c) both right and left Heschl's gyrus transitions significantly shorter in the Alzheimer disease group compared to the control group, and (d) right Sylvian fissure transition significantly shorter in the Alzheimer disease group compared to the control group. This neuronal length measurement method could supplement already existing neuropathological criteria for postmortem Alzheimer disease diagnostics. PMID:24719875

  20. Etanercept in Alzheimer disease

    PubMed Central

    Butchart, Joseph; Brook, Laura; Hopkins, Vivienne; Teeling, Jessica; Püntener, Ursula; Culliford, David; Sharples, Richard; Sharif, Saif; McFarlane, Brady; Raybould, Rachel; Thomas, Rhodri; Passmore, Peter; Perry, V. Hugh

    2015-01-01

    Objectives: To determine whether the tumor necrosis factor α inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia. Methods: In a double-blind study, patients with mild to moderate Alzheimer disease dementia were randomized (1:1) to subcutaneous etanercept (50 mg) once weekly or identical placebo over a 24-week period. Tolerability and safety of this medication was recorded including secondary outcomes of cognition, global function, behavior, and systemic cytokine levels at baseline, 12 weeks, 24 weeks, and following a 4-week washout period. This trial is registered with EudraCT (2009-013400-31) and ClinicalTrials.gov (NCT01068353). Results: Forty-one participants (mean age 72.4 years; 61% men) were randomized to etanercept (n = 20) or placebo (n = 21). Etanercept was well tolerated; 90% of participants (18/20) completed the study compared with 71% (15/21) in the placebo group. Although infections were more common in the etanercept group, there were no serious adverse events or new safety concerns. While there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function. Conclusions: This study showed that subcutaneous etanercept (50 mg/wk) was well tolerated in this small group of patients with Alzheimer disease dementia, but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients. Classification of evidence: This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia. PMID:25934853

  1. Alzheimer's Disease

    MedlinePlus

    ... risk of urinary tract and other serious infections. Malnutrition or dehydration: People who have Alzheimer’s disease may ... swallow. It’s important to watch for signs of malnutrition. If you think that a loved one might ...

  2. Coping & Caring: Living with Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Leroux, Charles

    This guide on Alzheimer's disease is for those who care for Alzheimer's patients, as well as those who want to learn more about the disease. It answers these questions: (1) what is Alzheimer's? (2) how does the disease progress and how long does it last? (3) how do families cope? and (4) who can provide assistance and information? The guide also…

  3. The influence of cognitive rehabilitation on cognitive competence in patients with Alzheimer's disease.

    PubMed

    Oresnik, Milan

    2008-06-01

    The development of dementia in Alzheimer's disease is known to be influenced by various factors. The research was carried out on 16 patients with a probable diagnosis of Alzheimer's disease (AD), who were first evaluated with MMSE. The patients were then divided according to gender, age, and the progress of the illness into two equal groups. The first group of patients was assigned an additional cognitive therapy for improving cognitive abilities alongside regular treatment while the second group was assigned only regular treatment. After 6 months the patients were re-evaluated using MMSE. The results show a statistically significant difference in cognitive abilities between the two groups with regard to the pre-therapy results. The results of the research are consistent with the results of other researches which imply a slower decrease in cognitive abilities in AD patients who are mentally active. PMID:18587287

  4. [Music therapy and Alzheimer disease].

    PubMed

    Tromeur, Emilie

    2014-01-01

    Music therapy and Alzheimer's dementia. Dementia such as Alzheimer's leads to the deterioration of the patient's global capacities. The cognitive disorders associated with it are disabling and affect every area of the patient's life. Every therapy's session undertaken with and by patients can act as a mirror of the progress of their disease and help to feel better, as described in this article on music therapy. PMID:24908841

  5. Effect of Psychotropic Drugs on Development of Diabetes Mellitus in Patients With Alzheimer's Disease

    PubMed Central

    Chang, Ki Jung; Hong, Chang Hyung; Lee, Yunhwan; Lee, Kang Soo; Roh, Hyun Woong; Back, Joung Hwan; Jung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Kim, Hyun Chung; Choi, Seong Hye; Kim, Seong Yoon; Na, Duk L.; Seo, Sang Won; Lee, Soojin; Son, Sang Joon

    2015-01-01

    Abstract We aimed to examine risk of diabetes mellitus (DM) among older adults with Alzheimer's disease receiving 3 types of psychotropic drugs, that is, antipsychotics, antidepressants, and sedative anxiolytics. We retrospectively analyzed data from a hospital-based Clinical Research Center for Dementia of South Korea (CREDOS) study conducted between January 1, 2008 and December 31, 2012. Participants (n = 3042) with Alzheimer's disease were aged 65 or older and had no preexisting history of DM. Development of DM was identified using claims for initiating at least 1 prescription of antidiabetic medications or a diagnosis of DM during the follow-up period. Cox proportional hazards regression was used to demonstrate the Hazard ratio of DM in use of each psychotropic drug. Among the 3042 participants, 426 patients (14.0%) developed DM, representing an incidence rate of 5.2/100 person-years during an average 2.9 years of follow-up period. Among the 3 types of psychotropic drugs, antipsychotic users had a significantly higher risk of DM (hazard ratio = 1.74, 95% confidence interval = 1.10, 2.76) than nonusers, after adjusting covariates. Antidepressants and sedative anxiolytics did not achieve statistical significance. These results suggested that the diabetes risk was elevated in Alzheimer patients on antipsychotic treatment. Therefore, patients with Alzheimer's disease receiving antipsychotic treatment should be carefully monitored for the development of DM. PMID:26061313

  6. Familiar Music as an Enhancer of Self-Consciousness in Patients with Alzheimer's Disease

    PubMed Central

    Arroyo-Anlló, Eva M.; Díaz, Juan Poveda; Gil, Roger

    2013-01-01

    The main objective of this paper is to examine the impact of familiar music on self-consciousness (SC) in patients with Alzheimer's disease (AD). For this purpose, two AD groups of 20 patients matched by age, educational level, gender, illness duration, and cognitive state were assessed using an SC questionnaire before and after music intervention. The SC questionnaire measured several aspects: personal identity, anosognosia, affective state, body representation, prospective memory, introspection and moral judgments. One AD group received familiar music stimulation and another AD group unfamiliar music stimulation over three months. The AD patients who received a familiar music intervention showed a stabilization or improvement in aspects of SC. By contrast, control AD group showed a deterioration of most of the SC aspects after unfamiliar music stimulation, except the SC aspects of body representation and affective state. Familiar music stimulation could be considered as an enhancer of SC in patients with Alzheimer's disease. PMID:24106716

  7. Familiar music as an enhancer of self-consciousness in patients with Alzheimer's disease.

    PubMed

    Arroyo-Anlló, Eva M; Díaz, Juan Poveda; Gil, Roger

    2013-01-01

    The main objective of this paper is to examine the impact of familiar music on self-consciousness (SC) in patients with Alzheimer's disease (AD). For this purpose, two AD groups of 20 patients matched by age, educational level, gender, illness duration, and cognitive state were assessed using an SC questionnaire before and after music intervention. The SC questionnaire measured several aspects: personal identity, anosognosia, affective state, body representation, prospective memory, introspection and moral judgments. One AD group received familiar music stimulation and another AD group unfamiliar music stimulation over three months. The AD patients who received a familiar music intervention showed a stabilization or improvement in aspects of SC. By contrast, control AD group showed a deterioration of most of the SC aspects after unfamiliar music stimulation, except the SC aspects of body representation and affective state. Familiar music stimulation could be considered as an enhancer of SC in patients with Alzheimer's disease. PMID:24106716

  8. Rapidly Versus Slowly Progressing Patients With Alzheimer's Disease: Differences in Baseline Cognition.

    PubMed

    Seidl, Jennifer N Travis; Massman, Paul J

    2016-06-01

    Rate of progression of cognitive deficits is variable among patients with Alzheimer's disease (AD). The purpose of the current study was to compare demographic characteristics and performance on neuropsychological measures at baseline evaluation between rapidly and slowly progressing patients. Participants were divided into 2 groups based on change in Alzheimer's Disease Assessment Scale-Cognitive subscale score from baseline to 2-year follow-up, and baseline performance was compared between the groups. Participants were 55 rapidly progressing and 55 slowly progressing patients with probable AD who had a follow-up evaluation 21 to 27 months after the baseline evaluation. The groups differed in age and initial Clinical Dementia Rating. Performance differed significantly between the groups on Verbal Series Attention Test time, Logical Memory I, Visual Reproduction I, Block Design, and Controlled Oral Word Association Test. Differences were found between rapidly and slowly progressing patients on baseline neuropsychological testing. PMID:26646117

  9. [Vitamin E and Alzheimer's Disease].

    PubMed

    Shinohara, Moeko; Yamada, Masahito

    2015-12-01

    It has been suggested that oxidative stress may contribute to the pathogenesis of Alzheimer's disease. Vitamin E is a potent antioxidant, and the results of some epidemiological studies have suggested that high intake of vitamin E through food is inversely associated with the incidence of Alzheimer's disease. Randomized controlled studies have shown that treatment with vitamin E could delay functional decline in patients with mild to moderate Alzheimer's disease. However, vitamin E had no cognitive benefits in patients with mild cognitive impairment or in generally healthy older women. Well-designed clinical trials or preventive interventions with vitamin E are necessary to establish its efficacy as therapeutic or preventive agents for Alzheimer's disease. PMID:26618765

  10. [Proceeding memory in Alzheimer's disease].

    PubMed

    Arroyo-Anlló, Eva Ma; Chamorro-Sánchez, Jorge; Díaz-Marta, Juan Poveda; Gil, Roger

    2013-01-01

    Procedural learning can acquire or develop skills through performance and repetition of a task unconsciously or unintentionally. Procedural skills are considered as the cornerstone in the neuropsychological rehabilitation to promote the autonomy of patients with brain damage, as those with Alzheimer's disease. This review presents data about procedural skills in Alzheimer's disease. Over the past three decades, we have found 40 articles studying various procedural skills in the Alzheimer's disease: motor, perceptual-motor, cognitive, perceptual-cognitive and those developed through serial reaction-time paradigm. We analyzed every study evaluating a procedural skill, indicating the used task and preservation or no preservation of procedural learning. Overall, most of the papers published describe conservation of learning procedures or relatively conserved in Alzheimer's disease, which could be used to promote patient autonomy. PMID:24021069

  11. Differential Expression of Ribosomal Genes in Brain and Blood of Alzheimer's Disease Patients.

    PubMed

    Rasmussen, Lucas; de Labio, Roger W; Viani, Gustavo A; Chen, Elizabeth; Villares, Joao; Bertolucci, Paulo-Henrique; Minett, Thais S; Turecki, Gustavo; Cecyre, Danielle; Drigo, Sandra A; Smith, Marilia C; Payao, Spencer L M

    2015-01-01

    Changes in rRNA and rDNA expression have been associated with cellular and organism aging and have been linked to Alzheimer's disease (AD) pathogenesis. In this study, we investigated the mRNA expression of ribosomal genes (28S/18S) and β-amyloid precursor protein (APP) in different post mortem brain tissue regions (the entorhinal and auditory cortices and the hippocampus) of AD patients and elderly control subjects and also evaluated the extent of expression in peripheral blood from young, healthy, elderly, and Alzheimer's disease patients in order to investigate whether these individuals experienced the effects of aging. The comparative threshold cycle (CT) method via Real Time Polymerase Chain Reaction and the Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) were used to analyze gene expression and the Apolipoprotein E (APOE) genotype, respectively. When the brain areas were analyzed collectively, we observed a significant decrease in APP expression and a significant increase in levels of mRNA of 18S and 28S in Alzheimer's disease patients compared to healthy elderly individuals. Furthermore, there was a significant upregulation of 28SrRNA in the entorhinal cortex and hippocampus, but not in the auditory cortex of patients with AD. On the other hand, tests of blood samples verified a decreased expression of 28S rRNA in patients with AD. These results support the hypothesis that changes in rRNA are present in AD patients, are tissue-specific, and seem to occur independently and differently in each tissue. However, the next challenge is to discover the mechanisms responsible for the differences in expression observed in the blood and the brain in both healthy elderly individuals and Alzheimer's disease patients, as well as the impact of these genes on AD pathogenesis. PMID:26502820

  12. Sexuality in patients with Parkinson's disease, Alzheimer's disease, and other dementias.

    PubMed

    Bronner, Gila; Aharon-Peretz, Judith; Hassin-Baer, Sharon

    2015-01-01

    Sexual dysfunction (SD) is common among patients with Parkinson's disease (PD), Alzheimer's disease (AD), and other dementias. Sexual functioning and well-being of patients with PD and their partners are affected by many factors, including motor disabilities, non-motor symptoms (e.g., autonomic dysfunction, sleep disturbances, mood disorders, cognitive abnormalities, pain, and sensory disorders), medication effects, and relationship issues. The common sexual problems are decreased desire, erectile dysfunction, difficulties in reaching orgasm, and sexual dissatisfaction. Hypersexuality is one of a broad range of impulse control disorders reported in PD, attributed to antiparkinsonian therapy, mainly dopamine agonists. Involvement of a multidisciplinary team may enable a significant management of hypersexuality. Data on SD in demented patients are scarce, mainly reporting reduced frequency of sex and erectile dysfunction. Treatment of SD is advised at an early stage. Behavioral problems, including inappropriate sexual behavior (ISB), are distressing for patients and their caregivers and may reflect the prevailing behavior accompanying dementia (disinhibition or apathy associated with hyposexuality). The neurobiologic basis of ISB is still only vaguely understood but assessment and intervention are recommended as soon as ISB is suspected. Management of ISB in dementia demands a thorough evaluation and understanding of the behavior, and can be treated by non-pharmacologic and pharmacologic interventions. PMID:26003251

  13. Microprobe PIXE analysis of aluminium in the brains of patients with Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Yumoto, S.; Horino, Y.; Mokuno, Y.; Kakimi, S.; Fujii, K.

    1996-04-01

    To investigate the cause of Alzheimer's disease (senile dementia), we examined aluminium (Al) in the rat liver, and in the brains (hippocampus) of Alzheimer's disease patients using heavy ion (5 MeV Si 3+) microprobe and proton (2 MeV) microprobe PIXE analysis. Heavy ion microprobes (3 MeV Si 2+) have several time's higher sensitivity for Al detection than 2 MeV proton microprobes. (1) In the rat liver, Al was detected in the cell nuclei, where phosphorus (P) was most densely distributed. (2) We also demonstrated Al in the cell nuclei isolated from Alzheimer's disease brains using heavy ion (5 MeV Si 3+) microprobes. Al spectra were detected using 2 MeV proton microprobes in the isolated brain cell nuclei. Al could not be observed in areas where P was present in relatively small amounts, or was absent. Our results indicate that Alzheimer's disease is caused by irreversible accumulation of Al in the nuclei of brain cells.

  14. First episodes of behavioral symptoms in Alzheimer's disease patients at age 90 and over, and early-onset Alzheimer's disease: comparison with senile dementia of Alzheimer's type.

    PubMed

    Hori, Koji; Oda, Tatsuro; Asaoka, Toshiyasu; Yoshida, Masahiro; Watanabe, Shoichi; Oyamada, Reiko; Tominaga, Itaru; Inada, Toshiya

    2005-12-01

    We evaluated dementia symptoms to clarify the character of dementia with Alzheimer's disease (AD) observed in the oldest old patients and that of dementia with early-onset AD. Subjects were consecutive AD inpatients admitted for the first time at age of 90 years and over because of behavioral symptoms (demented nonagenarian group: D90G; n=18) and those with 24 consecutive inpatients with AD with early-onset (EOG). The Gottfries, Brane and Steen's scale and the Dementia Behavior Disturbance scale were used to evaluate the symptoms and troublesome behaviors. The scores of these scales in D90G and in EOG were compared with those of 26 sex distribution-, severity of dementia-, and disease duration-matched inpatients with AD with late-onset (LOG). Compared with LOG, wakefulness was more impaired and waking up at night was more frequent in D90G, while memory, orientation and inappropriate behaviors were more severe in EOG. These results suggest that the clinical features of dementia in EOG were quantitatively different from those of LOG. In contrast, the clinical feature of dementia of D90G were sleep-wake pattern disturbance and were qualitatively different from those of LOG. PMID:16401251

  15. Analysis of lipophilic fluorescent products in blood of Alzheimer's disease patients.

    PubMed

    Chmátalová, Zuzana; Vyhnálek, Martin; Laczó, Jan; Hort, Jakub; Skoumalová, Alice

    2016-07-01

    Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by cognitive decline. Prodromal stage of AD, also called mild cognitive impairment (MCI), especially its amnestic type (aMCI), precedes dementia stage of AD. There are currently no reliable diagnostic biomarkers of AD in the blood. Alzheimer's disease is accompanied by increased oxidative stress in brain, which leads to oxidative damage and accumulation of free radical reaction end-products. In our study, specific products of lipid peroxidation in the blood of AD patients were studied. Lipophilic extracts of erythrocytes (AD dementia = 19, aMCI = 27, controls = 16) and plasma (AD dementia = 11, aMCI = 17, controls = 16) were analysed by fluorescence spectroscopy. The level of these products is significantly increased in erythrocytes and plasma of AD dementia and aMCI patients versus controls. We concluded that oxidative stress end-products are promising new biomarkers of AD, but further detailed characterisation of these products is needed. PMID:26991927

  16. Pure Word Deafness in a Patient with Early-Onset Alzheimer's Disease: An Unusual Presentation

    PubMed Central

    Kim, Sook Hui; Suh, Mee Kyung; Seo, Sang Won; Chin, Juhee; Han, Seol-Heui

    2011-01-01

    Background and Purpose The occurrence of PWD in neurodegenerative disease is very rare, and this is the first report of it being related to early-onset AD. We describe a patient with early-onset Alzheimer's disease (AD) who presented with pure word deafness (PWD). Case Report The patient had experienced PWD for 2 years, followed by other cognitive deficits suggestive of parietotemporal dysfunction. Brain imaging including 18FDG-PET and [11C] PIB-PET supported the diagnosis of AD. Conclusions Our case highlights the clinical variability that characterizes early-onset AD. PMID:22259620

  17. Impact of White Matter Lesions on Depression in the Patients with Alzheimer's Disease

    PubMed Central

    Lee, Jung Jae; Lee, Eun Young; Lee, Seok Bum; Park, Joon Hyuk; Kim, Tae Hui; Jeong, Hyun-Ghang; Kim, Jae Hyoung; Han, Ji Won

    2015-01-01

    Objective Comorbid depression is common in patients with Alzheimer's disease (AD). An increase in white matter lesions (WMLs) has been associated with depression in both elderly individuals with normal cognition and patients with Alzheimer's disease. We investigated whether the severity and location of WMLs influence the association between WMLs and comorbid depression in AD. Methods We enrolled 93 AD patients from Seoul National University Bundang Hospital. We administered both the Mini International Neuropsychiatric Inventory (MINI) and the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K) clinical and neuropsychological battery. Subjects also underwent brain magnetic resonance imaging (MRI). We diagnosed AD according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. We diagnosed depressive disorders according to the DSM-IV diagnostic criteria, and evaluated the severity of depressive symptoms using the Korean version of the Geriatric Depression Scale (GDS-K). We quantified the WML volumes from the brain MRI using a fully automated segmentation algorithm. Results The log of the WML volume in the frontal lobe was significantly associated with depressive disorders (odds ratio=1.905, 95% CI=1.027-3.533, p=0.041), but not with the severity of depressive symptoms as measured by the GDS-K. Conclusion The WML volume in the frontal lobe conferred a risk of comorbid depressive disorders in AD, which implies that comorbid depression in AD may be attributed to vascular causes. PMID:26508963

  18. [Language Symptoms of Alzheimer's Disease].

    PubMed

    Shinagawa, Shunichiro

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative disorder mainly characterized by progressive memory disturbance. Language symptoms are considered to be less disease specific and therefore did not attract many researchers, interest until recently. Typical patients with AD present amnesic aphasia in the early disease stage followed by transcortical sensory aphasia; however, their language symptoms are varied. Recently, the concept of logopenic variant of primary progressive aphasia (PPA) has been developed, which is reported to have Alzheimer's neuropathology. Clinicians should verify patients' language abilities, as language can be the key to reveal their true cognitive functions. PMID:27156508

  19. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease.

    PubMed

    Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L; Perrotin, Audrey; Landeau, Brigitte; Mézenge, Florence; Jagust, William J; Dore, Vincent; Miller, Bruce L; Egret, Stéphanie; Seeley, William W; van der Flier, Wiesje M; La Joie, Renaud; Ames, David; van Berckel, Bart N M; Scheltens, Philip; Barkhof, Frederik; Rowe, Christopher C; Masters, Colin L; de La Sayette, Vincent; Bouwman, Femke; Rabinovici, Gil D

    2016-09-01

    See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid

  20. Progress Report on Alzheimer Disease: Volume III.

    ERIC Educational Resources Information Center

    National Inst. on Aging (DHHS/PHS), Bethesda, MD.

    This report summarizes advances in the understanding of Alzheimer's disease, the major cause of mental disability among older Americans. The demography of the disease is discussed, noting that approximately 2.5 million American adults are afflicted with the disease and that the large increase in the number of Alzheimer's disease patients is due to…

  1. Caregiver Response to Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Novak, Mark; Guest, Carol

    1989-01-01

    Examined correlates of caregiver burden among 30 caregivers of Alzheimer's disease patients. Results revealed no significant correlation between length of time a caregiver had given care to a particular patient and the caregiver's subjective feelings of caregiver burden. Found significant, moderate correlation between caregiver burden and patient…

  2. Evidence-Based Research in Complementary and Alternative Medicine III: Treatment of Patients with Alzheimer's Disease

    PubMed Central

    Chiappelli, Francesco; Navarro, Audrey M.; Moradi, David R.; Manfrini, Ercolano; Prolo, Paolo

    2006-01-01

    This paper presents the novel domain of evidence-based research (EBR) in the treatment of patients with Alzheimer's disease (AD) from the perspective of traditional medicine and of complementary and alternative medicine. In earlier lectures we have described the process of evidence-based medicine as a methodological approach to clinical practice that is directed to aid clinical decision-making. Here, we present a practical example of this approach with respect to traditional pharmacological interventions and to complementary and alternative treatments for patients with AD. PMID:17173104

  3. Longitudinal study of cerebrospinal fluid amyloid proteins and apolipoprotein E in patients with probable Alzheimer's disease.

    PubMed

    Pirttilä, T; Koivisto, K; Mehta, P D; Reinikainen, K; Kim, K S; Kilkku, O; Heinonen, E; Soininen, H; Riekkinen, P; Wisniewski, H M

    1998-06-12

    Levels of soluble amyloid beta protein (sAbeta), amyloid beta precursor protein (APP) and apolipoprotein E (apoE) were examined in cerebrospinal fluid (CSF) obtained twice, at baseline and after 3-year follow-up, from 25 patients with probable Alzheimer's disease (AD). Levels of sAbeta and apoE from patients with the apoE4 allele decreased with time, whereas the levels were similar in patients without apoE4 allele. Changes of sAbeta and apoE concentrations correlated significantly with those of mini-mental state examination (MMSE) scores. Levels of sAbeta did not change with time in patients with mild dementia, whereas they decreased significantly in patients with moderate dementia. ApoE concentrations decreased in both groups whereas APP levels were similar. We conclude that measurements of CSF sAbeta and apoE levels may be helpful in monitoring progression of the disease. PMID:9672379

  4. Dementia: Depression and Alzheimer's Disease

    MedlinePlus

    MENU Return to Web version Dementia | Depression and Alzheimer’s Disease What is depression? When doctors talk about ... time Thoughts about death or suicide What is Alzheimer's disease? Alzheimer's disease is the most common type ...

