Science.gov

Sample records for alzheimers disease patients

  1. Fungal infection in patients with Alzheimer's disease.

    PubMed

    Alonso, Ruth; Pisa, Diana; Marina, Ana Isabel; Morato, Esperanza; Rábano, Alberto; Carrasco, Luis

    2014-01-01

    Alzheimer's disease is a progressive neurodegenerative disorder that leads to dementia mainly among the elderly. This disease is characterized by the presence in the brain of amyloid plaques and neurofibrillary tangles that provoke neuronal cell death, vascular dysfunction, and inflammatory processes. In the present work, we have analyzed the existence of fungal infection in Alzheimer's disease patients. A proteomic analysis provides compelling evidence for the existence of fungal proteins in brain samples from Alzheimer's disease patients. Furthermore, PCR analysis reveals a variety of fungal species in these samples, dependent on the patient and the tissue tested. DNA sequencing demonstrated that several fungal species can be found in brain samples. Together, these results show that fungal macromolecules can be detected in brain from Alzheimer's disease patients. To our knowledge these findings represent the first evidence that fungal infection is detectable in brain samples from Alzheimer's disease patients. The possibility that this may represent a risk factor or may contribute to the etiological cause of Alzheimer's disease is discussed.

  2. Current treatments for patients with Alzheimer disease.

    PubMed

    Osborn, Gerald G; Saunders, Amanda Vaughn

    2010-09-01

    There is neither proven effective prevention for Alzheimer disease nor a cure for patients with this disorder. Nevertheless, a spectrum of biopsychosocial therapeutic measures is available for slowing progression of the illness and enhancing quality of life for patients. These measures include a range of educational, psychological, social, and behavioral interventions that remain fundamental to effective care. Also available are a number of pharmacologic treatments, including prescription medications approved by the US Food and Drug Administration for Alzheimer disease, "off-label" uses of medications to manage target symptoms, and controversial complementary therapies. Physicians must make the earliest possible diagnosis to use these treatments most effectively. Physicians' goals should be to educate patients and their caregivers, to plan long-term care options, to maximally manage concurrent illnesses, to slow and ameliorate the most disabling symptoms, and to preserve effective functioning for as long as possible. The authors review the various current treatments for patients with Alzheimer disease.

  3. 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

  4. Immune blood biomarkers of Alzheimer disease patients.

    PubMed

    Avagyan, Hripsime; Goldenson, Ben; Tse, Eric; Masoumi, Ava; Porter, Verna; Wiedau-Pazos, Martina; Sayre, James; Ong, Reno; Mahanian, Michelle; Koo, Patrick; Bae, Susan; Micic, Miodrag; Liu, Philip T; Rosenthal, Mark J; Fiala, Milan

    2009-05-29

    Alzheimer disease (AD) patients have an impairment of anti-amyloid-beta (Abeta) innate immunity and a defect in immune gene transcription [Fiala, M., Liu, P.T., Espinosa-Jeffrey, A., Rosenthal, M.J., Bernard, G., Ringman, J.M., Sayre, J., Zhang, L., Zaghi, J., Dejbakhsh, S., Chiang, B., Hui, J., Mahanian, M., Baghaee, A., Hong, P., Cashman, J., 2007b. Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin. Proc. Natl. Acad. Sci. U. S. A. 104, 12849-12854]. Early diagnosis is a cornerstone of preventive approaches to AD. Phospho-tau and Abeta CSF levels are useful markers of neurodegeneration but not of a process leading to neurodegeneration. To detect an early biomarker of AD, we developed a flow cytometric test of Abeta phagocytosis, which was 94% positive (<400 MFI units) in AD patients (mean age+/-SEM 77+2.2 years; mean score+/-SEM 198.6+/-25.5 MFI units) and 60% positive in MCI patients (77+/-5.6 years; 301+/-106 MFI units). Control subjects, active senior university professors, were 100% negative (74.2+/-4.2 years; 1348+/-174 MFI units). The test had a low specificity in older caregivers and older amyotrophic lateral sclerosis (ALS) patients. We also tested transcriptional regulation of the genes MGAT-III and Toll-like receptor-3 in macrophages. Macrophages of "Type I" patients (a majority of patients) showed gene down regulation at baseline and up regulation by curcuminoids; macrophages of "Type II" patients showed opposite responses. The results of flow cytometric testing suggest that normal Abeta phagocytosis is associated with healthy cognition and lesser risk of AD. The significance of abnormal results in aged persons should be investigated by prospective studies to determine the risk of AD.

  5. [Caring for patients with Alzheimer's disease].

    PubMed

    Hirono, Nobutsugu

    2010-07-01

    The term "caring" refers to the process aimed at enabling people with disabilities to achieve and maintain optimal functioning. According to the International Classification of Functioning, Disability and Health (ICF) proposed by the World Health Organization in 2001, the functioning involves all aspects of daily life and applies to 3 levels: body functions and structures, activities, and participation. Caring is of 2 types; (1) therapeutic care, which restores and maintains the body functions; and (2) compensatory care, which compensates for the impairment of body functions and thus enhances and maintains the level of activity and participation. Alzheimer disease impairs multiple domains, including cognitive function and behaviors; therefore, it is very important to systematically and individually assess these impairments in each domain. Because there is inadequate data on the efficacy of cognitive training, compensatory care is principally used to overcome cognitive dysfunction. Caregivers should be equipped with skills required to cope with behavioral problems so that they can compensate for and even reduce these problems. Further, caregivers should not be overburdened, as this is reported to be a significant predictor for the poor outcome of patients with Alzheimer disease. Therefore, appropriate information regarding the disease, the impairments caused by it, the skills required to cope with these impairments, and social support services should be provided to the caregivers.

  6. Micronutrient supplementation in mild Alzheimer disease patients.

    PubMed

    Planas, M; Conde, M; Audivert, S; Pérez-Portabella, C; Burgos, R; Chacón, P; Rossello, J; Boada, M; Tàrraga, L L

    2004-04-01

    To evaluate if nutritional supplementation with or without micronutrient enhancement prevent weight loss and the progression of the disease in mild Alzheimer's Disease (AD) patients. Mild AD patients were recruited from an Alzheimer Day Centre. Subjects received oral liquid supplements with (Study-group: S) or without (Control-group: C) micronutrient enhancement. Intake assessment, nutritional status, biochemical parameters, cognitive function, and eating behaviour disorders were determined at baseline and at 6 months of treatment. At baseline both groups were not different in any variable measured. They were norm nourished, with normal biochemical parameters. Blandford scale demonstrated a mild alteration of feeding behaviour, the cognitive scale classified the patients as impaired and there was presence of memory complaints. After 6 months of nutritional supplements, a similar increase in energy consumption was observed in both groups of patients (P<0.05). In the within-group analysis, we found a trend (P=0.05) to increase body mass index; a significant increase in triceps skin fold thickness, mid-upper-arm circumference and serum magnesium, zinc and selenium, and a significant reduction in serum vitamin E (P<0.001, each). Serum cholesterol decreased substantially only in the S-group (P=0.025). No significant differences at baseline, within-group, neither between-group analysis in feeding behaviour nor in cognitive function were observed. According to our results no benefits in the progression of the disease was observed with micronutrient enhancement supplements. Effectiveness of nutritional supplements in preventing weight loss in mild AD patients showed a similar behaviour as observed in other populations. Due to the beneficial evolution of serum cholesterol in the S-group, this intervention deserves further investigation.

  7. Alzheimer Disease

    MedlinePlus

    ... CPR: A Real Lifesaver Kids Talk About: Coaches Alzheimer Disease KidsHealth > For Kids > Alzheimer Disease Print A ... slow it down. When Someone You Love Has Alzheimer Disease You might feel sad or angry — or ...

  8. Voluntary Imitation in Alzheimer's Disease Patients.

    PubMed

    Bisio, Ambra; Casteran, Matthieu; Ballay, Yves; Manckoundia, Patrick; Mourey, France; Pozzo, Thierry

    2016-01-01

    Although Alzheimer's disease (AD) primarily manifests as cognitive deficits, the implicit sensorimotor processes that underlie social interactions, such as automatic imitation, seem to be preserved in mild and moderate stages of the disease, as is the ability to communicate with other persons. Nevertheless, when AD patients face more challenging tasks, which do not rely on automatic processes but on explicit voluntary mechanisms and require the patient to pay attention to external events, the cognitive deficits resulting from the disease might negatively affect patients' behavior. The aim of the present study was to investigate whether voluntary motor imitation, i.e., a volitional mechanism that involves observing another person's action and translating this perception into one's own action, was affected in patients with AD. Further, we tested whether this ability was modulated by the nature of the observed stimulus by comparing the ability to reproduce the kinematic features of a human demonstrator with that of a computerized-stimulus. AD patients showed an intact ability to reproduce the velocity of the observed movements, particularly when the stimulus was a human agent. This result suggests that high-level cognitive processes involved in voluntary imitation might be preserved in mild and moderate stages of AD and that voluntary imitation abilities might benefit from the implicit interpersonal communication established between the patient and the human demonstrator.

  9. 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.

  10. [Neuroimaging for patients with Alzheimer disease in routine practice].

    PubMed

    Matsuda, Hiroshi

    2010-07-01

    In routine practice neuroimaging has been applied as an adjunct technique for early and differential diagnosis of Alzheimer disease in routine practice. Of the several neuroimaging modalities, magnetic resonance imaging (MRI) and brain perfusion single-photon emission computed tomography (SPECT) have been commonly used in Japan; further software programs are used to aid statistical analysis of the imaging results. For example voxel-based specific regional analysis system for Alzheimer disease (VSRAD) for MRI and easy Z-score imaging system (eZIS) are used for the analysis of MRI and SPECT. In the early stage of Alzheimer disease, specific findings of regional atrophy and perfusion reduction are observed in some areas. In the posterior cingulate gyrus precuneus and parietal cortex, perfusion reduction was more frequently observed than atrophy. On the other hand, in the medial temporal structures, perfusion reduction was less frequently observed than atrophy. Perfusion reduction in the the posterior cingulate gyrus precuneus and in the parietal cortex was more prominent in the case of patients with early-onset Alzheimer disease than in the case of patients with late-onset Alzheimer disease. Further, atrophy in the medial temporal structures was more prominent in the case of patients with late-onset Alzheimer disease than in the case of those with early-onset Alzheimer disease. These findings are helpful for differentiating of Alzheimer disease from other diseases characterized by dementia.

  11. 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…

  12. 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…

  13. Alzheimer disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000760.htm Alzheimer disease To use the sharing features on this page, ... of brain function that occurs with certain diseases. Alzheimer disease is one form of dementia. It affects memory, ...

  14. Weak central coherence in patients with Alzheimer's disease(•).

    PubMed

    Mårdh, Selina

    2013-03-15

    Central coherence refers to the ability to interpret details of information into a whole. To date, the concept of central coherence is mainly used in research of autism, Asperger's syndrome and recently in the research on eating disorders. The main purpose of the present study was to examine central coherence in patients with Alzheimer's disease. Nine Alzheimer's disease patients and ten age- and gender-matched control subjects, who differed significantly in neurological assessment, were shown a picture of a fire. Compared to control subjects, the Alzheimer's disease patients described the picture in a fragmented way by mentioning details and separate objects without perceiving the context of the fire. In conclusion, patients with Alzheimer's disease are at the weak end of central coherence, and hence suffer from a fragmented view of their surroundings. The findings have important clinical implications for the understanding of patients with Alzheimer's diseaseand also for the possibility of caregivers to meet the Alzheimer's disease individual in an appropriate way in the everyday care.

  15. Changes in Semantic Memory in Early Stage Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Weingartner, Herbert J.; And Others

    1993-01-01

    Contrasts changes in semantic memory in elderly normal controls and Alzheimer's disease (AD) patients before patients expressed symptoms. Found that controls generated more uncommon exemplars from closed semantic categories (fruits and vegetables) than did AD patients prior to presumed onset of AD. AD patients were just as productive as controls…

  16. Sentence Comprehension in Slovak-Speaking Patients with Alzheimer's Disease

    ERIC Educational Resources Information Center

    Marková, Jana; Horváthová, Lubica; Králová, Mária; Cséfalvay, Zsolt

    2017-01-01

    Background: According to some studies, sentence comprehension is diminished in Alzheimer's disease (AD) patients, but they differ on what underlies the sentence comprehension impairment. Sentence comprehension in AD patients has been studied mainly in the English language. It is less clear how patients with AD speaking a morphologically rich…

  17. Clinical aspects of Alzheimer's disease in black and white patients.

    PubMed Central

    Hargrave, R.; Stoeklin, M.; Haan, M.; Reed, B.

    1998-01-01

    This article examines the association between ethnicity and psychiatric symptoms in patients with Alzheimer's disease. Data from a cross-sectional study of patients evaluated at nine California Department of Health Alzheimer's Disease Diagnostic and Treatment Centers (ADDTCs) were used. Using the ADDTC patient database, sociodemographic and clinical variables in 207 black patients and 1818 white patients with probable and possible Alzheimer's disease were compared. Logistic and linear regression analysis indicated the following results: 1) black patients had fewer years of education and more often had hypertension, 2) black patients reported shorter duration of illness at the time of initial diagnosis of dementia, 3) black patients had lower Mini-Mental State Examination scores and higher Blessed Roth Dementia Rating Scale scores at the time of initial diagnosis, and 4) black patients more frequently reported insomnia and less frequently reported anxiety. Additional studies are needed to validate these findings and to generate hypotheses about the role of cardiovascular disease and pathophysiology of psychiatric symptoms in ethnic populations with Alzheimer's disease. PMID:9510621

  18. Dysphagia in Alzheimer's disease.

    PubMed

    Seçil, Yaprak; Arıcı, Şehnaz; İncesu, Tülay Kurt; Gürgör, Nevin; Beckmann, Yeşim; Ertekin, Cumhur

    2016-06-01

    To investigate electrophysiological parameters of swallowing in all stages of Alzheimer's disease. Forty Alzheimer's disease patients, 20 age-matched normal controls and 20 young normal controls were included. Dysphagia limit (DL) and sequential water swallowing (SWS) tests were performed. Cardiac rhythm, respiration and sympathetic skin responses were concomitantly recorded. Dysphagia was found in 30/40 (75%) of Alzheimer's disease patients. Mean volume at the DL test was significantly reduced (16.5±1.0mL) in the Alzheimer's disease group. Swallowing and apnea times in the SWS test were significantly prolonged in elderly controls, but even longer in Alzheimer's disease patients. Alzheimer's disease patients had electrophysiological features of dysphagia, even in the early period of disease. The cortical involvement and severity of cognitive disorder can increase swallowing problems, but subclinical signs of dysphagia may be observed even in patients with mild or moderate Alzheimer's disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Sundown syndrome in severely demented patients with probable Alzheimer's disease.

    PubMed

    Little, J T; Satlin, A; Sunderland, T; Volicer, L

    1995-04-01

    A retrospective review of 71 patients with probable Alzheimer's disease was analyzed with respect to nursing evaluations of sundowning status (recurring confusion or agitation in the late afternoon or early evening). The prevalence of sundowning (including probable sundowners) was 24%. Sundowners and non-sundowners differed with regard to number of sedatives received daily, particularly chloral hydrate, and the number of days on the inpatient unit. There were no differences between sundowners and non-sundowners with respect to other types of medications, medical diagnoses, current age, age of onset of Alzheimer's disease, or Mini-Mental State Exam. Restlessness was the most common sundowning behavior, although multiple behavioral disturbances were seen. This survey suggests that the sundown syndrome is a common problem in severely demented Alzheimer's patients and requires further study.

  20. 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…

  1. 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…

  2. 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…

  3. Investigational medications for treatment of patients with Alzheimer disease.

    PubMed

    Potter, Pamela E

    2010-09-01

    Development of effective treatments for patients with Alzheimer disease has been challenging. Currently approved treatments include acetylcholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine hydrochloride. To investigate treatments in development for patients with Alzheimer disease, the author conducted a review of the literature. New approaches for treatment or prevention focus on several general areas, including cholinergic receptor agonists, drugs to decrease β-amyloid and tau levels, antiinflammatory agents, drugs to increase nitric oxide and cyclic guanosine monophosphate levels, and substances to reduce cell death or promote cellular regeneration. The author focuses on medications currently in clinical trials. Cholinergic agents include orthostatic and allosteric muscarinic M1 agonists and nicotinic receptor agonists. Investigational agents that target β-amyloid include vaccines, antibodies, and inhibitors of β-amyloid production. Anti-inflammatory agents, including nonsteroidal anti-inflammatory drugs, the natural product curcumin, and the tumor necrosis factor α inhibitor etanercept, have also been studied. Some drugs currently approved for other uses may also show promise for treatment of patients with Alzheimer disease. Results of clinical trials with many of these investigational drugs have been disappointing, perhaps because of their use with patients in advanced stages of Alzheimer disease. Effective treatment may need to begin earlier-before neurodegeneration becomes severe enough for symptoms to appear.

  4. Memantine-associated hyperkalaemia in a patient with Alzheimer's disease.

    PubMed

    Tsukamoto, Tatsuo; Yamada, Hidetaka; Uchimura, Naohisa

    2013-09-01

    Memantine is an N-methyl-D-aspartate glutamate receptor antagonist that may improve cognitive functions in patients with Alzheimer's disease. It is predominantly excreted unchanged via the kidneys, and patients with decreased creatinine clearance must be treated with lower doses of memantine. However, it is unclear whether memantine itself can lead to renal dysfunction and/or hyperkalaemia. We report a patient with renal impairment and hyperkalaemia possibly associated with memantine administration.

  5. [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.

  6. 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

  7. Rapidly progressive Alzheimer disease.

    PubMed

    Schmidt, Christian; Wolff, Martin; Weitz, Michael; Bartlau, Thomas; Korth, Carsten; Zerr, Inga

    2011-09-01

    Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years. This short review aims to provide an overview of the current knowledge of rapidly progressive Alzheimer disease. Furthermore, we suggest that rapid, in this context, should be defined as a Mini-Mental State Examination score decrease of 6 points per year.

  8. 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.

  9. Memantine-induced Myoclonus in a Patient with Alzheimer Disease

    PubMed Central

    Murgai, Aditya A.; LeDoux, Mark S.

    2015-01-01

    Background Myoclonus can be a clinical manifestation of numerous neurodegenerative disorders and an adverse drug reaction to medications used in their treatment. Case Report Herein, we report memantine-induced myoclonus in a patient with Alzheimer disease. The myoclonus seen in our patient was generalized (proximal limbs and trunk), present at rest and with action, and stimulus sensitive. A structured evaluation with the Unified Myoclonus Rating Scale showed that the myoclonus had no significant effect on functional capacity. After discontinuation of memantine, myoclonus slowly resolved over the course of several weeks. Discussion Memantine may cause myoclonus in susceptible individuals. PMID:26317045

  10. 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 ...

  11. Circulating plasmalogen levels and Alzheimer Disease Assessment Scale–Cognitive scores in Alzheimer patients

    PubMed Central

    Wood, Paul L.; Mankidy, Rishikesh; Ritchie, Shawn; Heath, Doug; Wood, Julie A.; Flax, John; Goodenowe, Dayan B.

    2010-01-01

    Background Plasmalogens, which are key structural phospholipids in brain membranes, are decreased in the brain and serum of patients with Alzheimer disease (AD). We performed this pilot study to evaluate the relation between the levels of circulating plasmalogens and Alzheimer Disease Assessment Scale–Cognitive (ADAS-Cog) scores in patients with AD. Methods We evaluated participants’ ADAS-Cog scores and serum plasmalogen levels. For the 40 included AD patients with an ADAS-Cog score between 20 and 46, we retested their ADAS-Cog score 1 year later. The levels of docosahexaenoic acid plasmalogen were measured by use of liquid chromatography–tandem mass spectrometry. Results We found that the ADAS-Cog score increased significantly in AD patients with circulating plasmalogen levels that were ≤ 75% of that of age-matched controls at entry into the study. There was no change in score among participants with normal serum plasmalogen levels at baseline (> 75%). Limitations This was a pilot study with 40 patients, and the results require validation in a larger population. Conclusion Our study demonstrates that decreased levels of plasmalogen precursors in the central nervous system correlate with functional decline (as measured by ADAS-Cog scores) in AD patients. The use of both ADAS-Cog and serum plasmalogen data may be a more accurate way of predicting cognitive decline in AD patients, and may be used to decrease the risk of including patients with no cognitive decline in the placebo arm of a drug trial. PMID:20040248

  12. Cerebrospinal fluid levels of insulin in patients with Alzheimer's disease.

    PubMed

    Molina, J A; Jiménez-Jiménez, F J; Vargas, C; Gómez, P; de Bustos, F; Gómez-Escalonilla, C; Zurdo, M; Tallón, A; Martínez-Salio, A; Porta-Etessam, J; Villanueva, C; Arenas, J

    2002-12-01

    Some previous reports suggested a potential role of insulin in memory and in the pathophysiology of Alzheimer's disease (AD). We assessed the cerebrospinal fluid (CSF) levels of insulin in patients with AD and in age and sex-matched controls trying to elucidate whether this value could be related with the risk or severity of AD. We measured the CSF insulin levels in 27 patients with AD and 16 matched controls using a RadioImmunoanalysis method. CSF insulin levels did not differ significantly between AD-patient and control groups. These values were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination in the AD group. These results suggest that CSF insulin concentrations are not related with the risk or severity of AD. Copyright Blackwell Munksgaard 2002

  13. Cognitive performance on Piagetian tasks by Alzheimer's disease patients.

    PubMed

    Thornbury, J M

    1992-02-01

    The purpose of this study was to examine cognitive abilities in Alzheimer's disease (AD) patients using Piaget's child developmental theory. Thirty elderly AD patients and 30 elderly control subjects were given two traditional Piagetian measures, the Infant Psychological Development Scale and the Concrete Operations Test. Half of the AD subjects (15) were in Piaget's sensorimotor or preoperational stages, while the remaining half of the AD subjects and all elderly control subjects were in Piaget's concrete operational stage, chi 2 [1, N = 60] = 17.42, p less than .001. If subsequent studies confirm that AD patients' cognitive characteristics are similar to Piaget's theoretical model, nursing care might be individualized based on mental competence, thus minimizing the commonly observed caregiver overestimation and underestimation of the AD patient's ability to understand and cooperate.

  14. 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

  15. Alzheimer's disease.

    PubMed

    De-Paula, Vanessa J; Radanovic, Marcia; Diniz, Breno S; Forlenza, Orestes V

    2012-01-01

    Alzheimer's disease (AD) is a chronic neurodegenerative disease with well-defined pathophysiological mechanisms, mostly affecting medial temporal lobe and associative neocortical structures. Neuritic plaques and neurofibrillary tangles represent the pathological hallmarks of AD, and are respectively related to the accumulation of the amyloid-beta peptide (Aβ) in brain tissues, and to cytoskeletal changes that arise from the hyperphosphorylation of microtubule-associated Tau protein in neurons. According to the amyloid hypothesis of AD, the overproduction of Aβ is a consequence of the disruption of homeostatic processes that regulate the proteolytic cleavage of the amyloid precursor protein (APP). Genetic, age-related and environmental factors contribute to a metabolic shift favoring the amyloidogenic processing of APP in detriment of the physiological, secretory pathway. Aβ peptides are generated by the successive cleavage of APP by beta-secretase (BACE-1) and gamma-secretase, which has been recently characterized as part of the presenilin complex. Among several beta-amyloid isoforms that bear subtle differences depending on the number of C-terminal amino acids, Aβ (1-42) plays a pivotal role in the pathogenesis of AD. The neurotoxic potential of the Aβ peptide results from its biochemical properties that favor aggregation into insoluble oligomers and protofibrils. These further originate fibrillary Aβ species that accumulate into senile and neuritic plaques. These processes, along with a reduction of Aβ clearance from the brain, leads to the extracellular accumulation of Aβ, and the subsequent activation of neurotoxic cascades that ultimately lead to cytoskeletal changes, neuronal dysfunction and cellular death. Intracerebral amyloidosis develops in AD patients in an age-dependent manner, but recent evidence indicate that it may be observed in some subjects as early as in the third or fourth decades of life, with increasing magnitude in late middle age

  16. Profiling of Alzheimer's disease patients in Puerto Rico: A comparison of two distinct socioeconomic areas.

    PubMed

    Camacho-Mercado, Clara L; Figueroa, Raúl; Acosta, Heriberto; Arnold, Steven E; Vega, Irving E

    2016-01-01

    The Latino/Hispanic community in the United States is at higher risk of developing Alzheimer's disease than other ethnic groups. Specifically, Caribbean Hispanics showed a more severe Alzheimer's disease symptomatology than any other ethnic group. In a previous study, we demonstrated that the mortality rate associated with Alzheimer's disease in Puerto Rico is higher than that reported in the United States. Moreover, the mortality rate associated with Alzheimer's disease was higher among Puerto Rican living in Puerto Rico than those in the mainland United States. There is also a differential geographical distribution of mortality rate associated with Alzheimer's disease in Puerto Rico, which may be associated with differential socioeconomic status and/or access to healthcare. However, there is no information regarding the clinical profile of Alzheimer's disease patients in Puerto Rico. Here, we present the results of a retrospective study directed to profile Alzheimer's disease patients clustered into two groups based on areas previously determined with low (Metro Region) and high (Northwest-Central Region) mortality rate associated with Alzheimer's disease in Puerto Rico. Significant difference in the age-at-diagnosis and years of education was found among patients within the two studied regions. Despite these differences, both regions showed comparable levels of initial and last Mini Mental State Examination scores and rate of cognitive decline. Significant difference was also observed in the occurance of co-morbidities associated with Alzheimer's disease. The differential profile of Alzheimer's disease patients correlated with differences in socioeconomic status between these two regions, suggesting that covariant associated with social status may contribute to increased risk of developing Alzheimer's disease. Further studies should be conducted to determine the role of socioeconomic factors and healthy living practices as risk factors for Alzheimer's disease.

  17. Effect of aromatherapy on patients with Alzheimer's disease.

    PubMed

    Jimbo, Daiki; Kimura, Yuki; Taniguchi, Miyako; Inoue, Masashi; Urakami, Katsuya

    2009-12-01

    Recently, the importance of non-pharmacological therapies for dementia has come to the fore. In the present study, we examined the curative effects of aromatherapy in dementia in 28 elderly people, 17 of whom had Alzheimer's disease (AD). After a control period of 28 days, aromatherapy was performed over the following 28 days, with a wash out period of another 28 days. Aromatherapy consisted of the use of rosemary and lemon essential oils in the morning, and lavender and orange in the evening. To determine the effects of aromatherapy, patients were evaluated using the Japanese version of the Gottfries, Brane, Steen scale (GBSS-J), Functional Assessment Staging of Alzheimer's disease (FAST), a revised version of Hasegawa's Dementia Scale (HDS-R), and the Touch Panel-type Dementia Assessment Scale (TDAS) four times: before the control period, after the control period, after aromatherapy, and after the washout period. All patients showed significant improvement in personal orientation related to cognitive function on both the GBSS-J and TDAS after therapy. In particular, patients with AD showed significant improvement in total TDAS scores. Result of routine laboratory tests showed no significant changes, suggesting that there were no side-effects associated with the use of aromatherapy. Results from Zarit's score showed no significant changes, suggesting that caregivers had no effect on the improved patient scores seen in the other tests. In conclusion, we found aromatherapy an efficacious non-pharmacological therapy for dementia. Aromatherapy may have some potential for improving cognitive function, especially in AD patients.

  18. Diagnosis and treatment of patients with severe Alzheimer's disease.

    PubMed

    Voisin, Thierry; Vellas, Bruno

    2009-01-01

    In contrast with the earlier stages and, in particular, the predementia stage, of Alzheimer's disease (AD), severe dementia is often neglected. However, the advanced stages of dementia are just as important as the earlier stages because of their frequency, their impact on the lives of patients and their caregivers, and their economic consequences. All patients with moderately severe to severe dementia must be evaluated for cognitive, functional, psychological and behavioural symptoms. Thorough and regular evaluation of patients in the advanced stages of the disease has the following objectives: improving patients' quality of life by encouraging use of their remaining capacities; setting up or modifying a care plan; playing a role in the follow-up of measures instituted; and documenting the natural history of the disease. Therapeutic trials with cholinesterase inhibitors and memantine have been conducted in patients with severe stages of AD. As a consequence, memantine has been approved by numerous drug agencies and donepezil has been approved by the US FDA for use in severe stages of the disease. However, it is important to note that at this stage of AD, and perhaps more than in any other, management must be global and multidisciplinary because of the expression of the disease, its complications and intercurrent disorders. Indeed, thorough knowledge by health professionals of the expression of all disease disorders and intercurrent disorders, and of their significance during the severe stage of AD, is important in the management of these patients to limit complications and facilitate prompt establishment of appropriate care. More effort is needed in both clinical and research settings to ensure that patients with severe AD and their relatives can be offered optimal management.

  19. Finger agnosia and cognitive deficits in patients with Alzheimer's disease.

    PubMed

    Davis, Andrew S; Trotter, Jeffrey S; Hertza, Jeremy; Bell, Christopher D; Dean, Raymond S

    2012-01-01

    The purpose of this study was to examine the presence of finger agnosia in patients with Alzheimer's disease (AD) and to determine if level of finger agnosia was related to cognitive impairment. Finger agnosia is a sensitive measure of cerebral impairment and is associated with neurofunctional areas implicated in AD. Using a standardized and norm-referenced approach, results indicated that patients with AD evidenced significantly decreased performance on tests of bilateral finger agnosia compared with healthy age-matched controls. Finger agnosia was predictive of cognitive dysfunction on four of seven domains, including: Crystallized Language, Fluid Processing, Associative Learning, and Processing Speed. Results suggest that measures of finger agnosia, a short and simple test, may be useful in the early detection of AD.

  20. [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.

  1. Serum cytokine levels in patients with Alzheimer's disease.

    PubMed Central

    Chao, C C; Ala, T A; Hu, S; Crossley, K B; Sherman, R E; Peterson, P K; Frey, W H

    1994-01-01

    Alzheimer's disease (AD) has been proposed to be an inflammatory disorder. In a recent study, markedly elevated levels of the anti-inflammatory cytokine transforming growth factor beta (TGF-beta) in the serum and cerebrospinal fluid of patients with advanced AD suggested a potential predictive value of this cytokine in patients with AD. In the present prospective study, we tested the hypothesis that the levels of TGF-beta in serum would be increased in patients with AD and could thereby serve as a diagnostic marker. We found that serum TGF-beta levels but not proinflammatory cytokine levels were significantly (P < 0.05) elevated in patients with AD (n = 22) in comparison with the levels in their healthy spousal controls. Also, serum TGF-beta levels were positively correlated (r = 0.45; P < 0.05) with disease severity. Nevertheless, the elevation in serum TGF-beta levels in patients with Ad was modest, and considerable overlap with the control values suggests that the diagnostic usefulness of this cytokine for AD is limited. PMID:8556481

  2. 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

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

    PubMed

    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.

  4. Emotional arousal enhances declarative memory in patients with Alzheimer's disease.

    PubMed

    Satler, C; Garrido, L M; Sarmiento, E P; Leme, S; Conde, C; Tomaz, C

    2007-12-01

    To verify whether the long-term retention of an emotionally arousing story is stronger than the retention of a neutral story, and the enhancing effects of emotional arousal on declarative memory in Alzheimer's disease (AD) patients. Twenty subjects (10 with AD and 10 controls matched for age and educational level) were studied. After the audiovisual presentation (neutral story), the subjects rated the narrative's emotionality. Later, they answered a multiple-choice questionnaire about the stories. Two weeks later, they watched the emotionally arousing story. Subjects who watched the emotionally arousing story assigned a score of emotionality higher than the subjects in the neutral group (P = 0.023). In addition, the participants remembered more details of the arousing story, and had a higher score in the questionnaire (P < 0.001). We demonstrated that an emotionally arousing content enhances long-term declarative memory in AD. Furthermore, present finding supports the use of this instrument for clinical and research purposes.

  5. Cerebrospinal fluid levels of selenium in patients with Alzheimer's disease.

    PubMed

    Meseguer, I; Molina, J A; Jiménez-Jiménez, F J; Aguilar, M V; Mateos-Vega, C J; González-Muñoz, M J; de Bustos, F; Ortí-Pareja, M; Zurdo, M; Berbel, A; Barrios, E; Martínez-Para, M C

    1999-01-01

    We compared CSF and serum selenium levels, measured by atomic absorption spectrophotometry, in 27 patients with Alzheimer's disease (AD) (13 females, 14 males, mean +/- SD age 73.6 +/- 7.4 years) without major clinical signs of undernutrition, and 34 matched controls (18 females, 16 males, mean +/- SD age 70.7 +/- 7.8 years). CSF and serum selenium levels did not differ significantly between AD-patient (11.4 +/- 7.8 ng/ml and 28.5 +/- 13.0 ng/ml, respectively) and control groups (13.3 +/- 7.0 ng/ml and 22.5 +/- 17.5 ng/ml). These values were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination in the AD group. Weight and body mass index were significantly lower in AD patients than in controls. These results suggest that CSF selenium concentrations are apparently unrelated with the reported oxidative stress processes in patients with AD.

  6. The minute hand phenomenon in the Clock Test of patients with early Alzheimer disease.

    PubMed

    Leyhe, Thomas; Milian, Monika; Müller, Stephan; Eschweiler, Gerhard W; Saur, Ralf

    2009-06-01

    Common scoring systems for the Clock Test do not sufficiently emphasize the correct time representation by the clock hands. We compared Clock Drawing, Clock Setting, and Clock Reading in healthy control persons, patients with mild cognitive impairment, early Alzheimer disease and progressed Alzheimer disease particularly analyzing clock time representation. We found that healthy control persons and participants with mild cognitive impairment did not show any impairment in Clock Test performance. Patients with early Alzheimer disease could be discriminated from healthy control persons and participants with mild cognitive impairment solely by misplacement of the minute hand in Clock Drawing and Clock Setting. The progressed Alzheimer disease group showed significantly more impairments in all Clock Test variants. It is assumed that early stage Alzheimer disease patient deficits in Clock Tests are mainly determined by a reduced access to semantic memory about the appearance and functionality of a clock.

  7. Implications of comorbidity on costs for patients with Alzheimer disease.

    PubMed

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

    2008-08-01

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

  8. Polymicrobial Infections In Brain Tissue From Alzheimer's Disease Patients.

    PubMed

    Pisa, Diana; Alonso, Ruth; Fernández-Fernández, Ana M; Rábano, Alberto; Carrasco, Luis

    2017-07-17

    Several studies have advanced the idea that the etiology of Alzheimer's disease (AD) could be microbial in origin. In the present study, we tested the possibility that polymicrobial infections exist in tissue from the entorhinal cortex/hippocampus region of patients with AD using immunohistochemistry (confocal laser scanning microscopy) and highly sensitive (nested) PCR. We found no evidence for expression of early (ICP0) or late (ICP5) proteins of herpes simplex virus type 1 (HSV-1) in brain sections. A polyclonal antibody against Borrelia detected structures that appeared not related to spirochetes, but rather to fungi. These structures were not found with a monoclonal antibody. Also, Borrelia DNA was undetectable by nested PCR in the ten patients analyzed. By contrast, two independent Chlamydophila antibodies revealed several structures that resembled fungal cells and hyphae, and prokaryotic cells, but most probably were unrelated to Chlamydophila spp. Finally, several structures that could belong to fungi or prokaryotes were detected using peptidoglycan and Clostridium antibodies, and PCR analysis revealed the presence of several bacteria in frozen brain tissue from AD patients. Thus, our results show that polymicrobial infections consisting of fungi and bacteria can be revealed in brain tissue from AD patients.

  9. CSF tau levels influence cortical plasticity in Alzheimer's disease patients.

    PubMed

    Koch, Giacomo; Esposito, Zaira; Kusayanagi, Hajime; Monteleone, Fabrizia; Codecá, Claudia; Di Lorenzo, Francesco; Caltagirone, Carlo; Bernardi, Giorgio; Martorana, Alessandro

    2011-01-01

    Alzheimer's disease (AD) is a neurodegenerative process characterized by progressive neuronal degeneration, reduced levels of neurotransmitters, and altered forms of synaptic plasticity. In animal models of AD, amyloid-β (Aβ) and tau proteins are supposed to interfere with synaptic transmission. In the current study, we investigated the correlation between motor cortical plasticity, measured with 1 Hz repetitive transcranial magnetic stimulation (rTMS), and the levels of Aβ₁₋₄₂, total tau (t-Tau), and phosphorylated tau (p-Tau) detected in cerebrospinal fluid (CSF) of AD patients. We found that the overall rTMS after effects were milder in AD patients in comparison with controls. In AD patients the amount of rTMS-induced inhibition correlated with CSF t-Tau, but not with Aβ₁₋₄₂ CSF levels. Surprisingly, higher CSF t-Tau levels were associated to a stronger inhibition of the motor evoked potentials, implying that the expected effects of the 1 Hz rTMS protocol were more evident in patients with more pathological t-Tau CSF levels. These data could be interpreted as the consequence of CSF t-Tau mediated abnormal excitatory activity and could suggest that CSF t-Tau may impact mechanisms of cortical plasticity.

  10. Factors associated with caregiver burden in patients with Alzheimer's disease.

    PubMed

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

    2014-04-01

    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. 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. 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. Therefore, interventions to help maintain activities of daily living in patients with AD may alleviate caregiver burden and improve caregiver well-being.

  11. Alzheimer Disease

    PubMed Central

    Apostolova, Liana G.

    2016-01-01

    ABSTRACT Purpose of Review: This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD). Recent Findings: In recent years, significant advances have been made in the fields of genetics, neuroimaging, clinical diagnosis, and staging of AD. One of the most important recent advances in AD is our ability to visualize amyloid pathology in the living human brain. The newly revised criteria for diagnosis of AD dementia embrace the use for biomarkers as supportive evidence for the underlying pathology. Guidelines for the responsible use of amyloid positron emission tomography (PET) have been developed, and the clinical and economic implications of amyloid PET imaging are actively being explored. Summary: Our improved understanding of the clinical onset, progression, neuroimaging, pathologic features, genetics, and other risk factors for AD impacts the approaches to clinical diagnosis and future therapeutic interventions. PMID:27042902

  12. Alzheimer Disease.

    PubMed

    Apostolova, Liana G

    2016-04-01

    This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD). In recent years, significant advances have been made in the fields of genetics, neuroimaging, clinical diagnosis, and staging of AD. One of the most important recent advances in AD is our ability to visualize amyloid pathology in the living human brain. The newly revised criteria for diagnosis of AD dementia embrace the use for biomarkers as supportive evidence for the underlying pathology. Guidelines for the responsible use of amyloid positron emission tomography (PET) have been developed, and the clinical and economic implications of amyloid PET imaging are actively being explored. Our improved understanding of the clinical onset, progression, neuroimaging, pathologic features, genetics, and other risk factors for AD impacts the approaches to clinical diagnosis and future therapeutic interventions.

  13. Nutritional status of selenium in Alzheimer's disease patients.

    PubMed

    Cardoso, Bárbara Rita; Ong, Thomas Prates; Jacob-Filho, Wilson; Jaluul, Omar; Freitas, Maria Isabel d'Avila; Cozzolino, Silvia M Franciscato

    2010-03-01

    Studies have shown that various antioxidants are decreased in different age-related degenerative diseases and thus, oxidative stress would have a central role in the pathogenesis of many disorders that involve neuronal degeneration, including Alzheimer's disease (AD). The present study aimed to assess the nutritional status of Se in AD patients and to compare with control subjects with normal cognitive function. The case-control study was carried out on a group of elderly with AD (n 28) and compared with a control group (n 29), both aged between 60 and 89 years. Se intake was evaluated by using a 3-d dietary food record. Se was evaluated in plasma, erythrocytes and nails by using the method of hydride generation atomic absorption spectroscopy. Deficient Se intake was largely observed in the AD group. AD patients showed significantly lower Se levels in plasma, erythrocytes and nails (32.59 microg/l, 43.74 microg/l and 0.302 microg/g) when compared with the control group (50.99 microg/l, 79.16 microg/l and 0.400 microg/g). The results allowed us to suggest that AD has an important relation with Se deficiency.

  14. Neuropathology of parkinsonism in patients with pure Alzheimer's disease.

    PubMed

    Horvath, Judit; Burkhard, Pierre R; Herrmann, François R; Bouras, Constantin; Kövari, Enikö

    2014-01-01

    About one third of Alzheimer's disease (AD) patients develop some parkinsonian features, yet half of them do not have Lewy body pathology at autopsy. The neuropathological substrate of parkinsonism in AD is still unclear. In the present study, we measured neuronal and neurofibrillary tangles (NFTs) densities in the substantia nigra pars compacta (SN) and in the putamen of 22 AD patients, 11 with and 11 without parkinsonism, here defined as the presence of bradykinesia and at least one of resting tremor, rigidity, or gait disorders. Our study showed that parkinsonism associated with AD was related to a significant loss of neurons both in the SN and in the putamen, suggesting pre-and postsynaptic alterations of the nigrostriatal pathway. Neuronal tau deposition was a less important factor as density of NFTs correlated with parkinsonism only in the SN but not in the putamen. We propose that a subgroup of pure AD patients develop parkinsonian symptoms as a result of neuronal loss in the basal ganglia, indicating a prominent subcortical involvement, which appears unrelated to the Braak stage of AD.

  15. Gait and balance impairments in Alzheimer disease patients.

    PubMed

    Mazoteras Muñoz, Virginia; Abellan van Kan, Gabor; Cantet, Christelle; Cortes, Frederic; Ousset, Pierre-Jean; Rolland, Yves; Vellas, Bruno

    2010-01-01

    To describe the characteristics and associated factors of Alzheimer disease (AD) patients with balance and gait impairments. Balance and gait impairments were assessed in 380 AD patients using the Tinetti test. A total of 120 (31.5%) patients had an abnormal Tinetti test, 96 (25.2%) had balance impairments, and 72 (18.9%) patients presented gait impairments. Global Tinetti score was associated with age [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.05-1.14], Mini-Mental State Examination (MMSE) score (OR, 0.94; 95% CI, 0.90-0.99), activities of daily living (ADL) score (OR, 0.62; 95% CI, 0.47-0.83), and being man (OR, 0.44; 95% CI, 0.25-0.78). Balance impairment was associated with age (OR, 1.11; 95% CI, 1.05-1.17), ADL score (OR, 0.60; 95% CI, 0.43-0.84), and being female (OR, 0.19; 95% CI, 0.08-0.49). Gait impairment was associated with age (OR, 1.09; 95% CI, 1.03-1.15), MMSE score (OR, 0.92; 95% CI, 0.87-0.98), ADL score (OR, 0.63; 95% CI, 0.46-0.87), body mass index (OR, 1.10; 95% CI, 1.01-1.18), presence of comorbidities (OR, 2.13; 95% CI, 1.14-3.96), and the Cornell score (OR, 2.97; 95% CI, 1.12-7.89). AD patients are frequently concerned with balance and gait impairments. These impairments were associated to factors related to the severity of the disease (low MMSE and low ADL); nonmodifiable factors such as age or sex; and modifiable factors such as depression, obesity, and presence of comorbidities.

  16. Circadian rhythms of agitation in institutionalized patients with Alzheimer's disease.

    PubMed

    Martin, J; Marler, M; Shochat, T; Ancoli-Israel, S

    2000-05-01

    Agitation is a common problem in institutionalized patients with Alzheimer's disease (AD). "Sundowning," or agitation that occurs primarily in the evening, is estimated to occur in 10-25% of nursing home patients. The current study examined circadian patterns of agitation in 85 patients with AD living in nursing homes in the San Diego, California, area. Agitation was assessed using behavioral ratings collected every 15 minutes over 3 days, and activity and light exposure data were collected continuously using Actillume recorders. A five-parameter extension of the traditional cosine function was used to describe the circadian rhythms. The mean acrophase for agitation was 14:38, although there was considerable variability in the agitation rhythms displayed by the patients. Agitation rhythms were more robust than activity rhythms. Surprisingly, only 2 patients (2.4%) were "sundowners." In general, patients were exposed to very low levels of illumination, with higher illumination during the night being associated with less robust agitation rhythms with higher rhythm minima (i.e., some agitation present throughout the day and night). Seasonality was examined; however, there were no consistent seasonal patterns found. This is the largest study to date to examine agitation rhythms using behavioral observations over multiple 24 h periods. The results suggest that, although sundowning is uncommon, agitation appears to have a strong circadian component in most patients that is related to light exposure, sleep, and medication use. Further research into the understanding of agitation rhythms is needed to examine the potential effects of interventions targeting sleep and circadian rhythms.

  17. Donepezil treatment in ethnically diverse patients with Alzheimer disease.

    PubMed

    Tinklenberg, Jared R; Kraemer, Helena C; Yaffe, Kristine; O'Hara, Ruth; Ringman, John M; Ashford, John W; Yesavage, Jerome A; Taylor, Joy L

    2015-04-01

    To compare the outcome of donepezil treatment in ethnically diverse Alzheimer disease (AD) patients with ethnically diverse AD patients who did not receive donepezil. Patients meeting NINCDS-ADRA criteria for probable or possible AD from a consortium of California sites were systematically followed for at least 1 year in this prospective, observational study. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria. Patients self-identified their ethnicity. The 64 ethnically diverse AD patients who completed the study and received donepezil treatment had an average 1-year decline of 2.30 points (standard deviation: 3.9) on the 30-point Mini-Mental State Exam compared with a 1.70-point (standard deviation: 4.2) decline in the 74 ethnically diverse completers who received no donepezil or other anti-AD drugs during the study period. This difference was not statistically significant. The overall Cohen effect size of this treatment-associated difference was estimated at -0.15. After using propensity analyses and other techniques to assess factors that could bias prescribing decisions, the lack of benefits associated with donepezil treatment remained. The lack of donepezil benefits also remained when more traditional analyses were applied to these data. Ethnically diverse AD patients in this study apparently did not benefit from 1 year of donepezil treatment. These unpromising results are in contrast to modest benefits of donepezil treatment measured in a directly comparable California study involving white non-Latino AD patients. Published by Elsevier Inc.

  18. 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.

  19. 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. Published by Elsevier Ltd.

  20. Antibodies against phosphorylcholine are not altered in plasma of patients with Alzheimer's disease.

    PubMed

    Silajdžić, Edina; Björkqvist, Maria; Hansson, Oskar

    2015-02-05

    Phosphorylcholine is one of the major epitopes of oxidised low density lipoprotein. Low levels of IgM antibodies against phosphorylcholine (anti-PC) are associated with development of myocardial infarction and stroke. It has been shown that patients with Alzheimer's disease and other dementias have significantly lower serum anti-PC levels compared to controls, suggesting that low levels of atheroprotective anti-PC may play a role in AD and dementia. We quantified levels of anti-PC levels using an ELISA in plasma from 176 controls, 125 patients with Alzheimer's disease, 19 patients with vascular dementia and 63 patients with other dementias. We observed similar plasma anti-PC levels in controls, patients with Alzheimer's disease, and other dementias. Our data suggests that anti-PC is not useful as a biomarker for Alzheimer's disease.

  1. Sentence comprehension in Slovak-speaking patients with Alzheimer's disease.

    PubMed

    Marková, Jana; Horváthová, Ľubica; Králová, Mária; Cséfalvay, Zsolt

    2017-07-01

    According to some studies, sentence comprehension is diminished in Alzheimer's disease (AD) patients, but they differ on what underlies the sentence comprehension impairment. Sentence comprehension in AD patients has been studied mainly in the English language. It is less clear how patients with AD speaking a morphologically rich language with grammatical morphemes indicating case and through it even thematic roles process reversible sentences. To compare the comprehension of various syntactic constructions in Slovak-speaking AD patients and cognitively intact elderly people. We were concerned with the influence of the following aspects on sentence comprehension: its length, the order of thematic roles and the presence of a morphological cue placed on the first noun (or at the beginning of a sentence). We used our own Slovak test of sentence comprehension based on matching pictures to spoken sentences. These sentences contain transitive verbs and two nouns (person/animal), one functioning as a subject and the other as an object, which both can perform the action expressed by the verb. We assessed 62 healthy elderly people and two groups of AD patients. The first group consisted of 34 participants with a mild degree of AD and the other group of 43 participants with a moderate degree of AD. Statistical comparisons showed that the elderly controls were significantly better in the comprehension of simple active OVS (object-verb-subject word order) sentences and complex EO sentences (a centre-embedded relative clause with a relative pronoun substituting for an object) than patients with a mild degree of AD. In patients with a moderate degree of AD, comprehension of all tested sentence types was worse than in healthy elderly people. The results also indicated that even mild AD patients have more serious problems with processing sentences with non-canonical order of thematic roles regardless of a morphological cue at the beginning of a sentence. The results point to

  2. 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.

  3. 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.

  4. Proper names in patients with early Alzheimer's disease.

    PubMed

    Semenza, C; Mondini, S; Borgo, F; Pasini, M; Sgaramella, M T

    2003-01-01

    The objective of this study was to seek evidence of the particular sensitivity of proper name retrieval and to check the usefulness of proper names as diagnostic material in the early stages of Alzheimer's disease (AD). Whether a generalized naming deficit is an early symptom of AD it is not yet clear. Previous studies suggest that proper names might be the category of names that is indeed more sensitive to AD. Seventy AD patients (subdivided into "very mild", "mild" and "moderate") and 47 control subjects participated in the study. The performances in two short distinct tests requiring proper name retrieval (Naming People on Definition and Naming Faces), one test of common name retrieval, short (MMSE, 3MS) and long (MODA) batteries for the detection of dementia were compared. Proper name retrieval tests were shown to be more sensitive to early AD than any other tests and batteries that failed to distinguish "very mild" AD from controls. These findings suggest that proper name retrieval tasks might be profitably included in diagnostic tools for the early diagnosis of AD.

  5. Alzheimer's Disease and Depression.

    ERIC Educational Resources Information Center

    Teri, Linda; Wagner, Amy

    1992-01-01

    Reviews research on depression in Alzheimer's disease (AD). Discusses evidence suggesting that depression affects many AD patients and can have profound effects on patient long-term functioning and caregiver well-being. Notes that field is dominated by studies of prevalence, as opposed to studies of etiology, association with other aspects of…

  6. Alzheimer's Disease and Depression.

    ERIC Educational Resources Information Center

    Teri, Linda; Wagner, Amy

    1992-01-01

    Reviews research on depression in Alzheimer's disease (AD). Discusses evidence suggesting that depression affects many AD patients and can have profound effects on patient long-term functioning and caregiver well-being. Notes that field is dominated by studies of prevalence, as opposed to studies of etiology, association with other aspects of…

  7. Cerebrolysin in Alzheimer's disease.

    PubMed

    Antón Álvarez, X; Fuentes, Patricio

    2011-07-01

    Cerebrolysin is a neuropeptide preparation mimicking the action of endogenous neurotrophic factors. Positive effects of Cerebrolysin on β-amyloid- and tau-related pathologies, neuroinflammation, neurotrophic factors, oxidative stress, excitotoxicity, neurotransmission, brain metabolism, neuroplasticity, neuronal apoptosis and degeneration, neurogenesis and cognition were demonstrated in experimental conditions. These pleiotropic effects of Cerebrolysin on Alzheimer's disease-related pathogenic events are consistent with a neurotrophic-like mode of action, and seems to involve the activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 β intracellular signaling pathway. The clinical efficacy of Cerebrolysin in Alzheimer's disease was evaluated in several randomized, double-blind, clinical trials, showing consistent benefits on global clinical function and cognition, improvements in behavior at high doses, and minor effects on daily living activities in patients with mild to moderate Alzheimer's disease, as well as in subgroups of moderate to moderately severe patients. In addition, the clinical benefits of Cerebrolysin were largely maintained for several months after ending treatment, a finding that supports its discontinuous administration. Cerebrolysin was generally well tolerated and did not induce significant adverse events in Alzheimer's patients. Although long-term studies are needed, the data available suggest that Cerebrolysin is effective as monotherapy and constitutes a promising option for combined therapy in Alzheimer's disease.