  5. Concordance of occupational and environmental exposure information elicited from patients with Alzheimer's disease and surrogate respondents

    SciTech Connect

    Chong, J.P.; Turpie, I.; Haines, T.; Muir, G.; Farnworth, H.; Cruttenden, K.; Julian, J.; Verma, D.; Hillers, T.

    1989-01-01

    Identification of risk factors for Alzheimer's disease through the use of well designed case-control studies has been described as a research priority. Increasing recognition of the neurotoxic potential of many industrial chemicals such as organic solvents raises the question of the occupational and environmental contribution to the etiology of this high-priority health problem. The intention of this study was to develop and evaluate a methodology that could be used in a large scale case-control study of the occupational and environmental risk factors for dementia or a population-based surveillance system for neurotoxic disorders. The specific objectives of this study were to investigate: (1) the reliability of exposure-eliciting, interviewer-administered questionnaires given to patients with Alzheimer's disease (SDAT); (2) the reliability of exposure-eliciting interviewer-administered questionnaires given to the family of patients with SDAT and the agreement with the responses of the patient or surrogate respondents; (3) the reliability and agreement of responses of age- and sex-matched control patients and their families selected from geriatric care institutions and the community, with respect to the same exposure-eliciting and interviewer-administered questionnaire; and (4) the reliability of agent-based exposure ascertainment by a single, trained rater. The results of the study demonstrate that occupational and environmental histories from which exposure information can be derived is most reliably elicited from job descriptions of cases and control subjects rather than job titles alone or detailed probes for potential neurotoxic exposures. This will necessitate the use of standardized interviewer-administered instruments to derive this information in case-control studies of Alzheimer's disease or population-based surveillance systems for occupational and environmental neurotoxicity.

  6. Impairment of vocal expression of negative emotions in patients with Alzheimer's disease.

    PubMed

    Han, Kyung-Hun; Zaytseva, Yuliya; Bao, Yan; Pöppel, Ernst; Chung, Sun Yong; Kim, Jong Woo; Kim, Hyun Taek

    2014-01-01

    Vocal expression of emotions (EE) in retrieval of events from autobiographical memory was investigated in patients in early stages of Alzheimer's disease (AD). Twenty-one AD patients and 19 controls were interviewed, and EE of the reported memories was rated by 8 independent evaluators. The AD group had lower EE of both recent and remote memory than controls, although EE in remote memories was better preserved in both groups. We observed positive correlations between EE and indicators of cognitive competence in AD patients. AD Patients are impaired in the ability to express emotions already at early stages of the disease, and EE seems to deteriorate along with the progression of cognitive impairment. PMID:24904413

  7. Diagnostic Assessment and Management of Dysphagia in Patients with Alzheimer's Disease.

    PubMed

    Boccardi, Virginia; Ruggiero, Carmelinda; Patriti, Alberto; Marano, Luigi

    2016-01-01

    A growing concern in patients affected by Alzheimer's disease (AD) is dysphagia, or swallowing impairment, which leads to malnutrition, dehydration, weight loss, functional decline and fear of eating and drinking, as well as a decrease in the quality of life. Thus the diagnostic assessment of dysphagia in patients with AD is imperative to ensure that they receive effective management, avoiding complications, and reducing comorbidity and mortality in such a growing population. Dysphagia management requires a multidisciplinary approach considering that no single strategy is appropriate for all patients. However, evidence for clinical diagnostic assessment, interventions, and medical management of dysphagia in these patients are still limited: few studies are reporting the evaluation and the management among this group of patients. Here we analyzed the most recent findings in diagnostic assessment and management of swallowing impairment in patients affected by AD. PMID:26836016

  8. Neuroinflammation in Alzheimer's disease.

    PubMed

    Heneka, Michael T; Carson, Monica J; El Khoury, Joseph; Landreth, Gary E; Brosseron, Frederic; Feinstein, Douglas L; Jacobs, Andreas H; Wyss-Coray, Tony; Vitorica, Javier; Ransohoff, Richard M; Herrup, Karl; Frautschy, Sally A; Finsen, Bente; Brown, Guy C; Verkhratsky, Alexei; Yamanaka, Koji; Koistinaho, Jari; Latz, Eicke; Halle, Annett; Petzold, Gabor C; Town, Terrence; Morgan, Dave; Shinohara, Mari L; Perry, V Hugh; Holmes, Clive; Bazan, Nicolas G; Brooks, David J; Hunot, Stéphane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A; Breitner, John C; Cole, Greg M; Golenbock, Douglas T; Kummer, Markus P

    2015-04-01

    Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. PMID:25792098

  9. Amyloid beta peptide immunotherapy in Alzheimer disease.

    PubMed

    Delrieu, J; Ousset, P J; Voisin, T; Vellas, B

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation. PMID:25459121

  10. Seizures in Alzheimer's disease.

    PubMed

    Born, H A

    2015-02-12

    Alzheimer's disease (AD) increases the risk for late-onset seizures and neuronal network abnormalities. An elevated co-occurrence of AD and seizures has been established in the more prevalent sporadic form of AD. Recent evidence suggests that nonconvulsive network abnormalities, including seizures and other electroencephalographic abnormalities, may be more commonly found in patients than previously thought. Patients with familial AD are at an even greater risk for seizures, which have been found in patients with mutations in PSEN1, PSEN2, or APP, as well as with APP duplication. This review also provides an overview of seizure and electroencephalography studies in AD mouse models. The amyloid-β (Aβ) peptide has been identified as a possible link between AD and seizures, and while Aβ is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability. Nonconvulsive epileptiform activity, such as seizures or network abnormalities that are shorter in duration but may occur with higher frequency, may contribute to cognitive impairments characteristic of AD, such as amnestic wandering. Finally, the review discusses recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients. Understanding the mechanistic link between epileptiform activity and AD is a research area of growing interest. Further understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies. PMID:25484360

  11. Androgen deprivation therapy did not increase the risk of Alzheimer's and Parkinson's disease in patients with prostate cancer.

    PubMed

    Chung, S D; Lin, H C; Tsai, M C; Kao, L T; Huang, C Y; Chen, K C

    2016-05-01

    Androgen deprivation therapy (ADT) has been the standard treatment for advanced prostate cancer for many decades. Although potential adverse effects of ADT have been reported, there are no empirical studies investigating the association between ADT and Alzheimer's disease. Therefore, this retrospective cohort study explored the relationship between the use of ADT and the subsequent risk of Alzheimer's disease in men with prostate cancer using a population-based database. We retrieved data from the "Taiwan Longitudinal Health Insurance Database 2000." The study included 1335 patients with prostate cancer and 4005 age-matched comparison patients without prostate malignancy. We then individually tracked each patient (n = 5340) for a 5-year period to discriminate those who subsequently received a diagnosis of Alzheimer's disease. The Cox proportional hazard regression showed that the hazard ratio (HR) for Alzheimer's disease during the 5-year follow-up period for prostate cancer patients was 1.71 (95% confidence interval (CI) = 0.90~3.25) over that of comparison patients. We further analyzed the hazard ratio for Alzheimer's disease and Parkinson's disease between prostate cancer patients who did and those who did not receive ADT, but we failed to observe a significant difference in the hazard ratio for both diseases during the 5-year follow-up period (adjusted HR = 1.76, 95% CI = 0.55~5.62, and HR = 1.13, 95% CI = 0.58~2.20, respectively). In conclusion, this study demonstrated that the use of androgen deprivation therapy in patients with prostate cancer was not associated with a higher risk of Alzheimer's and Parkinson's disease during the follow-up period. PMID:27062333

  12. Quality of life in Alzheimer disease: a comparison of patients' and caregivers' points of view.

    PubMed

    Zucchella, Chiara; Bartolo, Michelangelo; Bernini, Sara; Picascia, Marta; Sinforiani, Elena

    2015-01-01

    Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected by Alzheimer Disease (AD) has not been well established, primarily because of the difficulties stemming from the study of patients with cognitive disorders. Because no cure is currently available for AD, the optimization of QoL represents the best possible outcome attainable in all stages of disease, making QoL assessment mandatory. This study identified variables related to patients' QoL and examined the agreement between patients' and caregivers' QoL ratings. A total of 135 dyads (patient and principal caregiver) were enrolled in the study. Patients' QoL evaluations showed a negative relationship with depressive mood and a positive relationship with Activities of Daily Living (ADL), whereas caregivers' QoL ratings showed a negative relationship with patients' depressive mood and behavioral disturbances. Caregivers tended to underestimate patients' QoL compared with the patients' own self-evaluations, with patients' dependency in performing ADL and behavioral disorders as well as caregivers' burdens and depression being the main factors associated with the discrepancy in these evaluations. These findings suggest that the use of proxies as a substitute for the self-report of QoL data should be treated with caution, always accounting for the presence of potential bias. PMID:24936799

  13. [Altered identification with relative preservation of emotional prosody production in patients with Alzheimer's disease].

    PubMed

    Templier, Lorraine; Chetouani, Mohamed; Plaza, Monique; Belot, Zoé; Bocquet, Patrick; Chaby, Laurence

    2015-03-01

    Patients with Alzheimer's disease (AD) show cognitive and behavioral disorders, which they and their caregivers have difficulties to cope with in daily life. Psychological symptoms seem to be increased by impaired emotion processing in patients, this ability being linked to social cognition and thus essential to maintain good interpersonal relationships. Non-verbal emotion processing is a genuine way to communicate, especially so for patients whose language may be rapidly impaired. Many studies focus on emotion identification in AD patients, mostly by means of facial expressions rather than emotional prosody; even fewer consider emotional prosody production, despite its playing a key role in interpersonal exchanges. The literature on this subject is scarce with contradictory results. The present study compares the performances of 14 AD patients (88.4±4.9 yrs; MMSE: 19.9±2.7) to those of 14 control subjects (87.5±5.1 yrs; MMSE: 28.1±1.4) in tasks of emotion identification through faces and voices (non linguistic vocal emotion or emotional prosody) and in a task of emotional prosody production (12 sentences were to be pronounced in a neutral, positive, or negative tone, after a context was read). The Alzheimer's disease patients showed weaker performances than control subjects in all emotional recognition tasks and particularly when identifying emotional prosody. A negative relation between the identification scores and the NPI (professional caregivers) scores was found which underlines their link to psychological and behavioral disorders. The production of emotional prosody seems relatively preserved in a mild to moderate stage of the disease: we found subtle differences regarding acoustic parameters but in a qualitative way judges established that the patients' productions were as good as those of control subjects. These results suggest interesting new directions for improving patients' care. PMID:25786430

  14. Evaluation of patients with Alzheimer's disease before and after dental treatment.

    PubMed

    Rolim, Thaís de Souza; Fabri, Gisele Maria Campos; Nitrini, Ricardo; Anghinah, Renato; Teixeira, Manoel Jacobsen; Siqueira, José Tadeu T de; Cesari, José Augusto Ferrari; Siqueira, Silvia Regina Dowgan Tesseroli de

    2014-12-01

    Oral infections may play a role in Alzheimer's disease (AD). Objective To describe the orofacial pain, dental characteristics and associated factors in patients with Alzheimer's Disease that underwent dental treatment. Method 29 patients with mild AD diagnosed by a neurologist were included. They fulfilled the Mini Mental State Exam and Pfeffer's questionnaire. A dentist performed a complete evaluation: clinical questionnaire; research diagnostic criteria for temporomandibular disorders; McGill pain questionnaire; oral health impact profile; decayed, missing and filled teeth index; and complete periodontal investigation. The protocol was applied before and after the dental treatment. Periodontal treatments (scaling), extractions and topic nystatin were the most frequent. Results There was a reduction in pain frequency (p=0.014), mandibular functional limitations (p=0.011) and periodontal indexes (p<0.05), and an improvement in quality of life (p=0.009) and functional impairment due to cognitive compromise (p<0.001) after the dental treatment. Orofacial complaints and intensity of pain also diminished. Conclusion The dental treatment contributed to reduce co-morbidities associated with AD and should be routinely included in the assessment of these patients. PMID:25517641

  15. Clinical implications of quantitative electroencephalography and current source density in patients with Alzheimer's disease.

    PubMed

    Kim, Ji-Sun; Lee, Seung-Hwan; Park, Gewnhi; Kim, Sangrae; Bae, Sung-Man; Kim, Do-Won; Im, Chang-Hwan

    2012-10-01

    This study examined whether quantitative electroencephalography (qEEG) and current source density (CSD) can be used to evaluate symptom severity in Alzheimer's disease (AD) patients. Thirty AD patients (13 mild and 17 moderate severity) and 30 normal control (NC) subjects were recruited. The Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet and the Global Deterioration Scale were measured. qEEG and CSD data were analyzed in five frequency bands: delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-25 Hz), and gamma (30-50 Hz). Compared with the NC subjects, the moderate AD patients had significantly increased theta and decreased beta power. Compared with the mild AD patients, the moderate AD patients had significantly decreased beta power. In the AD patients, the theta power was significantly correlated with a poor performance for global cognition; however, beta power was positively correlated with a good performance for global cognition, attention, memory, visuospatial function, and executive function. The CSD of the theta band in the superior temporal gyrus, transverse temporal gyrus, insula, postcentral gyrus, cuneus, and lingual gyrus was significantly different between NC subjects and moderate AD patients and between mild and moderate AD patients. The theta CSD of these regions was significantly correlated with a poor performance for global cognition, memory, visuospatial function, execution, and language. The results suggest that qEEG and the CSD of the theta and beta bands are useful biological markers in AD patients. PMID:22736322

  16. PIXE analysis of low concentration aluminum in brain tissues of an Alzheimer's disease patient

    SciTech Connect

    Ishihara, R.; Takeuchi, T.; Hanaichi, T.; Ektessabi, A. M.

    1999-06-10

    An excess accumulation and presence of metal ions may significantly alter a brain cell's normal functions. There have been increasing efforts in recent years to measure and quantify the density and distribution of excessive accumulations of constituent elements (such as Fe, Zn, Cu, and Ca) in the brain, as well as the presence and distribution of contaminating elements (such as Al). This is particularly important in cases of neuropathological disorders such as Alzheimer's disease, Parkinson's disease and ALS. The aim of this paper was to measure the Al present in the temporal cortex of the brain of an Alzheimer's disease patient. The specimens were taken from an unfixed autopsy brain which has been preserved for a period of 4 years in the deep freezer at -80 degree sign C. Proton Induced X-ray Emission Spectroscopy was used for the measurement of Al concentration in this brain tissue. A tandem accelerator with 2 MeV of energy was also used. In order to increase the sensitivity of the signals in the low energy region of the spectra, the absorbers were removed. The results show that the peak height depends on the measurement site. However, in certain cases an extremely high concentration of Al was observed in the PIXE spectra, with an intensity higher than those in the other major elements of the brain's matrix element. Samples from tissues affected by the same disease were analyzed using the EDX analyzer. The results are quantitatively in very good agreement with those of the PIXE analysis.

  17. Intact cross-modality text-specific repetition priming in patients with Alzheimer's disease.

    PubMed

    Carlesimo, G A; Mauri, M; Fadda, L; Turriziani, P; Caltagirone, C

    2001-10-01

    This study was aimed at investigating the basic mechanisms of the normal repetition priming evoked by text re-reading procedures in Alzheimer's disease (AD) patients (Monti, Gabrieli, Wilson, & Reminger, 1994; Monti et al., 1997). For this purpose, we contrasted the reading facilitation elicited by previous reading or listening to a text in a sample of AD patients and a group of age-matched normal controls. Consistent with previous evidence in normal undergraduates (Levy & Kirsner, 1989), previous listening to a text decreased the successive reading time of the same text (cross-modality priming). However, the reading facilitation elicited by previous reading of the same text (within-modality priming) was significantly larger than the facilitation evoked by previous listening. Compared to normal controls, AD patients showed intact cross-modality and within-modality priming. These data are discussed in the light of alternative hypotheses regarding the basic mechanisms of impaired and spared repetition priming in degenerative demented patients. PMID:11778634

  18. Alcohol consumption and mortality in patients with mild Alzheimer's disease: a prospective cohort study

    PubMed Central

    Berntsen, Sine; Kragstrup, Jakob; Siersma, Volkert; Waldemar, Gunhild; Waldorff, Frans Boch

    2015-01-01

    Objective To investigate the association between alcohol consumption and mortality in patients recently diagnosed with mild Alzheimer's disease (AD). Design A post hoc analysis study based on a clinical trial population. Setting The data reported were collected as part of the Danish Alzheimer's Intervention Study (DAISY), a longitudinal multicentre randomised controlled study on the efficacy of psychosocial intervention in patients with mild AD across five county districts in Denmark. Participants 321 patients with mild AD (Mini-Mental State Examination ≥20) were included. Data regarding current daily alcohol consumption were obtained from the patient's primary caregivers at inclusion. Main outcome All-cause mortality retrieved from The Danish Civil Registration System over a period of 36 months after baseline. Results Information about alcohol consumption was obtained from all 321 study participants: 8% were abstinent, 71% only had alcohol occasionally (1 or <1 unit/day), 17% had 2–3 units/day and 4% had more than 3 units/day. An analysis adjusted for a range of potential confounders demonstrated a reduced mortality for patients with moderate alcohol consumption (2–3 units/day): HR 0.23 (95% CI (0.08 to 0.69)) compared with patients who had 1 or <1 unit/day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than 3 units/day, compared with patients drinking 1 or <1 unit/day. Conclusions In this cohort of patients with mild AD, moderate alcohol consumption (2–3 units/day) was associated with a significantly lower mortality over a period of 36 months. Further studies are needed in this area. These may especially focus on the association between alcohol consumption and cognitive decline in patients with AD. PMID:26656463

  19. Gait Disorder in a Cohort of Patients With Mild and Moderate Alzheimer's Disease.

    PubMed

    Castrillo, A; Olmos, L M García; Rodríguez, F; Duarte, J

    2016-05-01

    Gait disturbance results in an increase in the risk of falls in patients with Alzheimer's disease (AD). The falls are events that might be related to an increase in the number of fractures, loss of mobility, being bedridden, early institutionalization, and increased use of medication. Therefore, the reduction in the number of falls is important for the maintenance of the functional independence of the patients as well as for the prevention of sequelae resulting from those events. Alterations in the gait occur very frequently in AD, and the gait disturbance occurs relatively early in the course of the disease. This study has important implications for public health and clinical practice. This study and previous studies have reported that abnormal gait predicts greater risk of falls, dementia, institutionalization, and death. The high prevalence and incidence of abnormal gait and its association with multiple adverse outcomes in older adults require urgent attention. Our results allow us to identify the risk factors. PMID:26395024

  20. Home Safety for People with Alzheimer's Disease

    MedlinePlus

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... NAPA) About ADEAR Home Safety for People with Alzheimer's Disease Introduction Caring for a person with Alzheimer's ...

  1. [Verbal and gestural communication in interpersonal interaction with Alzheimer's disease patients].

    PubMed

    Schiaratura, Loris Tamara; Di Pastena, Angela; Askevis-Leherpeux, Françoise; Clément, Sylvain

    2015-03-01

    Communication can be defined as a verbal and non verbal exchange of thoughts and emotions. While verbal communication deficit in Alzheimer's disease is well documented, very little is known about gestural communication, especially in interpersonal situations. This study examines the production of gestures and its relations with verbal aspects of communication. Three patients suffering from moderately severe Alzheimer's disease were compared to three healthy adults. Each one were given a series of pictures and asked to explain which one she preferred and why. The interpersonal interaction was video recorded. Analyses concerned verbal production (quantity and quality) and gestures. Gestures were either non representational (i.e., gestures of small amplitude punctuating speech or accentuating some parts of utterance) or representational (i.e., referring to the object of the speech). Representational gestures were coded as iconic (depicting of concrete aspects), metaphoric (depicting of abstract meaning) or deictic (pointing toward an object). In comparison with healthy participants, patients revealed a decrease in quantity and quality of speech. Nevertheless, their production of gestures was always present. This pattern is in line with the conception that gestures and speech depend on different communicational systems and look inconsistent with the assumption of a parallel dissolution of gesture and speech. Moreover, analyzing the articulation between verbal and gestural dimensions suggests that representational gestures may compensate for speech deficits. It underlines the importance for the role of gestures in maintaining interpersonal communication. PMID:25786429

  2. 2014-2015 Alzheimer's Disease Progress Report

    MedlinePlus

    ... Advocate for strategies to empower patients and engage citizens Alzheimer’s Disease and Related Dementias Dr. Alois Alzheimer ... complex disease day by day. NIH, with the participation of all who search for answers, has set ...

  3. IL-4 in vitro production is upregulated in Alzheimer's disease patients treated with acetylcholinesterase inhibitors.

    PubMed

    Lugaresi, Alessandra; Di Iorio, Angelo; Iarlori, Carla; Reale, Marcella; De Luca, Giovanna; Sparvieri, Eleonora; Michetti, Alessia; Conti, Pio; Gambi, Domenico; Abate, Giuseppe; Paganelli, Roberto

    2004-04-01

    Cytokines appear to be involved in the pathogenesis of Alzheimer's Disease (AD). Their modulation by treatment has been investigated only in a few studies. The aim of our study was to evaluate the effect of acetylcholinesterase inhibitors (AChEI) on Interleukin-4 (IL-4) production in AD patients. IL-4 levels were measured by ELISA on peripheral blood mononuclear cell cultures in the presence or absence of Concanavalin A or Phytohaemagglutinin. Linear regression analysis shows that patients who have been treated, have higher levels of IL-4 independently from age, gender and comorbidity. The increased production of IL-4 in AChEI treated patients might represent an additional mechanism through which AChEI act on AD progression. PMID:15050302

  4. Vulnerability of husband and wife caregivers of Alzheimer disease patients to caregiving stressors.

    PubMed

    Croog, S H; Sudilovsky, A; Burleson, J A; Baume, R M

    2001-01-01

    This study assessed relationships between problem behaviors in 199 Alzheimer Disease patients and vulnerability factors in the well being and emotional health of their spouse caregivers. Among caregiver wives and the younger caregiver husbands (64 years old and under) the volume of patient problem behavior was significantly negatively associated with total scores on a summary well being measure. The association was not found within the older husband caregiver group. Considering five subdimensions of the summary well being scale (Anxiety, Depressive Symptoms, Positive Well Being, Vitality and General Health), correlational analyses showed that the total patient problems measure appeared to have impact primarily among wife caregivers, particularly those 64 years old and under. Multiple regression analyses showed that one patient problem behavior category, Emotional Lability, was the single strongest predictor of impaired well being of the caregiver among all five subdimensions of the caregiver well being measure. Although Destructive Behavior of the patient was not significant by itself, an Age by Destructive Behavior interaction showed that high levels of patient Destructive Behavior predicted high levels of Depression, Anxiety, and low levels of Positive Well Being more among younger caregivers. Husband caregivers had significantly higher Anxiety scores than wife caregivers. These findings document how particular patient problem behaviors can affect caregivers. They point up as well how both gender and age may help target which caregivers are most vulnerable to the stress of specific Alzheimer patient behavior problems. They also suggest the utility of examining specific dimensions of well being rather than a total score alone for purposes of understanding the relationship of particular patient behavior problems to caregiver emotional and physical health. PMID:11723371

  5. Assessing the Impact and Social Perception of Self-Regulated Music Stimulation with Patients with Alzheimer's Disease

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'Reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Grumo, Gianluca; Pinto, Katia; Stasolla, Fabrizio; Signorino, Mario; Groeneweg, Jop

    2013-01-01

    We assessed the impact and social rating of an active and a passive music condition implemented with six patients with Alzheimer's disease. In the active condition, the patients used a simple hand response and a microswitch to self-regulate music stimulation inputs. In the passive condition, music stimulation was automatically presented throughout…

  6. Risk factors for hip fracture among elderly patients with Alzheimer's disease.

    PubMed

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

    2004-08-30

    Incidence of hip fracture among patients with Alzheimer's disease (AD), especially in elderly patients, is high. To analyze risk factors of hip fracture, we prospectively studied a cohort of elderly female patients with AD. Subjects studied were 225 female patients with AD, and the average age was 76 years old. At baseline, we recorded body mass index (BMI), a score of Mini-Mental State Examination (MMSE) and bone mineral density (BMD), and measured serum concentrations of ionized calcium, intact parathyroid hormone (PTH), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), intact bone Gla protein (BGP), 25-hydroxyvitamin (25-OHD) and 1, 25-dihydroxyvitamin D (1, 25-[OH]2D). The patients were followed for 2 years. During the 2-year study, hip fractures occurred in 29 patients. We compared baseline variables between the 29 patients with and 176 patients without hip fracture. AD patients with lower BMD, low concentrations of serum ionized calcium and 25-OHD (mean 3.0 ng/ml) with compensatory hyperparathyroidism were found to have an increased risk of hip fracture. Also, concentrations of serum ICTP and BGP were higher in the fracture group than in the nonfracture group. Elderly female AD patients with low BMD and serum 25-OHD concentrations <5 ng/ml with secondary hyperparathyroidism have a high risk of hip fracture, and the risk may be reduced by vitamin D supplementation. PMID:15337610

  7. Oxidative stress in patients with Alzheimer's disease: effect of extracts of fermented papaya powder.

    PubMed

    Barbagallo, Mario; Marotta, Francesco; Dominguez, Ligia J

    2015-01-01

    Brain tissue is particularly susceptible to oxidative stress (OS). Increased production of reactive oxygen species (ROS), reduced antioxidant systems, and decreased efficiency in repairing mechanisms have been linked to Alzheimer's disease (AD). Postmortem studies in AD patients' brains have shown oxidative damage markers (i.e., lipid peroxidation, protein oxidative damage, and glycoxidation). Fermented papaya (FPP, a product of Carica papaya Linn fermentation with yeast) is a nutraceutical supplement with favorable effects on immunological, hematological, inflammatory, and OS parameters in chronic/degenerative diseases. We studied 40 patients (age 78.2 ± 1.1 years), 28 AD patients, and 12 controls. Urinary 8-OHdG was measured to assess OS. Twenty AD patients were supplemented with FPP (Immunage, 4.5 grams/day) for 6 months, while controls did not receive any treatment. At baseline, 8-OHdG was significantly higher in patients with AD versus controls (13.7 ± 1.61 ng/mL versus 1.6 ± 0.12 ng/mL, P < 0.01). In AD patients FPP significantly decreased 8-OHdG (14.1 ± 1.7 ng/mL to 8.45 ± 1.1 ng/mL, P < 0.01), with no significant changes in controls. AD is associated with increased OS, and FPP may be helpful to counteract excessive ROS in AD patients. PMID:25944987

  8. Patient Mood and Instrumental Activities of Daily Living in Alzheimer Disease: Relationship Between Patient and Caregiver Reports.