  8. 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

  9. Does a positive Pittsburgh Compound B scan in a patient with dementia equal Alzheimer disease?

    PubMed

    Ducharme, Simon; Guiot, Marie-Christine; Nikelski, James; Chertkow, Howard

    2013-07-01

    The clinical role of amyloid brain positron emission tomographic imaging in the diagnosis of Alzheimer disease is currently being formulated. The specificity of a positive amyloid scan is a matter of contention. An 83-year-old Canadian man presented with a 5-year history of predominantly short-term memory loss and functional impairment. Clinical evaluation revealed significant, gradually progressive short-term memory loss in the absence of any history of strokes or other neuropsychiatric symptoms. The patient met clinical criteria for probable Alzheimer disease but had a higher than expected burden of white matter disease on magnetic resonance imaging. A positron emission tomographic Pittsburgh Compound B scan was highly positive in typical Alzheimer disease distribution. The patient died of an intracerebral hemorrhage 6 months after the assessment. Autopsy revealed cerebral amyloid angiopathy in the complete absence of amyloid plaques or neurofibrillary tangles. This patient demonstrates that a positive Pittsburgh Compound B scan in a patient with clinical dementia meeting criteria for probable Alzheimer disease is not proof of an Alzheimer disease pathophysiological process. A positive Pittsburgh Compound B scan in typical Alzheimer disease distribution in a patient with dementia can be secondary to cerebral amyloid angiopathy alone.

  10. Efficacy of music therapy in treatment for the patients with Alzheimer's disease.

    PubMed

    Fukui, H; Arai, A; Toyoshima, K

    2012-01-01

    We report that music therapy is effective in the treatment of Alzheimer's disease. We found that the secretion of 17β-estradiol and testosterone, hormones that are supposed to have preventive effects on Alzheimer's disease, is significantly increased by music therapy. During the sessions, patients with Alzheimer's disease were allowed to listen to music and songs with verbal contact from the therapist. It was found that problematic behaviors such as poriomania (fugue) had decreased. Music therapy has the potential as an alternative treatment for adverse hormone replacement therapy.

  11. Efficacy of Music Therapy in Treatment for the Patients with Alzheimer's Disease

    PubMed Central

    Fukui, H.; Arai, A.; Toyoshima, K.

    2012-01-01

    We report that music therapy is effective in the treatment of Alzheimer's disease. We found that the secretion of 17β-estradiol and testosterone, hormones that are supposed to have preventive effects on Alzheimer's disease, is significantly increased by music therapy. During the sessions, patients with Alzheimer's disease were allowed to listen to music and songs with verbal contact from the therapist. It was found that problematic behaviors such as poriomania (fugue) had decreased. Music therapy has the potential as an alternative treatment for adverse hormone replacement therapy. PMID:23056992

  12. Confirmatory factor analysis of the quality of life in Alzheimer's disease scale in patients with Alzheimer's disease.

    PubMed

    Gómez-Gallego, María; Gomez-García, Juan; Ato-García, Manuel

    2014-01-01

    BACKGROUND/STUDY CONTEXT: Quality of life (QoL) has become an important outcome measure in clinical trials for Alzheimer's disease (AD). The Quality of Life in Alzheimer's Disease (QoL-AD) Scale is widely used for assessing QoL of patients with AD. This research aims to determine the factor structure of the QoL-AD Scale in AD patients. One hundred thirty-nine patients with mild-to-moderate AD were administered the QoL-AD Scale. Based on the model proposed for healthy people, confirmatory factor models were built using modification indices and residual analysis to improve the model fit. Confirmatory factor analysis indicated poor fit for both the initial model and the single-factor model. Two models showed a good fit: a three-factor model (perceived health, perceived environment and perceived functional ability) and a two-factor model (perceived physical health and perceived psychological health). Because no differences in fit were found between both models, the authors proposed the more parsimonious solution as the best model. These results provide evidence supporting the construct validity of the QoL-AD Scale. This instrument seems to measure the perception of two related constructs (behavioral competence and environment) and could be used together with instruments measuring psychological well-being and the perception of health.

  13. Perception of Fechner Illusory Colors in Alzheimer Disease Patients.

    PubMed

    Kaubrys, Gintaras; Bukina, Vera; Bingelytė, Ieva; Taluntis, Vladas

    2016-11-30

    BACKGROUND Alzheimer disease (AD) primarily affects cognition. A variety of visual disorders was established in AD. Fechner illusory colors are produced by a rotating disk with a black and white pattern. The purpose of our research was to explore the perception of illusory colors in AD. MATERIAL AND METHODS W recruited 40 AD patients (MMSE ≥14) and 40 normal controls (CG group) matched by age, education, gender in this prospective, cross-sectional, case-control study. An achromatic Benham's disk attached to a device to control the speed and direction of rotation was used to produce illusory colors. Primary, secondary, and tertiary RGB system colors were used for matching of illusory and physical colors. RESULTS Subjects in the AD group perceived less illusory colors in 5 arcs (p<0.05) of the 8 arcs assessed. The biggest difference was found between AD and CG groups for pure blue (χ²=26.87, p<0.001 clockwise, χ²=22.75, p<0.001 counter-clockwise). Groups did not differ in perception of pure yellow opponent colors (p>0.05). Mixed colors of the blue-yellow axis were perceived less often in AD, but more frequently than pure blue (#0000FF). The sequence of colors on Benham's disk followed a complex pattern, different from the order of physical spectral colors and opponent processes-based colors. CONCLUSIONS AD patients retained reduced perception of illusory colors. The perception of pure blue illusory color is almost absent in AD. The asymmetrical shift to the yellow opponent is observed in AD with red prevailing over green constituent. This may indicate cortical rather than retinal impairment.

  14. [Biomarkers of Alzheimer disease].

    PubMed

    Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

    2014-01-01

    Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

  15. Seizures in an Alzheimer's disease patient as a complication of colonoscopy premedication with meperidine.

    PubMed

    Nagler, Jerry; Hammarth, Patricia M; Poppers, David M

    2008-01-01

    We describe the first reported case of generalized tonic-clonic seizures induced by meperidine premedication for a colonoscopy procedure in a 63-year-old woman with Alzheimer's disease. The active metabolite of meperidine, normeperidine, is postulated to be the precipitating cause of the seizures, although a cholinesterase inhibitor and an N-methyl-D: -aspartate receptor antagonist, both routinely used for treatment of Alzheimer's disease, may have contributed by reducing the seizure threshold. The neuronal changes which occur in Alzheimer's disease can themselves also predispose to seizures. We recommend avoidance of meperidine for all flexible endoscopic procedures on patients with Alzheimer's disease and in any patient with a condition that predisposes to seizures, and suggest the use of alternative opioids.

  16. NEURODEM: assessment of the iatrogenic alert indicator for nursing home patients with Alzheimer's or Alzheimer-like disease.

    PubMed

    Henni, Samir; Damier, Florence Delamarre; Sonnic, Anne; Feinard, Gwennaelle; Veyrac, Gwennäelle; Pujol, Jean-Francois; de Decker, Laure; Berrut, Gilles; Piessard, Sylvie

    2016-10-01

    Neuroleptics are known to induce Parkinsonism, tardive dyskinesia and their long-term use was associated with increased risk of hip fractures and impaired cognitive function and even death. The primary objective of Neurodem study was to determine the IAI of patients with Alzheimer's disease in French NH. 1022 patients were enrolled. The IAI was 24.8 %. Multivariate logistic analysis showed that having a severe form of dementia, resident without MMS evaluation the last 12 months and having a prescription for an anxiolytic drug were associated with a higher risk of having a prescription for an antipsychotic drug. The results from our study show that the percentage of patients receiving an antipsychotic drug (24.8 %) was higher than the national average (18 %). Effective educational activities about appropriate use of antipsychotic drugs in patients with Alzheimer's disease are needed.

  17. Inflammatory signaling in Alzheimer disease and depression.

    PubMed

    Barber, Robert

    2011-08-01

    To help define the relationships among inflammation, Alzheimer disease, and depression, the Texas Alzheimer's Research Consortium analyzed an array of inflammatory biomarkers in a cohort of patients with Alzheimer disease and in controls. Inflammation severity was highly correlated with earlier age at onset of Alzheimer disease and was also associated with cognitive decline. The relationship between inflammation and depression was not as clear, and it varied with aspects of depression, gender, and the presence of Alzheimer disease.

  18. 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.…

  19. 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.…

  20. Modern care for patients with Alzheimer disease: rationale for early intervention.

    PubMed

    Galluzzi, Katherine E; Appelt, Denah M; Balin, Brian J

    2010-09-01

    More than 5 million people in the United States are afflicted with Alzheimer disease, a condition that is the seventh leading cause of death in the nation. Lacking definitive disease-modifying treatments, modern care for individuals with Alzheimer disease is necessarily multimodal, combining the use of approved pharmaceutic agents (ie, acetylcholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists, antipsychotics), lifestyle and behavioral interventions, and components of palliative care. Some promising experimental treatments are undergoing clinical trials, including immunotherapy to prevent the deposition of β-amyloid, a protein implicated as an etiologic factor in the disease. The authors briefly examine the rationale and methods for screening patients for early indications of the onset of Alzheimer disease. They also describe current and potential treatments for patients with this disease.

  1. Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition.

    PubMed

    Goos, Jeroen D C; Kester, M I; Barkhof, Frederik; Klein, Martin; Blankenstein, Marinus A; Scheltens, Philip; van der Flier, Wiesje M

    2009-11-01

    Microbleeds (MBs) are commonly observed in Alzheimer disease. A minority of patients has multiple MBs. We aimed to investigate associations of multiple MBs in Alzheimer disease with clinical and MRI characteristics and cerebrospinal fluid biomarkers. Patients with Alzheimer disease with multiple (>or=8) MBs on T2*-weighted MRI were matched for age, sex, and field strength with patients with Alzheimer disease without MBs on a 1:2 basis. We included 21 patients with multiple MBs (73+/-7 years, 33% female) and 42 patients without MBs (72+/-7 years, 38% female). Mini-Mental State Examination was used to assess dementia severity. Cognitive functions were assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4), global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30) were assessed using visual rating scales. In a subset, apolipoprotein E genotype and cerebrospinal fluid amyloid beta 1-42, total tau and tau phosphorylated at threonine 181 were determined. Patients with multiple MBs performed worse on Mini-Mental State Examination (multiple MB: 17+/-7; no MB: 22+/-4, P<0.05) despite similar disease duration. Atrophy was not related to presence of MBs, but patients with multiple MBs had more white matter hyperintensities (multiple MB: 8.8+/-4.8; no MB: 3.2+/-3.6, P<0.05). Adjusted for age, sex, white matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group additionally performed worse on Visual Association Test object naming and animal fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid beta 1-42 levels (307+/-61) than patients without MBs (505+/-201, P<0.05). Adjusted for the same covariates, total tau, and tau phosphorylated at threonine 181 were higher in the multiple MB group. Microbleeds are associated with the clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting possible involvement of MBs in the pathogenesis of Alzheimer disease.

  2. 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.

  3. The Short-Term Effects of In-Hospital Respite on the Patient with Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Seltzer, Benjamin; And Others

    1988-01-01

    Assessed cognitive and functional status levels of Alzheimer's disease patients prior to admission to two-week in-hospital respite program and at conclusion of respite. Found that patients with poorest status tended to show improvement on some measures following respite. Patients with higher initial levels of performance tended to show slight…

  4. The Short-Term Effects of In-Hospital Respite on the Patient with Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Seltzer, Benjamin; And Others

    1988-01-01

    Assessed cognitive and functional status levels of Alzheimer's disease patients prior to admission to two-week in-hospital respite program and at conclusion of respite. Found that patients with poorest status tended to show improvement on some measures following respite. Patients with higher initial levels of performance tended to show slight…

  5. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

    PubMed

    Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

    2010-03-01

    White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

  6. Alzheimer's Disease: The Death of the Disease.

    ERIC Educational Resources Information Center

    McBroom, Lynn W.

    1987-01-01

    Alzheimer's disease, a form of dementia in middle-age and older adults is becoming more evident because of growing numbers of older people and better diagnosis and detection methods. Describes the behavioral and physical symptoms of the disease as well as specific suggestions for care of patients with Alzheimer's disease, including dealing with…

  7. Changes in daily cognition and behavior of Alzheimer's patients over time: a three-year evaluation using a daily cognition and behavior for Alzheimer's disease scale.

    PubMed

    Suzuki, Chieko; Yokote, Yoshie; Takahashi, Toru

    2015-01-01

    In Japan, the number of older people with dementia was 2.26 million as of 2010, and Alzheimer's disease accounted for the greatest morbidity rate among older people with dementia. The purposes of this longitudinal study were to assess whether the Daily Cognition and Behavior for Alzheimer's Disease scale might help observe changes in daily cognition and behavior among Alzheimer's disease patients and to determine whether the scale could be used by non-professional caregivers. Data obtained from 111 rater-patient pairs were analysed. The scores for Daily Cognition and Behavior for Alzheimer's Disease used by staff members were compared with those for two other scales designed for professional use. Comparisons were made using one-way repeated-measures ANOVA. The scores for Daily Cognition and Behavior for Alzheimer's Disease indicated a declining pattern similar to those for the other scales. There was no significant difference in scores by rater occupations. Findings suggest Daily Cognition and Behavior for Alzheimer's Disease might help observe changes in daily cognition and behavior among Alzheimer's disease patients, and that Daily Cognition and Behavior for Alzheimer's Disease can be used by non-professional caregivers. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. Diagnostic Significance of Cortical Superficial Siderosis for Alzheimer Disease in Patients with Cognitive Impairment.

    PubMed

    Inoue, Y; Nakajima, M; Uetani, H; Hirai, T; Ueda, M; Kitajima, M; Utsunomiya, D; Watanabe, M; Hashimoto, M; Ikeda, M; Yamashita, Y; Ando, Y

    2016-02-01

    Because the diagnostic significance of cortical superficial siderosis for Alzheimer disease and the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds have been unclear, we investigated the association between cortical superficial siderosis and clinicoradiologic characteristics of patients with cognitive impairment. We studied 347 patients (217 women, 130 men; mean age, 74 ± 9 years) who visited our memory clinic and underwent MR imaging (3T SWI). We analyzed the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds plus clinical characteristics including types of dementia. We used multivariate logistic regression analysis to determine the diagnostic significance of cortical superficial siderosis for Alzheimer disease. Twelve patients (3.5%) manifested cortical superficial siderosis. They were older (P = .026) and had strictly lobar cerebral microbleeds significantly more often than did patients without cortical superficial siderosis (50.0% versus 19.4%, P = .02); the occurrence of strictly deep and mixed cerebral microbleeds, however, did not differ in the 2 groups. Alzheimer disease was diagnosed in 162 (46.7%) patients. Of these, 8 patients (4.9%) had cortical superficial siderosis. In the multivariate logistic regression analysis for the diagnosis of Alzheimer disease, lacunar infarcts were negatively and independently associated with Alzheimer disease (P = .007). Although cortical superficial siderosis was associated with a strictly lobar cerebral microbleed location, it was not independently associated with Alzheimer disease in a memory clinic setting. Additional studies are required to investigate the temporal changes of these cerebral amyloid angiopathy-related MR imaging findings. © 2016 by American Journal of Neuroradiology.

  9. Nutritional and psycho-functional status in elderly patients with Alzheimer's disease.

    PubMed

    Saragat, B; Buffa, R; Mereu, E; Succa, V; Cabras, S; Mereu, R M; Viale, D; Putzu, P F; Marini, E

    2012-03-01

    Analysis of variations of nutritional status in relation to psycho-functional conditions in elderly patients with mild to moderate Alzheimer's disease (AD) by means of bioelectrical impedance vector analysis (BIVA). Cross-sectional study. Alzheimer Center, SS. Trinità Hospital, Cagliari (Italy). 83 free-living patients (29 men, 54 women) with mild-moderate Alzheimer's disease, aged 66 to 96 years, and 91 age-matched controls (37 men and 54 women). Nutritional status was evaluated by anthropometry (weight, height, waist and upper arm circumferences, triceps skinfold; body mass index, BMI; arm muscle area, AMA); Mini Nutritional Assessment, MNA®; bioelectrical impedance vector analysis, BIVA. Psycho-functional status was assessed by the Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL). Compared to the control groups, patients with Alzheimer's disease had a worse psycho-functional and nutritional status. BIVA detected lower body cell mass in Alzheimer's patients with respect to controls (men: T²= 23.4; women: T²=27.3; p<0.01), as well as in the female patients with lower levels of IADL and MMSE (respectively, T²= 8.0; T²=7.4; p<0.05). In patients with AD, a worse psycho-functional status was associated with obesity. The psycho-functional decline of patients with AD is related to body composition variations, with a relative increase of fat mass with respect to the muscle component. The BIVA technique distinguished patients from controls and patients with different levels of cognitive decline. Therefore, it is a suitable tool for the screening and monitoring of nutritional status in Alzheimer's disease.

  10. 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.

  11. Genetics of Alzheimer's Disease

    PubMed Central

    Ridge, Perry G.; Ebbert, Mark T. W.; Kauwe, John S. K.

    2013-01-01

    Alzheimer's disease is the most common form of dementia and is the only top 10 cause of death in the United States that lacks disease-altering treatments. It is a complex disorder with environmental and genetic components. There are two major types of Alzheimer's disease, early onset and the more common late onset. The genetics of early-onset Alzheimer's disease are largely understood with variants in three different genes leading to disease. In contrast, while several common alleles associated with late-onset Alzheimer's disease, including APOE, have been identified using association studies, the genetics of late-onset Alzheimer's disease are not fully understood. Here we review the known genetics of early- and late-onset Alzheimer's disease. PMID:23984328

  12. An Intervention That Delays Institutionalization of Alzheimer's Disease Patients: Treatment of Spouse-Caregivers.

    ERIC Educational Resources Information Center

    Mittelman, Mary S.; And Others

    1993-01-01

    Randomly assigned spouse-caregivers of Alzheimer's disease patients to treatment group (individual and family counseling, support group participation, and ad hoc consultation) or control group (only routine support). Treatment group had less than half as many nursing home placements as control group. Placement also was affected by patient's need…

  13. Caregivers of Alzheimer's Disease and Stroke Patients: Immunological and Psychological Considerations.

    ERIC Educational Resources Information Center

    Reese, Dawn R.; And Others

    1994-01-01

    Examined psychological and immunological changes among 25 caregivers of Alzheimer's disease (AD) patients, 25 caregivers of stroke patients, and 25 noncaregivers. Found that AD caregiving group was more psychologically distressed than stroke group, and both caregiving groups were more psychologically distressed than controls. Found no differences…

  14. An Intervention That Delays Institutionalization of Alzheimer's Disease Patients: Treatment of Spouse-Caregivers.

    ERIC Educational Resources Information Center

    Mittelman, Mary S.; And Others

    1993-01-01

    Randomly assigned spouse-caregivers of Alzheimer's disease patients to treatment group (individual and family counseling, support group participation, and ad hoc consultation) or control group (only routine support). Treatment group had less than half as many nursing home placements as control group. Placement also was affected by patient's need…

  15. Comprehension of metaphors and idioms in patients with Alzheimer's disease: a longitudinal study.

    PubMed

    Papagno, C

    2001-07-01

    Language in patients with Alzheimer's disease has been extensively studied, with the exception of non-literal language comprehension. However, in our speech, we often make use of expressions, which are not necessarily interpreted on a literal ground. Comprehension of metaphors and idioms was examined in 39 patients with probable early Alzheimer's disease. The results showed that the decline of figurative language is not an early symptom of dementia and can occur independently from the impairment of propositional language. It was also found that metaphors and idioms differ as far as the predominant kind of error is concerned.

  16. [Driving and Alzheimer's disease].

    PubMed

    Roche, Jean

    2005-09-01

    Although most aged people remain safe drivers, a greater risk for crashes due to medical conditions is observed in the elderly. Impairment of important functions for safe driving such as visuospatial skills, attention, memory and judgement are observed in dementia, particularly in Alzheimer's disease. The accident rate increases from 9.4 accidents per million vehicle kilometers traveled for 80 to 85 year-old drivers, but raises to 163.6 for drivers with moderate AD. Patients and their families should be informed that patients with mild dementia related to Alzheimer's disease (stage 1 on the Clinical Dementia Rating, CDR), have a substantially increased rate of traffic accidents and therefore should not drive. But subjects in the pre-dementia phase (stage 0.5 at the CDR, mild cognitive impairment) also pose significant driving safety problems. In most States of the USA, and many European countries, but not in France, law requires regular investigating of driving performance in the elderly.

  17. Volumetric analysis of the pons, cerebellum and hippocampi in patients with Alzheimer's disease.

    PubMed

    Mrzilková, Jana; Zach, Petr; Bartoš, Aleš; Tintěra, Jiří; Řípová, Daniela

    2012-01-01

    Our goal was to find out whether a decrease in hippocampal volume in Alzheimer's disease measured via magnetic resonance imaging is accompanied by a similar volume decrease in the pons and cerebellum. We also tried to evaluate whether there are any accompanying hippocampal, pontine and cerebellar asymmetries between the left and right side. We performed a manual volumetric magnetic resonance analysis of the pons, cerebellum and hippocampi in 29 healthy controls and 26 patients with Alzheimer's disease, divided into two groups according to the Mini-Mental State Examination score. We confirmed a known decrease in hippocampal volume in Alzheimer's disease patients but found that there is no similar volume decrease in the pons or cerebellum that could serve as a radiologic diagnostic tool in Alzheimer's disease diagnosis. Also, there was no statistically significant right-left asymmetry in all three measured structures. Only hippocampal volume and not pontine and cerebellar volumes could serve as a magnetic resonance diagnostic tool in Alzheimer's disease. Copyright © 2012 S. Karger AG, Basel.

  18. Presentation and stability of noncognitive symptom patterns in patients with Alzheimer disease.

    PubMed

    Haupt, M; Jänner, M; Ebeling, S; Stierstorfer, A; Kretschmar, C

    1998-12-01

    The purpose of this study was to investigate noncognitive symptoms in Alzheimer disease to identify symptom patterns and to study stability of such patterns prospectively. Furthermore, variables were examined that could be associated with certain types of symptom patterns or could be predictors of change of these patterns. Forty-eight patients with the clinical diagnosis of probable Alzheimer disease were included in this study and were assessed weekly over a 3-week period. Noncognitive symptoms were rated according to the Behavioral Abnormalities in Alzheimer's Disease Rating Scale and the Dementia Mood Assessment Scale and to a set of items that specifically assess misidentifications. By means of principal component factor analysis different noncognitive symptom patterns were obtained, yielding a four-factor solution. They mapped onto rational domains with respect to clinical experience: depression, apathy, psychotic symptoms/aggression, and misidentifications/agitation. Demographic and clinical variables were not associated with the factor solutions and did not predict change of the factor values. The results demonstrate that in Alzheimer disease there are distinct noncognitive symptom patterns that hold at least short-term prospective stability. None of the examined clinical variables, such as age at entry, the status of the patients (outpatient or inpatient), or dementia severity, exerted substantial influence on the noncognitive symptom patterns. Further investigations should concentrate on the pathological and prognostic correlates of noncognitive symptom patterns in Alzheimer disease.

  19. Music enhances category fluency in healthy older adults and Alzheimer's disease patients.

    PubMed

    Thompson, R G; Moulin, C J A; Hayre, S; Jones, R W

    2005-01-01

    Exposure to some music, in particular classical music, has been reported to produce transient increases in cognitive performance. The authors investigated the effect of listening to an excerpt of Vivaldi's Four Seasons on category fluency in healthy older adult controls and Alzheimer's disease patients. In a counterbalanced repeated-measure design, participants completed two, 1-min category fluency tasks whilst listening to an excerpt of Vivaldi and two, 1-min category fluency tasks without music. The authors report a positive effect of music on category fluency, with performance in the music condition exceeding performance without music in both the healthy older adult control participants and the Alzheimer's disease patients. In keeping with previous reports, the authors conclude that music enhances attentional processes, and that this can be demonstrated in Alzheimer's disease.

  20. The use of a wearable camera improves autobiographical memory in patients with Alzheimer's disease.

    PubMed

    Woodberry, Emma; Browne, Georgina; Hodges, Steve; Watson, Peter; Kapur, Narinder; Woodberry, Ken

    2015-01-01

    Despite the marked impairment of recent episodic memories in Alzheimer's disease, there have been few attempts to rehabilitate these deficits. We used a novel external memory aid to promote recall of episodic memories in patients with mild to moderate Alzheimer's disease. SenseCam, a small wearable camera, recorded significant events in the lives of six Alzheimer's disease patients. Every two days for two weeks each patient's memory for an event was assessed, followed by a structured review of the SenseCam images. Longer-term recall was tested one and three months later. A written diary control condition followed the same procedure. Across 40 events the SenseCam review method resulted in significantly more details of an event being recalled over two weeks than the written diary method in five out of the six patients. At three months post event, four out of five patients (one had dropped out) recalled significantly more details of events in the SenseCam condition while the other patient showed no significant difference. Viewing SenseCam images of personally experienced events may significantly improve autobiographical memory in patients with even moderate Alzheimer's disease.

  1. Genetics Home Reference: Alzheimer disease

    MedlinePlus

    ... Email Facebook Twitter Home Health Conditions Alzheimer disease Alzheimer disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alzheimer disease is a degenerative disease of the brain ...

  2. 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…

  3. 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…

  4. Walking difficulties in patients with Alzheimer's disease might originate from gait apraxia

    PubMed Central

    Della, S; Spinnler, H; Venneri, A

    2004-01-01

    Objectives: To investigate whether gait apraxia is a possible cause for some of the walking abnormalities shown by patients with Alzheimer's disease. Methods: 60 patients with Alzheimer's disease, selected as being free from overt extrapyramidal impairment or other potential causes of walking deficits, were assessed with a new test evaluating aspects of walking and related movements. Norms for this test were collected from a sample of 182 healthy volunteers. Results: 40% of the Alzheimer group performed below the cut off score on this test, and half performed poorly. Performance of the Alzheimer group in the walking skills test correlated highly with scores in a test assessing limb apraxia and with dementia severity. Conclusions: Gait apraxia may be the cause of walking disorders found in a subgroup of patients with Alzheimer's disease. Its detection is made easier by the use of a standardised test, but still relies heavily on the exclusion of other causes of walking deficits. It is a recognisable and independent form of apraxia. PMID:14742586

  5. 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.

  6. Effects of a feeding intervention in patients with Alzheimer's disease and dysphagia.

    PubMed

    Chen, Li-Li; Li, Hong; Lin, Rong; Zheng, Jian-Huang; Wei, Yan-Ping; Li, Jing; Chen, Ping; Chen, Hui-Ying

    2016-03-01

    This study aimed to investigate the effects of a feeding intervention in patients with Alzheimer's disease with dysphagia. In patients with Alzheimer's disease, inadequate food and fluid intake can result in malnutrition, dehydration and increased morbidity and mortality. Patients may lose self-care abilities such as self-feeding. A prospective cohort study. A three-month self-control feeding intervention was conducted prospectively in 30 nursing home residents with Alzheimer's disease with dysphagia. Pre- and post-intervention measures included the Kubota water swallow test, type and amount of food intake and assessment of nutritional status by triceps skinfold thickness, upper arm circumference, serum albumin and haemoglobin. We used the Edinburgh Feeding Evaluation in Dementia scale to evaluate eating compliance and the Mini- Mental State Examination to evaluate cognitive function. Pre- and post-intervention results were compared to evaluate the effects of nursing intervention. Patients' eating/feeding abilities improved overall, including significantly increased food intake (p < 0·001), decreased levels on the Kubota water swallow test (p < 0·001) and significant differences in skinfold thickness, arm circumference, serum albumin and haemoglobin (all p < 0·01), indicating improved nutritional status. Edinburgh Feeding Evaluation in Dementia scale scores decreased significantly, showing improved eating compliance. No changes were noted in cognition post-intervention. Among 22 patients who initially required feeding, five patients resumed self-feeding after the intervention (p = 0·06). Results of this study show that a feeding intervention can improve food intake, eating compliance and nutritional status in patients with Alzheimer's disease with dysphagia and prevent further decline in swallowing function. The significant improvement in eating/feeding measures suggest that this feeding intervention model could be developed as a feeding skills programme to

  7. 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…

  8. [Aluminum, hypothetic cause of Alzheimer disease].

    PubMed

    Pailler, F M; Bequet, D; Corbé, H; Giudicelli, C P

    1995-03-11

    A great deal of research has focused on aluminium as a putative causative factor in Alzheimer's disease. We measured by atomic absorption spectrophotometry aluminium levels in blood, urine and cerebrospinal fluid from 15 patients with Alzheimer's disease, compared with 20 control individuals. There were no statistically significant differences between the two groups. This suggests that aluminium is not a causative factor for Alzheimer's disease.

  9. 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…

  10. Simple method for evaluation of planum temporale pyramidal neurons shrinkage in postmortem tissue of Alzheimer disease patients.

    PubMed

    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.

  11. Effects of a multidisciplinar cognitive rehabilitation program for patients with mild Alzheimer's disease

    PubMed Central

    Viola, Luciane F.; Nunes, Paula V.; Yassuda, Monica S.; Aprahamian, Ivan; Santos, Franklin S.; Santos, Glenda D.; Brum, Paula S.; Borges, Sheila M.; Oliveira, Alexandra M.; Chaves, Gisele F. S.; Ciasca, Eliane C.; Ferreira, Rita C. R.; de Paula, Vanessa J. R.; Takeda, Oswaldo H.; Mirandez, Roberta M.; Watari, Ricky; Falcão, Deusivania V. S.; Cachioni, Meire; Forlenza, Orestes V.

    2011-01-01

    OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatric symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and

  12. 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…

  13. The Influences of Physical Activity on Patterns of Sleep Behavior of Patients with Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Namazi, Kevan H.; And Others

    1995-01-01

    A light exercise program was set up for 11 patients with Alzheimer's disease who exercised each day for 40 minutes. Their sleep patterns were compared with a control group who did not exercise. Results indicate that those who participated in the exercise program manifested 40% less restless behavior, while those in the non-exercise group showed a…

  14. 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…

  15. The Effects of Alzheimer's Disease on Close Relationships between Patients and Caregivers.

    ERIC Educational Resources Information Center

    Blieszner, Rosemary; Shifflett, Peggy A.

    1990-01-01

    Interviewed 11 caregivers for early-stage Alzheimer's patients to investigate changes in relationships concurrently with onset and progress of disease. Over 18 months, intimacy declined in both spouse and parent-child relationships. Caregivers were saddened at loss of reciprocal aspects of relationship and had difficulty coping with uncertain…

  16. 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…

  17. [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.

  18. [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.

  19. Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative.

    PubMed

    Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

    2011-09-01

    Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic

  20. [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.

  1. Immunotherapy for Alzheimer disease.

    PubMed

    Gouras, Gunnar K

    2009-01-01

    Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque pathology and improve behavior in transgenic mouse models of the disease. Several ongoing immunotherapy clinical trials for Alzheimer disease are in progress. The background and ongoing challenges for these immunological approaches for the treatment of Alzheimer disease are discussed.

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

    PubMed

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

    2011-07-01

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

  3. Head trauma and Alzheimer's disease.

    PubMed

    Nandoe, Rishi D S; Scheltens, Philip; Eikelenboom, Piet

    2002-08-01

    The authors describe a case of a 55 year old woman who was diagnosed with Alzheimer's disease 1.5 years after a car accident in which she experienced a mild concussion. Extensive history taking disclosed no cognitive changes prior to the car accident. The case is discussed in view of the inflammation hypothesis regarding Alzheimer's disease and the role of the apolipoprotein E4 genotype of the patient.

  4. Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients

    PubMed Central

    Kälin, Andrea M.; Park, Min T. M.; Chakravarty, M. Mallar; Lerch, Jason P.; Michels, Lars; Schroeder, Clemens; Broicher, Sarah D.; Kollias, Spyros; Nitsch, Roger M.; Gietl, Anton F.; Unschuld, Paul G.; Hock, Christoph; Leh, Sandra E.

    2017-01-01

    Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59–82, 47.8% female), future converters at baseline (n = 10, age range 66–84, 90% female) and at time of conversion (age range 68–87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61–81, 47.8% female; n = 10, age range 66–82, 80% female; n = 10, age range 68–82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced

  5. Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients.

    PubMed

    Kälin, Andrea M; Park, Min T M; Chakravarty, M Mallar; Lerch, Jason P; Michels, Lars; Schroeder, Clemens; Broicher, Sarah D; Kollias, Spyros; Nitsch, Roger M; Gietl, Anton F; Unschuld, Paul G; Hock, Christoph; Leh, Sandra E

    2017-01-01

    Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59-82, 47.8% female), future converters at baseline (n = 10, age range 66-84, 90% female) and at time of conversion (age range 68-87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61-81, 47.8% female; n = 10, age range 66-82, 80% female; n = 10, age range 68-82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced hippocampal

  6. Nicotine for Alzheimer's disease.

    PubMed

    López-Arrieta, J M; Rodríguez, J L; Sanz, F

    2000-01-01

    Nicotine is a cholinergic agonist that acts, not only post-synaptically, but also releases pre-synaptic acetylcholine, and in animal models has been shown to reverse spatial memory decline in rats with lesion in the medial septal nucleus and to show recovery on memory in aged monkeys. Nicotine also has effects on other transmitters like serotonin (5HT), dopamine, or GABA. On the other hand, because nicotine has serious adverse effects, especially concerning cardiovascular risks in elderly people, and also on sleep and behavior, there are several important reasons to conduct a systematic review to assess the clinical efficacy and safety of nicotine in patients with AD. The aim of this review is to determine whether there is evidence of beneficial effect, and to assess its safety profile, when nicotine is used for Alzheimer's disease. The Cochrane Controlled Trials Register (Issue 2, 99) was searched using the terms nicotin* and alzheimer*. Three references to trials were deemed suitable for inclusion but are awaiting consideration while the investigators are contacted. All unconfounded, double-blind, randomized trials in which treatment with nicotine patches or administration of nicotine intravenously was administered for more than a day and compared to placebo in people with Alzheimer's disease. As no trials were suitable for inclusion, no data have been extracted or pooled in a meta-analysis. One trial is awaiting consideration, and if included in an update of this review, any available data will be incorporated. The poor quality of the trials did not allow any synthesis of results across studies. However, the data available in trials considered are compatible with nicotine producing harm, no change or improvement. This review is not able to provide reliable evidence that nicotine is a useful treatment for Alzheimer's disease.

  7. Bioelectrical impedance vector analysis detects low body cell mass and dehydration in patients with Alzheimer's disease.

    PubMed

    Buffa, R; Mereu, R M; Putzu, P F; Floris, G; Marini, E

    2010-12-01

    This paper evaluates the nutritional status in patients with mild-moderate and severe Alzheimer's disease (AD) by bioelectrical impedance vector analysis (BIVA). Cross-sectional study. Alzheimer Center, SS. Trinita Hospital, Cagliari, and "Monsignor Angioni" Nursing Home, Quartu Sant'Elena (Cagliari, Italy). 83 free-living patients with mild-moderate Alzheimer's disease (29 men, 54 women), 9 institutionalized women in the severe stage; 468 age-matched controls (202 men, 266 women). Mini Nutritional Assessment (MNA), anthropometric (height, weight, BMI), bioelectrical (R, Xc) and biochemical variables (serum albumin) were assessed. Bioelectrical characteristics were significantly different in the patients with mild-moderate AD with respect to controls, indicating low body cell mass (men, T2= 12.8; women, T2=34.9; p < 0.01). Women with severe AD showed low body cell mass and dehydration with respect to patients with mild-moderate AD (T2=17.1; p < 0.01). The phase angle, R/H and Z/H were significantly correlated (p < 0.05) with MNA (phase: r = 0.31; R/H: r =-0.37; Z/H: r =-0.37) and albumin (phase: r=0.47; R/H: r=-0.36; Z/H: r=-0.36). Alzheimer's disease is characterized by a tendency to malnutrition, present even in the mild-moderate stages, and a tendency to dehydration that appears in the severe stage. The BIVA technique is a promising tool for the screening and monitoring of nutrition and hydration status in Alzheimer's disease.

  8. Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels.

    PubMed

    Weiler, Marina; de Campos, Brunno Machado; Teixeira, Camila Vieira de Ligo; Casseb, Raphael Fernandes; Carletti-Cassani, Ana Flávia Mac Knight; Vicentini, Jéssica Elias; Magalhães, Thamires Naela Cardoso; Talib, Leda Leme; Forlenza, Orestes Vicente; Balthazar, Marcio Luiz Figueredo

    2017-04-04

    In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

  9. Visual evoked potentials in dementia: a meta-analysis and empirical study of Alzheimer's disease patients.

    PubMed

    Pollock, V E; Schneider, L S; Chui, H C; Henderson, V; Zemansky, M; Sloane, R B

    1989-04-15

    A meta-analytic review of flash and pattern reversal visual evoked potential research indicates that elderly demented patients have longer P100 latencies than age-matched control subjects. In the present empirical research, patients with research diagnoses of probable Alzheimer's disease were compared with sex- and age-matched control subjects using P100 latencies of visual evoked potentials (VEP) elicited by flash and pattern reversal. As compared to control subjects, Alzheimer's disease patients showed significantly longer P100 latencies of the VEP elicited by pattern reversal; the flash P100 only marginally distinguished them. These findings are discussed within the context of VEP recording practices, patient selection, sex and age matching of control subjects, and the visual system.

  10. 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.

  11. Attenuation of Choroidal Thickness in Patients With Alzheimer Disease: Evidence From an Italian Prospective Study.

    PubMed

    Trebbastoni, Alessandro; Marcelli, Michela; Mallone, Fabiana; D'Antonio, Fabrizia; Imbriano, Letizia; Campanelli, Alessandra; de Lena, Carlo; Gharbiya, Magda

    2017-01-01

    To compare the 12-month choroidal thickness (CT) change between Alzheimer disease (AD) patients and normal subjects. In this prospective, observational study, 39 patients with a diagnosis of mild to moderate AD and 39 age-matched control subjects were included. All the subjects underwent neuropsychological (Mini Mental State Examination, Alzheimer disease Assessment Scale-Cognitive Subscale, and the Clinical Dementia Rating Scale) and ophthalmological evaluation, including spectral domain optical coherence tomography, at baseline and after 12 months. CT was measured manually using the caliper tool of the optical coherence tomography device. After 12 months, AD patients had a greater reduction of CT than controls (P≤0.05, adjusted for baseline CT, age, sex, axial length, and smoking). CT in patients with AD showed a rate of thinning greater than what could be expected during the natural course of aging.

  12. 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

  13. Health-related quality of life in caregivers of patients with Alzheimer's disease.

    PubMed

    Garzón-Maldonado, F J; Gutiérrez-Bedmar, M; García-Casares, N; Pérez-Errázquin, F; Gallardo-Tur, A; Martínez-Valle Torres, M D

    2017-10-01

    Informal caregivers of patients with Alzheimer's disease (AD) have a poor health-related quality of life (HRQOL). HRQOL is an increasingly common user-focused outcome measure. We have evaluated HRQOL longitudinally in caregivers of AD patients at baseline and at 12 months. Ninety-seven patients diagnosed with AD according to the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke, and Alzheimer's Disease and Related Disorders Association) and their 97 respective primary caregivers were included in the study. We analysed the following data at the baseline visit: sociodemographic data of both patients and carers, patients' clinical variables, and data related to the healthcare provided to patients by carers. HRQOL of caregivers was measured with the SF-36 questionnaire at baseline and 12 months later. At 12 months, primary caregivers scored lower in the 8 subscales of the SF-36 questionnaire; differences were statistically significant in all dimensions except for 'physical function' and 'social function'. Baseline scores in our sample were lower than those of the general population. 'Vitality' is the dimension that presented the lowest scores. HRQOL in caregivers of patients with Alzheimer's disease deteriorates over time and is poorer than that of the age- and sex-matched general population. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease.

    PubMed

    Satlin, A; Volicer, L; Ross, V; Herz, L; Campbell, S

    1992-08-01

    The authors tested the hypothesis that evening bright light pulses would improve sleep-wake patterns and reduce agitation in patients with Alzheimer's disease who have severe sundowning (a syndrome of recurring confusion and increased agitation in the late afternoon or early evening) and sleep disorders. Ten inpatients with Alzheimer's disease on a research ward of a veterans' hospital were studied in an open clinical trial. All patients had sundowning behavior and sleep disturbances. After a week of baseline measurements, patients received 2 hours/day of exposure to bright light between 7:00 p.m. and 9:00 p.m. for 1 week. During the baseline week, the treatment week, and a posttreatment week, patients were rated by nurses for agitation, sleep-wake patterns, use of restraints, and use of prescribed-as-needed medication. On the last 2 days of each week, patients wore activity monitors. Activity counts were analyzed for circadian rhythmicity. Clinical ratings of sleep-wakefulness on the evening nursing shift improved with light treatment in eight of the 10 patients. The proportion of total daily activity occurring during the nighttime decreased during the light-treatment week. The relative amplitude of the circadian locomotor activity rhythm, a measure of its stability, increased during the light-treatment week. More severe sundowning at baseline predicted greater clinical improvement. Evening bright light pulses may ameliorate sleep-wake cycle disturbances in some patients with Alzheimer's disease. This effect may be mediated through a chronobiological mechanism.

  15. Effect of aerobic exercise on physical performance in patients with Alzheimer's disease.

    PubMed

    Sobol, Nanna Aue; Hoffmann, Kristine; Frederiksen, Kristian Steen; Vogel, Asmus; Vestergaard, Karsten; Brændgaard, Hans; Gottrup, Hanne; Lolk, Annette; Wermuth, Lene; Jakobsen, Søren; Laugesen, Lars; Gergelyffy, Robert; Høgh, Peter; Bjerregaard, Eva; Siersma, Volkert; Andersen, Birgitte Bo; Johannsen, Peter; Waldemar, Gunhild; Hasselbalch, Steen Gregers; Beyer, Nina

    2016-12-01

    Knowledge about the feasibility and effects of exercise programs to persons with Alzheimer's disease is lacking. This study investigated the effect of aerobic exercise on physical performance in community-dwelling persons with mild Alzheimer's disease. The single blinded multi-center RCT (ADEX) included 200 patients, median age 71 yrs (50-89). The intervention group received supervised moderate-to-high intensity aerobic exercise 1 hour × 3/week for 16 weeks. Assessments included cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy. Significant between-group differences in change from baseline (mean [95%CI]) favored the intervention group for cardiorespiratory fitness (4.0 [2.3-5.8] ml/kg/min, P <0.0001) and exercise self-efficacy (1.7 [0.5-2.8] points, P =0.004). Furthermore, an exercise attendance of ≥66.6% resulted in significant positive effects on single-task physical performance and dual-task performance. Aerobic exercise has the potential to improve cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy in community-dwelling patients with mild Alzheimer's disease. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  16. 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.

  17. Genetics of Alzheimer Disease

    PubMed Central

    Bekris, Lynn M.; Yu, Chang-En; Bird, Thomas D.; Tsuang, Debby W.

    2011-01-01

    Alzheimer disease (AD) is the most common causes of neurodegenerative disorder in the elderly individuals. Clinically, patients initially present with short-term memory loss, subsequently followed by executive dysfunction, confusion, agitation, and behavioral disturbances. Three causative genes have been associated with autosomal dominant familial AD (APP, PSEN1, and PSEN2) and 1 genetic risk factor (APOEε4 allele). Identification of these genes has led to a number of animal models that have been useful to study the pathogenesis underlying AD. In this article, we provide an overview of the clinical and genetic features of AD. PMID:21045163

  18. 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.

  19. Ethical Considerations for Deep Brain Stimulation Trials in Patients with Early-Onset Alzheimer's Disease.

    PubMed

    Viaña, John Noel M; Bittlinger, Merlin; Gilbert, Frederic

    2017-01-01

    Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimer's disease, with several recruiting participants <65 and thus have early-onset Alzheimer's disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression. These considerations include appropriate patient selection and signing of an informed consent for genetic testing; appropriate study design; potential outcomes that people with EOAD could expect; and accurate interpretation and balanced discussion of trial results. Finally, recommendations for future DBS for AD trials will be made to ensure that EOAD patients will not experience avoidable harms should they be enrolled in these experimental studies.

  20. 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.

  1. Alzheimer disease update.

    PubMed

    Matthews, Brandy R

    2010-04-01

    Alzheimer disease (AD) is a progressive neurodegenerative disorder affecting more than 37 million people worldwide and increasing in incidence based on its primary risk factor, advancing age. A growing body of knowledge regarding amyloid and tau neuropathology, genetic and environmental risk modifiers, early and atypical clinical presentations, and the use of symptom-modifying medical and psychosocial therapies is available to aid in the diagnosis and management of patients with AD. Exciting recent advances in neurobiology render the areas of genetic susceptibility, biomarkers for early disease detection and assessment of disease progression, and novel therapeutic strategies to modify the natural history of the disease compelling, but in need of further study before implementation into routine clinical practice is feasible.

  2. Different modes of weight loss in Alzheimer disease: a prospective study of 395 patients.

    PubMed

    Guérin, Olivier; Andrieu, Sandrine; Schneider, Stéphane M; Milano, Morgan; Boulahssass, Rabia; Brocker, Patrice; Vellas, Bruno

    2005-08-01

    Alzheimer disease is often accompanied and worsened by malnutrition. Patterns of weight loss can differ by the patients concerned and by the outcome and interventions required. Our aim was to describe and analyze 2 modes of weight loss (progressive and severe) in the course of Alzheimer disease. This was a prospective study of 395 patients with Alzheimer disease, who had a mean age of 75.4 y. A standardized gerontologic evaluation was conducted at 6 mo and 1 y, including assessments of nutrition, neuropsychology, function, and caregiver burden. We investigated 2 modes of weight loss. The first, progressive loss (4% in 1 y), affected 33.4% of subjects. Disease severity was a risk factor [odds ratio (OR): 7.2; 95% CI: 1.4, 38.2 for a Reisberg score > or = 5], whereas treatment with cholinesterase inhibitors at baseline decreased this risk (OR: 0.33; 95% CI: 0.14, 0.79). The second mode of weight loss, a severe loss of > or =5 kg in 6 mo, affected 10.2% of subjects. The existence of an acute phase reaction was a risk factor (OR: 2.4; 95% CI: 1.2, 4.8), as was an intercurrent event, such as hospitalization, acute disease, institutionalization, and change of living arrangements (OR: 6.8; 95% CI: 1.2, 39.9). During the follow-up of patients with Alzheimer disease, risk factors for these 2 modes of weight loss should be sought to identify patients who would benefit from a nutritional intervention. Our findings lead us to advocate follow-up, which involves an assessment of functional, nutritional, and neuropsychologic status every 6 mo.

  3. Trace metal concentrations in hair and nails from Alzheimer's disease patients: Relations with clinical severity.

    PubMed

    Koseoglu, Emel; Koseoglu, Rahmi; Kendirci, Murat; Saraymen, Recep; Saraymen, Burak

    2017-01-01

    Metals, especially transition metals, seem to be important in the pathogenesis of Alzheimer disease. This study aims to determine the relationship of trace metal elements to the pathogenesis and/or course of Alzheimer Disease in terms of clinical severity. The hair and nail trace metal levels of 62 Alzheimer Disease patients at different clinical stages (21 mild, 20 moderate, 21 severe) and 60 healthy control subjects were measured by using inductively coupled plasma-mass spectrometry. The statistical comparisons were performed with regards to the study groups, clinical stages, disease duration and age. The patient and control groups were significantly different from each other in regards to Mn, Fe, Cu, Cd, Hg (p<0.001), Zn (p<0.01) in nail concentrations and, Na, Al, Pb, Co (p<0.001), Fe, Mn (p=0.001), Hg, Cu, Cd, K in hair concentrations (p<0.01). No difference was detected in the levels of Mg and Ca. Nail Na level showed differences among different clinical stages of the disease (p<0.01). In comparing the mild degree Alzheimer patients to the control group; significant differences were detected in nail Mn, Fe, Cu, Co (p<0.001), Hg, Zn (p<0.01) and, hair Pb, Al (p<0.001), Na, K levels (p<0.01). Our results have shown that transition and posttransition metals are especially important metals for the disease process. The relation of nail Na level with clinical stages of AD is an interesting new finding, making someone to think that alkali metals may be important in the progression of the disease. Copyright © 2016. Published by Elsevier GmbH.

  4. Do Alzheimer's disease patients want to participate in a treatment decision, and would their caregivers let them?

    PubMed

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

    2005-06-01

    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. Interviews were conducted with 48 patients in the mild-to-moderate stage of Alzheimer's disease and their caregivers. Ninety-two percent of patients indicated they would participate in an Alzheimer's disease treatment decision, whereas 71% of caregivers thought the patient would participate. Half of the caregivers who indicated that their relatives would participate had relatives who did not have the capacity to make the decision based on a consensus of three expert psychiatrists. Patients' insight into their diagnosis and prognosis, and having less cognitive impairment, being a female caregiver, and being a spousal caregiver were all associated with the likelihood that the patient would participate in the treatment decision. Patients talked about wanting to be involved in the process of making a treatment decision, whereas caregivers talked about assessing whether their relative could participate in the process of decision making. Mild-to-moderate stage Alzheimer's disease patients want to be involved in making treatment decisions, and caregivers are generally willing to involve them. Caregivers of Alzheimer's disease patients talk about patient participation in relation to elements of the capacity to make a treatment decision. Clinicians can provide guidance and education to assist caregivers in understanding how to assess their relatives' abilities to make decisions and navigate the decision-making process.

  5. Relative importance of patient disease indicators on informal care and caregiver burden in Alzheimer's disease.

    PubMed

    Bergvall, Niklas; Brinck, Per; Eek, Daniel; Gustavsson, Anders; Wimo, Anders; Winblad, Bengt; Jönsson, Linus

    2011-02-01

    Cognition, abilities in activities of daily living (ADL), and behavioral disturbances in patients with Alzheimer's disease (AD) all influence the number of hours informal caregivers spend caring for their patients, and the burden caregivers experience. However, the direct effect and relative importance of each disease severity measure remains unclear. Cross-sectional interviews were conducted with 1,222 AD patients and primary caregivers in Spain, Sweden, the U.K. and the U.S.A. Assessments included informal care hours, caregiver burden (Zarit Burden Inventory; ZBI), cognition (Mini-mental State Examination; MMSE), ADL-abilities (Disability Assessment for Dementia scale; DAD), and behavioral symptoms (Neuropsychiatric Inventory Questionnaire; NPI-severity). Multivariate analyses of 866 community-dwelling patients revealed that ADL-ability was the strongest predictor of informal care hours (36% decrease in informal care hours per standard deviation (SD) increase in DAD scores). Severity of behavioral disturbances was the strongest predictor of caregiver burden (0.35 SD increase in ZBI score per SD increase in NPI-Q severity score). In addition, the effect of ADL-abilities was, although attenuated, not negligible (0.28 SD increase in ZBI score per SD increase in DAD score). Decreasing cognition (MMSE) was associated with more informal care hours and increased caregiver burden in univariate, but not in adjusted analyses. For patients residing in community dwellings, the direct influence of patients' cognition on caregiver burden is limited and rather mediated by other disease indicators. Instead, the patients' ADL-abilities are the main predictor of informal care hours, and both ADL-abilities and behavioral disturbances are important predictors of perceived caregiver burden, where the latter has the strongest effect. These results were consistent across Sweden, U.K. and the U.S.A.