    PubMed

    Votruba, Kristen L; Persad, Carol; Giordani, Bruno

    2015-09-01

    This retrospective study investigated the relationship between self-reports and caregiver perceptions of patients' depressive symptoms and the respective ability of these reports to predict instrumental activities of daily living (IADLs) beyond what is accounted for by cognitive abilities in 71 patients with mild Alzheimer disease. Patients completed the Geriatric Depression Scale-Short Form, and caregivers completed the Behavior Rating Scale for Dementia assessing their perception of patients' depressive symptoms. Caregivers also completed IADL items from the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory. Cognitive measures included the Mini-Mental State Examination, Logical Memory from the Wechsler Memory Scale III, and Trail Making Test, Part B. The relationship between self-reported depressive symptoms and caregiver report of patients' depressive symptoms showed a trend toward significance (r = .22, P = .06). Measures of depressive symptoms significantly predicted 12.5% of the variance in IADLs performance, beyond that accounted for by patient demographics and cognitive functioning. Interestingly, patients' reports, rather than caregivers', were particularly useful in this prediction. PMID:26071443

  9. Inferring design: evidence of a preference for teleological explanations in patients with Alzheimer's disease.

    PubMed

    Lombrozo, Tania; Kelemen, Deborah; Zaitchik, Deborah

    2007-11-01

    Unlike educated adults, young children demonstrate a "promiscuous" tendency to explain objects and phenomena by reference to functions, endorsing what are called teleological explanations. This tendency becomes more selective as children acquire increasingly coherent beliefs about causal mechanisms, but it is unknown whether a widespread preference for teleology is ever truly outgrown. The study reported here investigated this question by examining explanatory judgments in patients with Alzheimer's disease (AD), whose dementia affects the rich causal beliefs adults typically consult in evaluating explanations. The results indicate that unlike healthy adults, AD patients systematically and promiscuously prefer teleological explanations, suggesting that an underlying tendency to construe the world in terms of functions persists throughout life. This finding has broad relevance not only to understanding conceptual impairments in AD, but also to theories of development, learning, and conceptual change. Moreover, this finding sheds light on the intuitive appeal of creationism. PMID:17958715

  10. Contribution of non-reference alleles in mtDNA of Alzheimer's disease patients.

    PubMed

    Casoli, Tiziana; Di Stefano, Giuseppina; Spazzafumo, Liana; Balietti, Marta; Giorgetti, Belinda; Giuli, Cinzia; Postacchini, Demetrio; Fattoretti, Patrizia; Conti, Fiorenzo

    2014-04-01

    Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChip v2.0 array. Our analysis identified 270 significantly different nps which, with one exception, showed an increased contribution of non-reference alleles in AD patients. Principal component analysis (PCA) and cluster analysis showed that five of these nps could discriminate AD from control subjects with 80% of cases correctly classified. Our data support the hypothesis of mtDNA alterations as an important factor in the etiology of AD. PMID:25590040

  11. Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer's Disease Patients.

    PubMed

    Spuch, Carlos; Antequera, Desireé; Pascual, Consuelo; Abilleira, Soledad; Blanco, María; Moreno-Carretero, María José; Romero-López, Jesús; Ishida, Tetsuya; Molina, Jose Antonio; Villarejo, Alberto; Bermejo-Pareja, Felix; Carro, Eva

    2015-01-01

    Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer's disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD. PMID:25926771

  12. CHRNA7 Gene and Response to Cholinesterase Inhibitors in an Italian Cohort of Alzheimer's Disease Patients.

    PubMed

    Clarelli, Ferdinando; Mascia, Elisabetta; Santangelo, Roberto; Mazzeo, Salvatore; Giacalone, Giacomo; Galimberti, Daniela; Fusco, Federica; Zuffi, Marta; Fenoglio, Chiara; Franceschi, Massimo; Scarpini, Elio; Forloni, Gianluigi; Magnani, Giuseppe; Comi, Giancarlo; Albani, Diego; Martinelli Boneschi, Filippo

    2016-04-16

    Previous studies suggest that genetic variants in CHRNA7, which encodes for the major subunit of the acetylcholine receptor (α7-nAChR), are associated with the clinical response to cholinesterase inhibitors (ChEI) in Alzheimer's disease (AD) patients. We sought to replicate the association of two SNPs in the CHRNA7 gene, rs6494223 and rs8024987, with response to ChEI treatment in an Italian cohort of 169 AD patients, further extending the study to gene-level analysis. None of the tested variants was associated with clinical response. However, rs6494223 showed a consistent effect direction (OR = 1.4; p = 0.17), which after meta-analysis with previous study yielded a significant result (OR = 1.57, p = 0.02, I2 = 0%). PMID:27104904

  13. What belgian neurologists and neuropsychiatrists tell their patients with Alzheimer disease and why: a national survey.

    PubMed

    Tarek, Meriem Essabiri; Segers, Kurt; Van Nechel, Christian

    2009-01-01

    To check their opinions concerning the disclosure of the diagnosis of Alzheimer disease (AD), a questionnaire was sent to all neurologists and neuropsychiatrists currently active in Belgium, excluding neuropediatricians. Of 573 questionnaires, 44% were returned. Sixty-eight percent of the responders always announce the diagnosis to their patients, 24% prefer to reveal the diagnosis only to patients with mild dementia. Doctors who announce the diagnosis to all their patients and who believe that its a benefit for the patient (67%) were more likely to be younger, to be neurologists, and to speak Dutch. The most important arguments in favor of announcing the diagnosis were the patient's right to know and the reinforcement of the doctor-patient relationship. The main arguments against revealing the diagnosis were the patient's right not to know and fear of provoking a depression. Two-third of the participants informed the patients about the prognosis and natural evolution of AD. These doctors tended to be younger, to be neurologists, and to speak Dutch. Young doctors tend to be more "open" toward their patients concerning the diagnosis of AD, consistent with the current guidelines. The differences between Dutch and French speaking doctors might be partially due to the fact that in French, "démence" has a psychiatric connotation. PMID:18695591

  14. Down Syndrome and Alzheimer's Disease

    MedlinePlus

    ... A A A Share Plus on Google Plus Alzheimer's & Dementia alz.org | IHaveAlz Overview What Is Dementia ... chapter Join our online community Down Syndrome and Alzheimer's Disease As they age, those affected by Down ...

  15. Healing gardens and cognitive behavioral units in the management of Alzheimer's disease patients: the Nancy experience.

    PubMed

    Rivasseau Jonveaux, Therese; Batt, Martine; Fescharek, Reinhard; Benetos, Athanase; Trognon, Alain; Bah Chuzeville, Stanislas; Pop, Alina; Jacob, Christel; Yzoard, Manon; Demarche, Laetitia; Soulon, Laure; Malerba, Gabriel; Bouvel, Bruno

    2013-01-01

    The French Alzheimer Plan 2008-2012 anticipates the implementation of new Units specialized in cognitive rehabilitation and psycho-behavioral therapy of Alzheimer's disease (AD) patients. Conceived for AD and other dementia patients of all ages, their objectives are to propose a cognitive rehabilitation program, to prevent or treat psycho-behavioral crises, and to provide support and educational therapy to the family and professional caregivers, in order to ease the patient's return to his or her previous way of life. Studies on green spaces and healing gardens in health-care settings have revealed objective and measurable improvements in the patient's well-being. The Plan officially stipulates for the first time the need to make healing gardens an integral part of these Units, but it does not provide specific recommendations or criteria for implementing such gardens. Although green spaces and gardens are available in many French Care Units, they are rarely specifically adapted to the needs of AD patients. In Nancy, the Art, Memory and Life garden, a specific concept guided by a neuropsychological approach, was developed and complemented by an artistic vision based on cultural invariants. The main objective of this article is to describe the various steps of the process that led to the creation of this garden: the collection of experiences and information by a pilot group, surveys of patients, visitors, and caregivers before and after establishment of the garden, and implementation of a multi-professional group project. The specifications, the organizational criteria, the therapeutic project, and the criteria for the conception of such a garden stemming from our clinical experience with the Art, Memory and Life garden in Nancy, are described herein. We also present the first assessment following the implementation of the project. PMID:23207487

  16. Donated Blood Won't Transmit Alzheimer's, Parkinson's Disease

    MedlinePlus

    ... fullstory_159577.html Donated Blood Won't Transmit Alzheimer's, Parkinson's Disease Swedish study of nearly 1.5 ... who have received blood transfusions from patients with Alzheimer's or Parkinson's disease," said Dr. Irving Gomolin, a ...

  17. The use of fiber tractography for identifying patients with Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Dong, Kyung-Rae; Goo, Eun-Hoe; Lee, Jae-Seung; Chung, Woon-Kwan

    2013-01-01

    This study examined the usefulness of fiber tractography (FT) for identifying patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) through diffusion tensor imaging (DTI). DTI was performed on twelve patients with AD (four males and eight females, mean age: 78.1 ± 7.5 years) and an eleven patients with MCI (five males and six females, mean age: 69.3 ± 8.0 years) from January to December 2011 by using a 3.0T scanner. Two regions of interest were drawn on the pyramidal tract of Pons and the posterior limb of the internal capsule, which passed through both cortico spinal tracts on the color-cored fractional anisotropy (FA) map. The numbers of white matter fibers on the DTIs in the patients with AD and MCI were determined. The numbers of white matter fibers in the AD patients were 1055.67 ± 333.12 and 860.75 ± 355.50 on the left and the right, respectively. In the patients with MCI, the numbers of white matter fibers and were 1329.82 ± 238.99 and 1316.55 ± 215.25 on the left and the right, respectively. The difference between the right and the left sides in the AD patients was slightly higher than that in the MCI patients.

  18. Preserved conceptual implicit memory for pictures in patients with Alzheimer's disease.

    PubMed

    Deason, Rebecca G; Hussey, Erin P; Flannery, Sean; Ally, Brandon A

    2015-10-01

    The current study examined different aspects of conceptual implicit memory in patients with mild Alzheimer's disease (AD). Specifically, we were interested in whether priming of distinctive conceptual features versus general semantic information related to pictures and words would differ for the mild AD patients and healthy older adults. In this study, 14 healthy older adults and 15 patients with mild AD studied both pictures and words followed by an implicit test section, where they were asked about distinctive conceptual or general semantic information related to the items they had previously studied (or novel items). Healthy older adults and patients with mild AD showed both conceptual priming and the picture superiority effect, but the AD patients only showed these effects for the questions focused on the distinctive conceptual information. We found that patients with mild AD showed intact conceptual picture priming in a task that required generating a response (answer) from a cue (question) for cues that focused on distinctive conceptual information. This experiment has helped improve our understanding of both the picture superiority effect and conceptual implicit memory in patients with mild AD in that these findings support the notion that conceptual implicit memory might potentially help to drive familiarity-based recognition in the face of impaired recollection in patients with mild AD. PMID:26291521

  19. Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer's Disease Patients?

    PubMed

    Femminella, Grazia D; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe

    2016-01-01

    The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration. PMID:27189470

  20. Risk classification in mild cognitive impairment patients for developing Alzheimer's disease.

    PubMed

    Zhou, Bin; Nakatani, Eiji; Teramukai, Satoshi; Nagai, Yoji; Fukushima, Masanori

    2012-01-01

    The objective of this study was to develop new risk classifications for conversion to Alzheimer's disease (AD) by comparing the relative reliability of classifiers in patients with mild cognitive impairment (MCI). The 397 MCI subjects and all baseline data, including characteristics, neuropsychological tests, cerebrospinal fluid biomarkers and MRI findings in Alzheimer's Disease Neuroimaging Initiative (ADNI), were used for analysis by Cox proportional hazard regression, bootstrap sampling, and c-index. Multivariate Cox regression analysis revealed the following factors to be associated with increased risk of conversion from MCI to AD during the 53-month follow-up period: AVLT 30-minute delayed recall, AVLT trial 1, Boston naming, logical delayed recall, trail-making B, CDR-sob, ADAS13, the cortical thickness of the right inferior temporal lobe (st91ta), and the left hippocampus volume. The combinations of ADAS13 at a cutoff point of 15.67 with CDR-sob at 1.5 or with the cortical thickness of the right inferior temporal lobe at 2.56 mm3 produced high conversion rates of 92.7% (82.4%-100.0%) and 88.8% (77.3%-100.0%), respectively, at 48 months. The discriminative ability based on c-index for the proposed combination was 0.68. The sample size was estimated as 504 in the group with a combination of ADAS13 and CDR-sob whose conversion rate is highest. The combination of ADAS13 with CDR-sob at an optimal cutoff point has a high reliability in classifying the MCI patients into high- and low-risk conversion to AD and will be benefit for patients' assessment and potentially facilitate the clinical development of novel therapeutics. PMID:22426014

  1. A predictor for side effects in patients with Alzheimer's disease treated with deferoxamine mesylate.

    PubMed

    Kruck, T P; Fisher, E A; McLachlan, D R

    1993-01-01

    In a previously reported clinical trial, patients with Alzheimer's disease were treated with deferoxamine mesylate, which resulted in a 50% reduction in the average rate of deterioration over 2 years. There were five deaths in the untreated group during the trial and no deaths in the treated group, although five of 25 treated patients reported anorexia. Deferoxamine metabolite analysis of urine for 24 hours after deferoxamine injection from sensitive and nonsensitive patients showed marked differences. Occurrence of side effects correlated with increased formation of a monoamine oxidase catalyzed (major) metabolite, MFO1. The metabolite ratio, MFO1/total metabolites, plus parent drug (TOT) showed a bimodal distribution with a mean +/- SD value of 0.68 +/- 0.06 for the nonsensitive and 0.79 +/- 0.04 for sensitive patients. The MFO1/TOT ratio discriminates between sensitive and nonsensitive patients, and we suggest that the half difference mark between the two mean values (0.735) can be used as a predictor of side effects. Patients with a MFO1/TOT ratio of greater than 0.70 would be considered at risk and observed for onset of side effects. Patients with a MFO1/TOT ratio greater than 0.80 would be considered for immediate adjunct treatment with isoniazid or other monoamine oxidase inhibitors. PMID:8422739

  2. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials

    PubMed Central

    Rollin-Sillaire, Adeline; Breuilh, Laetitia; Salleron, Julia; Bombois, Stéphanie; Cassagnaud, Pascaline; Deramecourt, Vincent; Mackowiak, Marie-Anne; Pasquier, Florence

    2013-01-01

    Aim To assess reasons that prevent Alzheimer's disease (AD) patients from being included in clinical trials. Methods In 2009, we reviewed the Lille Memory Clinic's case database to identify patients suitable for inclusion in four AD clinical trials. An initial selection was made on the basis of four criteria: (i) a diagnosis of AD (with or without white matter lesions [WML]), (ii) age, (iii) mini mental state examination (MMSE) score and (iv) symptomatic treatment of AD (cholinesterase inhibitors/memantine). Next, data on patients fulfilling these criteria were reviewed against all the inclusion/exclusion criteria for four clinical trials performed in 2009 at the Memory Clinic. Reasons for non-inclusion were analyzed. Results Two hundred and five patients were selected according to the four initial criteria. Reasons for subsequently not including some of patients in clinical trials were abnormalities on MRI (56.9%, 88.9% of which were WML), unauthorized medication (37.3%), the lack of a study partner/informant (37.1%), the presence of a non-authorized disease (24.4%), contraindication to MRI (9%), a change in diagnosis over time (3.9%), visual/auditory impairments (2.9%), alcohol abuse (2%) and an insufficient educational level (1%). Conclusion A high proportion of AD patients presented with vascular abnormalities on MRI. This was not unexpected, since the patients were selected from the database and, as shown in epidemiologic studies, cerebrovascular diseases are frequently associated with AD. The presence of a study partner is essential for enabling a patient to participate in clinical trials because of the need to record reliably primary and secondary outcomes. PMID:22891847

  3. Anti-ATP synthase autoantibodies from patients with Alzheimer's disease reduce extracellular HDL level.

    PubMed

    Vacirca, Davide; Barbati, Cristiana; Scazzocchio, Beatrice; Masella, Roberta; Rosano, Giuseppe; Malorni, Walter; Ortona, Elena

    2011-01-01

    Aside from being an integral protein involved in the synthesis and hydrolysis of ATP, Ecto-F1-ATPase plays a role in cholesterol homeostasis. We demonstrated the presence of autoantibodies to ecto-F1-ATPase (ASabs) in sera and cerebrospinal fluids from patients with Alzheimer's disease (AD). Herein we show that ASabs, unlike irrelevant antibodies, can increase cellular uptake of HDL, a risk factor for the development of AD, via a mechanism involving the prototypical function of ecto-F1-ATPase: the generation of ADP due to the hydrolysis of ATP. Piceatannol, a specific inhibitor ecto-F1-ATPase, completely hindered these effects. We hypothesize that ASabs could exert a pathogenetic role in AD. PMID:21677380

  4. Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer's disease patients at an early disease stage.

    PubMed

    Peng, Guoping; Wang, Jianqin; Feng, Zhan; Liu, Ping; Zhang, Yafei; He, Fangping; Chen, Zhongqin; Zhao, Kui; Luo, Benyan

    2016-01-01

    To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer's disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes. PMID:27377199

  5. Prevalence and correlates of cognitive asymmetry in a large sample of Alzheimer's disease patients.

    PubMed

    Alverson, W Alexander; Massman, Paul J; Doody, Rachelle S

    2016-06-01

    Previous research has suggested that a significant minority of patients with Alzheimer's disease (AD) exhibit asymmetric cognitive profiles (greater verbal than visuospatial impairment or vice versa) and that these patient subgroups may differ in demographic and other characteristics. Prior studies have been relatively small, and this investigation sought to examine correlates of asymmetry in a large patient sample (N = 438). Patients were classified into the following cognitive profile groups: low verbal, symmetric, and low visuospatial. Consistent with past research, 28.3% of participants were classified as having asymmetric cognitive profiles, with more participants in the low visuospatial subgroup. Low visuospatial participants were younger than members of the other subgroups, and low verbal participants performed worse on a measure estimating premorbid verbal intelligence. Findings regarding apolipoprotein E (ApoE) ε4 genotype were equivocal, although results provided some evidence for an effect of the ɛ4 allele on cognitive asymmetry. These results suggest systematic differences between neuropsychological asymmetry profiles that support the possibility of distinct subgroups of the disease. PMID:26757777

  6. Disrupted Network Topology in Patients with Stable and Progressive Mild Cognitive Impairment and Alzheimer's Disease

    PubMed Central

    Pereira, Joana B.; Mijalkov, Mite; Kakaei, Ehsan; Mecocci, Patricia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilka; Spenger, Christian; Lovestone, Simmon; Simmons, Andrew; Wahlund, Lars-Olof; Volpe, Giovanni; Westman, Eric

    2016-01-01

    Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology. PMID:27178195

  7. Disrupted Network Topology in Patients with Stable and Progressive Mild Cognitive Impairment and Alzheimer's Disease.

    PubMed

    Pereira, Joana B; Mijalkov, Mite; Kakaei, Ehsan; Mecocci, Patricia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilka; Spenger, Christian; Lovestone, Simmon; Simmons, Andrew; Wahlund, Lars-Olof; Volpe, Giovanni; Westman, Eric

    2016-08-01

    Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology. PMID:27178195

  8. Alzheimer's disease treated patients showed different patterns for oxidative stress and inflammation markers.

    PubMed

    Gubandru, Miriana; Margina, Denisa; Tsitsimpikou, Christina; Goutzourelas, Nikos; Tsarouhas, Konstantinos; Ilie, Mihaela; Tsatsakis, Aristidis Michael; Kouretas, Demetrios

    2013-11-01

    Alzheimer's disease (AD) is the most common type of dementia accounting for 60-80% of the reported cases. The aim of this study was to evaluate levels of certain parameters of oxidative stress and markers of endothelial dysfunction in the blood of 21 AD patients under standard treatment compared with 10 controls, in an attempt to elucidate the contribution of AD to the total oxidative stress status of the patients. Results indicate that IL-6, TNF-α, ADMA and homocysteine levels were significantly elevated in AD patients. Protein carbonyls levels were higher in AD group, while glutathione reductase and total antioxidant capacity were lower, depicting decreased defense ability against reactive oxygen species. Besides, a higher level of advanced glycation end-products was observed in AD patients. Depending on the treatment received, a distinct inflammatory and oxidative stress profile was observed: in Rivastigmine-treated group, IL6 levels were 47% lower than the average value of the remaining AD patients; homocysteine and glutathione reductase were statistically unchanged in the Rivastigmine and Donepezil-Memantine, respectively Donepezil group. Although the study is based on a limited population, the results could constitute the basis for further studies regarding the effect of medication and diet on AD patients. PMID:23871825

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

    PubMed Central

    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. PMID:26727258

  10. 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. PMID:26727258

  11. G1/S Cell Cycle Checkpoint Defect in Lymphocytes from Patients with Alzheimer's Disease

    PubMed Central

    Song, Misun; Kwon, Young-Ah; Lee, Yujin; Kim, Hyeran; Yun, Ji Hea; Kim, Seonwoo

    2012-01-01

    Objective We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle. Methods Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin. Results The patients with AD were older than the normal controls (AD 74.03±7.90 yr vs. control 68.28±6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29±6.32% vs. 76.03±9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45±6.09% vs. 6.03±5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects. Conclusion The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death. PMID:23251208

  12. Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease

    PubMed Central

    Roh, Hyun Woong; Hong, Chang Hyung; Lee, SooJin; Lee, Yunhwan; Lee, Kang Soo; Chang, Ki Jung; Oh, Byoung Hoon; Choi, Seong Hye; Kim, Seong Yoon; Back, Joung Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Son, Sang Joon

    2015-01-01

    Abstract To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD). Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline. After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97–1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88–0.99). The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD. PMID:26559259

  13. A computer-aided program for helping patients with moderate Alzheimer's disease engage in verbal reminiscence.

    PubMed

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Ferlisi, Gabriele; Zullo, Valeria; Schirone, Simona; Prisco, Raffaella; Denitto, Floriana

    2014-11-01

    This study assessed a simple computer-aided program for helping patients with moderate Alzheimer's disease engage in verbal reminiscence. In practice, the program was aimed at fostering the patient's verbal engagement on a number of life experiences/topics previously selected for him or her and introduced in the sessions through a friendly female, who appeared on the computer screen. The female asked the patient about the aforementioned experiences/topics, and provided him or her with positive attention, and possibly verbal guidance (i.e., prompts/encouragements). Eight patients were involved in the study, which was carried out according to non-concurrent multiple baseline designs across participants. Seven of them showed clear improvement during the intervention phase (i.e., with the program). Their mean percentages of intervals with verbal engagement/reminiscence ranged from close to zero to about 15 during the baseline and from above 50 to above 75 during the intervention. The results were discussed in relation to previous literature on reminiscence therapy, with specific emphasis on the need for (a) replication studies and (b) the development of new versions of the technology-aided program to improve its impact and reach a wider number of patients. PMID:25124700

  14. An outline for a cost-effectiveness analysis of a drug for patients with Alzheimer's disease.

    PubMed

    Busschbach, J J; Brouwer, W B; van der Donk, A; Passchier, J; Rutten, F F

    1998-01-01

    This article provides an outline for a cost-effectiveness analysis of a drug that slows the consequences of Alzheimer's disease. Such an analysis cannot easily be performed for 2 main reasons. The first is that often relatives and friends, rather than professionals, take care of the patient. This means that informal care plays an important role in the analysis. However, consensus on how to value informal care is lacking. In this article, we have recommended the shadow-price method because this is an option that can be practically applied. The second reason is that the primary source of information on quality of life, the patients themselves, is unreliable because of cognitive disturbances. The solution is to ask 'significant others' to indicate quality of life instead of the patient. As well as measuring the patient's quality of life, the quality of life of the informal caregiver is also often measured. This is recommended here, but as a separate item in the analysis. In this way, double-counting in the final cost-effectiveness ratio can be avoided. Several instruments for measuring a patient's and caregiver's quality of life are discussed and recommendations about suitable methods are made. PMID:10175983

  15. Deficits on irregular verbal morphology in Italian-speaking Alzheimer's disease patients

    PubMed Central

    Walenski, Matthew; Sosta, Katiuscia; Cappa, Stefano; Ullman, Michael T.