  6. Effectiveness of a community-based multidomain cognitive intervention program in patients with Alzheimer's disease.

    PubMed

    Kim, Hee-Jin; Yang, YoungSoon; Oh, Jeong-Gun; Oh, Seongil; Choi, Hojin; Kim, Kyoung Hee; Kim, Seung Hyun

    2016-02-01

    The aim of the present study was to evaluate the efficacy of a multidomain program in patients with Alzheimer's disease (AD). A total of 53 patients with probable AD participated in the present study. The participants were classified to a cognitive programming group (n = 32) and control group (n = 21). Participants in the cognitive intervention program received multidomain cognitive stimulation including art, music, recollection and horticultural therapy, each period of intervention lasting 1 h. This program was repeated five times per week over a period of 6 months at the Seongdong-gu Center for Dementia. The Mini-Mental State Examination, the Korean version of Consortium to Establish a Registry for Alzheimer's Disease, Clinical dementia rating scales, and the Korean version of the Quality of Life-Alzheimer's Disease were used to evaluate cognitive ability at baseline and after intervention. After 6 months, cognitive abilities were compared between patients actively participating in cognitive intervention and the pharmacotherapy only group. Patients receiving cognitive intervention showed significant cognitive improvement in the word-list recognition and recall test scores versus the control. There was no change in the overall Clinical dementia rating score, but the domain of community affairs showed a significant improvement in the cognitive intervention group. Quality of Life-Alzheimer's Disease of caregivers was slightly improved in the cognitive intervention group after 6 months. Multidomain cognitive intervention by regional dementia centers has great potential in helping to maintain cognitive function in patients with dementia, increase their social activity and reduce depression, while enhancing the quality of life of caregivers. © 2015 Japan Geriatrics Society.

  7. Therapeutic efficacy of neuromuscular electrical stimulation and electromyographic biofeedback on Alzheimer's disease patients with dysphagia.

    PubMed

    Tang, Yi; Lin, Xiang; Lin, Xiao-Juan; Zheng, Wei; Zheng, Zhi-Kai; Lin, Zhao-Min; Chen, Jian-Hao

    2017-09-01

    To study the therapeutic effect of neuromuscular electrical stimulation and electromyographic biofeedback (EMG-biofeedback) therapy in improving swallowing function of Alzheimer's disease patients with dysphagia.A series of 103 Alzheimer's disease patients with dysphagia were divided into 2 groups, among which the control group (n = 50) received swallowing function training and the treatment group (n = 53) received neuromuscular electrical stimulation plus EMG-biofeedback therapy. The mini-mental state scale score was performed in all patients along the treatment period. Twelve weeks after the treatment, the swallowing function was assessed by the water swallow test. The nutritional status was evaluated by Mini Nutritional Assessment (MNA) as well as the levels of hemoglobin and serum albumin. The frequency and course of aspiration pneumonia were also recorded.No significant difference on mini-mental state scale score was noted between 2 groups. More improvement of swallowing function, better nutritional status, and less frequency and shorter course of aspiration pneumonia were presented in treatment group when compared with the control group.Neuromuscular electrical stimulation and EMG-biofeedback treatment can improve swallowing function in patients with Alzheimer's disease and significantly reduce the incidence of adverse outcomes. Thus, they should be promoted in clinical practice.

  8. [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.

  9. Role of methylglyoxal in Alzheimer's disease.

    PubMed

    Angeloni, Cristina; 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.

  10. Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease.

    PubMed

    Evatt, Marian L; Delong, Mahlon R; Khazai, Natasha; Rosen, Ami; Triche, Shirley; Tangpricha, Vin

    2008-10-01

    A role for vitamin D deficiency in Parkinson disease (PD) has recently been proposed. To compare the prevalence of vitamin D deficiency in a research database cohort of patients with PD with the prevalence in age-matched healthy controls and patients with Alzheimer disease (AD). Survey study and blinded comparison of plasma 25-hydroxyvitamin D (25[OH]D) concentrations of stored samples in a clinical research database at Emory University School of Medicine. Referral center (PD and AD patients), primary care clinics, and community setting (controls). Participants were recruited into the study between May 1992 and March 2007. Every fifth consecutively enrolled PD patient was selected from the clinical research database. Unrelated AD (n = 97) and control (n = 99) participants were randomly selected from the database after matching for age, sex, race, APOE genotype, and geographic location. Prevalence of suboptimal vitamin D and mean 25(OH)D concentrations. Significantly more patients with PD (55%) had insufficient vitamin D than did controls (36%) or patients with AD (41%; P = .02, chi(2)test). The mean (SD) 25(OH)D concentration in the PD cohort was significantly lower than in the AD and control cohorts (31.9 [13.6] ng/mL vs 34.8 [15.4] ng/mL and 37.0 [14.5] ng/mL, respectively; P = .03). This report of 25(OH)D concentrations in a predominantly white PD cohort demonstrates a significantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD. These data support a possible role of vitamin D insufficiency in PD. Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of PD.

  11. Deciphering Alzheimer disease.

    PubMed

    Selkoe, Dennis; Mandelkow, Eckhard; Holtzman, David

    2012-01-01

    Alzheimer disease represents an insidious impairment of intellect and emotional well-being. However, recent advances in biochemical pathology and human genetics offer promise that effective therapeutic agents may soon be developed.

  12. Alzheimer's Disease - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Alzheimer's Disease URL of this page: https://medlineplus.gov/languages/alzheimersdisease.html Other topics A-Z Expand Section ...

  13. Predictors of family caregiver ratings of patient quality of life in Alzheimer disease: cross-sectional results from the Canadian Alzheimer's Disease Quality of Life Study.

    PubMed

    Naglie, Gary; Hogan, David B; Krahn, Murray; Black, Sandra E; Beattie, B Lynn; Patterson, Christopher; Macknight, Chris; Freedman, Morris; Borrie, Michael; Byszewski, Anna; Bergman, Howard; Streiner, David; Irvine, Jane; Ritvo, Paul; Comrie, Janna; Kowgier, Matthew; Tomlinson, George

    2011-10-01

    To assess whether the core symptoms of Alzheimer disease (AD) and caregiver factors consistently predict family caregiver ratings of patient quality of life (QOL) as assessed by a variety of QOL measures in a large national sample. : Cross-sectional. Fifteen dementia and geriatric clinics across Canada. : Family caregivers (n = 412) of community-living patients with AD of all severities. Caregiver ratings of patient QOL using three utility indexes, the European Quality of Life-5 Dimensions, Quality of Well-Being Scale and Health Utilities Index; a global QOL visual analogue scale; a disease-specific measure, the Quality of Life-Alzheimer's Disease; and a generic health status measure, the Short Form-36. Patient cognition was assessed with the cognitive subscale of the Alzheimer's Disease Assessment Scale and Mini-Mental State Examination, function with the Disability Assessment for Dementia, and behavioral and psychological symptoms with the Neuropsychiatric Inventory and the Geriatric Depression Scale. Caregiver burden was assessed with the Zarit Burden Interview and caregiver depression with the Center for Epidemiologic Studies Depression scale. One-way analysis of variance and fully adjusted multiple linear regression were used to assess the relationship between patient dementia symptom and caregiver variables with QOL ratings. In multivariable analyses, caregiver ratings of patient function and depressive symptoms were the only consistent independent predictors of caregiver-rated QOL across the QOL measures. Caregiver ratings of patient function and depression were consistent independent predictors of caregiver-rated QOL, using a spectrum of QOL measures, while measures of patient cognition and caregiver burden and depression were not. These findings support the continued use of caregiver ratings as an important source of information about patient QOL and endorse the inclusion in AD clinical trials of caregiver-rated measures of patient function, depression

  14. Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease patients are unchanged.

    PubMed

    Timmer, Nienke M; Herbert, Megan K; Claassen, Jurgen A H R; Kuiperij, H Bea; Verbeek, Marcel M

    2015-03-01

    Decreased cerebral protein and activity levels of glutamine synthetase (GS) have been reported for Alzheimer's disease (AD) patients. Using a recently established method, we quantified total GS levels in cerebrospinal fluid (CSF) from AD patients and control subjects. Furthermore, we investigated if total GS levels in CSF could differentiate AD from frontotemperal dementia and dementia with Lewy bodies patients. As we found no significantly altered total GS levels in any of the patient groups compared with control subjects, we conclude that levels of total GS in CSF have no diagnostic value for AD, dementia with Lewy bodies, or frontotemperal dementia.

  15. Depth perception in Alzheimer's disease.

    PubMed

    Mendez, M F; Cherrier, M M; Meadows, R S

    1996-12-01

    Abnormal depth perception contributes to visuospatial deficits in Alzheimer's disease. Disturbances in stereopsis, motion parallax, and the interpretation of static monocular depth cues may result from neuropathology in the visual cortex. We evaluated 15 patients with mild Alzheimer's disease and 15 controls matched for age, sex, and education on measures of local stereopsis (stereoscopic testing), global stereopsis (random dots), motion parallax (Howard-Dolman apparatus), and monocular depth perception by relative size, interposition, and perspective. Compared to controls, the patients were significantly impaired in over-all depth perception. This impairment was largely due to disturbances in local stereopsis and in the interpretation of depth from perspective, independent of other visuospatial functions. Patients with Alzheimer's disease have disturbed interpretation of monocular as well as binocular depth cues. This information could lead to optic interventions to improve their visual depth perception.

  16. Sunlight exposure is important for preventing hip fractures in patients with Alzheimer's disease, Parkinson's disease, or stroke.

    PubMed

    Iwamoto, J; Takeda, T; Matsumoto, H

    2012-04-01

    Hypovitaminosis D as a result of malnutrition or sunlight deprivation, increased bone resorption, low bone mineral density (BMD), or an increased risk of falls may contribute to an increased risk of hip fractures in patients with neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. The purpose of this study was to clarify the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with such neurological diseases. The English literature was searched using PubMed, and randomized controlled trials evaluating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke were identified. The relative risk and the 95% confidence interval were calculated for individual randomized controlled trials, and a pooled data analysis (meta-analysis) was performed. Three randomized controlled trials were identified. Sunlight exposure improved hypovitaminosis D and increased the BMD. The relative risk (95% confidence interval) of hip fractures was 0.22 (0.05, 1.01) for Alzheimer's disease, 0.27 (0.08, 0.96) for Parkinson's disease, and 0.17 (0.02, 1.36) for stroke. The relative risk (95% confidence interval) calculated for the pooled data analysis was 0.23 (0.10, 0.56) (P = 0.0012), suggesting a significant risk reduction rate of 77%. The present meta-analysis added additional evidence indicating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke. © 2011 John Wiley & Sons A/S.

  17. [Hearing loss and Alzheimer's disease].

    PubMed

    Bakhos, David; Villeuneuve, Alexandre; Kim, Soo; Hammoudi, Karim; Hommet, Caroline

    2015-06-01

    Recent studies suggest that subjects with hearing loss are more likely to develop Alzheimer's disease. Hearing loss can be consecutive to presbycusis and/or to central auditory dysfunction. Standard audiometric measures (pure tone and speech intelligibility) allow the diagnosis of presbycusis. However, to demonstrate central auditory dysfunction, specific audiometric tests are needed such as noisy and/or dichotic tests. Actually, no consensus exists to investigate hearing loss in people with Alzheimer's disease though hearing loss may be an early manifestation of Alzheimer's disease. Until now, investigations and clinical procedure related to the diagnosis of Alzheimer's disease ignored the hearing ability of the patient. However, the major part of care management and investigations implies the patient's communication ability with the caregivers. Hearing loss may be one of the most unrecognized deficit in subjects with Alzheimer's disease. Auditory rehabilitation could benefit to the patient in order to lessen cognitive decline, but this must be investigated during longitudinal studies in order to clearly demonstrate their efficiency.

  18. Burden and associated pathologies in family caregivers of Alzheimer's disease patients in Spain.

    PubMed

    Cotelo, Natalia Vérez; Rodríguez, N Floro Andrés; Pérez, José A Fornos; Iglesias, J Carlos Andrés; Lago, Marcos Ríos

    2015-01-01

    To evaluate the profile of family caregivers of Alzheimer's disease patients, identify any signs of psychopathology, quantify the level of perceived burden on the caregiver, and determine the caregiver's relationship with their pharmacist. A cross-sectional study was conducted at a community pharmacy in Pontevedra, Spain. Demographic variables were collected, and the following questionnaires were administered: the Beck Depression Inventory-II, STAI-Anxiety Questionnaire, Zarit Burden Scale, family APGAR scale, and the Duke-UNC questionnaire. The typical caregiver profile consists of a 55-year old first degree relative (mostly daughters) with a primary education who belongs to a functional or mildly dysfunctional family. Nearly one quarter (24%) of caregivers had a high perception of burden, with anxiety in 20% of caregivers and symptoms of depression in 20%. Family caregivers usually went to the same pharmacy as the patients (96%), were treated with psychotropic drugs (68%), and interacted with the pharmacist (92%). This study confirmed that psychological distress and burden is present among family caregivers. Care for caregivers should be integrated into patient care as part of a national plan, including grants and subsidies, which will result in better care of Alzheimer's patients. Pharmacists are the most accessible health care professionals and can provide information about Alzheimer's disease management to caregivers to ease the burden of care.

  19. Cerebrospinal Fluid from Alzheimer's Disease Patients Contains Fungal Proteins and DNA.

    PubMed

    Alonso, Ruth; Pisa, Diana; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    The identification of biomarkers for Alzheimer's disease is important for patient management and to assess the effectiveness of clinical intervention. Cerebrospinal fluid (CSF) biomarkers constitute a powerful tool for diagnosis and monitoring disease progression. We have analyzed the presence of fungal proteins and DNA in CSF from AD patients. Our findings reveal that fungal proteins can be detected in CSF with different anti-fungal antibodies using a slot-blot assay. Additionally, amplification of fungal DNA by PCR followed by sequencing distinguished several fungal species. The possibility that these fungal macromolecules could represent AD biomarkers is discussed.

  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. [Management of Alzheimer disease].

    PubMed

    Belmin, Joël; Péquignot, Renaud; Konrat, Cécile; Pariel-Madjlessi, Sylvie

    2007-10-01

    Management of Alzheimer disease is based on drug and nondrug treatments. Specific drug treatment includes acetylcholinesterase inhibitors and memantine. They show moderate efficacy superior to that of placebo for global condition, cognitive disorders, need for care, and behavioral problems, but do not prevent further decline. These treatments remain underused. The efficacy of psychotropic drugs (antidepressants, neuroleptics, and antipsychotic agents) in treating behavioral problems is not well documented. Nondrug activities and interventions have not been sufficiently evaluated scientifically. These involve interventions against the consequences of the disease (loss of autonomy, malnutrition) and helping patients' family caregivers. Among these activities, the best evaluated and most interesting are: educational programs for caregivers, occupational therapy at home, and interventions at home by nurses specially trained as case managers.

  2. Bioavailability and pharmacokinetic disposition of tacrine in elderly patients with Alzheimer's disease.

    PubMed Central

    Lou, G; Montgomery, P R; Sitar, D S

    1996-01-01

    The pharmacokinetic disposition of intravenous and oral doses of tacrine was determined in 5 elderly patients (aged 64 to 96 y) with the clinical diagnosis of Alzheimer's disease. The bioavailability of the oral formulation was low (9.9% to 36.4%), and the plasma half-life was not altered by route of drug delivery. These data indicate that tacrine elimination occurs by a 1st-order process. Plasma clearance of tacrine varied more than its half-life, which is consistent with a modulating effect of apparent volume of distribution (Vd). Our findings, together with other limited published studies, suggest that use of tacrine for the treatment of Alzheimer's disease (AD) will be confounded by the high interindividual variability in its kinetic disposition. PMID:8973053

  3. 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…

  4. Melatonin in Alzheimer's disease.

    PubMed

    Lin, Li; Huang, Qiong-Xia; Yang, Shu-Sheng; Chu, Jiang; Wang, Jian-Zhi; Tian, Qing

    2013-07-12

    Alzheimer's disease (AD), an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP) of aggregated β-amyloid (Aβ) and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubule-associated protein tau. Multiple factors contribute to the etiology of AD in terms of initiation and progression. Melatonin is an endogenously produced hormone in the brain and decreases during aging and in patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with Aβ. Our studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood, a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting the cholinergic system and in anti-inflammation. The aim of this review is to stimulate interest in melatonin as a potentially useful agent in the prevention and treatment of AD.

  5. Bingo vs. physical intervention in stimulating short-term cognition in Alzheimer's disease patients.

    PubMed

    Sobel, B P

    2001-01-01

    Past research has shown that pharmacological measures can enhance cognitive and functional capacities for patients with Alzheimer's disease, but may result in unacceptable side effects. Investigations using nonpharmacological treatments are limited. This study evaluates the therapeutic effect of the game of Bingo as cognitive stimulation, versus daily physical activity, on short-term memory, concentration, word retrieval, and word recognition. Informed consent was obtained from the designated representatives of 50 subjects from six community adult day care centers on Long Island. The results show that cognitive stimulation enhanced performance on the Boston Naming Test and a Word List Recognition Task; physical intervention, however, did not reach statistical significance. Thus, a simple cognitive activity such as Bingo can be of great value to the daily management of Alzheimer's patients.

  6. Observed behaviors of patients with probable Alzheimer's disease who are hospitalized for diagnostic tests.

    PubMed

    Day, N; Musallam, K; Wells, M

    1999-11-01

    This study examines observed behaviors of hospitalized patients with probable Alzheimer's disease (AD) undergoing invasive diagnostic procedures. Data was obtained from nursing documentation in the medical records of 30 patients, 10 in each stage of AD (i.e., mild, moderate, severe). In general, analysis of the data revealed that changes in behavior occurred immediately prior to, during, and following these procedures. Specifically, the moderately impaired patients showed the most significant curve over the 5-day observation period, while patients in the mildly impaired group showed a high peak of behavioral change on the test day. The severely impaired group of patients had a higher sustained level of activity throughout the 5-day period. Routine assessment of the patients' usual behaviors, care-givers' knowledge of the stage of disease, and awareness of the potential impact that diagnostics may have on cognitively impaired patients could help care providers decide what interventions most likely would lead to successful outcomes.

  7. 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

  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.

  9. Skill learning in patients with moderate Alzheimer's disease: a prospective pilot-study of waltz-lessons.

    PubMed

    Rösler, Alexander; Seifritz, Erich; Kräuchi, Kurt; Spoerl, David; Brokuslaus, Ilona; Proserpi, Sara-Maria; Gendre, Annekäthi; Savaskan, Egemen; Hofmann, Marc

    2002-12-01

    The authors report the effect of a 12-day prospective, blinded dance-learning trial in 5 patients with moderate Alzheimer's disease (AD) and 5 age-matched depressed patients. Patients with AD showed a significant effect in procedural learning whereas depressed patients did not. These findings suggest potential implications for therapeutic interventions in patients with moderate AD.

  10. [Support for patients with Alzheimer's disease and their caregivers by gerontechnology].

    PubMed

    Rigaud, Anne-Sophie; Pino, Maribel; Wu, Ya-Huei; DE Rotrou, Jocelyne; Boulay, Melodie; Seux, Marie-Laure; Hugonot-Diener, Laurence; DE Sant'anna, Martha; Moulin, Florence; LE Gouverneur, Gregory; Cristancho-Lacroix, Victoria; Lenoir, Hermine

    2011-03-01

    The increasing number of people suffering from Alzheimer's disease raises the question of their caring at home, especially when the disease causes disability and negative consequences in daily life such as isolation, falls, wandering, errors in drug taking. Furthermore, caregivers bear a substantial burden that can have adverse effects on their physical and mental health. New technologies of information could play an additional role as care providers without substituting family or professional caregivers help. A review of literature focused on the different technological solutions conceived for patients suffering from Alzheimer's disease and their carers shows that these appliances could help to provide reminders in daily life (drugs, tasks and appointments, meals cooking), to activate residual cognitive resources by computerized cognitive stimulation intervention, to reduce stress, anxiety and depressive symptoms in patients by visual contact with families and professionals (webconference), to contribute to patients safety by detecting falls and wandering, and to help families in the caring of patients with computerized information and counselling interventions. We also discuss the current limitations for a widespread use of these technologies and outline future research avenues. True needs of end-users are still poorly known and should be more clearly defined. Simplicity of the use of these appliances should be further improved. Demonstration of medical and social benefits for elderly people should be carried out in randomized, controlled studies. Ethical reflexion should be developed in conjunction with the use of these gerontechnologies. Finally, the economical model which would enable the providing of these appliances to the largest number of patients and caregivers should be implemented. Although these gerontechnologies are promising, research is still needed to tailor them properly to the needs of end-users, assess their benefit in ecological context of

  11. The use of errorless learning strategies for patients with Alzheimer's disease: a literature review.

    PubMed

    Li, Ruijie; Liu, Karen P Y

    2012-12-01

    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 'errorless learning or practice' and 'Alzheimer's disease'. Four studies that fulfilled the inclusion criteria were selected and reviewed. Two of the studies were clinical controlled trials: one was a single-group pretest-post-test trial and the other was a multiple single-participant study. Demographic variables, design, treatment and outcome measures were summarized. Recall trials were used as the primary outcome measure. Results indicate that the use of errorless learning promotes better retention of specific types of information. Errorless learning is effective in memory rehabilitation of older adults with Alzheimer's disease. However, it would require more studies with unified outcome measures to allow for the formulation of standardized clinical protocol and recommendations.

  12. Epidemiology of Alzheimer disease.

    PubMed

    Mayeux, Richard; Stern, Yaakov

    2012-08-01

    The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040. As the population worldwide continues to age, the number of individuals at risk will also increase, particularly among the very old. Alzheimer disease is the leading cause of dementia beginning with impaired memory. The neuropathological hallmarks of Alzheimer disease include diffuse and neuritic extracellular amyloid plaques in brain that are frequently surrounded by dystrophic neurites and intraneuronal neurofibrillary tangles. The etiology of Alzheimer disease remains unclear, but it is likely to be the result of both genetic and environmental factors. In this review we discuss the prevalence and incidence rates, the established environmental risk factors, and the protective factors, and briefly review genetic variants predisposing to disease.

  13. Epidemiology of Alzheimer Disease

    PubMed Central

    Mayeux, Richard; Stern, Yaakov

    2012-01-01

    The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040. As the population worldwide continues to age, the number of individuals at risk will also increase, particularly among the very old. Alzheimer disease is the leading cause of dementia beginning with impaired memory. The neuropathological hallmarks of Alzheimer disease include diffuse and neuritic extracellular amyloid plaques in brain that are frequently surrounded by dystrophic neurites and intraneuronal neurofibrillary tangles. The etiology of Alzheimer disease remains unclear, but it is likely to be the result of both genetic and environmental factors. In this review we discuss the prevalence and incidence rates, the established environmental risk factors, and the protective factors, and briefly review genetic variants predisposing to disease. PMID:22908189

  14. 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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. [Relationships between weight loss and circulating cytokines in patients with Alzheimer's disease].

    PubMed

    Mahieux, Florence; Couderc, Rémy; Fénelon, Gilles; Maachi, Mustapha

    2006-12-01

    106 consecutive patients with Alzheimer's disease living in the community were examined in a memory clinic from a neurological department. They were screened for weight loss over the last 2 years. Age, duration of the disease, behavioral disorders, mini mental status examination, body mass index were recorded. Tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), interleukin 6 (IL-6) and interleukin 2 (IL-2) blood levels were measured. Weight loss was reported in 42.5% of the patients. TNFalpha levels were significantly higher in these patients (18.8 versus 15.8 pg/mL; p=0.04) than in patients without weight loss. Weight loss was also associated with a lower MMSE score (16.9 versus 19.3; p=0.03), current pacing (20% versus 1.6%; p=0.002), and hallucinations (20.0% versus 3.3%; p=0.008). The levels of the other cytokines did not differ between the patients with and without weight loss. Our findings suggest an association between high levels of circulating TNFalpha and unexplained weight loss in Alzheimer's disease.

  16. Anxiety and Alzheimer's disease.

    PubMed

    Ferretti, L; McCurry, S M; Logsdon, R; Gibbons, L; Teri, L

    2001-01-01

    This study investigated symptoms of anxiety in two samples of clinic outpatients diagnosed with Alzheimer's disease (AD). Clinician and caregiver reports were obtained using standardized measures to characterize a broad array of anxiety symptoms. Anxiety symptoms were reported for a substantial proportion of subjects, regardless of whether clinician or caregiver ratings were used. Anxious or worried appearance was most common (68% to 71%), followed by fearfulness, tension, restlessness, and fidgeting (37% to 57%). Sleep disturbance and various somatic symptoms were less common (8% to 34%). Although anxiety symptoms were prevalent, only 5% to 6% of subjects met Diagnostic and Statistical Manual of Mental Disorders criteria for the diagnosis of generalized anxiety disorder. In both samples, anxiety symptoms were associated with depression, behavioral disturbances, and increased cognitive impairment. Study findings support a high occurrence of anxiety in patients with dementia, and treatments for anxiety might therefore be helpful in reducing the psychiatric burden of AD.