    2010-01-01

    Studies of English have shown that temporal-lobe patients, including those with Alzheimer's disease, are spared at processing real and novel regular inflected forms (e.g., blick → blicked; walk → walked), but impaired at real and novel irregular forms (e.g., spling → splang; dig → dug). Here we extend the investigation cross-linguistically to the more complex system of Italian verbal morphology, allowing us to probe the generality of the previous findings in English, as well as to test different explanatory accounts of inflectional morphology. We examined the production of real and novel regular and irregular past-participle and present-tense forms by native Italian-speaking healthy control subjects and patients with probable Alzheimer's disease. Compared to the controls, the patients were impaired at inflecting real irregular verbs but not real regular verbs both for past-participle and present-tense forms, but were not impaired at real regular verbs either for past-participle or present-tense forms. For novel past participles, the patients exhibited this same pattern of impaired production of class II (irregular) forms but spared class I (regular) production. In the present tense, patients were impaired at the production of class II forms (which are regular in the present tense), but spared at production of class I (regular) forms. Contrary to the pattern observed in English, the errors made by the patients on irregulars did not reveal a predominance of regularization errors (e.g., dig → digged). The findings thus partly replicate prior findings from English, but also reveal new patterns from a language with a more complex morphological system that includes verb classes (which are not possible to test in English). The demonstration of an irregular deficit following temporal-lobe damage in a language other than English reveals the cross-linguistic generality of the basic effect, while also elucidating important language-specific differences in the neuro

  16. A blood based 12-miRNA signature of Alzheimer disease patients

    PubMed Central

    2013-01-01

    Background Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples. Results We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies. Conclusions The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases. PMID:23895045

  17. Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer's Disease and Mild Cognitive Impairment Patients

    PubMed Central

    Delbarba, A.; Abate, G.; Prandelli, C.; Marziano, M.; Buizza, L.; Arce Varas, N.; Novelli, A.; Cuetos, F.; Martinez, C.; Lanni, C.; Memo, M.; Uberti, D.

    2016-01-01

    It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer's disease (AD). However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in terms of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) isolated from AD and Mild Cognitive Impairment (MCI) patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI patients when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited highly nitrated MnSOD, index of a prooxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI patients' blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis. PMID:26881032

  18. Overexpression of Cell Cycle Proteins of Peripheral Lymphocytes in Patients with Alzheimer's Disease

    PubMed Central

    Kim, Hyeran; Kwon, Young-Ah; Ahn, Inn Sook; Kim, Sangha; Kim, Seonwoo; Jo, Sangmee Ahn

    2016-01-01

    Objective Biological markers for Alzheimer's disease (AD) will help clinicians make objective diagnoses early during the course of dementia. Previous studies have suggested that cell cycle dysregulation begins earlier than the onset of clinical manifestations in AD. Methods We examined the lymphocyte expression of cell cycle proteins in AD patients, dementia controls (DC), and normal controls (NC). One-hundred seventeen subjects (36 AD, 31 DC, and 50 NC) were recruited. The cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were measured in peripheral lymphocytes. Cell cycle protein expression in the three groups was compared after adjusting for age and sex. Results The levels of cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were significantly higher in AD patients than in the NC subjects. The DC group manifested intermediate levels of cell cycle proteins compared with the AD patients and the NC subjects. The present study indicates that cell cycle proteins are upregulated in the peripheral lymphocytes of AD patients. Conclusion Cell cycle dysregulation in peripheral lymphocytes may present a promising starting point for identifying peripheral biomarkers of AD. PMID:26766955

  19. Analysis of spontaneous MEG activity in patients with Alzheimer's disease using spectral entropies.

    PubMed

    Poza, Jesús; Hornero, Roberto; Abásolo, Daniel; Fernández, Alberto; Escudero, Javier

    2007-01-01

    The aim of this study was to explore the ability of several spectral entropies to discriminate between spontaneous magnetoencephalographic (MEG) oscillations from 20 Alzheimer's disease (AD) patients and 21 controls. Hence, the relative spectral power (RSP) in classical frequency bands was calculated from the averaged power spectral density. Given the fact that the RSP can be viewed as a probability distribution function, the Shannon spectral entropy, Tsallis spectral entropy, generalized escort-Tsallis spectral entropy and Rényi spectral entropy were calculated from the RSP. Significant differences for each parameter were assessed with Mann-Whitney U test, whereas classification performance was studied using binary logistic regression. Results revealed an increase in the RSP of control subjects at beta and gamma bands, while AD patients showed an increase in the RSP values at delta and theta bands. Entropies obtained statistically significant lower values for AD patients than for controls. This issue suggests a significant decrease in irregularity of AD patients' MEG activity. PMID:18003432

  20. Neural basis of three dimensions of agitated behaviors in patients with Alzheimer disease

    PubMed Central

    Banno, Koichi; Nakaaki, Shutaro; Sato, Junko; Torii, Katsuyoshi; Narumoto, Jin; Miyata, Jun; Hirono, Nobutsugu; Furukawa, Toshi A; Mimura, Masaru; Akechi, Tatsuo

    2014-01-01

    Background Agitated behaviors are frequently observed in patients with Alzheimer disease (AD). The neural substrate underlying the agitated behaviors in dementia is unclear. We hypothesized that different dimensions of agitated behaviors are mediated by distinct neural systems. Methods All the patients (n=32) underwent single photon emission computed tomography (SPECT). Using the Agitated Behavior in Dementia scale, we identified the relationships between regional cerebral blood flow (rCBF) patterns and the presence of each of three dimensions of agitated behavior (physically agitated behavior, verbally agitated behavior, and psychosis symptoms) in AD patients. Statistical parametric mapping (SPM) software was used to explore these neural correlations. Results Physically agitated behavior was significantly correlated with lower rCBF values in the right superior temporal gyrus (Brodmann 22) and the right inferior frontal gyrus (Brodmann 47). Verbally agitated behavior was significantly associated with lower rCBF values in the left inferior frontal gyrus (Brodmann 46, 44) and the left insula (Brodmann 13). The psychosis symptoms were significantly correlated with lower rCBF values in the right angular gyrus (Brodmann 39) and the right occipital lobe (Brodmann 19). Conclusion Our results support the hypothesis that three different agitated behaviors may represent distinct neural networks in AD patients. PMID:24600224

  1. [Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

    PubMed

    Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

    2013-01-01

    A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI. PMID:23329298

  2. Approximate entropy and auto mutual information analysis of the electroencephalogram in Alzheimer's disease patients.

    PubMed

    Abásolo, D; Escudero, J; Hornero, R; Gómez, C; Espino, P

    2008-10-01

    We analysed the electroencephalogram (EEG) from Alzheimer's disease (AD) patients with two nonlinear methods: approximate entropy (ApEn) and auto mutual information (AMI). ApEn quantifies regularity in data, while AMI detects linear and nonlinear dependencies in time series. EEGs from 11 AD patients and 11 age-matched controls were analysed. ApEn was significantly lower in AD patients at electrodes O1, O2, P3 and P4 (p < 0.01). The EEG AMI decreased more slowly with time delays in patients than in controls, with significant differences at electrodes T5, T6, O1, O2, P3 and P4 (p < 0.01). The strong correlation between results from both methods shows that the AMI rate of decrease can be used to estimate the regularity in time series. Our work suggests that nonlinear EEG analysis may contribute to increase the insight into brain dysfunction in AD, especially when different time scales are inspected, as is the case with AMI. PMID:18784948

  3. Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

    PubMed Central

    Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

    2015-01-01

    Background/Aims We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). Methods A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients. PMID:26483830

  4. Efficacy and safety studies of gantenerumab in patients with Alzheimer's disease.

    PubMed

    Panza, Francesco; Solfrizzi, Vincenzo; Imbimbo, Bruno P; Giannini, Michele; Santamato, Andrea; Seripa, Davide; Logroscino, Giancarlo

    2014-09-01

    Among active and passive anti-β-amyloid (Aβ) immunotherapies for Alzheimer's disease (AD), bapineuzumab and solanezumab, two humanized monoclonal antibodies, failed to show significant clinical benefits in mild-to-moderate AD patients in large Phase III clinical trials. Another ongoing Phase III trial of solanezumab aims to confirm positive findings in mild AD patients. Gantenerumab is the first fully human anti-Aβ monoclonal antibody directed to both N-terminal and central regions of Aβ. A 6-month PET study in 16 AD patients showed that gantenerumab treatment dose-dependently reduced brain Aβ deposition, possibly stimulating microglial-mediated phagocytosis. Two ongoing Phase III trials of gantenerumab in patients with prodromal or mild dementia due to AD will determine if any reduction in brain Aβ levels will translate into clinical benefits. An ongoing secondary prevention trial of gantenerumab in presymptomatic subjects with genetic mutations for autosomal-dominant AD will verify the utility of anti-Aβ monoclonal antibodies as prevention therapy. PMID:25081412

  5. Lack of contextual-word predictability during reading in patients with mild Alzheimer disease.

    PubMed

    Fernández, Gerardo; Manes, Facundo; Rotstein, Nora P; Colombo, Oscar; Mandolesi, Pablo; Politi, Luis E; Agamennoni, Osvaldo

    2014-09-01

    In the present work we analyzed the effect of contextual word predictability on the eye movement behavior of patients with mild Alzheimer disease (AD) compared to age-matched controls, by using the eyetracking technique and lineal mixed models. Twenty AD patients and 40 age-matched controls participated in the study. We first evaluated gaze duration during reading low and highly predictable sentences. AD patients showed an increase in gaze duration, compared to controls, both in sentences of low or high predictability. In controls, highly predictable sentences led to shorter gaze durations; by contrary, AD patients showed similar gaze durations in both types of sentences. Similarly, gaze duration in controls was affected by the cloze predictability of word N and N+1, whereas it was the same in AD patients. In contrast, the effects of word frequency and word length were similar in controls and AD patients. Our results imply that contextual-word predictability, whose processing is proposed to require memory retrieval, facilitated reading behavior in healthy subjects, but this facilitation was lost in early AD patients. This loss might reveal impairments in brain areas such as those corresponding to working memory, memory retrieval, and semantic memory functions that are already present at early stages of AD. In contrast, word frequency and length processing might require less complex mechanisms, which were still retained by AD patients. To the best of our knowledge, this is the first study measuring how patients with early AD process well-defined words embedded in sentences of high and low predictability. Evaluation of the resulting changes in eye movement behavior might provide a useful tool for a more precise early diagnosis of AD. PMID:25080188

  6. Alzheimer's Disease and Stem Cell Therapy

    PubMed Central

    Choi, Sung S.; Lee, Sang-Rae; Kim, Seung U.

    2014-01-01

    The loss of neuronal cells in the central nervous system may occur in many neurodegenerative diseases. Alzheimer's disease is a common senile disease in people over 65 years, and it causes impairment characterized by the decline of mental function, including memory loss and cognitive impairment, and affects the quality of life of patients. However, the current therapeutic strategies against AD are only to relieve symptoms, but not to cure it. Because there are only a few therapeutic strategies against Alzheimer's disease, we need to understand the pathogenesis of this disease. Cell therapy may be a powerful tool for the treatment of Alzheimer's disease. This review will discuss the characteristics of Alzheimer's disease and various available therapeutic strategies. PMID:24737939

  7. Pharmacogenomics in Alzheimer's disease.

    PubMed

    Cacabelos, Ramón

    2002-02-01

    Alzheimer's disease (AD) is a complex disorder associated with multiple genetic defects either mutational or of susceptibility. Information available on AD genetics does not explain in full the etiopathogenesis of AD, suggesting that environmental factors and/or epigenetic phenomena may also contribute to AD pathology and phenotypic expression of dementia. The genomics of AD is still in its infancy, but is helping to understand novel aspects of the disease including genetic epidemiology, multifactorial risk factors, pathogenic mechanisms associated with genetic networks and genetically-regulated metabolic cascades. AD genomics is also helping to develop new strategies in pharmacogenomic research and prevention. Functional genomics, proteomics, pharmacogenomics, high-throughput methods, combinatorial chemistry and modern bioinformatics will greatly contribute to accelerate drug development for AD and other complex disorders. Main genes involved in AD include mutational loci (APP, PS1, PS2, TAU) and multiple susceptibility loci (APOE, A2M, AACT, LRP1, IL1A, TNF, ACE, BACE, BCHE, CST3, MTHFR, GSK3B, NOS) distributed across the human genome. Genomic associations integrate bigenic, trigenic, tetragenic or polygenic matrix models to investigate the genomic organization of AD in comparison to the control population. Similar genetic models are used in pharmacogenomics to elucidate genotype-specific responses of AD patients to a particular drug or combination of drugs. Using APOE-related monogenic models it has been demonstrated that the therapeutic response to drugs in AD is genotype-specific. A multifactorial therapy combining 3 different drugs yielded positive results during the 6-12 months in approximately 60% of the patients. With this therapeutic strategy, APOE-4/4 carriers were the worst responders, and patients with the APOE-3/4 genotype were the best responders. In bigenic and trigenic models it was possible to differentiate the influencial effect of PS1 and PS2

  8. Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

    PubMed

    Fowler, Kevin D; Funt, Jason M; Artyomov, Maxim N; Zeskind, Benjamin; Kolitz, Sarah E; Towfic, Fadi

    2015-01-01

    To generate new insights into the biology of Alzheimer's Disease (AD), we developed methods to combine and reuse a wide variety of existing data sets in new ways. We first identified genes consistently associated with AD in each of four separate expression studies, and confirmed this result using a fifth study. We next developed algorithms to search hundreds of thousands of Gene Expression Omnibus (GEO) data sets, identifying a link between an AD-associated gene (NEUROD6) and gender. We therefore stratified patients by gender along with APOE4 status, and analyzed multiple SNP data sets to identify variants associated with AD. SNPs in either the region of NEUROD6 or SNAP25 were significantly associated with AD, in APOE4+ females and APOE4+ males, respectively. We developed algorithms to search Connectivity Map (CMAP) data for medicines that modulate AD-associated genes, identifying hypotheses that warrant further investigation for treating specific AD patient subsets. In contrast to other methods, this approach focused on integrating multiple gene expression datasets across platforms in order to achieve a robust intersection of disease-affected genes, and then leveraging these results in combination with genetic studies in order to prioritize potential genes for targeted therapy. PMID:26395074

  9. A Meta-Analysis of C-Reactive Protein in Patients With Alzheimer's Disease.

    PubMed

    Gong, Changguo; Wei, Daixin; Wang, Ying; Ma, Ji; Yuan, Chonggang; Zhang, Wei; Yu, Guohua; Zhao, Yulan

    2016-05-01

    Inflammation may be associated with Alzheimer's disease (AD). This meta-analysis aimed to compare the level of C-reactive protein (CRP) in patients having AD to healthy controls. A total of 10 cross-sectional studies (n = 2093) were identified from PubMed and EMBASE after systematic searching and evaluation. The combined standardized mean difference (SMD) of CRP level between the disease and control group was analyzed. In the meta-analysis, there was no significant difference in serum between the CRP level of patients with AD and that of healthy controls (SMD: -0.400, 95% confidence interval [CI]: -0.827 to 0.027,P= .066). However, when we stratified the studies by Mini-Mental State Examination (MMSE) scores, the level of CRP in the mild and moderate dementia subgroup (MMSE ≥ 10) was significantly lower than that in the control group (SMD: -0.582, 95% CI: -0.957 to -0.208,P= .002). Therefore, the diagnostic value of CRP for mild and moderate AD may be useful in clinical practice. PMID:26340961

  10. Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer's disease patients.

    PubMed

    Capo, Concetta R; Arciello, Mario; Squitti, Rosanna; Cassetta, Emanuele; Rossini, Paolo Maria; Calabrese, Lilia; Rossi, Luisa

    2008-06-01

    The level of the apo-form of the copper enzyme ceruloplasmin (CP) is an established peripheral marker in diseases associated with copper imbalance. In view of the proposal that disturbances of copper homeostasis may contribute to neurodegeneration associated with Alzheimer's disease (AD), the present work investigates, by Western blot and non-reducing SDS-PAGE followed by activity staining, the features of CP protein, and the copper/CP relationship in cerebrospinal fluid (CSF) and serum of AD patients. Results show that only a fraction of total copper is associated with CP in the CSF, at variance with serum, both in affected and in healthy individuals. Furthermore, a conspicuous amount of apo-ceruloplasmin and a decrease of CP oxidase activity characterize the CSF of the affected individuals, and confirm that an impairment of copper metabolism occurs in their central nervous system. In the CSF of AD patients the decrease of active CP, associated with the increase in the pool of copper not sequestered by this protein, may play a role in the neurodegenerative process. PMID:18060472

  11. Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients.

    PubMed

    Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; den Dunnen, Wilfred; Korf, Horst-Werner

    2015-01-01

    In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal pathology is still fragmentary. Investigation of serial 100 μm-thick brain tissue sections through the thalamus of clinically diagnosed AD patients with Braak and Braak AD stage V or VI cytoskeletal pathologies immunostained with the anti-tau AT8 antibody, along with the affection of the extraterritorial reticular nucleus of the thalamus, reveals a consistent and severe tau immunoreactive cytoskeletal pathology in the limbic nuclei of the thalamus (e.g., paraventricular, anterodorsal and laterodorsal nuclei, limitans-suprageniculate complex). The thalamic nuclei integrated into the associative networks of the human brain (e.g., ventral anterior and mediodorsal nuclei) are only mildly affected, while its motor precerebellar (ventral lateral nucleus) and sensory nuclei (e.g., lateral and medial geniculate bodies, ventral posterior medial and lateral nuclei, parvocellular part of the ventral posterior medial nucleus) are more or less spared. The highly stereotypical and characteristic thalamic distribution pattern of the AD-related tau cytoskeletal pathology represents an anatomical mirror of the hierarchical topographic distribution of the cytoskeletal pathology in the interconnected regions of the cerebral cortex of AD patients. These pathoanatomical parallels support the pathophysiological concept of a transneuronal spread of the disease process of AD along anatomical pathways. The AD-related tau cytoskeletal pathology in the thalamus most likely contributes substantially to the neuropsychiatric disease symptoms (e.g., dementia), attention deficits, oculomotor dysfunctions, altered non-discriminative aspects of pain experience of AD patients, and the disruption of their

  12. Preventing Alzheimer's Disease: What Do We Know?

    MedlinePlus

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... National Alzheimer's Project Act (NAPA) About ADEAR Preventing Alzheimer’s Disease: What Do We Know? Introduction The news ...

  13. Dissecting risk haplotypes in sporadic Alzheimer's disease.

    PubMed

    Soldner, Frank; Jaenisch, Rudolf

    2015-04-01

    Understanding how genetic risk variants contribute to complex diseases is crucial for predicting disease susceptibility and developing patient-tailored therapies. In this issue of Cell Stem Cell, Young et al. (2015) dissect the function of common non-coding risk haplotypes in the SORL1 locus in the pathogenesis of sporadic Alzheimer's disease using patient-derived induced pluripotent stem cells. PMID:25842969

  14. Ion beam analysis of the bone tissue of Alzheimer's disease patients

    NASA Astrophysics Data System (ADS)

    Robertson, J. D.; Samudralwar, D. L.; Markesbery, W. R.

    1992-02-01

    It has been hypothesized that perturbations in element metabolism play a role in the etiology and/or pathogenesis of Alzheimer's disease (AD). No conclusion regarding this hypothesis has been reached, however, as results for central nervous system tissues from different research groups are contradictory. We are currently utilizing external-beam thick-target FIXE and PIGE analyses to investigate the elemental concentrations in the bone tissue of AD patients. Because bone acts as a "repository" for many trace elements, these measurements should provide information on the long-term trace-element status of AD patients. With the simultaneous PIXE/PIGE measurements, we are able to instrumentally determine the concentrations of oxygen, phosphorus, calcium, and 12-15 minor and trace elements in a single 30 min irradiation. Initial results obtained from the IBA measurements of both cortical and trabecular bone autopsy samples from four AD patients and twelve age-matched controls indicate a possible imbalance in Zn, Br and Rb.