  17. 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. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Actual expense associated with patients with Alzheimer's disease in Colombia.

    PubMed

    Prada, Sergio I; Takeuchi, Yuri; Merchán-Galvis, Angela M; Ariza-Araújo, Yoseth

    2017-06-08

    There is paucity in the level of knowledge on the actual insurer expenses associated with patients suffering with dementia in the developing world. Less is known about direct costs by severity and how costs vary because of the presence of other comorbidities. Using claims data from an insurer for three years, we identified patients with AD with an algorithm that takes advantage of information on age, primary diagnosis, and services and drugs provided. Distribution by dementia stage was as follows: mild 21%, moderate 53%, severe 17%, and undetermined 9%. Expenses paid for all causes by the insurer were at least double than estimated in the literature and were increasing annually at rates higher than 30%. Also, 92% of patients have at least another chronic condition. Worldwide costs of dementia estimates maybe underestimating the actual costs to health systems in the developing world.

  19. A novel method and software for automatically classifying Alzheimer's disease patients by magnetic resonance imaging analysis.

    PubMed

    Previtali, F; Bertolazzi, P; Felici, G; Weitschek, E

    2017-05-01

    The cause of the Alzheimer's disease is poorly understood and to date no treatment to stop or reverse its progression has been discovered. In developed countries, the Alzheimer's disease is one of the most financially costly diseases due to the requirement of continuous treatments as well as the need of assistance or supervision with the most cognitively demanding activities as time goes by. The objective of this work is to present an automated approach for classifying the Alzheimer's disease from magnetic resonance imaging (MRI) patient brain scans. The method is fast and reliable for a suitable and straightforward deploy in clinical applications for helping diagnosing and improving the efficacy of medical treatments by recognising the disease state of the patient. Many features can be extracted from magnetic resonance images, but most are not suitable for the classification task. Therefore, we propose a new feature extraction technique from patients' MRI brain scans that is based on a recent computer vision method, called Oriented FAST and Rotated BRIEF. The extracted features are processed with the definition and the combination of two new metrics, i.e., their spatial position and their distribution around the patient's brain, and given as input to a function-based classifier (i.e., Support Vector Machines). We report the comparison with recent state-of-the-art approaches on two established medical data sets (ADNI and OASIS). In the case of binary classification (case vs control), our proposed approach outperforms most state-of-the-art techniques, while having comparable results with the others. Specifically, we obtain 100% (97%) of accuracy, 100% (97%) sensitivity and 99% (93%) specificity for the ADNI (OASIS) data set. When dealing with three or four classes (i.e., classification of all subjects) our method is the only one that reaches remarkable performance in terms of classification accuracy, sensitivity and specificity, outperforming the state

  20. A 6-month follow-up of nutritional status in institutionalized patients with Alzheimer's disease.

    PubMed

    Van Wymelbeke, V; Guédon, A; Maniere, D; Manckoundia, P; Pfitzenmeyer, P

    2004-01-01

    A follow up of nutritional status in institutionalized patients with Alzheimer's disease. Observational study. Specialized unit for patients with Alzheimer's disease in Dijon hospital, France. Fourteen women, aged 72-92 years. On admission of patients to the specialized unit for dementia, body weight, body mass index, arm muscle circumference (AMC) and triceps skin fold (TSF) were measured. Serum concentrations of albumin, prealbumin, homocysteine, orosomucoide, calcium, folates, vitamins B12 and B6 and C-reactive protein were recorded. The same clinical and biological measurements were repeated at day 30, 90 and 180. Both mean weight and mean BMI increased throughout the study with significant differences between day 0 and day 90, and day 180 (p<0.01). The weight gain was associated with a significant increase in AMC and TSF (p<0.01 and p<0.001, respectively). There was no significant difference for values of both mean serum levels of albumin and prealbumin between day 0 and day 180. Whatever the period, serum concentrations of folates and vitamin B12 were in the normal range, while mean levels of vitamin B6 were lower than the normal range; For all these values, there was no significant difference between day 0, 30, 90, 180. Mean levels of C-reactive protein and orosomucoide and lymphocyte counts were in the normal range both at admission and day 180. No significant difference was noted between value of homocysteine at admission and at day 180. In this special care unit, the patients with Alzheimer's disease who take part in daily activities and particularly preparation of the meal don't lose weight. It is certain that future studies recording food intake and energy expenditure are necessary to explain the benefits in the nutritional status observed in patients showing dementia when they are institutionalized in a special unit.

  1. Implicit motor learning in patients with Parkinson's and Alzheimer's disease: differences in learning abilities?

    PubMed

    van Tilborg, Ilse; Hulstijn, Wouter

    2010-07-01

    Experimental studies show intact implicit motor learning in patients with Alzheimer's disease (AD) but the results for patients with Parkinson's disease (PD) are inconclusive. This study tests implicit sequence learning in AD and PD patients, and healthy controls, using the classical Serial Reaction Time Task (SRTT), and a somewhat similar Pattern Learning Task (PLT), which involves stylus movements in different directions, and which allows detailed movement analysis. As expected, the time measures showed less implicit motor learning in the PD patients relative to the other groups in both tasks, but their error percentages increased when the sequence changed from a fixed to a random order, which is indicative of implicit learning. The AD patients showed a reversed pattern of results. Arguably, errors and time measures may reflect the involvement of separate processes, e.g., spatial and motor components, which could be differently affected in AD and PD.

  2. 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.

  3. Forecasting Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Fackelmann, Kathleen

    1996-01-01

    Suggests that doctors may one day be able to identify healthy people who will develop Alzheimer's disease. Discusses recent studies in which characteristics of a person's writing early in life appear to predict the disease, and brain scans can highlight changes that may precede dementia. (CCM)

  4. Characteristics of Alzheimer's disease among patients in Taiwan, Hong Kong, and Beijing.

    PubMed

    Yang, Yuan-Han; Wang, Huali; Lam, Linda; Chan, Wai-Chi; Yu, Xin; Li, Tao; Wang, Wen-Fu; Chiu, Pai-Yi; Lin, Yu-Te; Hu, Chaur-Jong; Fuh, Jong-Ling; Morris, John C

    2014-01-01

    In order to obtain data from patients with Alzheimer's disease dementia and their informants in a uniform manner and to foster further research among the Chinese and other races, we have conducted an international study to recruit patients diagnosed with Alzheimer's disease (AD) from Taiwan, Hong Kong, and Beijing. The Uniform Data Set was translated into Chinese and administrated to AD patients and their informants. A total of 1,107 AD dementia patients were recruited, including 691 from Taiwan, 244 from Beijing, and 172 from Hong Kong. There were differences in the AD patients: gender (p = 0.099), education (p < 0.001), age (p < 0.001), and handedness (p = 0.007). For informants, age (p = 0.679), gender (p = 0.117), education (p < 0.001), and living together or not (p < 0.001) differed in the three samples. Although three areas across the Taiwan Strait are ethnic Chinese, the clinical picture for patients and informants are very different. Further study is needed to clarify the significance of clinical characteristics in Chinese societies.

  5. Predictive Factors of Rapid Cognitive Decline in Patients with Alzheimer Disease.

    PubMed

    Barbe, Coralie; Morrone, Isabella; Novella, J L; Dramé, Moustapha; Wolak-Thierry, Aurore; Aquino, Jean-Pierre; Ankri, Joël; Jolly, Damien; Mahmoudi, Rachid

    2016-01-01

    To determine predictive factors associated with rapid cognitive decline (RCD) in elderly patients suffering from Alzheimer disease (AD). Patients suffering from mild to moderate AD were included. RCD was defined as the loss of at least 3 points on the Mini-Mental State Examination (MMSE) over 12 months. Factors associated with RCD were identified by logistic regression. Among 123 patients included, 61 were followed up until 12 months. RCD occurred in 46% of patients (n = 28). Polymedication (p < 0.0001), the fact that the caregiver was the child or spouse of the patient (p < 0.0001) and autonomy for washing (p < 0.0001) were protective factors against RCD, while the presence of caregiver burden (p < 0.0001) was shown to be a risk factor for RCD. Early detection of the RCD risk in AD patients could make it possible to anticipate the patient's medical needs and adjust the care plan for caregiver burden.

  6. Effects of hypertension and hypercholesterolemia on cognitive functioning in patients with alzheimer disease.

    PubMed

    Goldstein, Felicia C; Ashley, Angela V; Endeshaw, Yohannes W; Hanfelt, John; Lah, James J; Levey, Allan I

    2008-01-01

    This study investigated the relationship between the vascular comorbidities (VCs) of hypertension and hypercholesterolemia and the cognitive phenotype of Alzheimer disease (AD). Seventy-four AD patients underwent objective measurement of blood pressure and serum cholesterol levels, and they received a detailed neuropsychologic evaluation examining attention, memory, language, visuomotor/visuospatial skills, and executive functioning. Multiple regression analyses controlling for demographic variables, overall cognitive status, and the presence of diabetes/cardiac disease indicated that an increase in the number of VCs, but not their severity, was associated with poorer verbal and visual recall, visuoconstructive and spatial analysis, verbal reasoning, and set shifting. The findings demonstrate that VCs are associated with specific aspects of cognitive functioning in AD patients. The mechanisms likely involve the effects of VCs on cerebrovascular disease including white matter disruption. The results highlight the importance of controlling these risk factors in patients who carry the diagnosis of AD.

  7. 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.

  8. Alzheimer disease and anesthesia.

    PubMed

    Inan, Gözde; Özköse Satirlar, Zerrin

    2015-01-01

    Alzheimer disease (AD) is one of the most common neurodegenerative diseases and the most prevalent form of dementia. Some factors in the development of AD, age being the best-known one, have been suggested; however, no causes have been found yet. The pathophysiology of the disease is highly complex, current therapies are palliative, and a cure is still lacking. Adverse effects of anesthetics in the elderly have been reported since the 1950s; however, awareness of this old problem has recently gained inportance again. Whether exposure to surgery and general anesthesia (GA) is associated with the development of AD has been questioned. As the population is aging, many elderly patients will need to be anesthetized, and maybe some were already anesthetized before they were diagnosed. Exposure to anesthetics has been demonstrated to promote pathogenesis of AD in both in vitro and in vivo studies. However, to date, there have not been any clinical trials to address a link between exposure to GA and the development of AD in humans. Therefore, before making any conclusions we need further studies, but we should be aware of the potential risks and take cautions with vulnerable elderly patients.

  9. Cognitive outcomes after sertaline treatment in patients with depression of Alzheimer disease.

    PubMed

    Munro, Cynthia A; Longmire, Crystal Flynn; Drye, Lea T; Martin, Barbara K; Frangakis, Constantine E; Meinert, Curtis L; Mintzer, Jacobo E; Porsteinsson, Anton P; Rabins, Peter V; Rosenberg, Paul B; Schneider, Lon S; Weintraub, Daniel; Lyketsos, Constantine G

    2012-12-01

    Although many depressed patients with Alzheimer disease (AD) are treated with antidepressants, the effect of such treatment on cognitive performance in these patients is not known. The authors report cognitive outcomes in patients with depression of AD (dAD) after a 24-week trial of sertraline or placebo. Placebo-controlled, randomized, double-blind trial. Outpatient memory clinics at five academic medical centers in the United States. A total of 131 patients with dAD (60 men) and Mini-Mental State Examination scores of 10-26. Sertraline (n = 67), target dose of 100 mg daily or matching placebo (n = 64). Caregivers received standardized psychosocial intervention throughout the trial. Mini-Mental State Examination, cognitive subscale of the Alzheimer's Disease Assessment Scale, letter fluency, backward digit span, Symbol Digit Modalities Test, and Finger Tapping Test, administered at baseline, and 8, 16, and 24 weeks following baseline. A series of linear models indicated no effect of treatment or of depression remission on cognitive test performance at 24 weeks. Regardless of treatment condition, very little change in cognitive test performance was noted in general. Treatment with sertraline in patients with dAD is not associated with greater improvement in cognition at week 24 than treatment with placebo.

  10. [Early interventional group therapy for patients with incipient Alzheimer disease and their relatives].

    PubMed

    Scheurich, Armin; Schanz, Benno; Müller, Matthias J; Fellgiebel, Andreas

    2008-06-01

    Pilot study on an early-interventional group therapy for patients with incipient Alzheimer disease and their relatives. The present study investigates whether scientific progress in terms of earlier time of diagnostic certainty can be used for psychoeducation, maintenance of positive activities and prevention of comorbid depressive episodes. 12 patients (66.8 +/- 5.8 years, MMSE 24.0 +/- 4.0) together with 12 relatives have been treated with a bi-weekly group therapy program. For the patients treatment resulted in reduced anxiety, anergia and withdrawal, for their relatives reduced sleep disturbances, irascibility, and aggressiveness have been found. Only one of the patients suffered from a depressive episode. All participants expressed positive feedback and a high level of quality of life. By the straightforward psychosocial intervention it seems possible to use the earlier time of diagnostic certainty for early diagnosed patients suffering from incipient Alzheimer disease. However, results have to be replicated by a controlled, prospective study with larger sample sizes.

  11. Serum levels of coenzyme Q10 in patients with Alzheimer's disease.

    PubMed

    de Bustos, F; Molina, J A; Jiménez-Jiménez, F J; García-Redondo, A; Gómez-Escalonilla, C; Porta-Etessam, J; Berbel, A; Zurdo, M; Barcenilla, B; Parrilla, G; Enriquez-de-Salamanca, R; Arenas, J

    2000-01-01

    We compared serum levels of coenzyme Q10 and the coenzyme Q10/cholesterol ratio in 44 patients with Alzheimer's disease (AD), 17 patients with vascular dementia (VD), and 21 matched controls. The mean serum coenzyme Q10 and cholesterol levels and the coenzyme Q10/cholesterol ratio of patients with AD or VD did not differ significantly from those of controls. Coenzyme Q10 levels and coenzyme Q10/cholesterol ratio of AD or VD patients were not correlated with age, age at onset, duration of the disease or scores of the MiniMental State Examination. These results suggest that these values are not related with the risk for AD or VD.

  12. Lyme disease associated with Alzheimer's disease.

    PubMed

    Meer-Scherrer, Laurence; Chang Loa, Chien; Adelson, Martin E; Mordechai, Eli; Lobrinus, Johannes Alexander; Fallon, Brian A; Tilton, Richard C

    2006-04-01

    This case report discusses a patient with co-occurring neuroborreliosis and Alzheimer's disease (AD). Although no claim is made for causality nor is there objective evidence that spirochetes are involved in AD, co-infection may exacerbate the symptoms of either neuroborreliosis or AD. Much is to be learned about the role of spirochetes in degenerative central nervous system disease.

  13. Significance of lutein in red blood cells of Alzheimer's disease patients.

    PubMed

    Kiko, Takehiro; Nakagawa, Kiyotaka; Tsuduki, Tsuyoshi; Suzuki, Toshihide; Arai, Hiroyuki; Miyazawa, Teruo

    2012-01-01

    Red blood cells (RBC) of Alzheimer's disease (AD) patients are known to be in an excessively oxidized state (i.e., with a high accumulation of peroxidized phospholipids (PLOOH)). Previously we confirmed in vitro, in vivo murine, and in human studies that carotenoids can effectively inhibit accumulation of RBC PLOOH. Thus, the relationship between RBC carotenoids and PLOOH concentrations in AD patients is of interest. In this study, RBC carotenoids and PLOOH were evaluated in 28 normal control subjects (age: 74.1 ± 1.3 years) and 28 patients with AD (age: 72.5 ± 1.4 years). The concentrations of RBC carotenoids, especially lutein, in AD patients were significantly lower than in control subjects. An inverse relationship was seen between RBC carotenoids, especially lutein, and PLOOH concentrations in AD patients. These results suggest that RBC lutein, in particular, may contribute to suppression of PLOOH accumulation in RBC of AD patients.

  14. APOE-ɛ4 Carrier Status and Donepezil Response in Patients with Alzheimer's Disease.

    PubMed

    Waring, Jeffrey F; Tang, Qi; Robieson, Weining Z; King, David P; Das, Ujjwal; Dubow, Jordan; Dutta, Sandeep; Marek, Gerard J; Gault, Laura M

    2015-01-01

    Previous studies have investigated associations between apolipoprotein E (APOE)-ɛ4 allele status and acetylcholinesterase inhibitor treatment response in patients with Alzheimer's disease. The ability to draw definitive conclusions regarding the effect of APOE-ɛ4 genotype on treatment response has been hindered by inconsistent results among studies and methodological limitations that restrict interpretation of study findings. To determine whether APOE-ɛ4 carrier status influences the magnitude of change in 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) score associated with acetylcholinesterase inhibitor treatment (i.e., donepezil). Analyses were performed using pooled data from the donepezil and placebo treatment arms of three consecutive, similarly designed, 12-week, multi-national, randomized clinical studies that enrolled patients with mild-to-moderate Alzheimer's disease. Correlations between APOE-ɛ4 carrier status and ADAS-cog scores were evaluated using analysis of covariance. No appreciable interaction between donepezil response and APOE-ɛ4 carrier status or copy number was detected. Both carriers and non-carriers of APOE-ɛ4 who received donepezil experienced significant improvements from baseline in ADAS-cog score versus placebo (p <  0.05). Change from baseline to final observation in the donepezil treatment group was - 2.95 for APOE-ɛ4 carriers and - 4.09 for non-carriers (p = 0.23). In contrast, non-carriers of APOE-ɛ4 in the placebo treatment group exhibited a greater improvement from baseline versus carriers (-2.38 versus - 0.60, p = 0.05). Within this population, APOE genotype had no statistically significant effect on cognitive response to donepezil treatment; however, APOE-ɛ4 allele status was associated with a difference in the magnitude of the change in ADAS-cog of placebo-treated patients.

  15. The dramatic effects of Galantamine in a patient with early-onset Alzheimer's disease.

    PubMed

    Dev, Harveer; Agius, Mark; Zaman, Rashid

    2010-06-01

    We discuss the case of a 51 year old former mid-wife presented to the NHS Luton and Bedfordshire psychiatric services with a 2 year history of increasing forgetfulness with significant impairment to her daily function. She was diagnosed with non-familial early-onset Alzheimer's Disease (EOAD) and started on 8mg daily of the acetylcholinesterase inhibitor Galantamine. The information for this study was gathered from patient notes, consultant, collateral and personal accounts. Periodic outpatient consultations at the NHS Luton and Bedfordshire psychiatric services were used to monitor Mrs LF's global, functional and behavioral progress. These were supplemented with the mini mental state examination (MMSE) at each outpatient appointment. The graph of MMSE scores illustrates severe decline in scores, followed eventually by increase in score to sustained improvement while continuing on galantamine. Functionally, this lady has successfully negotiated a divorce, moved into her own accommodation, began travelling on holidays, including abroad, with friends, and has now embarked on a new relationship. Whilst only being a single case study, this demonstrates the significant benefits which are attainable with Galantamine in EOAD. The extent of this improvement may be a result of individual variation, or perhaps a greater efficacy for this drug in the subset of 'early-onset' AD patients, which has long been thought to share the same mechanism as traditional AD. The responsiveness to Galantamine in this patient may suggest an alternative mechanism of Early Onset Alzheimer's Disease to typical Alzheimer's Disease in the over 65's. The case raises interesting questions as to whether EOAD should be considered distinct to typical (over 65's) AD, given the greater than expected response to Galantamine.

  16. Genetic insights in Alzheimer's disease.

    PubMed

    Bettens, Karolien; Sleegers, Kristel; Van Broeckhoven, Christine

    2013-01-01

    In the search for new genes in Alzheimer's disease, classic linkage-based and candidate-gene-based association studies have been supplanted by exome sequencing, genome-wide sequencing (for mendelian forms of Alzheimer's disease), and genome-wide association studies (for non-mendelian forms). The identification of new susceptibility genes has opened new avenues for exploration of the underlying disease mechanisms. In addition to detecting novel risk factors in large samples, next-generation sequencing approaches can deliver novel insights with even small numbers of patients. The shift in focus towards translational studies and sequencing of individual patients places each patient's biomaterials as the central unit of genetic studies. The notional shift needed to make the patient central to genetic studies will necessitate strong collaboration and input from clinical neurologists.

  17. Iron accumulation in the substantia nigra of patients with Alzheimer disease and parkinsonism.

    PubMed

    Brar, Sonia; Henderson, David; Schenck, John; Zimmerman, Earl A

    2009-03-01

    Preliminary studies have shown an increase in iron accumulation in the substantia nigra but not in the hippocampus in patients with Parkinson disease without dementia and the reverse in patients with Alzheimer disease (AD) and no parkinsonism. To determine whether iron levels (measured as T2 shortening on magnetic resonance images) are greater in the substantia nigra of patients with AD who have parkinsonism than in those with AD alone. Case-control study. Albany Medical College, Albany, New York. Fifteen patients with only AD (controls) and 18 with AD as well as parkinsonism, aged 56 to 89 years, and with a total Clinical Dementia Rating of 5.0 to 11.5. Patients were selected according to the purity of their disease; patients with a Unified Parkinson's Disease Rating Scale motor score of 15 or greater were considered to have parkinsonism. Main Outcome Measure Area under the curve for short T2 (30 milliseconds) in patients with only AD vs patients with AD who developed parkinsonism. Patients who developed parkinsonism along with their existing dementia had significantly more iron in their substantia nigra than did patients with AD alone (P = .03, 2-sample t test). Iron accumulation may be a predictor of parkinsonism. The development of parkinsonism during the course of AD appears to be associated with the accumulation of iron, which in turn may contribute to the pathogenesis of neurologic decline.

  18. Altered beta-amyloid precursor protein isoforms in Mexican Alzheimer's Disease patients.

    PubMed

    Sánchez-González, V J; Ortiz, G G; Gallegos-Arreola, P; Macías-Islas, M A; Arias-Merino, E D; Loera-Castañeda, V; Martínez-Cano, E; Velázquez-Brizuela, I E; Rosales-Corral, S A; Curiel-Ortega, C R; Pacheco-Moisés, F; García, J J

    2006-01-01

    To determine the beta-amyloid precursor protein (betaAPP) isoforms ratio as a risk factor for Alzheimer's Disease and to assess its relationship with demographic and genetic variables of the disease. Blood samples from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting for betaAPP. A ratio of betaAPP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106-110 Kd) was obtained. Odds ratios were obtained to determine risk factor of this component. betaAPP ratio on AD subjects was lower than that of control subjects: 0.3662 +/- 0.1891 vs. 0.6769 +/- 0.1021 (mean +/- SD, p<0.05). A low betaAPP ratio (<0.6) showed an OR of 4.63 (95% CI 1.45-15.33). When onset of disease was taken into account, a betaAPP ratio on EOAD subjects of 0.3965 +/- 0.1916 was found vs. 0.3445 +/- 0.1965 on LOAD subjects (p>0.05). Altered betaAPP isoforms is a high risk factor for Alzheimer's disease, although it has no influence on the time of onset of the disease.

  19. A comparison of sleep profiles in patients with dementia with lewy bodies and Alzheimer's disease.

    PubMed

    Grace, J B; Walker, M P; McKeith, I G

    2000-11-01

    Sleep disturbances are common in healthy old age and in dementia syndromes. Polysomnography has demonstrated typical changes in both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) with AD being characterised by sundowning and sleep apnoea and DLB patients showing more disturbances of movement control during sleep. The technical difficulties associated with EEG sleep recordings mean that polysomnography is not possible out of specialist centres. To use questionnaires to assess the frequency of sleep disturbances in patients with Alzheimer's disease and dementia with Lewy bodies. The sleep profiles of twenty patients with AD and 17 with DLB were assessed using three questionnaires, one designed to assess night time sleep disturbance, one day time sleepiness and the last carer burden. The sleep questionnaires were repeated in a subgroup after treatment with a cholinesterase inhibitor (rivastigmine). Level of sleep disturbance in both groups was high. DLB patients had more overall sleep disturbance, more movement disorders whilst asleep and more abnormal day time sleepiness. Treatment with rivastigmine produced a trend towards normalisation of sleep profile in a small number of subjects. Both groups have extensive sleep problems. The DLB and AD groups have different sleep profiles that are of diagnostic importance and may suggest different treatment strategies. The results are consistent with those found from polysomnographic assessment and suggest that the questionnaires used are sensitive to detect differences previously documented with polysomnography.

  20. Histopathology and Florbetaben PET in Patients Incorrectly Diagnosed with Alzheimer's Disease.

    PubMed

    Sabbagh, Marwan N; Schäuble, Barbara; Anand, Keshav; Richards, Danielle; Murayama, Shigeo; Akatsu, Hiroyasu; Takao, Masaki; Rowe, Christopher C; Masters, Colin L; Barthel, Henryk; Gertz, Hermann-Josef; Peters, Oliver; Rasgon, Natalie; Jovalekic, Aleksandar; Sabri, Osama; Schulz-Schaeffer, Walter J; Seibyl, John

    2017-01-01

    Of 57 individuals diagnosed with Alzheimer's disease (AD) in a phase III study, 13 (23%) had amyloid-β (Aβ) levels on postmortem histopathology that did not explain the dementia. Based on postmortem histopathology, a wide range of different non-AD conditions was identified, including frontotemporal dementia, hippocampal sclerosis, and dementia with Lewy bodies. Of the histopathologically Aβ negative scored cases ante-mortem Florbetaben PET scans were classified as negative for Aβ in 11 patients based on visual analysis and in all 12 quantifiable cases based on composite standardized uptake value ratios. Thus, florbetaben PET can assist physicians in the differential diagnosis of neurodegenerative disorders by reliably excluding Aβ pathology.