  15. Regional analysis of spontaneous MEG rhythms in patients with Alzheimer's disease using spectral entropies.

    PubMed

    Poza, Jesús; Hornero, Roberto; Escudero, Javier; Fernández, Alberto; Sánchez, Clara I

    2008-01-01

    Alzheimer's disease (AD) is the most common form of dementia. Ageing is the greatest known risk factor for this disorder. Therefore, the prevalence of AD is expected to increase in western countries due to the rise in life expectancy. Nowadays, a low diagnosis accuracy is reached, but an early and accurate identification of AD should be attempted. In this sense, only a few studies have focused on the magnetoencephalographic (MEG) AD patterns. This work represents a new effort to explore the ability of three entropies from information theory to discriminate between spontaneous MEG rhythms from 20 AD patients and 21 controls. The Shannon (SSE), Tsallis (TSE), and Rényi (RSE) spectral entropies were calculated from the time-frequency distribution of the power spectral density (PSD). The entropies provided statistically significant lower values for AD patients than for controls in all brain regions (p < 0.0005). This fact suggests a significant loss of irregularity in AD patients' MEG activity. Maximal accuracy of 87.8% was achieved by both the TSE and RSE (90.0%, sensitivity; 85.7%, specificity). The statistically significant results obtained by both the extensive (SSE and RSE) and non-extensive (TSE) spectral entropies suggest that AD could disturb long and short-range interactions causing an abnormal brain function. PMID:17994279

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

    PubMed

    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

    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 [C(11)]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

  17. Effect of phosphatidylserine on memory in patients and rats with Alzheimer's disease.

    PubMed

    Zhang, Y Y; Yang, L Q; Guo, L M

    2015-01-01

    The aim of this study was to investigate the effect of phosphatidylserine (PS) on memory of patients and rats with Alzheimer's disease (AD). In total, 57 AD patients were recruited from our hospital, and were divided into two groups: 25 in the control group and 32 in the observation group. Next, 300 mg/d of PS was given to the rats in the observation group for 12 continuous weeks based on the control group. AD rats were divided into three groups: control group, PS 30 mg/kg group, and PS 15 mg/kg group. Learning memory ability and free radical levels in the brain were detected after treatment. In AD patients, vocabulary and picture matching scores in the two treatment groups increased after treatment (P < 0.05). Moreover, the scores in the treated group were significantly greater than the control group (P < 0.05). In AD rats, PS treatment reduced the escape latent period of AD rats, increased SOD and OH(-), and decreased acetylcholinesterase levels (P < 0.05). Compared with PS 15 mg/kg, PS 30 mg/kg group was significantly more efficacious (P < 0.05). Compared with the AD model group, hippocampal cells showed normal arrangement, karyopyknosis decreased, and the pathological changes in the two PS groups were considerable. In conclusion, PS decreased cholinesterase, improved memory, and improved hippocampal inflammation injury in AD brains by increasing SOD and OH(-) levels. PMID:26345866

  18. Exosomes in Alzheimer's disease.

    PubMed

    Malm, Tarja; Loppi, Sanna; Kanninen, Katja M

    2016-07-01

    Exosomes, nano-sized extracellular vesicles secreted by most cell types, are found everywhere in the body. The role of exosomes in cellular functions has in the past years developed from being considered little more than cellular trashcans, to being proven important intercellular messengers and notable contributors to both health and in disease. A vast number of studies have revealed the multiple, and somewhat controversial role of exosomes in Alzheimer's disease, the most common neurodegenerative disease. Exosomes have been shown to spread toxic amyloid-beta and hyperphosphorylated tau between cells, and they have been suspected of inducing apoptosis and thereby contributing to neuronal loss. On the other hand, exosomes seem to possess the ability to reduce brain amyloid-beta through microglial uptake, and they are known to transfer neuroprotective substances between cells. These features, among many others, make exosomes extremely interesting from the point of view of developing novel therapeutic approaches. The fact that exosomes derived from the central nervous system can be found in bodily fluids also makes them an appealing target for biomarker development, which is not limited only to Alzheimer's disease. PMID:27131734

  19. Alzheimer's disease: early diagnosis and treatment.

    PubMed

    Chu, L W

    2012-06-01

    With ageing of populations, the worldwide population of persons with dementia will reach over 81 million by 2040, of which the most common cause is Alzheimer's disease. In recent years, there have been major advances in the understanding of its pathogenesis, methods to diagnose it, and treatment. Magnetic resonance brain imaging, cerebrospinal fluid biomarkers, and Pittsburgh compound B and fluorodeoxyglucose positron emission tomography of the brain can facilitate an accurate diagnosis of Alzheimer's disease in its early stage, and diagnose the mild cognitive impairment stage of Alzheimer's disease. At present, only symptomatic but not disease-modifying drug treatments are available. Donepezil, rivastigmine and galantamine are the currently approved cholinesterase inhibitors for the treatment of mild, moderate, and severe Alzheimer's disease. Overall, cholinesterase inhibitors show beneficial effects on cognition, activity of daily living, behaviour, and overall clinical rating. Memantine is another symptomatic treatment for moderate-to-severe Alzheimer's disease patients. It has a small beneficial effect on cognition, activity of daily living, behaviour, and overall clinical rating. Vitamin E has antioxidant properties, and may be used in some Alzheimer's disease patients without vascular risk factors. Concurrent non-pharmacological and psychosocial management of patients and their caregivers have a very important role. Disease-modifying therapies are still under development, whilst immunotherapy may be a viable option in the near future. PMID:22665688

  20. Learning to Perceive Structure from Motion and Neural Plasticity in Patients with Alzheimer's Disease

    ERIC Educational Resources Information Center

    Kim, Nam-Gyoon; Park, Jong-Hee

    2010-01-01

    Recent research has demonstrated that Alzheimer's disease (AD) affects the visual sensory pathways, producing a variety of visual deficits, including the capacity to perceive structure-from-motion (SFM). Because the sensory areas of the adult brain are known to retain a large degree of plasticity, the present study was conducted to explore whether…

  1. Antioxidant Therapies for Alzheimer's Disease

    PubMed Central

    Feng, Ye; Wang, Xiaochuan

    2012-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disease featuring progressive impairments in memory, cognition, and behavior and ultimately leads to death. The histopathological changes of Alzheimer's disease include neuronal and synaptic loss, formation of extracellular senile plaques and intracellular neurofibrillary tangles in brain. Multiple lines of evidence indicate that oxidative stress not only strongly participates in an early stage of Alzheimer's disease prior to cytopathology, but plays an important role in inducing and activating multiple cell signaling pathways that contribute to the lesion formations of toxic substances and then promotes the development of Alzheimer's disease. Many years of studies show that antioxidant therapies have enjoyed general success in preclinical studies. Therefore, this paper mainly focuses on the recent developments of common used antioxidant therapies for Alzheimer's disease and thus provides indications for future potential antioxidant therapeutic strategies of neurodegenerative diseases. PMID:22888398

  2. Focused and divided attention in Alzheimer's disease.

    PubMed

    Nebes, R D; Brady, C B

    1989-06-01

    Visual search tasks were used to examine two aspects of selective attention (focused and divided attention) in normal young and older persons and in Alzheimer patients. Normal and demented subjects were equally efficient in using a color cue to selectively search only the relevant items in an array. Thus, focused attention abilities appear to be relatively unimpaired by Alzheimer's disease. By contrast, in comparison to normals, the search time of demented patients rose disproportionately as the number of items over which they had to distribute their attention was increased. This suggests that Alzheimer patients are less efficient than normals in dividing their attention. PMID:2758855

  3. Role of Methylglyoxal in Alzheimer's Disease

    PubMed Central

    Zambonin, Laura; Hrelia, Silvana

    2014-01-01

    Alzheimer's disease is the most common and lethal neurodegenerative disorder. The major hallmarks of Alzheimer's disease are extracellular aggregation of amyloid β peptides and, the presence of intracellular neurofibrillary tangles formed by precipitation/aggregation of hyperphosphorylated tau protein. The etiology of Alzheimer's disease is multifactorial and a full understanding of its pathogenesis remains elusive. Some years ago, it has been suggested that glycation may contribute to both extensive protein cross-linking and oxidative stress in Alzheimer's disease. Glycation is an endogenous process that leads to the production of a class of compounds known as advanced glycation end products (AGEs). Interestingly, increased levels of AGEs have been observed in brains of Alzheimer's disease patients. Methylglyoxal, a reactive intermediate of cellular metabolism, is the most potent precursor of AGEs and is strictly correlated with an increase of oxidative stress in Alzheimer's disease. Many studies are showing that methylglyoxal and methylglyoxal-derived AGEs play a key role in the etiopathogenesis of Alzheimer's disease. PMID:24734229

  4. Effects of acetylcholinesterase inhibitors and memantine on resting-state electroencephalographic rhythms in Alzheimer's disease patients.

    PubMed

    Babiloni, Claudio; Del Percio, Claudio; Bordet, Regis; Bourriez, Jean-Luis; Bentivoglio, Marina; Payoux, Pierre; Derambure, Philippe; Dix, Sophie; Infarinato, Francesco; Lizio, Roberta; Triggiani, Antonio Ivano; Richardson, Jill C; Rossini, Paolo M

    2013-05-01

    Acetylcholinesterase inhibitors (AChEIs) are the most widely used symptomatic treatment for mild to severe Alzheimer's disease (AD) patients, while N-methyl-d-aspartic acid (NMDA) receptor antagonist memantine is licensed for use in moderate to severe AD patients. In this article, the effect of these compounds on resting state eyes-closed electroencephalographic (EEG) rhythms in AD patients is reviewed to form a knowledge platform for the European Innovative Medicine Initiative project "PharmaCog" (IMI Grant Agreement No. 115009) aimed at developing innovative translational models for drug testing in AD. Indeed, quite similar EEG experiments and the same kind of spectral data analysis can be performed in animal models of AD and in elderly individuals with prodromal or manifest AD. Several studies have shown that AChEIs affect both resting state EEG rhythms and cognitive functions in AD patients. After few weeks of successful treatment, delta (0-3 Hz) or theta (4-7 Hz) rhythms decrease, dominant alpha rhythms (8-10 Hz) increase, and cognitive functions slightly improve. Beneficial effects of these rhythms and cognitive functions were also found in AD responders to the long-term successful treatment (i.e. 6-12 months). In contrast, only one study has explored the long-term effects of memantine on EEG rhythms in AD patients, showing reduced theta rhythms. The present review enlightens the expected effects of AChEIs on resting state EEG rhythms in AD patients as promising EEG markers for the development of translational protocols both within the PharmaCog project and for wider use. PMID:23098644

  5. Behavioural symptoms in patients with Alzheimer's disease and their association with cognitive impairment

    PubMed Central

    2010-01-01

    Background Behavioural and psychological symptoms of dementia (BPSD) are non-cognitive symptoms commonly associated to Alzheimer's disease (AD). The characterization of the clinical profile of AD patients might help to better understand disease evolution and to improve diagnosis and treatment. Thus, the aim of the present study is to describe the clinical profile of AD patients, and to correlate the presence of BPSD with the severity of the disease. Methods A cross-sectional, observational and multicenter study was conducted at 115 centres in Spain. Patients suffering from AD with higher and lower BPSD scores (ADAS-Noncog score 26-50 and ≤25, respectively) were included. Demographic and clinical data were collected, and dementia severity was assessed by the Mini Mental State Examination (MMSE) [mild 27-21, moderate 20-11, severe ≤10]. The use of ADAS-Noncog in clinical practice was also explored. Results A total of 1014 patients (463 with higher and 551 with lower BPSD scores) were included (mean age 77 ± 7 years, 65% women). Almost all patients (90%) had BPSD at inclusion, 17% of which reported psychotic outbreaks. The most prevalent symptoms were lack of concentration (56%), tremors (56%), depression (44%), lack of cooperation (36%), and delusions (32%). Patients with higher BPSD scores showed a significantly higher prevalence of psychotic symptoms (delusions, hallucinations, and delirium) and tremors, while emotional symptoms (tearfulness and apathy) predominated in patients with lower BPSD scores. MMSE and ADAS-Noncog scores were negatively associated (p = 0.0284), suggesting a correlation between cognitive impairment and BPSD. Lack of concentration and appetite change significantly correlated with MMSE (p = 0.0472 and p = 0.0346, respectively). Rivastigmine and donepezil were the first choice therapies in mild to moderate dementia. ADAS-Noncog was generally considered better or similar to other scales (82%), and 68% of the investigators were willing to

  6. Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls.

    PubMed

    Xu, Wuhua; Kawarabayashi, Takeshi; Matsubara, Etsuro; Deguchi, Kentaro; Murakami, Tetsuro; Harigaya, Yasuo; Ikeda, Masaki; Amari, Masakuni; Kuwano, Ryozo; Abe, Koji; Shoji, Mikio

    2008-07-11

    Antibodies to amyloid beta protein (Abeta) are present naturally or after Abeta vaccine therapy in human plasma. To clarify their clinical role, we examined plasma samples from 113 patients with Alzheimer's disease (AD) and 205 normal controls using the tissue amyloid plaque immunoreactivity (TAPIR) assay. A high positive rate of TAPIR was revealed in AD (45.1%) and age-matched controls (41.2%), however, no significance was observed. No significant difference was observed in the MMS score or disease duration between TAPIR-positive and negative samples. TAPIR-positive plasma reacted with the Abeta40 monomer and dimer, and the Abeta42 monomer weakly, but not with the Abeta42 dimer. TAPIR was even detected in samples from young normal subjects and young Tg2576 transgenic mice. Although the Abeta40 level and Abeta40/42 ratio increased, and Abeta42 was significantly decreased in plasma from AD groups when compared to controls, no significant correlations were revealed between plasma Abeta levels and TAPIR grading. Thus an immune response to Abeta40 and immune tolerance to Abeta42 occurred naturally in humans without a close relationship to the Abeta burden in the brain. Clarification of the mechanism of the immune response to Abeta42 is necessary for realization of an immunotherapy for AD. PMID:18534566

  7. 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; Fu, Xiaojie

    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

  8. Meta-analysis of apolipoprotein E levels in the cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Talwar, Puneet; Sinha, Juhi; Grover, Sandeep; Agarwal, Rachna; Kushwaha, Suman; Srivastava, M V Padma; Kukreti, Ritushree

    2016-01-15

    The possible association between Apolipoprotein E (ApoE) levels in the cerebrospinal fluid (CSF) and Alzheimer's disease (AD) has been studied extensively. However, previous findings have been inconsistent. We conducted a meta-analysis of observational studies, seeking to provide insights into ApoE's potential as a biomarker for AD. A systematic literature search of PubMed (MEDLINE), EMBASE, and Web of Science was performed to retrieve relevant studies evaluating ApoE levels in CSF from AD subjects and controls. The association between ApoE levels in the CSF and AD was estimated by the weighted mean difference (WMD) and 95% confidence interval (CI) using a random-effect model. We identified 24 studies that included 1064AD cases and 1338 non-demented controls. Although the pooled WMD did not indicate a significant association between AD and ApoE levels (-0.30mg/l; 95% CI: -0.69 to 0.09; P=0.13), sub-group analysis controlling for patient sample size (n≥43) revealed significantly lower ApoE levels (WMD: -0.66mg/l; 95% CI: -1.02 to -0.31; P=0.0002) among patients with AD than in controls. Publication bias was absent and sensitivity analysis did not result in any significant change in the pooled estimates, indicating highly stable results. The present meta-analysis indicates the potential of CSF ApoE levels as a predictor of AD association. PMID:26723997

  9. Osteopontin is increased in the cerebrospinal fluid of patients with Alzheimer's disease and its levels correlate with cognitive decline.

    PubMed

    Comi, Cristoforo; Carecchio, Miryam; Chiocchetti, Annalisa; Nicola, Stefania; Galimberti, Daniela; Fenoglio, Chiara; Cappellano, Giuseppe; Monaco, Francesco; Scarpini, Elio; Dianzani, Umberto

    2010-01-01

    Inflammation is believed to play a role in Alzheimer's disease (AD). Osteopontin (OPN) is a molecule involved in macrophage recruitment and activation and implicated in neurodegeneration. In order to elucidate the role of OPN in AD, we evaluated its levels in serum and cerebrospinal fluid (CSF) of 67 AD patients, 46 frontotemporal dementia (FTD) patients, and 69 controls. We found that OPN levels: i) are significantly increased in the CSF of AD patients; ii) correlate with MMSE score; and iii) are higher in the early disease phases ( 2 years). These findings support a role of OPN in AD pathogenesis. PMID:20308780

  10. Characteristics of Agraphia in Chinese Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment

    PubMed Central

    Zhou, Jiong; Jiang, Biao; Huang, Xian-Hong; Kong, Lin-Lin; Li, Hong-Lei

    2016-01-01

    Background: Patients with Alzheimer's disease (AD) manifest progressive decline in writing abilities. Most studies on agraphia in AD have been performed in the alphabetic system, such as English. However, these findings may not be applicable to other written language systems. The unique features of the Chinese written script could affect the patterns of agraphia in Chinese AD patients. The aim of this study was to explore the features of writing errors in Chinese patients with AD and amnestic mild cognitive impairment (a-MCI), as well as to study the relationship between their writing errors and neuropsychological functions. Methods: In this study, we performed an observational study in a group of subjects including 17 AD patients, 14 patients with a-MCI, and 16 elderly healthy controls. We analyzed the writing errors in these subjects and also studied the relationship between their writing errors and neuropsychological functions. Results: Our study showed that in patients whose mother tongue is Chinese, writing ability was comparatively well preserved in the MCI phase but significantly impaired when the disease progressed to the stage of AD. The writing errors showed corresponding increase with the severity of cognition decline, both in the types of errors and rate of occurrence. Analysis of the writing errors showed that word substitution and unintelligible words were the most frequent error types that occurred in all the three study groups. The occurrence rate of unintelligible words was significantly higher in the AD group compared with the a-MCI group (P = 0.024) and control group (P = 0.018). In addition, the occurrence rates of word substitution were also significantly higher in AD (P = 0.013) and a-MCI groups (P = 0.037) than that of control group. However, errors such as totally no response, visuospatial impairment, paragraph agraphia, ideograph, and perseverative writing errors were only seen in AD group. Besides, we also found a high occurrence rate of

  11. Exercise rehabilitation on home-dwelling patients with Alzheimer's disease - a randomized, controlled trial. Study protocol

    PubMed Central

    2010-01-01

    Background Besides cognitive decline, Alzheimer's disease (AD) leads to physical disability, need for help and permanent institutional care. The trials investigating effects of exercise rehabilitation on physical functioning of home-dwelling older dementia patients are still scarce. The aim of this study is to investigate the effectiveness of intensive exercise rehabilitation lasting for one year on mobility and physical functioning of home-dwelling patients with AD. Methods During years 2008-2010, patients with AD (n = 210) living with their spousal caregiver in community are recruited using central AD registers in Finland, and they are offered exercise rehabilitation lasting for one year. The patients are randomized into three arms: 1) tailored home-based exercise twice weekly 2) group-based exercise twice weekly in rehabilitation center 3) control group with usual care and information of exercise and nutrition. Main outcome measures will be Guralnik's mobility and balance tests and FIM-test to assess physical functioning. Secondary measures will be cognition, neuropsychiatric symptoms according to the Neuropsychiatric Inventory, caregivers' burden, depression and health-related quality of life (RAND-36). Data concerning admissions to institutional care and the use and costs of health and social services will be collected during a two year follow-up. Discussion To our knowledge this is the first large scale trial exploring whether home-dwelling patients with AD will benefit from intense and long-lasting exercise rehabilitation in respect to their mobility and physical functioning. It will also provide data on cost-effectiveness of the intervention. Trial registration ACTRN12608000037303 PMID:20925948

  12. Dissociable contributions of amygdala and hippocampus to emotion and memory in patients with Alzheimer's disease.

    PubMed

    Guzmán-Vélez, Edmarie; Warren, David E; Feinstein, Justin S; Bruss, Joel; Tranel, Daniel

    2016-06-01

    The amygdala and the hippocampus are associated with emotional processing and declarative memory, respectively. Studies have shown that patients with bilateral hippocampal damage caused by anoxia/ischemia, and patients with probable Alzheimer's disease (AD), can experience emotions for prolonged periods of time, even when they cannot remember what caused the emotion in the first place (Feinstein et al. (2010) Proc Natl Acad Sci USA 107:7674-7679; Guzmán-Vélez et al. (2014) Cogn Behav Neurol 27:117-129). This study aimed to investigate, for the first time, the roles of the amygdala and hippocampus in the dissociation between feelings of emotion and declarative memory for emotion-inducing events in patients with AD. Individuals with probable AD (N = 12) and age-matched healthy comparisons participants (HCP; N = 12) completed a high-resolution (0.44 × 0.44 × 0.80 mm) T2-weighted structural MR scan of the medial temporal lobe. Each of these individuals also completed two separate emotion induction procedures (sadness and happiness) using film clips. We collected real-time emotion ratings at baseline and multiple times postinduction, and administered a test of declarative memory shortly after each induction. Consistent with previous research, hippocampal volume was significantly smaller in patients with AD compared with HCP, and was positively correlated with memory for the film clips. Sustained feelings of emotion and amygdala volume did not significantly differ between patients with AD and HCP. Follow-up analyses showed a significant negative correlation between amygdala volume and sustained sadness, and a significant positive correlation between amygdala volume and sustained happiness. Our findings suggest that the amygdala is important for regulating and sustaining an emotion independent of hippocampal function and declarative memory for the emotion-inducing event. © 2015 Wiley Periodicals, Inc. PMID:26606553

  13. Investigating Associative Learning Effects in Patients with Prodromal Alzheimer's Disease Using the Temporal Context Model.

    PubMed

    Quenon, Lisa; de Xivry, Jean-Jacques Orban; Hanseeuw, Bernard; Ivanoiu, Adrian

    2015-10-01

    The purpose of this study was to investigate associative learning effects in patients with prodromal Alzheimer's disease (prAD) by referring to the Temporal Context Model (TCM; Howard, Jing, Rao, Provyn, & Datey, 2009), in an attempt to enhance the understanding of their associative memory impairment. TCM explains fundamental effects described in classical free-recall tasks and cued-recall tasks involving overlapping word pairs (e.g., A-B, B-C), namely (1) the contiguity effect, which is the tendency to successively recall nearby items in a list, and (2) the observation of backward (i.e., B-A) and transitive associations (i.e., A-C) between items. In TCM, these effects are hypothesized to rely on contextual representation, binding and retrieval processes, which supposedly depend on hippocampal and parahippocampal regions. As these regions are affected in prAD, the current study investigated whether prAD patients would show reduced proportions of backward and transitive associations in free and cued-recall, coupled to a reduced contiguity effect in free-recall. Seventeen older controls and 17 prAD patients performed a cued-recall task involving overlapping word pairs and a final free-recall task. Proportions of backward and transitive intrusions in cued-recall did not significantly differ between groups. However, in free-recall, prAD patients demonstrated a reduced contiguity effect as well as reduced proportions of backward and transitive associations compared to older controls. These findings are discussed within the hypothesis that the contextual representation, binding and/or retrieval processes are affected in prAD patients compared to healthy older individuals. PMID:26411265

  14. Drug treatments in Alzheimer's disease.

    PubMed

    Briggs, Robert; Kennelly, Sean P; O'Neill, Desmond

    2016-06-01

    Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimer's disease (AD) and these act to control symptoms rather than alter the course of the disease. Studies of potential disease-modifying therapy have generally been undertaken in patients with clinically detectable disease, yet evidence suggests that the pathological changes associated with AD begin several years before this. It is possible that pharmacological therapy may be beneficial in this pre-clinical stage before the neurodegenerative process is established. Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials. Recent results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution. Such medicines could potentially delay the onset of dementia and would therefore markedly reduce its prevalence. However, we currently remain a good distance away from clinically available disease-modifying therapy. PMID:27251914

  15. Causes of Alzheimer's disease

    PubMed Central

    Munoz, D G; Feldman, H

    2000-01-01

    It is now understood that genetic factors play a crucial role in the risk of developing Alzheimer's disease (AD). Rare mutations in at least 3 genes are responsible for early-onset familial AD. A common polymorphism in the apolipoprotein E gene is the major determinant of risk in families with late-onset AD, as well as in the general population. Advanced age, however, remains the major established risk factor for AD, although environmental variables may also have some role in disease expression. Some pathogenic factors directly associated with aging include oxidative damage and mutations in messenger RNA. Other factors unrelated to the aging process may, in the future, be amenable to therapeutic intervention by way of estrogen replacement therapy for postmenopausal women, anti-inflammatory drug therapy and reducing vascular risk factors. Older theories, such as aluminum playing a role in the pathogenesis of AD, have been mostly discarded as our understanding of pathogenic mechanisms of AD has advanced. PMID:11216203

  16. The safety and tolerability of donepezil in patients with Alzheimer's disease

    PubMed Central

    Jackson, Stephen; Ham, Richard J; Wilkinson, David

    2004-01-01

    Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug–drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients. Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors. There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use. Data from single- and multiple-dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both in vitro and clinical studies have shown that donepezil is not associated with drug–drug interactions. The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia

  17. Helping Kids Understand Alzheimer's Disease

    MedlinePlus

    Alzheimer ’s Caregiving Tips Helping Kids Understand Alzheimer’s Disease When a family member has Alzheimer’s disease, it affects everyone in the family, including children and grandchildren. It’s important to talk to ...

  18. Do cholinesterase inhibitors act primarily on attention deficit? A naturalistic study in Alzheimer's disease patients.

    PubMed

    Bracco, Laura; Bessi, Valentina; Padiglioni, Sonia; Marini, Sandro; Pepeu, Giancarlo

    2014-01-01

    Attention is the first non-memory domain affected in Alzheimer's disease (AD), before deficits in language and visuo-spatial function, and it is claimed that attention deficits are responsible for the difficulties with daily living in early demented patients. The aim of this longitudinal study in a group of 121 Caucasian, community-dwelling, mild-to-moderate AD patients (Mini-Mental State Examination (MMSE) score >17) was to detect which cognitive domains were most affected by the disease and whether one year treatment with cholinesterase inhibitors was more effective in preserving attention than memory. All subjects were evaluated by a neuropsychological battery including global measurements (MMSE, Information-Memory-Concentration Test) and tasks exploring verbal long-term memory, language, attention, and executive functions. The comparison between two evaluations, made 12 months apart, shows statistically significant differences, indicating deterioration compared to baseline, in the following tests: MMSE (with no gender differences), Composite Memory Score, Short Story Delayed Recall, Trail-Making Test A, Semantic Fluency Test, and Token Test. Conversely, there were no differences in the two evaluations of the Digit Span, Corsi Tapping Test, Short Story Immediate Recall, and Phonemic Fluency Tests. It appears that the treatment specifically attenuated the decline in tests assessing attention and executive functions. A stabilization of the ability to pay attention, with the ensuing positive effects on executive functions, recent memory, and information acquisition which depend on attention, appears to be the main neuropsychological mechanism through which the activation of the cholinergic system, resulting from cholinesterase inhibition, exerts its effect on cognition. PMID:24577458

  19. Basal Forebrain Atrophy Contributes to Allocentric Navigation Impairment in Alzheimer's Disease Patients.

    PubMed

    Kerbler, Georg M; Nedelska, Zuzana; Fripp, Jurgen; Laczó, Jan; Vyhnalek, Martin; Lisý, Jiří; Hamlin, Adam S; Rose, Stephen; Hort, Jakub; Coulson, Elizabeth J

    2015-01-01

    The basal forebrain degenerates in Alzheimer's disease (AD) and this process is believed to contribute to the cognitive decline observed in AD patients. Impairment in spatial navigation is an early feature of the disease but whether basal forebrain dysfunction in AD is responsible for the impaired navigation skills of AD patients is not known. Our objective was to investigate the relationship between basal forebrain volume and performance in real space as well as computer-based navigation paradigms in an elderly cohort comprising cognitively normal controls, subjects with amnestic mild cognitive impairment and those with AD. We also tested whether basal forebrain volume could predict the participants' ability to perform allocentric- vs. egocentric-based navigation tasks. The basal forebrain volume was calculated from 1.5 T magnetic resonance imaging (MRI) scans, and navigation skills were assessed using the human analog of the Morris water maze employing allocentric, egocentric, and mixed allo/egocentric real space as well as computerized tests. When considering the entire sample, we found that basal forebrain volume correlated with spatial accuracy in allocentric (cued) and mixed allo/egocentric navigation tasks but not the egocentric (uncued) task, demonstrating an important role of the basal forebrain in mediating cue-based spatial navigation capacity. Regression analysis revealed that, although hippocampal volume reflected navigation performance across the entire sample, basal forebrain volume contributed to mixed allo/egocentric navigation performance in the AD group, whereas hippocampal volume did not. This suggests that atrophy of the basal forebrain contributes to aspects of navigation impairment in AD that are independent of hippocampal atrophy. PMID:26441643

  20. Monoaminergic neurotransmitter alterations in postmortem brain regions of depressed and aggressive patients with Alzheimer's disease.

    PubMed

    Vermeiren, Yannick; Van Dam, Debby; Aerts, Tony; Engelborghs, Sebastiaan; De Deyn, Peter P

    2014-12-01

    Depression and aggression in Alzheimer's disease (AD) are 2 of the most severe and prominent neuropsychiatric symptoms (NPS). Altered monoaminergic neurotransmitter system functioning has been implicated in both NPS, although their neurochemical etiology remains to be elucidated. Left frozen hemispheres of 40 neuropathologically confirmed AD patients were regionally dissected. Dichotomization based on depression and aggression scores resulted in depressed/nondepressed (AD + D/AD - D) and aggressive/nonaggressive (AD + Agr/AD - Agr) groups. Concentrations of dopamine, serotonin (5-HT), (nor)epinephrine ((N)E), and respective metabolites were determined using reversed-phase high-performance liquid chromatography. Significantly lower 3-methoxy-4-hydroxyphenylglycol (MHPG) and higher homovanillic acid levels were observed in Brodmann area (BA) 9 and 10 of AD + D compared with AD - D. In AD + Agr, 5-hydroxy-3-indoleacetic acid (5-HIAA) levels in BA9, 5-HIAA to 5-HT ratios in BA11, and MHPG, NE, and 5-HIAA levels in the hippocampus were significantly decreased compared with AD - Agr. These findings indicate that brain region-specific altered monoamines and metabolites may contribute to the occurrence of depression and aggression in AD. PMID:24997673

  1. A Yoga and Compassion Meditation Program Reduces Stress in Familial Caregivers of Alzheimer's Disease Patients

    PubMed Central

    Danucalov, M. A. D.; Kozasa, E. H.; Ribas, K. T.; Galduróz, J. C. F.; Garcia, M. C.; Verreschi, I. T. N.; Oliveira, K. C.; Romani de Oliveira, L.; Leite, J. R.

    2013-01-01

    Familial caregivers of patients with Alzheimer's disease exhibit reduced quality of life and increased stress levels. The aim of this study was to investigate the effects of an 8-week yoga and compassion meditation program on the perceived stress, anxiety, depression, and salivary cortisol levels in familial caregivers. A total of 46 volunteers were randomly assigned to participate in a stress-reduction program for a 2-month period (yoga and compassion meditation program—YCMP group) (n = 25) or an untreated group for the same period of time (control group) (n = 21). The levels of stress, anxiety, depression, and morning salivary cortisol of the participants were measured before and after intervention. The groups were initially homogeneous; however, after intervention, the groups diverged significantly. The YCMP group exhibited a reduction of the stress (P < 0.05), anxiety (P < 0.000001), and depression (P < 0.00001) levels, as well as a reduction in the concentration of salivary cortisol (P < 0.05). Our study suggests that an 8-week yoga and compassion meditation program may offer an effective intervention for reducing perceived stress, anxiety, depression, and salivary cortisol in familial caregivers. PMID:23690846

  2. A yoga and compassion meditation program reduces stress in familial caregivers of Alzheimer's disease patients.

    PubMed

    Danucalov, M A D; Kozasa, E H; Ribas, K T; Galduróz, J C F; Garcia, M C; Verreschi, I T N; Oliveira, K C; Romani de Oliveira, L; Leite, J R

    2013-01-01

    Familial caregivers of patients with Alzheimer's disease exhibit reduced quality of life and increased stress levels. The aim of this study was to investigate the effects of an 8-week yoga and compassion meditation program on the perceived stress, anxiety, depression, and salivary cortisol levels in familial caregivers. A total of 46 volunteers were randomly assigned to participate in a stress-reduction program for a 2-month period (yoga and compassion meditation program-YCMP group) (n = 25) or an untreated group for the same period of time (control group) (n = 21). The levels of stress, anxiety, depression, and morning salivary cortisol of the participants were measured before and after intervention. The groups were initially homogeneous; however, after intervention, the groups diverged significantly. The YCMP group exhibited a reduction of the stress (P < 0.05), anxiety (P < 0.000001), and depression (P < 0.00001) levels, as well as a reduction in the concentration of salivary cortisol (P < 0.05). Our study suggests that an 8-week yoga and compassion meditation program may offer an effective intervention for reducing perceived stress, anxiety, depression, and salivary cortisol in familial caregivers. PMID:23690846

  3. Pericellular Innervation of Neurons Expressing Abnormally Hyperphosphorylated Tau in the Hippocampal Formation of Alzheimer's Disease Patients

    PubMed Central

    Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; DeFelipe, Javier

    2010-01-01

    Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered. PMID:20631843

  4. Micronutrients and Alzheimer's disease.

    PubMed

    Staehelin, Hannes B

    2005-11-01

    The current high life expectancy is overshadowed by neurodegenerative illnesses that lead to dementia and dependence. Alzheimer's disease (AD) is the most common of these conditions, and is considered to be a proteinopathy, with amyloid-beta42 as a key factor, leading via a cascade of events to neurodegeneration. Major factors involved are oxidative stress, perturbed Ca homeostasis and impaired energy metabolism. Protection against oxidative stress by micronutrients (including secondary bioactive substances) has been shown in transgenic Alzheimer model systems to delay AD. Epidemiological evidence is less conclusive, but the vast majority of the evidence supports a protective effect on cognitive functions in old age and AD. Thus, a diet rich in fruits and vegetables but also containing meat and fish is the most suitable to provide adequate micronutrients. The strong link between cardiovascular risk and AD may be explained by common pathogenetic mechanisms mediated, for example, by homocysteine and thus dependant on B-vitamins (folate and vitamins B(12) and B(6)). However, micronutrients may also be harmful. The high affinity of amyloid for metals (Fe, Al and Zn) favours the generation of reactive oxygen species and triggers an inflammatory response. Micronutrients in a balanced diet have a long-lasting, albeit low, protective impact on brain aging, hence prevention should be life long. PMID:16313699

  5. Accurate multimodal probabilistic prediction of conversion to Alzheimer's disease in patients with mild cognitive impairment☆

    PubMed Central

    Young, Jonathan; Modat, Marc; Cardoso, Manuel J.; Mendelson, Alex; Cash, Dave; Ourselin, Sebastien

    2013-01-01

    Accurately identifying the patients that have mild cognitive impairment (MCI) who will go on to develop Alzheimer's disease (AD) will become essential as new treatments will require identification of AD patients at earlier stages in the disease process. Most previous work in this area has centred around the same automated techniques used to diagnose AD patients from healthy controls, by coupling high dimensional brain image data or other relevant biomarker data to modern machine learning techniques. Such studies can now distinguish between AD patients and controls as accurately as an experienced clinician. Models trained on patients with AD and control subjects can also distinguish between MCI patients that will convert to AD within a given timeframe (MCI-c) and those that remain stable (MCI-s), although differences between these groups are smaller and thus, the corresponding accuracy is lower. The most common type of classifier used in these studies is the support vector machine, which gives categorical class decisions. In this paper, we introduce Gaussian process (GP) classification to the problem. This fully Bayesian method produces naturally probabilistic predictions, which we show correlate well with the actual chances of converting to AD within 3 years in a population of 96 MCI-s and 47 MCI-c subjects. Furthermore, we show that GPs can integrate multimodal data (in this study volumetric MRI, FDG-PET, cerebrospinal fluid, and APOE genotype with the classification process through the use of a mixed kernel). The GP approach aids combination of different data sources by learning parameters automatically from training data via type-II maximum likelihood, which we compare to a more conventional method based on cross validation and an SVM classifier. When the resulting probabilities from the GP are dichotomised to produce a binary classification, the results for predicting MCI conversion based on the combination of all three types of data show a balanced accuracy

  6. [Antibody therapy for Alzheimer's disease].

    PubMed

    Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

    2011-11-01

    In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially. PMID:22277519

  7. Antioxidants for Alzheimer Disease

    PubMed Central

    Galasko, Douglas R.; Peskind, Elaine; Clark, Christopher M.; Quinn, Joseph F.; Ringman, John M.; Jicha, Gregory A.; Cotman, Carl; Cottrell, Barbara; Montine, Thomas J.; Thomas, Ronald G.; Aisen, Paul

    2013-01-01

    Objective To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers. Design Double-blind, placebo-controlled clinical trial. Setting Academic medical centers. Participants Subjects with mild to moderate Alzheimer disease. Intervention Random assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo. Main Outcome Measures Changes from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale). Results Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aβ42, tau, and P-tau181 levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups. Conclusions Antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted. Trial Registration clinicaltrials.gov Identifier: NCT00117403 PMID:22431837

  8. Cerebrospinal fluid Aβ40 is similarly reduced in patients with Frontotemporal Lobar Degeneration and Alzheimer's Disease.

    PubMed

    Baldeiras, Inês; Santana, Isabel; Leitão, Maria João; Ribeiro, Maria Helena; Pascoal, Rui; Duro, Diana; Lemos, Raquel; Santiago, Beatriz; Almeida, Maria Rosário; Oliveira, Catarina Resende

    2015-11-15

    Cerebrospinal fluid (CSF) biomarkers have been increasingly studied for dementia diagnosis, however the accuracy to distinguish between different forms of dementia is still unsatisfactory. In this study, the added value of another CSF Aβ-peptide (Aβ40), along with the core CSF markers t-Tau, p-Tau, and Aβ42, in the discrimination between two large dementia groups of Frontotemporal Lobar Degeneration (FTLD; n=107), Alzheimer's Disease (AD; n=107) and non-demented subjects (n=33) was evaluated. In FTLD, t-Tau and p-Tau were significantly increased in relation to controls, but lower than in AD, while Aβ42 was similar in FTLD and controls, but higher than in AD. Equally reduced Aβ40 levels were seen in both dementia groups, and therefore the combination of Aβ40 with core CSF biomarkers optimally discriminated FTLD and AD patients from controls. Aβ42 and t-Tau were selected as the best biomarker subset to differentiate FTLD from AD, with no added value of Aβ40 to the model. Diagnostic accuracy between FTLD and AD was still sub-optimal, with a significant percentage (23%) of FTLD patients, in particularly women, carrying an ApoE-ε4 allele, showing a CSF-AD biomarkers profile. Although CSF Aβ40 does not appear to have an additional value in the distinction between FTLD and AD, it increases the discrimination between subjects with dementia from controls. A CSF-AD biomarker profile can be seen in patients with a clinical phenotype of FTLD, reinforcing the need for autopsy confirmation. PMID:26388316

  9. NK Cells are Activated in Amnestic Mild Cognitive Impairment but not in Mild Alzheimer's Disease Patients.

    PubMed

    Le Page, Aurélie; Bourgade, Karine; Lamoureux, Julie; Frost, Eric; Pawelec, Graham; Larbi, Anis; Witkowski, Jacek M; Dupuis, Gilles; Fülöp, Tamás

    2015-01-01

    Alzheimerś disease (AD) is a progressive irreversible neurological brain disorder characterized by accumulation of amyloid-β, amyloid plaques, and neurofibrillary tangles. Inflammation and immune alterations have been linked to AD, suggesting that the peripheral immune system plays a role during the asymptomatic period of AD. NK cells participate in innate immune surveillance against intracellular pathogens and malignancy but their role in AD remains controversial. We have investigated changes in peripheral NK cell phenotypes and functions in amnestic mild cognitive impairment (aMCI, n = 10), patients with mild AD (mAD, n = 11), and healthy elderly controls (n = 10). Patients selected according to NINCDS-ADRDA criteria were classified using neuropsychological assessment tests. Phenotype analysis revealed differences in expression of CD16 (increased in mAD), NKG2A (decreased in aMCI), and TLR2 and TLR9 (both decreased in mAD). Functional assays revealed that NK cell killing activity and degranulation (CD107 expression) were unchanged in the three groups. In contrast, expression of the CD95 receptor was increased in aMCI and mAD. Granzyme B expression and cytokine production (TNFα, IFNγ) were increased in aMCI but not in mAD. CCL19- but not CCL21-dependent chemotaxis was decreased in aMCI and mAD, despite the fact that CCR7 expression was increased in aMCI. Our data suggest that the number of alterations observed in peripheral NK cells in aMCI represent an activation state compared to mAD patients and that may reflect an active immune response against a still to be defined aggression. PMID:25720398

  10. HIV Patients Now Living Long Enough to Develop Alzheimer's

    MedlinePlus

    ... HIV Patients Now Living Long Enough to Develop Alzheimer's Findings upend previous beliefs about brain changes related ... 19, 2016 (HealthDay News) -- The first case of Alzheimer's disease diagnosed in a person with HIV highlights ...

  11. Altered phosphorylation of. tau. protein in heat-shocked rats and patients with Alzheimer disease

    SciTech Connect

    Papasozomenos, S.C.; Yuan Su Baylor College of Medicine, Houston, TX )

    1991-05-15

    Six hours after heat shocking 2- to 3-month-old male and female Sprague-Dawley rats at 42C for 15 min, the authors analyzed {tau} protein immunoreactivity in SDS extracts of cerebrums and peripheral nerves by using immunoblot analysis and immunohistochemistry with the anti-{tau} monoclonal antibody Tau-1, which recognizes a phosphate-dependent nonphosphorylated epitope, and with {sup 125}I-labeled protein A. In the cerebal extracts, the authors found altered phosphorylation of {tau} in heat-shocked females, characterized by a marked reduction in the amount of nonphosphorylated {tau}, a doubling of the ratio of total (phosphorylated plus nonphosphorylated) {tau} to nonphosphorylated {tau}, and the appearance of the slowest moving phosphorylated {tau} polypeptide (68 kDa). Similar, but milder, changes were observed in male rats. Quantitative immunoblot analysis of cortex and the underlying white matter with Tau-1 and {sup 125}I-labeled protein A showed that the amount of phosphorylated {tau} progressively increased in the Alzheimer disease-affected cerebral cortex, while concurrently a proportionally lesser amount of {tau} entered the white matter axons. The similar findings for the rat heat-shock model and Alzheimer disease suggest that life stressors may play a role in the etiopathogenesis of Alzheimer's disease.

  12. Useful Information on...Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Cohen, Gene D.

    This brochure provides information on Alzheimer's disease by examining who gets Alzheimer's disease and what to expect when someone has Alzheimer's disease. Abnormal brain tissue findings are discussed and three clinical features of Alzheimer's disease are listed: dementia; insidious onset of symptoms; and exclusion of all other specific causes of…

  13. Advancing frontiers in Alzheimer's disease research

    SciTech Connect

    Glenner, G.G.; Wurtman, R.J.

    1987-01-01

    This book contain 16 chapters. Some of the titles are: Transmitter Alterations in Alzheimer's Disease: Relation to Cortical Dysfunction as Suggested by Positron Emission Tomography; Single-Photon Emission Computed Tomography in the Clinical Evaluation of Dementia; Clinical Diagnosis of Alzheimer's Disease; Down's Syndrome and Alzheimer's Disease: What is the Relationship; and Beta Protein: A Possible Marker for Alzheimer's Disease.

  14. Early Alzheimer's disease genetics.

    PubMed

    Schellenberg, Gerard D

    2006-01-01

    The genetics community working on Alzheimer's disease and related dementias has made remarkable progress in the past 20 years. The cumulative efforts by multiple groups have lead to the identification of three autosomal dominant genes for early onset AD. These are the amyloid-beta protein precursor gene (APP), and the genes encoding presenilin1 and 2. The knowledge derived from this work has firmly established Abeta as a critical disease molecule and lead to candidate drugs currently in treatment trials. Work on a related disease, frontotemporal dementia with parkinsonism - chromosome 17 type has also added to our understanding of pathogenesis by revealing that tau, the protein component of neurofibrillary tangles, is also a critical molecule in neurodegeneration. Lessons learned that still influence work on human genetics include the need to recognize and deal with genetic heterogeneity, a feature common to many genetic disorders. Genetic heterogeneity, if recognized, can be source of information. Another critical lesson is that clinical, molecular, and statistical scientists need to work closely on disease projects to succeed in solving the complex problems of common genetic disorders. PMID:16914874

  15. A prospective study of nutrition education and oral nutritional supplementation in patients with Alzheimer's disease

    PubMed Central

    2011-01-01

    Background Weight loss in patients with Alzheimer's disease (AD) is a common clinical manifestation that may have clinical significance. Objectives To evaluate if there is a difference between nutrition education and oral nutritional supplementation on nutritional status in patients with AD. Methods A randomized, prospective 6-month study which enrolled 90 subjects with probable AD aged 65 years or older divided into 3 groups: Control Group (CG) [n = 27], Education Group (EG) [n = 25], which participated in an education program and Supplementation Group (SG) [n = 26], which received two daily servings of oral nutritional supplementation. Subjects were assessed for anthropometric data (weight, height, BMI, TSF, AC and AMC), biochemical data (total protein, albumin, and total lymphocyte count), CDR (Clinical Dementia Rating), MMSE (Mini-mental state examination), as well as dependence during meals. Results The SG showed a significant improvement in the following anthropometric measurements: weight (H calc = 22.12, p =< 0.001), BMI (H calc = 22.12, p =< 0.001), AC (H calc = 12.99, p =< 0.002), and AMC (H calc = 8.67, p =< 0.013) compared to the CG and EG. BMI of the EG was significantly greater compared to the CG. There were significant changes in total protein (H calc = 6.17, p =< 0.046), and total lymphocyte count in the SG compared to the other groups (H cal = 7.94, p = 0.019). Conclusion Oral nutritional supplementation is more effective compared to nutrition education in improving nutritional status. PMID:21943331

  16. Short-term memory binding deficits in Alzheimer's disease.

    PubMed

    Parra, Mario A; Abrahams, Sharon; Fabi, Katia; Logie, Robert; Luzzi, Simona; Della Sala, Sergio

    2009-04-01

    Alzheimer's disease impairs long term memories for related events (e.g. faces with names) more than for single events (e.g. list of faces or names). Whether or not this associative or 'binding' deficit is also found in short-term memory has not yet been explored. In two experiments we investigated binding deficits in verbal short-term memory in Alzheimer's disease. Experiment 1: 23 patients with Alzheimer's disease and 23 age and education matched healthy elderly were recruited. Participants studied visual arrays of objects (six for healthy elderly and four for Alzheimer's disease patients), colours (six for healthy elderly and four for Alzheimer's disease patients), unbound objects and colours (three for healthy elderly and two for Alzheimer's disease patients in each of the two categories), or objects bound with colours (three for healthy elderly and two for Alzheimer's disease patients). They were then asked to recall the items verbally. The memory of patients with Alzheimer's disease for objects bound with colours was significantly worse than for single or unbound features whereas healthy elderly's memory for bound and unbound features did not differ. Experiment 2: 21 Alzheimer's disease patients and 20 matched healthy elderly were recruited. Memory load was increased for the healthy elderly group to eight items in the conditions assessing memory for single or unbound features and to four items in the condition assessing memory for the binding of these features. For Alzheimer's disease patients the task remained the same. This manipulation permitted the performance to be equated across groups in the conditions assessing memory for single or unbound features. The impairment in Alzheimer's disease patients in recalling bound objects reported in Experiment 1 was replicated. The binding cost was greater than that observed in the healthy elderly group, who did not differ in their performance for bound and unbound features. Alzheimer's disease grossly impairs the

  17. Acetylcholinesterase Inhibitor Treatment is Associated with Relatively Slow Cognitive Decline in Patients with Alzheimer's Disease and AD + DLB

    PubMed Central

    Nelson, Peter T.; Kryscio, Richard J.; Abner, Erin L.; Schmitt, Frederick A.; Jicha, Gregory A.; Mendiondo, Marta S.; Cooper, Greg; Smith, Charles B.; Markesbery, William R.