  1. National Alzheimer's disease program.

    PubMed

    Sotton, J; Boursaly, J; Rapin, J R; Xuong, N G; Starton, P; Rancurel, G; Bouillon, D; Leponcin, M

    1989-01-01

    The psycho-behavioral troubles of patients with an Alzheimer's Disease (AD) are such that it is very difficult to keep those patients within the normal family environment, and that it therefore proves necessary to have them placed in a specially adapted residence manned by a highly specialised medical and para-medical staff. Within the frame of such an approach, a new type of residence has been devised "Asclepios Gardens", a one-level ranch-type residence, including 44 individual apartments, each opening, on the one hand, on a little private garden opening itself on a large, strictly enclosed and protected, 5-acre park, and, on the other hand, on a collective living structure conceived for social activities under attentive medical care, to help the patients restore their social structures. In a such residences, besides the special training given to the staff (medical, para-medical), aimed at developing as much as possible the patients' autonomy and self-reliance in every aspect of everyday life, you find a psychometric computerized "activation" program, devised both on a collective basis with differentiated subprograms, for groups of patients that have been classified according to the degree of seriousness of their problem, and-whenever possible, with individual attention programs; the whole of this "activation" method has thus clearly a double target; first to develop what is left of the patients' autonomy, for instance by psychometric exercises, and moreover, to have them start new activities, which they had never practised before--this latter action with a view to developing their neuroplasticity resources. And finally, a new chemical therapy is proposed. This substance induced a significant improvement in 40% of cases and a slight improvement in 20%. These results were observed through a series of specific psychometric tests (Visuo Retention Test of Benton, Mnesic profile of Rey), a global scale (Mini Mental State), and a general evaluation of the patients

  2. The clinical significance of brain microbleeds in patients with Alzheimer's disease: Preliminary study

    PubMed Central

    Heo, Jae-Hyeok; Im, Dong-Gyu; Lee, Seung-Hyeon; Ahn, Jin-Young

    2016-01-01

    Background: Microbleeds (MBs) are observed frequently in Alzheimer's disease (AD) and suggested to play a crucial role in the pathophysiology, but their clinical significance remains unclear. Materials and Methods: The study recruited 100 patients with AD who were diagnosed at the memory clinic in Seoul Medical Center in 2014. For each patient, baseline characteristics, neuropsychological tests, cerebrovascular risk factors, medial temporal lobe atrophy (MTLA), and severity of small vessel disease (SVD) according to the existence of MBs were evaluated. Results: The prevalence of MBs in patients with AD was 33%. The percentage of male gender, the severity of SVD and MTLA were significantly increased in MB(+) group. The MB(+) group showed more severe MTLA and SVD than MB(−) group. Conclusions: These results suggested that MBs might reflect the burden of amyloid and ischemic vascular pathology. PMID:27994360

  3. An assessment of the semantic network in patients with Alzheimer's disease.

    PubMed

    Chan, A S; Butters, N; Paulsen, J S; Salmon, D P; Swenson, M R; Maloney, L T

    1993-01-01

    Abstract The present study employed multidimensional scaling and ADDTREE clustering analyses to derive the cognitive maps and clustering representations of normal elderly controls (NC), patients with Alzheimer's disease (AD), and patients with Hun-tington's disease (HD); the analyses were performed on subjects' responses in a category fluency task that involved generating animal names for 60 sec. A measure of the proximity of animal names was used as an index of associational strength; MDS and ADDTREE estimates were based on this measure. A comparison of the NC, AD, and HD subjects' cognitive maps suggests that the semantic network of AD patients is abnormal in two ways. First, the organization of the semantic network is disrupted. Second, new abnormal associations and clusterings are formed. These results support the notion that AD is characterized by a breakdown in the structure of semantic knowledge and not primarily by a deficiency in the accessibility of semantic information.

  4. The picture superiority effect in patients with Alzheimer's disease and mild cognitive impairment.

    PubMed

    Ally, Brandon A; Gold, Carl A; Budson, Andrew E

    2009-01-01

    The fact that pictures are better remembered than words has been reported in the literature for over 30 years. While this picture superiority effect has been consistently found in healthy young and older adults, no study has directly evaluated the presence of the effect in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Clinical observations have indicated that pictures enhance memory in these patients, suggesting that the picture superiority effect may be intact. However, several studies have reported visual processing impairments in AD and MCI patients which might diminish the picture superiority effect. Using a recognition memory paradigm, we tested memory for pictures versus words in these patients. The results showed that the picture superiority effect is intact, and that these patients showed a similar benefit to healthy controls from studying pictures compared to words. The findings are discussed in terms of visual processing and possible clinical importance.

  5. Frontal defects contribute to the genesis of closing-in in Alzheimer's disease patients.

    PubMed

    De Lucia, Natascia; Grossi, Dario; Maria Fasanaro, Angiola; Carpi, Sabrina; Trojano, Luigi

    2013-08-01

    Closing-in (CI) refers to copying drawings near to or superimposed on the original model, and is often observed in Alzheimer's disease (AD) patients. Contrasting hypotheses have been suggested to explain CI, but no prospective study has directly verified these interpretations. We evaluated the role of frontal/executive versus visuo-spatial impairments in a prospective sample of AD patients, and also explored whether different types of CI are related to specific neuropsychological tasks. We enrolled 64 AD patients who underwent copying tasks and an extensive neuropsychological assessment of visuo-spatial and visuo-constructional skills, frontal/executive abilities and anterograde memory. AD patients with CI showed more severe impairment on frontal/executive functions than AD patients without CI. Moreover, the tendency to produce copies superimposed on the model was selectively associated with poor inhibitory control for irrelevant responses. On this basis, we suggest that different CI phenomena could be ascribed to distinctive frontal/executive defects.

  6. Discrepancy between subjective autobiographical reliving and objective recall: The past as seen by Alzheimer's disease patients.

    PubMed

    El Haj, Mohamad; Antoine, Pascal

    2017-03-01

    This paper investigated whether Alzheimer's disease (AD) patients may demonstrate a discrepancy between subjective autobiographical reliving and objective recall. To this end, 31 AD patients and 35 controls were asked to retrieve three autobiographical memories. For each memory, participants were asked to rate its subjective characteristics (e.g., reliving, travel in time, visual imagery…). Besides this subjective assessment, we analyzed recall objectively with regard to specificity. Results showed poorer subjective autobiographical reliving and objective recall in AD patients than in controls. A discrepancy (i.e., higher level of subjective reliving than of objective recall) was observed in AD but not in control participants. Despite a compromise in their objective recall, AD patients seemed to attribute a high value to their subjective autobiographical experience. This discrepancy can be attributed to a potential genuine consciousness experience in which mild AD patients can, to some extent, experience some subjective features of the past.

  7. Alzheimer's Disease Information Page

    MedlinePlus

    ... treat moderate to severe AD symptoms. View Full Treatment Information Definition Alzheimer's disease (AD) is an age-related, non-reversible ... that are developing and testing new and novel therapies that can relieve the symptoms of ... Alzheimer’s Plan . U.S. Secretary of Health and Human Services ...

  8. [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.

  9. What can we learn from study of Alzheimer's disease in patients with Down syndrome for early-onset Alzheimer's disease in the general population?

    PubMed Central

    2011-01-01

    The clinical and scientific study of dementia in adults with Down syndrome led to the development of the amyloid hypothesis as a fundamental concept in Alzheimer's disease pathogenesis. The journey started with the discovery of the structure and metabolic processing of β-amyloid brain deposits associated with Alzheimer's dementia in adults with Down syndrome, and then the prediction and confirmation of the amyloid precursor protein gene on chromosome 21. The processes and genes responsible for tau hyperphosphorylation contributing to toxic brain deposits were additionally identified. With increasing sophistication in genetic experimental techniques, additional mechanisms associated with excessive amyloid deposits were postulated and tested in brains of people with Down syndrome and Alzheimer's disease and in those with early-onset Alzheimer's disease. This in turn led to the proposal and testing for particular genetic defects associated with familial early-onset Alzheimer's disease. Nearly 200 genetic causes of early-onset types of Alzheimer's disease have since been identified. Only a minority of these causes are on chromosome 21, although the aetiology of excess amyloid production remains fundamental to their pathogenesis. Knowledge of the pathogenic mechanisms of Alzheimer's disease in predisposed families and in people with Down syndrome is a step closer to prevention or cure of this devastating disease. PMID:21542885

  10. Predictive validity of neuropsychiatric subgroups on nursing home placement and survival in patients with Alzheimer disease.

    PubMed

    Tun, Saw-Myo; Murman, Daniel L; Long, Heidi L; Colenda, Christopher C; von Eye, Alexander

    2007-04-01

    The aim of the study was to conceptualize neuropsychiatric symptoms in patients with Alzheimer disease as distinct symptom profiles with differential disease outcomes. Two outcomes of interest in the study were nursing home placement and survival. Cluster analysis was used to categorize 122 patients with Alzheimer disease based on their neuropsychiatric symptoms as assessed by the Neuropsychiatric Inventory. Both the presence as well as the severity and frequency of symptoms were considered. After identification of the subgroups, the predictive validity of the categorization was tested on time to nursing home placement and time to death over a three-year period. Cox proportional hazard models were used to perform survival analysis. Important covariates such as severity of cognitive and functional impairments, comorbid medical conditions, presence of parkinsonism, and marital status were adjusted at baseline. Based on the presence of neuropsychiatric symptoms, three subgroups were identified: minimally symptomatic, highly symptomatic, and affective/apathetic. Over a three-year period, the highly symptomatic group had an increased risk of nursing home placement. In addition, the rates of survival were significantly lower for the highly symptomatic and the affective/apathetic subgroups. Based on the severity and frequency of symptoms, two-cluster and four-cluster solutions were produced. The groupings based on severity and frequency of symptoms predicted significant differential outcomes in survival and nursing home placement. Neuropsychiatric subgroups were able to predict differential outcomes and identify those with an increased risk for a worse prognosis. The findings were discussed through their research and clinical implications.

  11. A practical guideline for intracranial volume estimation in patients with Alzheimer's disease

    PubMed Central

    2015-01-01

    Background Intracranial volume (ICV) is an important normalization measure used in morphometric analyses to correct for head size in studies of Alzheimer Disease (AD). Inaccurate ICV estimation could introduce bias in the outcome. The current study provides a decision aid in defining protocols for ICV estimation in patients with Alzheimer disease in terms of sampling frequencies that can be optimally used on the volumetric MRI data, and the type of software most suitable for use in estimating the ICV measure. Methods Two groups of 22 subjects are considered, including adult controls (AC) and patients with Alzheimer Disease (AD). Reference measurements were calculated for each subject by manually tracing intracranial cavity by the means of visual inspection. The reliability of reference measurements were assured through intra- and inter- variation analyses. Three publicly well-known software packages (Freesurfer, FSL, and SPM) were examined in their ability to automatically estimate ICV across the groups. Results Analysis of the results supported the significant effect of estimation method, gender, cognitive condition of the subject and the interaction among method and cognitive condition factors in the measured ICV. Results on sub-sampling studies with a 95% confidence showed that in order to keep the accuracy of the interleaved slice sampling protocol above 99%, the sampling period cannot exceed 20 millimeters for AC and 15 millimeters for AD. Freesurfer showed promising estimates for both adult groups. However SPM showed more consistency in its ICV estimation over the different phases of the study. Conclusions This study emphasized the importance in selecting the appropriate protocol, the choice of the sampling period in the manual estimation of ICV and selection of suitable software for the automated estimation of ICV. The current study serves as an initial framework for establishing an appropriate protocol in both manual and automatic ICV estimations with

  12. A practical guideline for intracranial volume estimation in patients with Alzheimer's disease.

    PubMed

    Sargolzaei, Saman; Sargolzaei, Arman; Cabrerizo, Mercedes; Chen, Gang; Goryawala, Mohammed; Noei, Shirin; Zhou, Qi; Duara, Ranjan; Barker, Warren; Adjouadi, Malek

    2015-01-01

    Intracranial volume (ICV) is an important normalization measure used in morphometric analyses to correct for head size in studies of Alzheimer Disease (AD). Inaccurate ICV estimation could introduce bias in the outcome. The current study provides a decision aid in defining protocols for ICV estimation in patients with Alzheimer disease in terms of sampling frequencies that can be optimally used on the volumetric MRI data, and the type of software most suitable for use in estimating the ICV measure. Two groups of 22 subjects are considered, including adult controls (AC) and patients with Alzheimer Disease (AD). Reference measurements were calculated for each subject by manually tracing intracranial cavity by the means of visual inspection. The reliability of reference measurements were assured through intra- and inter- variation analyses. Three publicly well-known software packages (Freesurfer, FSL, and SPM) were examined in their ability to automatically estimate ICV across the groups. Analysis of the results supported the significant effect of estimation method, gender, cognitive condition of the subject and the interaction among method and cognitive condition factors in the measured ICV. Results on sub-sampling studies with a 95% confidence showed that in order to keep the accuracy of the interleaved slice sampling protocol above 99%, the sampling period cannot exceed 20 millimeters for AC and 15 millimeters for AD. Freesurfer showed promising estimates for both adult groups. However SPM showed more consistency in its ICV estimation over the different phases of the study. This study emphasized the importance in selecting the appropriate protocol, the choice of the sampling period in the manual estimation of ICV and selection of suitable software for the automated estimation of ICV. The current study serves as an initial framework for establishing an appropriate protocol in both manual and automatic ICV estimations with different subject populations.

  13. Reflections on Alzheimer's disease.

    PubMed

    Kushnir, S L

    1982-02-01

    As longevity increases, society will face a silent epidemic of idiopathic dementias. The concept, Alzheimer's disease, reflects a cumbersome and vaguely-defined cluster of signs, symptoms and other variables which might more appropriately be labelled as the idiopathic dementias, Alzheimer-type or IDAT. Diagnosis, which is made by exclusion and treatment, primarily custodial, demonstrates the complex nature and unfortunate prognosis of the problem. Dramatic progress, nevertheless, has been made in various scientific aspects of the issue, namely, in histology, genetics and neurochemistry. The resulting evidence warrants further speculation on the role of central cholinergic neurotransmission in cognitive functioning.

  14. 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.

  15. 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.

  16. A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease.

    PubMed

    Loeb, Mark B; Molloy, D William; Smieja, Marek; Standish, Tim; Goldsmith, Charles H; Mahony, Jim; Smith, Stephanie; Borrie, Michael; Decoteau, Earl; Davidson, Warren; McDougall, Allan; Gnarpe, Judy; O'DONNell, Martin; Chernesky, Max

    2004-03-01

    To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimer's disease (AD). Randomized, triple-blind, controlled trial. Three tertiary care and two community geriatric clinics in Canada. One hundred one patients with probable AD and mild to moderate dementia. Oral daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months. The primary outcome was a change in Standardized Alzheimer's Disease Assessment Scale cognitive subscale (SADAScog) at 6 months. Secondary outcomes were changes in the SADAScog at 12 months and tests of dysfunctional behavior, depression, and functional status. There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence interval (CI)=-5.28 to -0.22, P=.034). At 12 months, the difference between groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P=.34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups. Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD. The mechanism is unlikely to be due to their effect on C. pneumoniae. More research is needed to investigate these agents.

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1999-06-01

    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 °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.

  19. Prevention of Alzheimer disease

    PubMed Central

    Scalco, Monica Zavaloni; van Reekum, Robert

    2006-01-01

    OBJECTIVE To review the evidence regarding prevention of Alzheimer disease (AD) in order to highlight the role of family medicine. QUALITY OF EVIDENCE Most of the evidence relating to prevention of AD is derived from observational (cross-sectional, case-control, or longitudinal) studies. Evidence from randomized controlled trials (RCTs) is available only for blood pressure control and for hormone replacement therapy for menopausal women. MAIN MESSAGE Many preventive approaches to AD have been identified, but no RCTs support their efficacy. Evidence from RCTs supports the effectiveness of blood pressure control in reducing incidence of AD, but demonstrates that postmenopausal women’s use of estrogen is ineffective in reducing it. Observational studies suggest that some preventive approaches, such as healthy lifestyle, ongoing education, regular physical activity, and cholesterol control, play a role in prevention of AD. These approaches can and should be used for every patient because they carry no significant risk. Currently, no effective pharmacologic interventions have been researched enough to support their use in prevention of AD. CONCLUSION Health professionals should educate patients, especially patients at higher risk of AD, about preventive strategies and potentially modifiable risk factors. PMID:16529393

  20. Predictors of mortality in patients with Alzheimer's disease living in nursing homes

    PubMed Central

    Gambassi, G.; Landi, F.; Lapane, K.; Sgadari, A.; Mor, V.; Bernabei, R.

    1999-01-01

    OBJECTIVES—To identify factors associated with mortality in patients with Alzheimer's disease, and to evaluate whether these factors vary according to severity of cognitive impairment.
METHODS—Data were from the SAGE database which includes information on all residents admitted between 1992 and 1995 to all Medicare/ Medicaid certified nursing homes of five US states. We conducted a longitudinal follow up study (median 23 months) on 9264 patients aged 65 years and above with a diagnosis of Alzheimer's disease. Patient data including demographic characteristics, dementia severity, comorbidity, and other clinical and treatment variables were collected with the Minimum Data Set. Information on death was derived through linkage to Medicare files. Baseline characteristics were used to predict survival in univariate and multivariate Cox proportional hazard models.
RESULTS—Overall mortality rate was 50%, with a first year rate of 25.7%. Increased age (risk ratio (RR) 1.83; 95% confidence interval (95% CI) 1.65-2.03, for patients 85+ years), male sex (RR 1.81; 95% CI 1.70-1.94), limitation in physical function (RR 1.45; 95% CI 1.27-1.66), a condition of malnutrition (RR 1.31; 95%CI 1.23-1.39), the presence of pressure ulcers (RR 1.24; 95% CI 1.13-1.36), a diagnosis of diabetes mellitus (RR 1.32; 95% CI 1.21-1.43), and of cardiovascular diseases (RR 1.22; 95% CI 1.14-1.30) were independent predictors of death, regardless of the severity of baseline dementia. Sensory problems (hearing and vision) and urinary incontinence were associated with increased mortality only among patients with less severe dementia. The presence of disruptive behaviour, aphasia, and a diagnosis of Parkinson's disease were not related to survival. African-Americans and other minority groups were less likely to die relative to white people.
CONCLUSIONS—Age, sex, functional limitation, and malnutrition seem to be the strongest predictors of death for patients with Alzheimer's disease in

  1. Goal setting and attainment in Alzheimer's disease patients treated with donepezil

    PubMed Central

    Rockwood, K; Graham, J; Fay, S

    2002-01-01

    Objectives: To understand the treatment goals of Alzheimer's disease (AD) patients, carers, and physicians; to estimate whether clinically important goals are met during treatment with donepezil; and to compare a measure of goal attainment with standard measures used to evaluate AD treatment. Methods: In a 12 month phase IV trial, 108 patients with mild to moderate AD, their primary carers, and treating physicians set goals assigned to five domains, using Goal Attainment Scaling (GAS) as the primary outcome. Goal attainment was assessed quarterly. GAS scores were correlated with standard outcomes, including the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog), and the Clinician's Interview-Based Impression of Change-Plus (CIBIC-plus). Results: Physicians set fewer goals (342, mean (SD) per patient=3 (1)) than patients/carers (855, mean=9 (3)), particularly in leisure (20% by physicians compared with 76% by patients/carers), and social interaction (24% versus 49%). Physicians observed statistically significant improvement in global goal attainment for six months, and patients/carers for nine months. Patients/carers described consistent goal attainment, whereas physicians observed variable effects, such as decline in cognition but improved social interaction and behaviour. Physician global GAS scores correlated highly with the CIBIC-plus at weeks 12 (r= -0.82) and 52 (r=-0.80), but not with the ADAS-cog (r=0.12 and r=-0.45, respectively). Patient/carer global GAS scores correlated moderately with the physician's CIBIC-plus (week 12 r=-0.51; week 52 r=-0.56), and nominally with the ADAS-cog. Conclusions: Patients/carers and physicians differ in their expectations and impressions of treatment effects. Clinically important changes correlated only modestly with psychometric tests. Attainment of treatment goals does not accord with a simplistic model in which successful AD treatment means that all declines uniformly improve. PMID:12397141

  2. Cognitive evaluation of patients with glaucoma and its comparison with individuals with Alzheimer's disease.

    PubMed

    Maurano, Stephanie Toledo Piza; da Silva, Delson José; Ávila, Marcos P; Magacho, Leopoldo

    2017-07-25

    To evaluate the cognitive performance of patients with glaucoma and compare it to individuals with Alzheimer's disease (AD). This is a prospective, cross-sectional and case-control study. All subjects were assessed using the Mini-Mental State Examination (MMSE) and its subtests verbal fluency, word list memory, delayed recall of the word list, word list recognition test, Boston naming and constructive praxis from Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The results were compared among the groups. A total of 50 healthy elderly with a mean age of 71.2 ± 5.2 years; 41 patients with glaucoma (72.2 ± 4.4 years); and 21 patients with AD (79.0 ± 7.6 years) were included. There was a reduction in all cognitive assessment tests evaluated, both for patients with glaucoma, and for those with AD compared with controls (p < 0.001 for all). Comparing the patients with glaucoma and AD, it was noted that the last had lower cognitive function (p < 0.001), except for the CERAD tests Boston (p = 0.1) and praxis (p = 0.6). Glaucoma patients, however, presented results of cognitive tests similar to those described for patients with mild AD, including lower values for MMSE (21.9 ± 3.7), Boston (10.6 ± 2.6) and praxis (5.9 ± 2.3). Glaucoma patients had reduction in cognition when compared to normal individuals. They were similar to the values reported in the literature for patients with mild AD, mostly, and also in some subjects with the presence of advanced AD.

  3. Elevated Galectin-3 Levels in the Serum of Patients With Alzheimer's Disease.

    PubMed

    Wang, Xuexin; Zhang, Shuping; Lin, Faliang; Chu, Wenzheng; Yue, Shouwei

    2015-12-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. Galectin-3 (Gal-3) is characterized by a conserved sequence within the carbohydrate recognition domain. The effect of Gal-3 in AD is presently unknown. In this study, we found significantly increased Gal-3 serum levels in patients with AD compared to control participants (P=.017). There was no significant difference between patients with mild cognitive impairment (MCI) and healthy controls (P=.143) or between patients with AD and MCI (P=.688). The degree of cognitive impairment, as measured by the Mini-Mental Status Examination score, was found to have a significant correlation with the Gal-3 serum levels in all patients and healthy controls. These data suggest that Gal-3 potentially plays a role in the neuropathogenesis of AD. The Gal-3 found in serum could be a potential candidate for a biomarker panel for AD diagnosis.

  4. [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.

  5. Altered Cell Viability and Proliferation Activity of Peripheral Lymphocytes in Patients with Alzheimer's Disease

    PubMed Central

    Yoon, Se Chang; Kwon, Young-Ah; Kim, Hyeran; Kim, Seonwoo; Ahn Jo, Sangmee

    2010-01-01

    Objective We evaluated cell viability and proliferation activity of peripheral lymphocytes as potential models of neuronal death in Alzheimer's disease (AD). Methods We analyzed the cell viability and proliferation activity of phytohemagglutinin (PHA)-activated lymphocytes from 68 AD patients and 33 normal controls. The cellular measures were made at baseline (0 hr), 24 hrs, 48 hrs, 72 hrs, and 96 hrs after PHA stimulation. Results Cell viability in the AD patients was significantly decreased at 72 hrs and 96 hrs, compared with the normal controls. The declining ramp of the proliferation activity from 48 hrs to 72 hrs after PHA stimulation was significantly related to cell viability at 72 hrs and at 96 hrs in the AD patients. Conclusion Lymphocytes from patients with AD have altered viability and proliferation characteristics in culture following PHA stimulation. These findings suggest that lymphocytes may be used as a peripheral tissue model of cell cycle dysregulation in AD. PMID:20396436

  6. 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 ...

  7. Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI

    PubMed Central

    Horng, Andy; Fero, Allison; Jagust, William J.

    2016-01-01

    Objective: To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective cohort study. Methods: We first investigated the reliability of florbetapir− PET in patients with AD and patients with MCI using CSF-Aβ1–42 as a comparison amyloid measurement. We then compared florbetapir− vs florbetapir+ patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data. Results: Florbetapir and CSF-Aβ1–42 +/− status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir− scans were a reliable representation of amyloid status. Florbetapir− AD (n = 27/177; 15%) and MCI (n = 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir+ counterparts (MCI 30%, AD 24%). Florbetapir− patients also had less AD-specific hypometabolism, lower CSF p-tau and t-tau, and better longitudinal cognitive performance, and were more likely to be taking medication for depression. In MCI only, florbetapir− participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir+ participants. Conclusions: Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir− ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype. PMID:26968515

  8. Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI.

    PubMed

    Landau, Susan M; Horng, Andy; Fero, Allison; Jagust, William J

    2016-04-12

    To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective cohort study. We first investigated the reliability of florbetapir- PET in patients with AD and patients with MCI using CSF-Aβ1-42 as a comparison amyloid measurement. We then compared florbetapir- vs florbetapir+ patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data. Florbetapir and CSF-Aβ1-42 +/- status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir- scans were a reliable representation of amyloid status. Florbetapir- AD (n = 27/177; 15%) and MCI (n = 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir+ counterparts (MCI 30%, AD 24%). Florbetapir- patients also had less AD-specific hypometabolism, lower CSF p-tau and t-tau, and better longitudinal cognitive performance, and were more likely to be taking medication for depression. In MCI only, florbetapir- participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir+ participants. Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir- ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype. © 2016 American Academy of Neurology.