    2009-01-01

    Dementia can be caused by different diseases including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or both (AD + DLB). University of Kentucky AD Center pathologically-diagnosed AD and AD + DLB cases were evaluated who had three or more longitudinal antemortem mental status examinations (n = 156). Patients with important concomitant pathology (n = 5) or patients that were profoundly demented at recruitment (intake MMSE < 20; n = 86) were excluded to strengthen our ability to test the association of specific clinical and pathological indices. Patients with pathologically-diagnosed AD + DLB (n = 25) lost cognitive capacity faster than patients with AD alone (n = 40). In both diseases, treatment with acetylcholinesterase inhibitors was associated with a slower rate of cognitive decline. PMID:19158418

  18. Words to Know (Alzheimer's Disease)

    MedlinePlus

    ... the National Institute on Aging Words to Know Aggression (uh-GRESH-un). When a person lashes out ... AD feel. Agitation may cause pacing, sleeplessness, or aggression. Alzheimer's disease (AD) (ALlz-high-merz duh-ZEEZ). ...

  19. Neuronutrition and Alzheimer's Disease

    PubMed Central

    Ramesh, Balenahalli N.; Rao, T.S. Sathyanarayana; Prakasam, Annamalai; Sambamurti, Kumar; Rao, K.S. Jagannatha

    2010-01-01

    Alzheimer's disease (AD) is a complex neurological disorder with several unequivocally identified genetic risk factors. Among the several environmental factors proposed for AD, dietary protective and risk factors have been most compelling. In particular, diets rich in saturated fatty acids and alcohol, and deficient in antioxidants and vitamins appear to promote the onset of the disease, while diets rich in unsaturated fatty acids, vitamins, antioxidants, and wine likely suppress its onset. Evidence suggests that diets rich in polyphenols and some spices suppress the onset of AD by scavenging free radicals and preventing oxidative damage. Metal ions are known to catalyze the production of free radicals and induce mental retardation or dementia. Several studies have also identified metals such as Pb, Fe, Al, Cu and Zn in AD pathogenesis. While specific chelators have been tested for therapy, they have not been very successful probably due to late administration after brain damage has been triggered. Since several dietary polyphenols are known to chelate metals, their routine use may also be protective against the onset of AD. PMID:20308778

  20. Quiz: Alzheimer's Disease Quiz | Alzheimer's disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Quiz Past Issues / Fall 2010 Table of ... How many people in the United States have Alzheimer's disease? as many as 5.1 million as ...

  1. Quiz: Alzheimer's Disease Quiz | Alzheimer's disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Quiz Past Issues / Fall 2010 Table of Contents How many people in the United States have Alzheimer's disease? as many as 5.1 million as many ...

  2. Memory Test Performance on Analogous Verbal and Nonverbal Memory Tests in Patients with Frontotemporal Dementia and Alzheimer's Disease

    PubMed Central

    Baldock, Deanna; Miller, Justin B.; Leger, Gabriel C.; Banks, Sarah Jane

    2016-01-01

    Background Patients with frontotemporal dementia (FTD) typically have initial deficits in language or changes in personality, while the defining characteristic of Alzheimer's disease (AD) is memory impairment. Neuropsychological findings in the two diseases tend to differ, but can be confounded by verbal impairment in FTD impacting performance on memory tests in these patients. Methods Twenty-seven patients with FTD and 102 patients with AD underwent a neuropsychological assessment before diagnosis. By utilizing analogous versions of a verbal and nonverbal memory test, we demonstrated differences in these two modalities between AD and FTD. Discussion Better differentiation between AD and FTD is found in a nonverbal memory test, possibly because it eliminates the confounding variable of language deficits found in patients with FTD. These results highlight the importance of nonverbal learning tests with multiple learning trials in diagnostic testing. PMID:26933437

  3. Effect of Tarenflurbil on Cognitive Decline and Activities of Daily Living in Patients With Mild Alzheimer Disease

    PubMed Central

    Green, Robert C.; Schneider, Lon S.; Amato, David A.; Beelen, Andrew P.; Wilcock, Gordon; Swabb, Edward A.; Zavitz, Kenton H.

    2010-01-01

    Context Amyloid-β peptide (Aβ42) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Aβ42-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial. Objective To determine the efficacy, safety, and tolerability of tarenflurbil. Design, Setting, and Patients A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted. Intervention Tarenflurbil, 800 mg, or placebo, administered twice a day. Main Outcome Measures Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale–Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies–activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification. Results Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, −0.9 to 1.1; P=.86 and −0.5 for ADCS-ADL; 95% CI, −1.9 to 0.9; P=.48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections. Conclusion Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD. PMID:20009055

  4. Ideational Action Impairments in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Chainay, H.; Louarn, C.; Humphreys, G. W.

    2006-01-01

    We report data from a group of patients with mild Alzheimer's disease on a range of tasks requiring either stored semantic knowledge about objects (e.g., naming object use) or the execution of action to objects (e.g., miming and using objects). We found that the patients were impaired at miming in response to objects, even when they could describe…

  5. Metaphor Comprehension in Alzheimer's Disease: Novelty Matters

    ERIC Educational Resources Information Center

    Amanzio, Martina; Geminiani, Giuliano; Leotta, Daniela; Cappa, Stefano

    2008-01-01

    The comprehension of non-literal language was investigated in 20 probable Alzheimer's disease (pAD) patients by comparing their performance to that of 20 matched control subjects. pAD patients were unimpaired in the comprehension of conventional metaphors and idioms. However, their performance was significantly lower in the case of…

  6. Importance and management of micronutrient deficiencies in patients with Alzheimer's disease.

    PubMed

    Cardoso, Bárbara Rita; Cominetti, Cristiane; Cozzolino, Silvia Maria Franciscato

    2013-01-01

    Alzheimer's disease (AD) is the most common form of dementia, and it generally affects the elderly. It has been suggested that diet is an intensively modifiable lifestyle factor that might reduce the risk of AD. Because epidemiological studies generally report the potential neuronal protective effects of various micronutrients, the aim of this study was to perform a literature review on the major nutrients that are related to AD, including selenium, vitamins C and E, transition metals, vitamin D, B-complex vitamins, and omega-3 fatty acids. PMID:23696698

  7. Diabetes and Alzheimer's disease crosstalk.

    PubMed

    Baglietto-Vargas, David; Shi, Jessica; Yaeger, Devin M; Ager, Rahasson; LaFerla, Frank M

    2016-05-01

    Despite intensive research efforts over the past few decades, the mechanisms underlying the etiology of sporadic Alzheimer's disease (AD) remain unknown. This fact is of major concern because the number of patients affected by this medical condition is increasing exponentially and the existing treatments are only palliative in nature and offer no disease modifying affects. Interestingly, recent epidemiological studies indicate that diabetes significantly increases the risk of developing AD, suggesting that diabetes may play a causative role in the development of AD pathogenesis. Therefore, elucidating the molecular interactions between diabetes and AD is of critical significance because it might offer a novel approach to identifying mechanisms that may modulate the onset and progression of sporadic AD cases. This review highlights the involvement of several novels pathological molecular mechanisms induced by diabetes that increase AD pathogenesis. Furthermore, we discuss novel findings in animal model and clinical studies involving the use of anti-diabetic compounds as promising therapeutics for AD. PMID:26969101

  8. Oxidative stress in Alzheimer disease

    PubMed Central

    Durany, Nuria

    2009-01-01

    Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress (e.g., protein oxidation, lipid oxidation, DNA oxidation and glycoxidation) during the course of the disease. Advanced glycation endproducts (AGEs) are present in amyloid plaques in AD, and its extracellular accumulation may be caused by an accelerated oxidation of glycated proteins. AGEs participate in neuronal death causing direct (chemical) and indirect (cellular) free radical production and consequently increase oxidative stress. The development of drugs for the treatment of AD that breaks the vicious cycles of oxidative stress and neurodegeneration offer new opportunities. These approaches include AGE-inhibitors, antioxidants and anti-inflammatory substances, which prevent free radical production. PMID:19372765

  9. Leptin in Alzheimer's disease.

    PubMed

    Magalhães, C A; Carvalho, M G; Sousa, L P; Caramelli, P; Gomes, K B

    2015-10-23

    Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly population. AD is histologically characterized by accumulation of amyloid-β protein (Aβ) on extracellular plaques and deposition of hyperphosphorylated tau protein in intracellular neurofibrillary tangles. Several studies have shown that obesity may precede dementia and that lifestyle factors play a critical role in the onset of AD. Furthermore, accumulating evidence indicates that obesity is an independent risk factor for developing AD. In this scenario, the understanding of the role of adipose tissue in brain health is essential to clarify the establishment of demential processes. The objective of this work was to review studies regarding leptin, an anorexigenic peptide hormone synthesized in adipocytes, in the context of dementia. Some authors proposed that leptin evaluation might be a better predictor of dementia than traditional anthropometric measures. Leptin, once established as a biomarker, could enhance the understanding of late-onset AD risk over the life course, as well as the clinical progression of prodromal state to manifested AD. Other studies have proposed that leptin presents neuroprotective activities, which could be explained by inhibiting the amyloidogenic process, reducing the levels of tau protein phosphorylation and improving the cognitive function. PMID:26279362

  10. Successful non-operative management of spontaneous type II gallbladder perforation in a patient with Alzheimer's disease

    PubMed Central

    Alessiani, Mario; Peloso, Andrea; Tramelli, Paola; Magnani, Enzo

    2014-01-01

    A 77-year-old man with Alzheimer's disease was admitted to a rural hospital in June 2012 and an acute cholecistytis was first diagnosed. Surgery was not considered as a possible option due to the critical condition of the patient and his severe comorbidities. After 2 days of broad-spectrum antibiotics, the patient worsened and developed severe sepsis. A gallbladder perforation with intrahepatic abscess formation was diagnosed on ultrasonography (US) and abdominal CT scan. The patient underwent percutaneous US-guided gallbladder drainage with resolution of the sepsis and rapid clinical improvement. After 1 month, the drainage was removed and the patient was discharged. He survived in good condition for 18 months and he passed away from pneumonitis in December 2013. This case shows that in a case of acute cholecystitis with gallbladder perforation, percutaneous gallbladder drainage can be a lifesaving procedure in elderly patients with severe comorbidities (including Alzheimer's disease) who are not candidates for elective surgery. PMID:24859733

  11. The biological substrates of Alzheimer's disease

    SciTech Connect

    Scheibel, A.B.; Wechsler, A.F.; Brazier, M.A.B.

    1986-01-01

    This book contains 21 selections. Some of the titles are: Dementia of the Alzheimer Type: Genetic Aspects; Determination of Cerebral Metabolic Patterns in Dementia Using Positron Emission Tomography; Pathology of the Basal Forebrain in Alzheimer's Disease and Other Dementias; Characterization of Neurofibrillary Tangles with Monoclonal Antibodies Raised Against Alzheimer Neurofibrillary Tangles; and HLA Associations in Alzheimer's Disease.

  12. Neurobiology of Alzheimer's disease.

    PubMed

    Mohandas, E; Rajmohan, V; Raghunath, B

    2009-01-01

    Alzheimer's disease (AD) is a devastating neurodegenerative disease, the most common among the dementing illnesses. The neuropathological hallmarks of AD include extracellular beta-amyloid (amyloid precursor protein (APP) deposits, intracellular neurofibrillary tangles (NFT)), dystrophic neuritis and amyloid angiopathy. The mismetabolism of APP and the defective clearance of beta amyloid generate a cascade of events including hyperphosphorylated tau (tau) mediated breakdown of microtubular assembly and resultant synaptic failure which results in AD. The exact aetiopathogenesis of AD is still obscure. The preeminent hypotheses of AD include amyloid cascade hypothesis and tau hyperphosphorylation. The amyloid hypothesis states that extracellular amyloid plaques formed by aggregates of Abeta peptide generated by the proteolytic cleavages of APP are central to AD pathology. Intracellular assembly states of the oligomeric and protofibrillar species may facilitate tau hyperphosphorylation, disruption of proteasome and mitochondria function, dysregulation of calcium homeostasis, synaptic failure, and cognitive dysfunction. The tau hypothesis states that excessive or abnormal phosphorylation of tau results in the transformation of normal adult tau into PHF-tau (paired helical filament) and NFTs. Vascular hypothesis is also proposed for AD and it concludes that advancing age and the presence of vascular risk factors create a Critically Attained Threshold of Cerebral Hypoperfusion (CATCH) which leads to cellular and subcellular pathology involving protein synthesis, development of plaques, inflammatory response, and synaptic damage leading to the manifestations of AD. Multiple other aetiological and pathogenetic hypotheses have been put forward including genetics, oxidative stress, dysfunctional calcium homeostasis, hormonal, inflammatory-immunologic, and cell cycle dysregulation with the resultant neurotransmitter dysfunctions and cognitive decline. The available

  13. Raman spectroscopy of Alzheimer's diseased tissue

    NASA Astrophysics Data System (ADS)

    Sudworth, Caroline D.; Krasner, Neville

    2004-07-01

    Alzheimer's disease is one of the most common forms of dementia, and causes steady memory loss and mental regression. It is also accompanied by severe atrophy of the brain. However, the pathological biomarkers of the disease can only be confirmed and examined upon the death of the patient. A commercial (Renishaw PLC, UK) Raman system with an 830 nm NIR diode laser was used to analyse brain samples, which were flash frozen at post-mortem. Ethical approval was sought for these samples. The Alzheimer's diseased samples contained a number of biomarkers, including neuritic plaques and tangles. The Raman spectra were examined by order to differentiate between normal and Alzheimer's diseased brain tissues. Preliminary results indicate that Alzheimer's diseased tissues can be differentiated from control tissues using Raman spectroscopy. The Raman spectra differ in terms of peak intensity, and the presence of a stronger amide I band in the 1667 cm-1 region which occurs more prominently in the Alzheimer's diseased tissue. These preliminary results indicate that the beta-amyloid protein originating from neuritic plaques can be identified with Raman spectroscopy.

  14. Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer's disease: a meta-analysis

    PubMed Central

    He, Xue-Fei; Liu, Yi-Ting; Peng, Cheng; Zhang, Fan; Zhuang, Shi; Zhang, Jin-Song

    2012-01-01

    AIM To investigate the difference of retinal nerve fiber layer (RNFL) thickness between Alzheimer's disease patients and normal people, so as to provide clue for the early diagnosis of Alzheimer's disease. METHODS The articles on the association of RNFL thickness and Alzheimer's disease were retrieved by searching international and national databases. The qualified articles were assessed by meta analysis with Stata11.0 software. The results were pooled using weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). RESULTS Totally 7 studies enrolled 324 eyes were included in the meta-analysis. The results of meta analysis showed that in AD patients, there was a significant average RNFL thickness reduction compared with the control group [WMD=-17.561, 95%CI: (-23.971, -11.151)]. There were significant differences in superior, inferior, nasal and temporal RNFL thickness between the two groups. WMD with a 95%CI were [-18.829, 95%CI:(-25.915, -11.743); P<0.05], [-25.775, 95%CI:(-34.304, -17.247); P<0.05], [-16.877, 95%CI: (-29.141, -4.613); P<0.001] and [-14.565, 95%CI:(-28.002, -1.128); P<0.001] respectively. Begg's test and Egger's test did not show significant difference, funnel plot was basically symmetrical, indicating that there was no publication bias existed. CONCLUSION There are significant differences in the RNFL thickness in all quadrants between the two groups. RNFL thickness is reduced in AD patients compared with the control group. PMID:22773997

  15. Safety and Efficacy of Rivastigmine in Patients With Alzheimer's Disease Not Responding Adequately to Donepezil: An Open-Label Study

    PubMed Central

    Figiel, Gary S.; Sadowsky, Carl H.; Strigas, John; Koumaras, Barbara; Meng, Xiangyi; Gunay, Ibrahim

    2008-01-01

    Objective: Switching patients with Alzheimer's disease from one cholinesterase inhibitor to another represents a viable option for patients not responding to current therapy. The objective of this large U.S.-based study was to evaluate the safety and efficacy of a treatment switch to rivastigmine in patients not responding adequately to or declining on treatment with donepezil. Method: In this 26-week, prospective, open-label, single-arm, multicenter study conducted from April 24, 2003, to June 25, 2004, patients with mild-to-moderate Alzheimer's disease (DSM-IV-TR criteria) who were not responding to donepezil were treated with rivastigmine 3–12 mg/day. Safety and tolerability were measured by the occurrence of adverse events and patient disposition. Treatment effects on global functioning were assessed using the Clinical Global Impression of Change (CGIC) scale. Results: Two hundred seventy patients with a mean age of 78.5 (SD = 7.56) years and a mean duration of dementia of 3.5 (SD = 2.06) years were included in the study. Sixty-nine percent of patients completed the study with 17.8% discontinuing due to adverse events. Eighty-three percent of patients reported at least 1 adverse event, with the most frequently occurring adverse events affecting the gastrointestinal system (54%). The majority of patients were reported to have either improvement or no decline on the CGIC. A limitation of the study is that the interpretation of the results is based on an overall completion rate of 69%. Conclusion: Immediately switching patients from donepezil to rivastigmine without a washout period was safe and well tolerated in the current study. Additionally, these results suggest that patients not responding adequately to or declining while taking donepezil may improve or stabilize after switching to rivastigmine. PMID:18787673

  16. A SPECT Imaging Study Of Driving Impairment In Patients With Alzheimer's Disease

    PubMed Central

    Ott, Brian R.; Heindel, William C.; Whelihan, William M.; Caron, Mark D.; Piatt, Andrea L.; Noto, Richard B.

    2012-01-01

    Single photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination. Driving impairment in Alzheimer's disease is related to changes in cortical function which vary according to severity of disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the Mini-Mental State Examination, that are weighted toward left hemisphere based verbal tasks. PMID:10765046

  17. Auditory spatial processing in Alzheimer's disease.

    PubMed

    Golden, Hannah L; Nicholas, Jennifer M; Yong, Keir X X; Downey, Laura E; Schott, Jonathan M; Mummery, Catherine J; Crutch, Sebastian J; Warren, Jason D

    2015-01-01

    The location and motion of sounds in space are important cues for encoding the auditory world. Spatial processing is a core component of auditory scene analysis, a cognitively demanding function that is vulnerable in Alzheimer's disease. Here we designed a novel neuropsychological battery based on a virtual space paradigm to assess auditory spatial processing in patient cohorts with clinically typical Alzheimer's disease (n = 20) and its major variant syndrome, posterior cortical atrophy (n = 12) in relation to healthy older controls (n = 26). We assessed three dimensions of auditory spatial function: externalized versus non-externalized sound discrimination, moving versus stationary sound discrimination and stationary auditory spatial position discrimination, together with non-spatial auditory and visual spatial control tasks. Neuroanatomical correlates of auditory spatial processing were assessed using voxel-based morphometry. Relative to healthy older controls, both patient groups exhibited impairments in detection of auditory motion, and stationary sound position discrimination. The posterior cortical atrophy group showed greater impairment for auditory motion processing and the processing of a non-spatial control complex auditory property (timbre) than the typical Alzheimer's disease group. Voxel-based morphometry in the patient cohort revealed grey matter correlates of auditory motion detection and spatial position discrimination in right inferior parietal cortex and precuneus, respectively. These findings delineate auditory spatial processing deficits in typical and posterior Alzheimer's disease phenotypes that are related to posterior cortical regions involved in both syndromic variants and modulated by the syndromic profile of brain degeneration. Auditory spatial deficits contribute to impaired spatial awareness in Alzheimer's disease and may constitute a novel perceptual model for probing brain network disintegration across the Alzheimer's disease

  18. Impact of gender on platelet membrane functions of Alzheimer's disease patients.

    PubMed

    Vignini, Arianna; Giusti, Lucia; Raffaelli, Francesca; Giulietti, Alessia; Salvolini, Eleonora; Luzzi, Simona; Provinciali, Leandro; Mazzanti, Laura; Nanetti, Laura

    2013-03-01

    There are many evidences suggesting that oxidative stress is one of the earliest events in Alzheimer disease (AD) pathogenesis and plays a key role in the development of the AD pathology. The existence of substantial gender-related differences in the clinical features of AD has been recently confirmed (i.e. pathophysiologic features and epidemiologic trends). In addition, study results appear to indicate that the etiopathogenetic mechanisms of AD differ significantly in the 2 sexes. Based on previous results regarding changes in AD platelet plasma membrane, the purpose of the present study was to assess the impact of gender in the same model above reported. In particular we aimed at studying platelets from AD patients (M-AD and F-AD) and matched controls (M-C and F-C), divided into gender, by studying nitric oxide (NO) and peroxynitrite (ONOO(-)) production, the intracellular Ca(2+) concentration ([Ca(2+)]i), membrane Na(+)/K(+)-ATPase activity and fluidity. NO production was significantly elevated in platelets from both F-AD and M-AD compared to matched controls. M-AD showed NO production significantly higher than F-AD and it was the same between M-C and F-C. A similar trend was seen for ONOO(-). Platelets of both M-AD and F-AD had intracellular Ca(2+) concentrations significantly higher than F-C and M-C, while membrane Na(+)/K(+)-ATPase activity showed an opposite trend, but these differences are still significant. M-AD male subjects showed a significantly increased DPH fluorescence anisotropy (r) compared with controls, while for F-AD this discrepancy was not significant. The difference in DHP fluorescence anisotropy remained significant between M-AD and F-AD as well as between M-C and F-C. The TMA-DPH fluorescence anisotropy showed the same trend, but there were no significant differences between M-AD and F-AD, as well as between controls. The results of the current research support the conclusion that F-AD is not at greater risk than M-AD for oxidative stress

  19. 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.

  20. Noradrenergic dysfunction in Alzheimer's disease

    PubMed Central

    Gannon, Mary; Che, Pulin; Chen, Yunjia; Jiao, Kai; Roberson, Erik D.; Wang, Qin

    2015-01-01

    The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer's disease (AD) patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located) is a predominant site where AD-related pathology begins. Mounting evidence indicates that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed. PMID:26136654

  1. Home Safety for People with Alzheimer's Disease: General Safety Concerns

    MedlinePlus

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... NAPA) About ADEAR Home Safety for People with Alzheimer's Disease General Safety Concerns People with Alzheimer's disease ...

  2. Alzheimer's Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Living with Alzheimer's Disease Past Issues / Winter 2015 Table of Contents ... delay or prevent the disease. Free Guide for Alzheimer's Caregivers Caring for a person with Alzheimer's disease ...

  3. Subjective experience of family stigma as reported by children of Alzheimer's disease patients.

    PubMed

    Werner, Perla; Goldstein, Dovrat; Buchbinder, Eli

    2010-02-01

    In this study we explored the subjective experience of family stigma as reported by children of persons with Alzheimer's disease (AD). Our data indicated that family stigma in the area of AD was primarily experienced in three dimensions: caregivers' stigma, lay public's stigma, and structural stigma. We found that in all these dimensions family stigma follows a process characterized by three core elements: cognitive attributions, emotional reactions, and behavioral responses. Findings of this study highlight the profound stigma confronting caregivers of persons with AD. What emerges is a poignant picture of adult children living with stigmatic beliefs while providing care for their parents with AD. We suggest that swift steps be taken to deal with these stigmatic beliefs. Mainly, structural discrimination must end if all citizens are to receive truly fair and equitable health care services and benefits. PMID:20065304

  4. Enhancing conversation skills in patients with Alzheimer's disease using a prosthetic memory aid.

    PubMed Central

    Bourgeois, M S

    1990-01-01

    The effectiveness of teaching Alzheimer's disease subjects to use a prosthetic memory aid when conversing with familiar partners was evaluated. Effects of the training of three topics by caregivers was assessed in daily probes with the experimenter and twice weekly probes with a familiar conversational partner. All 3 subjects learned to use the memory aid with both conversational partners and improved the quality of their conversational content. Subjects made significantly more statements of fact and fewer ambiguous utterances after training on each topic according to a multiple baseline design. All subjects also generated novel, untrained statements in conversations with both partners. Treatment effects were maintained at high levels throughout training and at 3- and 6-week follow-up sessions. Naive judges rated baseline and posttreatment conversational samples as significantly improved on all eight conversational dimensions. Images Figure 1 Figure 2 Figure 3 PMID:2139873

  5. [Drug treatment of Alzheimer's disease].

    PubMed

    González González, J A

    2001-01-01

    The Alzheimer's disease is caused by a today unknown plurietiopathology that does not allow to establish an effective treatment. In the last years, important advances about neuronal physiology and its molecular bases of functioning has been attempt. At the same time, the research and finding of medicaments which used individually or together allow us to advance from a symptomatic treatment to influence and be effective etiopathologically in the Alzheimer's disease. A few are trying to maintain the structure and function of the neurons (synapsis). Others are concentrated on prevent their death or substitute the damaged cells by embryonic mother cells. Nowadays, there are important projects in an experimental stage of research with the hope that "they will be useful for everything" or unless to slow down or stop the Alzheimer's disease. We are going to talk about these medicaments in this article. PMID:11783035

  6. [Alzheimer's disease, supporting carers].

    PubMed

    Lottin, Arlette; Botter, René

    2016-03-01

    The association France Alzheimer provides carers with resources. It runs training programmes and organises "Memory Cafes". These initiatives give carers the opportunity to talk about their daily struggles, close to home, and to obtain advice on how to better manage their situation. PMID:26975685

  7. Alzheimer's Disease Research Centers

    MedlinePlus

    ... Street Phoenix, AZ 85006 Website: www.azalz.org Social media: Information Line: 602-239-6500 Director's e-mail: ... CA 95817-4540 Website: http://alzheimer.ucdavis.edu Social media: Information Line: 916-734-5496 Director's e-mail: ...

  8. About Alzheimer's Disease: Risk Factors and Prevention

    MedlinePlus

    ... About ADEAR About Alzheimer's Disease: Risk Factors and Prevention We can’t control some risk factors for ... as well. NIA Information on Risk Factors and Prevention 2014-2015 Alzheimer's Disease Progress Report: Advancing Research ...

  9. Effects of change in FreeSurfer version on classification accuracy of patients with Alzheimer's disease and mild cognitive impairment.

    PubMed

    Chepkoech, Joy-Loi; Walhovd, Kristine B; Grydeland, Håkon; Fjell, Anders M

    2016-05-01

    Studies have found non-negligible differences in cortical thickness estimates across versions of software that are used for processing and quantifying MRI-based cortical measurements, and issues have arisen regarding these differences, as obtained estimates could potentially affect the validity of the results. However, more critical for diagnostic classification than absolute thickness estimates across versions is the inter-subject stability. We aimed to investigate the effect of change in software version on classification of older persons in groups of healthy, mild cognitive impairment and Alzheimer's Disease. Using MRI samples of 100 older normal controls, 100 with mild cognitive impairment and 100 Alzheimer's Disease patients obtained from the Alzheimer's Disease Neuroimaging Initiative database, we performed a standard reconstruction processing using the FreeSurfer image analysis suite versions 4.1.0, 4.5.0 and 5.1.0. Pair-wise comparisons of cortical thickness between FreeSurfer versions revealed significant differences, ranging from 1.6% (4.1.0 vs. 4.5.0) to 5.8% (4.1.0 vs. 5.1.0) across the cortical mantle. However, change of version had very little effect on detectable differences in cortical thickness between diagnostic groups, and there were little differences in accuracy between versions when using entorhinal thickness for diagnostic classification. This lead us to conclude that differences in absolute thickness estimates across software versions in this case did not imply lacking validity, that classification results appeared reliable across software versions, and that classification results obtained in studies using different FreeSurfer versions can be reliably compared. Hum Brain Mapp 37:1831-1841, 2016. © 2016 Wiley Periodicals, Inc. PMID:27018380

  10. Development and Implementation of Nonpharmacologic Protocols for the Management of Patients with Alzheimer's Disease and Their Families in a Multiracial Primary Care Setting

    ERIC Educational Resources Information Center

    Austrom, Mary Guerriero; Damush, Teresa M.; Hartwell, Cora West; Perkins, Tony; Unverzagt, Frederick; Boustani, Malaz; Hendrie, Hugh C.; Callahan, Christopher M.

    2004-01-01

    Purpose. Most patients and families with dementia are cared for in primary care clinics. These clinics are seldom designed to provide the necessary comprehensive care. The purpose of this article is to describe nonpharmacologic protocols for the management of patients with Alzheimer's disease and their families that are administered as part of a…

  11. Cerebrolysin improves symptoms and delays progression in patients with Alzheimer's disease and vascular dementia.

    PubMed

    Allegri, R F; Guekht, A

    2012-04-01

    Dementia is the result of various cerebral disorders, leading to an acquired loss of memory and impaired cognitive ability. The most common forms are Alzheimer's disease (AD) and vascular dementia (VaD). Neurotrophic factors are essential for the survival and differentiation of developing neurons and protecting them against damage under pathologic conditions. Cerebrolysin is a peptide preparation that mimics the pleiotropic effects of neurotrophic factors. Several clinical trials investigating the therapeutic efficacy of Cerebrolysin in AD and VaD have confirmed the proof of concept. The results of these trials have shown statistically significant and clinically relevant treatment effects of Cerebrolysin on cognitive, global and functional domains in mild to moderately severe stages of dementia. Doses of 10 and 30 mL were the most effective, but higher doses of up to 60 mL turned out to be most effective in improving neuropsychiatric symptoms, which become relevant at later stages of the disease. Combining treatment with cholinesterase inhibitors and Cerebrolysin indicated long-term synergistic treatment effects in mild to moderate AD. The efficacy of Cerebrolysin persisted for up to several months after treatment suggesting Cerebrolysin has not merely symptomatic benefits, but a disease-delaying potential. This paper reviews the clinical efficacy of Cerebrolysin in the treatment of dementia. Data were obtained from international, multicenter, randomized clinical trials performed in compliance with Good Clinical Practice and the principles of the Declaration of Helsinki (1964) and subsequent revisions. PMID:22514793

  12. Caring for Alzheimer's Patients. Supplement to Caregivers' Practical Help to Assist Those Who Care for Patients with Dementia Related Diseases = El Cuidado de los Pacientes de Alzheimer. Suplemento de Ayuda Practica para las Personas Encargadas para Ayudar a los que Cuidan a Pacientes que Sufren de Enfermedades Relacionadas con la Demencia.

    ERIC Educational Resources Information Center

    New York State Office for the Aging, Albany.

    This manual is intended for caregivers of homebound patients with Alzheimer's disease and others who are mentally impaired. It deals with the nature of Alzheimer's, the decline in a patient's abilities, information about available services, and legal and financial issues. The manual provides guidance and suggestions to lessen the daily stress…

  13. Glucose Metabolism: A Sweet Relief of Alzheimer's Disease.

    PubMed

    Duran-Aniotz, Claudia; Hetz, Claudio

    2016-09-12

    Patients and individuals at risk for Alzheimer's disease show reduced glucose metabolism in the brain. A new study takes advantage of a fly model of Alzheimer's disease to demonstrate that enhancing glucose uptake in neurons has strong neuroprotective effects involving improved proteostasis. PMID:27623263

  14. Are Judgments of Semantic Relatedness Systematically Impaired in Alzheimer's Disease?

    ERIC Educational Resources Information Center

    Hornberger, M.; Bell, B.; Graham, K. S.; Rogers, T. T.

    2009-01-01

    We employed a triadic comparison task in patients with Alzheimer's disease (AD) and healthy controls to contrast (a) multidimensional scaling (MDS) and accuracy-based assessments of semantic memory, and (b) degraded-store versus degraded-access accounts of semantic impairment in Alzheimer's disease (AD). Similar to other studies using triadic…

  15. Graphomotor perseveration and wandering in Alzheimer's disease.

    PubMed

    Ryan, J P; McGowan, J; McCaffrey, N; Ryan, G T; Zandi, T; Brannigan, G G

    1995-10-01

    Perseveration, spatial orientation, and attention/concentration were assessed in 15 patients with a probable diagnosis of senile dementia of the Alzheimer's type. Subjects were divided into two groups, wanderers and nonwanderers, based on caregiver ratings using a modified version of the Caregiver Checklist. Graphic productions of wanderers on the Bender Visual Motor Gestalt Test and Clock Drawing Test displayed greater total perseveration and more recurrent and continuous perseverations than those of nonwanderers. Spatial orientation and attention/concentration were similar between groups. These preliminary results suggest that graphomotor perseverations exhibited during the mild to moderate stages may serve as a marker for wandering in Alzheimer's disease. PMID:8561833

  16. Prescribing patterns for Alzheimer disease

    PubMed Central

    Hillmer, Melinda; Krahn, Murray; Hillmer, Michael; Pariser, Pauline; Naglie, Gary

    2006-01-01

    OBJECTIVE To describe Canadian family physicians’ prescribing practices with regard to Alzheimer disease (AD). DESIGN Cross-sectional survey administered by facsimile. SETTING Four regions in Canada (British Columbia, the Prairie Provinces, Ontario, and the Atlantic Provinces). PARTICIPANTS A stratified random sample of 1000 Canadian family physicians (250 per region) chosen from the Canadian Medical Directory; 81 of whom were excluded as ineligible. MAIN OUTCOME MEASURES Prescribing practices regarding cholinesterase inhibitors (ChIs) for patients with AD. RESULTS Response rate was 36.3%. About 27% of respondents reported that ChIs were prescribed for less than 10% of their AD patients, while 12.5% reported that ChIs were prescribed for more than 90% of their AD patients. More physicians prescribed ChIs in the two regions with provincial formulary coverage (Prairie Provinces and Ontario) than in the two regions without coverage (British Columbia and Atlantic Provinces). Factors that significantly predicted lower prescribing rates included female sex, perception of ChIs’ effectiveness, and self-reported knowledge of ChIs. CONCLUSION Canadian physicians’ prescribing patterns for ChIs vary; the optimal prescribing rate is unclear. Provincial coverage of these drugs along with physicians’ sex, knowledge of ChIs, and perception of the effectiveness of ChIs appear to influence prescribing rates. PMID:16926965

  17. Anatomical heterogeneity of Alzheimer disease

    PubMed Central

    Noh, Young; Jeon, Seun; Seo, Sang Won; Kim, Geon Ha; Cho, Hanna; Ye, Byoung Seok; Yoon, Cindy W.; Kim, Hee Jin; Chin, Juhee; Park, Kee Hyung; Heilman, Kenneth M.

    2014-01-01

    Objective: Because the signs associated with dementia due to Alzheimer disease (AD) can be heterogeneous, the goal of this study was to use 3-dimensional MRI to examine the various patterns of cortical atrophy that can be associated with dementia of AD type, and to investigate whether AD dementia can be categorized into anatomical subtypes. Methods: High-resolution T1-weighted volumetric MRIs were taken of 152 patients in their earlier stages of AD dementia. The images were processed to measure cortical thickness, and hierarchical agglomerative cluster analysis was performed using Ward's clustering linkage. The identified clusters of patients were compared with an age- and sex-matched control group using a general linear model. Results: There were several distinct patterns of cortical atrophy and the number of patterns varied according to the level of cluster analyses. At the 3-cluster level, patients were divided into (1) bilateral medial temporal–dominant atrophy subtype (n = 52, ∼34.2%), (2) parietal-dominant subtype (n = 28, ∼18.4%) in which the bilateral parietal lobes, the precuneus, along with bilateral dorsolateral frontal lobes, were atrophic, and (3) diffuse atrophy subtype (n = 72, ∼47.4%) in which nearly all association cortices revealed atrophy. These 3 subtypes also differed in their demographic and clinical features. Conclusions: This cluster analysis of cortical thickness of the entire brain showed that AD dementia in the earlier stages can be categorized into various anatomical subtypes, with distinct clinical features. PMID:25344382

  18. Amyloid-aβ Peptide in olfactory mucosa and mesenchymal stromal cells of mild cognitive impairment and Alzheimer's disease patients.

    PubMed

    Ayala-Grosso, Carlos A; Pieruzzini, Rosalinda; Diaz-Solano, Dylana; Wittig, Olga; Abrante, Ligia; Vargas, Leslie; Cardier, Jose

    2015-03-01

    Patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD) might develop olfactory dysfunction that correlates with progression of disease. Alteration of olfactory neuroepithelium associated with MCI may be useful as predictor of cognitive decline. Biomarkers with higher sensitivity and specificity would allow to understand the biological progression of the pathology in association with the clinical course of the disease. In this study, magnetic resonance images, apolipoprotein E (ApoE) load, Olfactory Connecticut test and Montreal Cognitive Assessment (MoCA) indices were obtained from noncognitive impaired (NCI), MCI and AD patients. We established a culture of patient-derived olfactory stromal cells from biopsies of olfactory mucosa (OM) to test whether biological properties of mesenchymal stromal cells (MSC) are concurrent with MCI and AD psychophysical pathology. We determined the expression of amyloid Aβ peptides in the neuroepithelium of tissue sections from MCI and AD, as well as in cultured cells of OM. Reduced migration and proliferation of stromal (CD90(+) ) cells in MCI and AD with respect to NCI patients was determined. A higher proportion of anosmic MCI and AD cases were concurrent with the ApoE ε4 allele. In summary, dysmetabolism of amyloid was concurrent with migration and proliferation impairment of patient-derived stem cells. PMID:25040401

  19. Posture Recognition in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Mozaz, Maria; Garaigordobil, Maite; Rothi, Leslie J. Gonzalez; Anderson, Jeffrey; Crucian, Gregory P.; Heilman, Kenneth M.

    2006-01-01

    Background: Apraxia is neurologically induced deficit in the ability perform purposeful skilled movements. One of the most common forms is ideomotor apraxia (IMA) where spatial and temporal production errors are most prevalent. IMA can be associated Alzheimer's disease (AD), even early in its course, but is often not identified possibly because…

  20. Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

    SciTech Connect

    Poduslo, S.E.; Schwankhaus, J.D.

    1994-09-01

    A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal, and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.

  1. Genetic heterogeneity and Alzheimer`s disease

    SciTech Connect

    Schellenberg, G.D.; Wijsman, E.M.; Bird, T.D.

    1994-09-01

    In some early-onset Alzheimer`s disease (AD) families, inheritance is autosomal dominant. (Early-onset AD is arbitarily defined as onset at {le} 60 years.) Two loci have been identified which are causative for early-onset familial AD (FAD). One is the amyloid precursor protein gene in which specific mutation have been identified. The second is a locus at 14q24.3 (AD3) which has been localized by linkage analysis; the gene and specific mutations have not been identified. Linkage studies place this locus between D14S61 and D14S63. These 2 loci, however, do not account for all early-onset FAD. The Volga German (VG) kindreds are descendants of families which emigrated from Germany to the Volga river region of Russia and subsequently to the US; AD in these families is hypothesized to be the result of a common genetic founder. The average age-at-onset in these families is 57 years. Linkage analysis for this group has been negative for the APP gene and for chromosome 14 markers. Thus, there is at least 1 other early-onset FAD locus. Recently, the {epsilon}4 allele of apolipoprotein E (ApoE) was identified as a risk-factor for late-onset AD. In a series of 53 late-onset kindreds, a strong genetic association was observed between the ApoE {epsilon}4 allele and AD. However, when linkage analysis was performed using a highly polymorphic locus at the ApoCII gene, which is within 30 kb of ApoE, significant evidence for co-segregation was not observed. This and other data suggests that while ApoE is an age-at-onset modifying locus, another gene(s), located elsewhere, contribute(s) to late-onset AD. Thus, there is probably at least 1 other late-onset locus. Once the VG locus is identified, it will be possible to determine whether an allelic variant of this locus is responsible for late-onset FAD.

  2. Alzheimer's disease and euthanasia.

    PubMed

    Alvargonzález, David

    2012-12-01

    Employing the tenets of philosophical materialism, this paper discusses the ethical debate surrounding assisted suicide for persons suffering end-stage Alzheimer's. It first presents a classification of the dissociative situations between "human individual" and "human person". It then moves on to discuss challenges to diagnosed persons and their caregivers in relation to the cardinal virtues of Spinozistic ethics--strength of character (fortitudo), firmness (animositas) and generosity (generositas). Finally, a number of ideas attached to the debate--"right of choice", "death with dignity", "quality of life" and "compassion in dying"--are discussed in order to clarify their foundations. PMID:22939533

  3. Immunotherapeutic Approaches to Alzheimer's Disease

    NASA Astrophysics Data System (ADS)

    Monsonego, Alon; Weiner, Howard L.

    2003-10-01

    Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system-based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.

  4. Glycation in Parkinson's disease and Alzheimer's disease.

    PubMed

    Vicente Miranda, Hugo; El-Agnaf, Omar M A; Outeiro, Tiago Fleming

    2016-06-01

    Glycation is a spontaneous age-dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α-synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society. PMID:26946341

  5. Music Therapy Using Singing Training Improves Psychomotor Speed in Patients with Alzheimer's Disease: A Neuropsychological and fMRI Study

    PubMed Central

    Satoh, Masayuki; Yuba, Toru; Tabei, Ken-ichi; Okubo, Yukari; Kida, Hirotaka; Sakuma, Hajime; Tomimoto, Hidekazu

    2015-01-01

    Background/Aims To investigate the effect of singing training on the cognitive function in Alzheimer's disease (AD) patients. Methods Ten AD patients (mean age 78.1 years) participated in music therapy using singing training once a week for 6 months (music therapy group). Each session was performed with professional musicians using karaoke and a unique voice training method (the YUBA Method). Before and after the intervention period, each patient was assessed by neuropsychological batteries, and functional magnetic resonance imaging (fMRI) was performed while the patients sang familiar songs with a karaoke device. As the control group, another 10 AD patients were recruited (mean age 77.0 years), and neuropsychological assessments were performed twice with an interval of 6 months. Results In the music therapy group, the time for completion of the Japanese Raven's Colored Progressive Matrices was significantly reduced (p = 0.026), and the results obtained from interviewing the patients' caregivers revealed a significant decrease in the Neuropsychiatric Inventory score (p = 0.042) and a prolongation of the patients' sleep time (p = 0.039). The fMRI study revealed increased activity in the right angular gyrus and the left lingual gyrus in the before-minus-after subtraction analysis of the music therapy intervention. Conclusion Music therapy intervention using singing training may be useful for dementia patients by improving the neural efficacy of cognitive processing. PMID:26483829

  6. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features.

    PubMed

    Ossenkoppele, Rik; Pijnenburg, Yolande A L; Perry, David C; Cohn-Sheehy, Brendan I; Scheltens, Nienke M E; Vogel, Jacob W; Kramer, Joel H; van der Vlies, Annelies E; La Joie, Renaud; Rosen, Howard J; van der Flier, Wiesje M; Grinberg, Lea T; Rozemuller, Annemieke J; Huang, Eric J; van Berckel, Bart N M; Miller, Bruce L; Barkhof, Frederik; Jagust, William J; Scheltens, Philip; Seeley, William W; Rabinovici, Gil D

    2015-09-01

    A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural-predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59

  7. Cerebrovascular disease in ageing and Alzheimer's disease.

    PubMed

    Love, Seth; Miners, J Scott

    2016-05-01

    Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease. PMID:26711459

  8. Medical foods for Alzheimer's disease.

    PubMed

    Shah, Raj C

    2011-06-01

    Alzheimer's disease (AD) is a neurodegenerative condition associated with cognitive loss, behavioural changes, functional ability decline and caregiver burden. Given the worldwide public health impact of AD, novel interventions to reduce suffering experienced by AD patients need to be developed. Foods may offer a mechanism for intervention complementary to drugs, devices, biologicals and vaccines. Apart from foods with health claims (including dietary supplements), medical foods are also being explored as an intervention option. The purpose of this article is to describe how medical foods may complement other interventions for AD patients by: (i) defining what a medical food is; (ii) discussing whether AD is a condition amenable to medical food intervention; (iii) reviewing current clinical trial data on medical foods used in participants with AD; and (iv) highlighting steps needed to establish a more comprehensive framework for developing medical foods for AD. While medical foods may be defined differently in other countries, the US Orphan Drug Act of 1998 defined a medical food as a food formulated for enteral intake, taken under physician supervision, and intended to meet the distinctive nutritional requirements identified for a disease or condition. For AD to be amenable to medical food intervention, it must: (i) result in limited or impaired capacity to ingest, digest, absorb or metabolize ordinary foodstuff or certain nutrients; or (ii) have unique, medically determined nutrient requirements; and (iii) require dietary management that cannot be achieved by modification of the normal diet alone. While these criteria are most likely met in advanced AD, identifying unique nutritional requirements in early AD that cannot be met by normal diet modification requires a better understanding of AD pathophysiology. A PubMed search using the terms 'medical food' and 'Alzheimer', limited to clinical trials published in English with human participants with AD aged >65

  9. Using mental imagery to improve memory in patients with Alzheimer disease: trouble generating or remembering the mind's eye?

    PubMed

    Hussey, Erin P; Smolinsky, John G; Piryatinsky, Irene; Budson, Andrew E; Ally, Brandon A

    2012-01-01

    This study was conducted to understand whether patients with mild Alzheimer disease (AD) could use general or self-referential mental imagery to improve their recognition of visually presented words. Experiment 1 showed that, unlike healthy controls, patients generally did not benefit from either type of imagery. To help determine whether the patients' inability to benefit from mental imagery at encoding was due to poor memory or due to an impairment in mental imagery, participants performed 4 imagery tasks with varying imagery and cognitive demands. Experiment 2 showed that patients successfully performed basic visual imagery, but degraded semantic memory, coupled with visuospatial and executive functioning deficits, impaired their ability to perform more complex types of imagery. Given that patients with AD can perform basic mental imagery, our results suggest that episodic memory deficits likely prevent AD patients from storing or retrieving general mental images generated during encoding. Overall, the results of both experiments suggest that neurocognitive deficits do not allow patients with AD to perform complex mental imagery, which may be most beneficial to improving memory. However, our data also suggest that intact basic mental imagery and rehearsal could possibly be helpful if used in a rehabilitation multisession intervention approach. PMID:21946012

  10. Endocannabinoid signalling in Alzheimer's disease.

    PubMed

    Maroof, Nazia; Pardon, Marie Christine; Kendall, David A

    2013-12-01

    The ECs (endocannabinoids) AEA (anandamide) and 2-AG (2-arachidonoylglycerol) and their lipid congeners OEA (N-oleoylethanolamide) and PEA (N-palmitoylethanolamide) are multifunctional lipophilic signalling molecules. The ECs, OEA and PEA have multiple physiological roles including involvement in learning and memory, neuroinflammation, oxidative stress, neuroprotection and neurogenesis. They have also been implicated in the pathology of, or perhaps protective responses to, neurodegenerative diseases. This is particularly the case with Alzheimer's disease, the most common age-related dementia associated with impairments in learning and memory accompanied by neuroinflammation, oxidative stress and neurodegeneration. The present mini-review examines the evidence supporting the roles that ECs appear to play in Alzheimer's disease and the potential for beneficial therapeutic manipulation of the EC signalling system. PMID:24256258