  9. Ibuprofen and Alzheimer's disease.

    PubMed

    Dokmeci, Dikmen

    2004-01-01

    There is epidemiological observation that long-term treatment of patients suffering from rheumatoid arthritis with ibuprofen results in reduced risk and delayed onset of Alzheimer's disease (AD). Chronic central nervous system inflammation in AD brain is implicated in the pathology, but how ibuprofen impacts the pathogenic AD pathways is unclear. Ibuprofen, a commonly used over-the-counter nonsteroidal anti-inflammatory drug (NSAID) that is a cyclooxygenase (COX)-1 and COX-2 inhibitor as well as a peroxisome proliferator-activated receptor (PPAR) agonist, decreases the production of nitric oxide (NO), protects neurons against glutamate toxicity and decreases the production of proinflammatory cytokines. Ibuprofen crosses the blood brain barrier and suppresses neuritic plaque pathology and inflammation in AD brain. Furthermore, ibuprofen is a potent free radical scavenger, and it could reduce lipid peroxidation and free radical generation. Because of neuroprotective activity, relative safety, and its long history of use, ibuprofen is currently being developed for clinical use in AD. Ibuprofen may be a promising new therapeutic avenue for the treatment of neurodegenerative diseases such as AD.

  10. [Biomarkers in Alzheimer's disease].

    PubMed

    García-Ribas, G; López-Sendón Moreno, J L; García-Caldentey, J

    2014-04-01

    The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

  11. Predictors of patient dependence in mild-to-moderate Alzheimer's disease.

    PubMed

    Benke, Thomas; Sanin, Günter; Lechner, Anita; Dal-Bianco, Peter; Ransmayr, Gerhard; Uranüs, Margarete; Marksteiner, Josef; Gaudig, Maren; Schmidt, Reinhold

    2015-01-01

    Patient dependence has rarely been studied in mild-to-moderate Alzheimer's disease (AD). To identify factors which predict patient dependence in mild-to-moderate AD. We studied 398 non-institutionalized AD patients (234 females) of the ongoing Prospective Registry on Dementia (PRODEM) in Austria. The Dependence Scale (DS) was used to assess patient dependence. Patient assessment comprised functional abilities, neuropsychiatric symptoms and cognitive functions. A multiple linear regression analysis was performed to identify predictors of patient dependence. AD patients were mildly-to-moderately impaired (mean scores and SDs were: CDR 0.84 ± 0.43; DAD 74.4 ± 23.3, MMSE = 22.5 ± 3.6). Psychopathology and caregiver burden were in the low range (mean NPI score 13.2, range 0 to 98; mean ZBI score 18, range 0-64). Seventy five percent of patients were classified as having a mild level of patient dependence (DS sum score 0 to 6). Patient dependence correlated significantly and positively with age, functional measures, psychopathology and depression, disease duration, and caregiver burden. Significant negative, but low correlations were found between patient dependence, cognitive variables, and global cognition. Activities of daily living, patient age, and disease severity accounted for 63% of variance in patient dependence, whereas cognitive variables accounted for only 11%. Dependence in this cohort was mainly related to age and functional impairment, and less so to cognitive and neuropsychiatric variables. This differs from studies investigating patients in more advanced disease stages which found abnormal behavior and impairments of cognition as main predictors of patient dependence.

  12. Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imaging.

    PubMed

    Wang, Dan; Li, Yan-Ying; Luo, Jian-Hua; Li, Yue-Hua

    2014-01-01

    This study aimed to investigate age-related iron deposition changes in healthy subjects and Alzheimer disease patients using susceptibility weighted imaging. The study recruited 182 people, including 143 healthy volunteers and 39 Alzheimer disease patients. All underwent conventional magnetic resonance imaging and susceptibility weighted imaging sequences. The groups were divided according to age. Phase images were used to investigate iron deposition in the bilateral head of the caudate nucleus, globus pallidus and putamen, and the angle radian value was calculated. We hypothesized that age-related iron deposition changes may be different between Alzheimer disease patients and controls of the same age, and that susceptibility weighted imaging would be a more sensitive method of iron deposition quantification. The results revealed that iron deposition in the globus pallidus increased with age, up to 40 years. In the head of the caudate nucleus, iron deposition peaked at 60 years. There was a general increasing trend with age in the putamen, up to 50-70 years old. There was significant difference between the control and Alzheimer disease groups in the bilateral globus pallidus in both the 60-70 and 70-80 year old group comparisons. In conclusion, iron deposition increased with age in the globus pallidus, the head of the caudate nucleus and putamen, reaching a plateau at different ages. Furthermore, comparisons between the control and Alzheimer disease group revealed that iron deposition changes were more easily detected in the globus pallidus.

  13. [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.

  14. Alternative Medicine and Alzheimer's Disease

    PubMed Central

    Kelley, Brendan J.; Knopman, David S.

    2009-01-01

    Background Alternative medicine has an extensive worldwide history and is commonly used by older patients. A number of different alternative medicines are used by patients having Alzheimer's disease. It is both desirable and expected for clinicians to be acquainted with these medications. Review Summary This paper discusses the available clinical trial evidence regarding eight agents commonly used by people having Alzheimer's disease. We provide an overview of the history and basic scientific evidence available for each agent, followed by a critical analysis of the evidence available from clinical trials, including the number of participants, trial duration and specific outcomes evaluated. Conclusion While many of these compounds have been associated with interesting basic science, none has shown clear clinical benefit to date. Data available for some, such as ginkgo biloba, curcumin and huperzine A, suggest that further evaluation is warranted. Familiarity with this literature will allow clinicians to provide meaningful recommendations to patients who wish to use these agents. PMID:18784599

  15. Sundowning and circadian rhythms in Alzheimer's disease.

    PubMed

    Volicer, L; Harper, D G; Manning, B C; Goldstein, R; Satlin, A

    2001-05-01

    The goal of this study was to determine changes of circadian rhythms induced by Alzheimer's disease and to explore relationships among rhythm disturbances, sundowning, and sleep disturbances in patients with Alzheimer's disease. "Sundowning" is the occurrence or exacerbation of behavioral symptoms of Alzheimer's disease in the afternoon and evening. Circadian rhythms of core body temperature and motor activity were measured in 25 patients with diagnoses of probable Alzheimer's disease and in nine healthy individuals. The subjects with Alzheimer's disease were divided according to the occurrence of sundowning as determined by staff reports. The subjects with Alzheimer's disease had less diurnal motor activity, a higher percentage of nocturnal activity, lower interdaily stability of motor activity, and a later activity acrophase (time of peak) than did the healthy individuals. They also had a higher mesor (fitted mean) temperature, higher amplitude of the fitted cosine temperature curve, and later temperature acrophase than did the healthy subjects. The severity of sundowning was associated with later acrophase of temperature, less correlation of circadian temperature rhythm with a 24-hour cycle, and lower amplitude of temperature curve. These data indicate that Alzheimer's disease causes disturbances of circadian rhythms and that sundowning is related to a phase delay of body temperature caused by Alzheimer's disease.

  16. Genetics of Alzheimer's disease.

    PubMed

    Alonso Vilatela, María Elisa; López-López, Marisol; Yescas-Gómez, Petra

    2012-11-01

    Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly and represents an important and increasing clinical challenge in terms of diagnosis and treatment. This review highlights the role of genetics in understanding the pieces of the complex AD puzzle and summarizes the genes known to be involved in Alzheimer's disease. The amount of risk of Alzheimer's disease that is attributable to genetics is estimated to be ∼70%. Mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) are responsible for early-onset autosomal dominant AD. Although mutations in these genes account for ∼1% of AD cases, their identification has been crucial to understand the molecular mechanisms of AD. For the more common complex late-onset AD, the ɛ-4 allele of the gene encoding apolipoprotein E (APOE) has been recognized as a major genetic risk factor. More recently, several potential disease risk genes have been identified with the use of advanced genomic methods like genome-wide association studies (GWAS). In the end, the knowledge of the pathophysiological mechanisms leading to AD will enable the development of more accurate diagnostic tests and new disease-treating strategies. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

  17. Comparison of reading and spelling in patients with probable Alzheimer's disease.

    PubMed

    Glosser, G; Grugan, P; Friedman, R B

    1999-07-01

    Patients with probable Alzheimer's disease (AD) are reported to show mild, but reliable, difficulties reading aloud and spelling to dictation exception words, which have unusual or unpredictable correspondence between their spelling and pronunciation (e.g., touch). To understand the cognitive dysfunction responsible for these impairments, 21 patients and 27 age-and education-matched controls completed specially designed tests of single-word oral reading and spelling to dictation. AD patients performed slightly below controls on all tasks and showed mildly exaggerated regularity effects (i.e., the difference in response accuracy between words with regular spellings minus exception words) in reading and spelling. Qualitative analyses, however, did not demonstrate response patterns consistent with impairment in central lexical orthographic processing. The authors conclude that the mild alexia and agraphia in AD reflect semantic deficits and nonlinguistic impairments rather than a specific disturbance in lexical orthographic processing.

  18. Naming in patients with Alzheimer's disease: influence of age of acquisition and categorical effects.

    PubMed

    Silveri, Maria Caterina; Cappa, Antonella; Mariotti, Paolo; Puopolo, Maria

    2002-09-01

    The role of age of acquisition (AoA) and other variables classically supposed to influence lexical semantic tasks is explored in Alzheimer's disease (AD) patients. A naming test that included living and nonliving items was given to patients and controls. Measures of AoA of the test items were obtained from normal subjects. Living items were acquired earlier than nonliving items. Semipartial correlation analyses were performed to determine the independent contribution of each variable to naming. The "category" (living vs. nonliving items) was included as an independent factor. It emerged that AoA, name agreement and category (with living category predicting lower scores) were the main predictors of naming in AD patients. Only factor agreement reached significance in control groups. The hypothesis is discussed that the category dissociation may be produced by the different nature of the semantic correlation network that makes the categories differentially demanding of processing resources.

  19. Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor.

    PubMed

    Ferreira, Daniel; Westman, Eric; Eyjolfsdottir, Helga; Almqvist, Per; Lind, Göran; Linderoth, Bengt; Seiger, Ake; Blennow, Kaj; Karami, Azadeh; Darreh-Shori, Taher; Wiberg, Maria; Simmons, Andrew; Wahlund, Lars-Olof; Wahlberg, Lars; Eriksdotter, Maria

    2015-01-01

    New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age- and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.

  20. Multiple microbleeds are related to cerebral network disruptions in patients with early Alzheimer's disease.

    PubMed

    Heringa, Sophie M; Reijmer, Yael D; Leemans, Alexander; Koek, Huiberdina L; Kappelle, L Jaap; Biessels, Geert Jan

    2014-01-01

    Cerebral microbleeds are a manifestation of small vessel disease and are common in patients with Alzheimer's disease (AD). However, their clinical significance in this condition is uncertain. We hypothesized that microbleeds contribute to disturbances of the cerebral network in AD and as such may affect cognition. The goal of this study was to examine the relationship between microbleeds and brain networks in patients with amnestic mild cognitive impairment (aMCI) or early AD. Sixty-seven patients (77.9 ± 7.5 years) with aMCI (n = 29) or early AD (n = 38) underwent cognitive testing and 3Tesla MRI. Microbleeds were rated visually. Diffusion tensor imaging and graph theoretical analysis were used to reconstruct brain networks and to quantify network efficiency for each patient. Network measures were compared between patients without and with ≥1 microbleeds and between patients without or with ≥3 microbleeds. In secondary analyses, cognitive functioning was compared between groups. Analyses were adjusted for age and gender, and additionally for other markers of small vessel disease and atrophy. Network measures did not differ between patients with ≥1 microbleed (n = 26) and patients without microbleeds (n = 41). However, patients with ≥3 microbleeds (n = 11) showed significant white matter disruptions, longer path length, and less global efficiency than patients without microbleeds, independent of other markers of small vessel disease and atrophy. Cognitive functioning did not differ between patients without microbleeds and patients with ≥1 or ≥3 microbleeds. Multiple microbleeds are related to structural network disruption in patients with early AD, but their direct impact on cognitive functioning appears to be limited.

  1. 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…

  2. 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…

  3. Enhanced levels of mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 in patients with Alzheimer disease and multiple sclerosis.

    PubMed

    Kristofiková, Zdena; Bocková, Markéta; Hegnerová, Katerina; Bartos, Ales; Klaschka, Jan; Rícný, Jan; Rípová, Daniela; Homola, Jirí

    2009-10-01

    The multifunctional mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 might play a role in the development of Alzheimer disease via its high-affinity binding to amyloid beta peptides and its neuronal over-expression. It is suggested that the cerebrospinal fluid levels of the enzyme, free or bound to amyloid beta peptides, are a potential specific biomarker of Alzheimer disease. However, mitochondrial dysfunction seems to play a role in many neurological diseases including multiple sclerosis. In this study, the specificity of changes in relation to the enzyme over-expression was evaluated using enzyme-linked immunosorbent and surface plasmon resonance sensors. The data indicated pronounced increases in the enzyme levels, specifically to 179% in multiple sclerosis and to 573% in Alzheimer disease when compared to the age-matched controls. Although the differences between both diseases were statistically significant, enzyme levels do not appear to be a highly specific biomarker of Alzheimer disease. On the other hand, enhancement in levels of the enzyme bound to amyloid beta peptides was only observed in people with Alzheimer disease, which suggests that the complex should be further considered as a possible biomarker. In patients with multiple sclerosis, our results are the first to demonstrate significant changes in enzyme expression and to suggest possible alterations in amyloid beta peptides.

  4. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease.

    PubMed

    Mittelman, Mary S; Haley, William E; Clay, Olivio J; Roth, David L

    2006-11-14

    To determine the effectiveness of a counseling and support intervention for spouse caregivers in delaying time to nursing home placement of patients with Alzheimer disease (AD), and identify the mechanisms through which the intervention accomplished this goal. We conducted a randomized controlled trial of an enhanced counseling and support intervention compared to usual care. Participants were a referred volunteer sample of 406 spouse caregivers of community-dwelling patients who had enrolled in the study over a 9.5-year period. The intervention consisted of six sessions of individual and family counseling, support group participation, and continuous availability of ad hoc telephone counseling. Structured questionnaires were administered at baseline and at regular follow-up intervals, every 4 months for the first year and every 6 months thereafter. Cox proportional hazard models were used to test the effects of the intervention on the time to nursing home placement for the patients after controlling for multiple time-invariant and time-dependent predictors of placement. Patients whose spouses received the intervention experienced a 28.3% reduction in the rate of nursing home placement compared with usual care controls (hazard ratio = 0.717 after covariate adjustment, p = 0.025). The difference in model-predicted median time to placement was 557 days. Improvements in caregivers' satisfaction with social support, response to patient behavior problems, and symptoms of depression collectively accounted for 61.2% of the intervention's beneficial impact on placement. Greater access to effective programs of counseling and support could yield considerable benefits for caregivers, patients with Alzheimer disease, and society.

  5. Modifications of platelet from Alzheimer disease patients: a possible relation between membrane properties and NO metabolites.

    PubMed

    Vignini, Arianna; Nanetti, Laura; Moroni, Cinzia; Tanase, Laura; Bartolini, Marco; Luzzi, Simona; Provinciali, Leandro; Mazzanti, Laura

    2007-07-01

    Alzheimer disease (AD) is a chronic neurodegenerative disorder characterised by a progressive loss of memory and cognitive functions. The formation of nitric oxide (NO), by astrocytes, has been suggested to contribute to the neurodegnerative process. Some studies have described the participation of different isoforms of NOS in the progression of AD. The present work was conducted in order to investigate the role played by NO and peroxynitrite in platelets from AD patients, the possible correlation with Na(+)/K(+)-ATPase activity and the intracellular Ca(2+) in the same group of patients as well as the expression of NOS isoenzymes and nitrotyrosine as markers of NO synthesis and reactive protein nitration. NO production was significantly elevated in the platelets from AD patients compared to controls as well as l-arginine/NO-dependent ONOO(-). Membrane Na(+)/K(+)-ATPase activity was significantly decreased in patients than in controls while intracellular Ca(2+) concentration shows an opposite trend. Platelet from AD patients showed a significantly increased 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence anisotropy compared with controls. Western blot analysis using anti-iNOS and eNOS monoclonal antibodies demonstrated that both isoforms were detectable in cell lysates as well as nitrotyrosine more pronounced in the cell lysates from AD patients than controls. In conclusion, the increased expression and activity of nitrergic system may produce platelet membrane alteration or vice versa. These modifications may contribute further to the neurodegenerative process in AD because the abnormal function of Alzheimer platelets play a very important role in the pathogenesis of the disease.

  6. Identifying patients with Alzheimer's disease using resting-state fMRI and graph theory.

    PubMed

    Khazaee, Ali; Ebrahimzadeh, Ata; Babajani-Feremi, Abbas

    2015-11-01

    Study of brain network on the basis of resting-state functional magnetic resonance imaging (fMRI) has provided promising results to investigate changes in connectivity among different brain regions because of diseases. Graph theory can efficiently characterize different aspects of the brain network by calculating measures of integration and segregation. In this study, we combine graph theoretical approaches with advanced machine learning methods to study functional brain network alteration in patients with Alzheimer's disease (AD). Support vector machine (SVM) was used to explore the ability of graph measures in diagnosis of AD. We applied our method on the resting-state fMRI data of twenty patients with AD and twenty age and gender matched healthy subjects. The data were preprocessed and each subject's graph was constructed by parcellation of the whole brain into 90 distinct regions using the automated anatomical labeling (AAL) atlas. The graph measures were then calculated and used as the discriminating features. Extracted network-based features were fed to different feature selection algorithms to choose most significant features. In addition to the machine learning approach, statistical analysis was performed on connectivity matrices to find altered connectivity patterns in patients with AD. Using the selected features, we were able to accurately classify patients with AD from healthy subjects with accuracy of 100%. Results of this study show that pattern recognition and graph of brain network, on the basis of the resting state fMRI data, can efficiently assist in the diagnosis of AD. Classification based on the resting-state fMRI can be used as a non-invasive and automatic tool to diagnosis of Alzheimer's disease. Copyright © 2015 International Federation of Clinical Neurophysiology. All rights reserved.

  7. Quantitative EEG and apolipoprotein E-genotype improve classification of patients with suspected Alzheimer's disease.

    PubMed

    Hatz, F; Benz, N; Hardmeier, M; Zimmermann, R; Rueegg, S; Schindler, C; Miserez, A R; Gschwandtner, U; Monsch, A U; Fuhr, P

    2013-11-01

    To establish a model for better identification of patients in very early stages of Alzheimer's disease, AD (including patients with amnestic MCI) using high-resolution EEG and genetic data. A total of 26 patients in early stages of probable AD and 12 patients with amnestic MCI were included. Both groups were similar in age and education. All patients had a comprehensive neuropsychological examination and a high resolution EEG. Relative band power characteristics were calculated in source space (LORETA inverse solution for spectral data) and compared between groups. A logistic regression model was calculated including relative band-power at the most significant location, ApoE status, age, education and gender. Differences in the delta band at 34 temporo-posterior source locations (p<.01) between AD and MCI groups were detected after correction for multiple comparisons. Classification slightly increased when ApoE status was added (p=.06 maximum likelihood test). Adjustment of analyses for the confounding factors age, gender and education did not alter results. Quantitative EEG (qEEG) separates between patients with amnestic MCI and patients in early stages of probable AD. Adding information about Apo ε4 allele frequency slightly enhances diagnostic accuracy. qEEG may help identifying patients who are candidates for possible benefit from future disease modifying treatments. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Weight loss, nutritional status and physical activity in patients with Alzheimer's disease. A controlled study.

    PubMed

    Wang, Pei-Ning; Yang, Chueh-Lien; Lin, Ker-Neng; Chen, Wei-Ta; Chwang, Leh-Chii; Liu, Hsiu-Chih

    2004-03-01

    The etiology of weight loss in Alzheimer's disease (AD) patients is still uncertain. This study was designed to investigate the possible factors that might contribute to weight change of AD patients. From July 1999 to June 2001, we recruited 51 AD patients and 27 non-demented controls. Demographic data, neuropsychological tests, Geriatric Depression Scale-Short Form, eating behavior questionnaire, dietary and physical activity diaries, anthropometric and laboratory measures of nutritional status were assessed. More than half of our AD patients developed body weight loss, and overall, the AD patients were significantly thinner than the non-demented subjects. Anthropometric and laboratory measures suggested a poorer nutritional status in the AD patients. The AD patients had fewer daily physical activities. More AD patients had the problem of poor appetite. However, daily calorie intake was not significantly different between the two groups. The AD patients, especially those who presented with body weight loss, even consumed more calories per body weight kilogram (kg) per day. In the food composition analysis, AD patients took more carbohydrate than controls. Multivariate regression analysis showed the existence of AD and poor appetite were the main risk factors of weight loss. We suggest that the pathophysiological process in AD gives rise to the changes of appetite and metabolic state in AD patients, and that these changes contribute to the weight loss.

  9. Weight loss and rapid cognitive decline in community-dwelling patients with Alzheimer's disease.

    PubMed

    Soto, Maria E; Secher, Marion; Gillette-Guyonnet, Sophie; Abellan van Kan, Gabor; Andrieu, Sandrine; Nourhashemi, Fati; Rolland, Yves; Vellas, Bruno

    2012-01-01

    Weight loss is a frequent complication of Alzheimer's disease (AD) and a strong predictor of adverse outcomes in patients suffering from this disease. The aim of this study was to determine whether weight loss was a predictor of rapid cognitive decline (RCD) in AD. Four hundred fourteen community-dwelling ambulatory patients with a diagnosis of probable AD and a Mini-Mental State Examination (MMSE) score between 10 and 26 from the REAL.FR (REseau sur la maladie d'ALzheimer FRançais) cohort were studied and followed up during 4 years. Patients were classified in 2 groups according to weight loss defined by a loss of 4% or more during the first year of follow-up. RCD was defined as the loss of 3 points or more in MMSE over 6 months. The incidence of RCD was determined among both groups over the last 3 years of follow-up. MMSE, Katz's Activity of Daily Living scale, Mini-Nutritional Assessment scale, co-morbidities, behavioral and psychological symptoms of dementia, medication, level of education, living arrangement, and caregiver's burden were assessed every 6 months. Eighty-seven patients (21.0%) lost 4% or more of their initial weight during the first year. The incidence of RCD for all patients was 57.6 (95% confidence interval (CI) = 51.6-64.8) per 100 person-year (median follow-up of 15.1 months). In Cox proportional hazards models, after controlling for potential confounders, weight loss was a significant predictor factor of RCD (adjusted hazard ratio (HR) = 1.50, 95% CI = 1.04-2.17). In conclusion, weight loss predicted RCD in this cohort. Whether the prevention of weight loss (by improving nutritional status) impacts cognitive decline remains an open question.

  10. Hallucinations and signs of parkinsonism help distinguish patients with dementia and cortical Lewy bodies from patients with Alzheimer's disease at presentation: a clinicopathological study.

    PubMed Central

    Ala, T A; Yang, K H; Sung, J H; Frey, W H

    1997-01-01

    OBJECTIVES: To compare, in a retrospective clinicopathological study, the presentation features of patients with dementia and cortical Lewy bodies (Lewy body dementia) with those of patients with Alzheimer's disease. METHODS: From a population of 426 cases from the dementia brain bank, 39 cases of Lewy body dementia and 61 cases of Alzheimer's disease with presentation details were identified. RESULTS: The Lewy body dementia group had significantly more frequent hallucinations (23% v 3%, P = 0.006) and signs of parkinsonism (41% v 5%, P < 0.0001) than the Alzheimer's disease group. The Lewy body dementia group also had a greater proportion of men (62% v 34%, P = 0.013). CONCLUSION: Hallucinations and signs of parkinsonism help distinguish Lewy body dementia from Alzheimer's disease at presentation. These indicators may not be very sensitive, because they were reported for less than half of the patients with Lewy body dementia. PMID:9010394

  11. Immunotherapy for Alzheimer's Disease

    PubMed Central

    Wisniewski, Thomas; Goni, Fernando

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD the normal soluble amyloid β (sAβ) peptide is converted into oligomeric/fibrillar Aβ. The oligomeric forms of Aβ are thought to be the most toxic, while fibrillar Aβ becomes deposited as amyloid plaques and congophilic angiopathy, which serve as neuropathological markers of the disease. In addition the accumulation of abnormally phosphorylated tau as soluble toxic oligomers and as neurofibrillary tangles is a critical part of the pathology. Numerous therapeutic interventions are under investigation to prevent and treat AD. Among the more exciting and advanced of these approaches is vaccination. Active and passive Immunotherapy targeting only Aβ has been successful in many AD model animal trials; however, the more limited human data has shown much less benefit so far, with encephalitis occurring in a minority of patients treated with active immunization and vasogenic edema or amyloid-related imaging abnormalities (ARIA) being a complication in some passive immunization trials. Therapeutic intervention targeting only tau has been tested only in mouse models; and no approaches targeting both pathologies concurrently has been attempted, until very recently. The immune approaches tried so far were targeting a self-protein, albeit in an abnormal conformation; however, effective enhanced clearance of the disease associated conformer has to be balanced with the potential risk of stimulating excessive toxic inflammation. The design of future more effective immunomodulatory approaches will need to target all aspects of AD pathology, as well as specifically targeting pathological oligomeric conformers, without the use of any self-antigen. PMID:24412277

  12. [Calcium hypothesis of Alzheimer disease].

    PubMed

    Riazantseva, M A; Mozhaeva, G N; Kaznacheeva, E V

    2012-01-01

    Alzheimer's disease is the most common neurodegenerative disorder characterized by progressive memory and cognitive abilities loss. The etiology of Alzheimer's disease is poorly understood. In this regard, there is no effective treatment for the disease. Various hypotheses to explain the nature of the pathology of Alzheimer's disease led to the development of appropriate therapeutics. Despite of decades of research and clinical trials available therapeutics, at best, can only slow down the progression of the disease, but cannot cure it. This review dedicated to the one of modern hypotheses of Alzheimer's disease pathogenesis implied the impairment of calcium homeostasis as a key event for the development of neurodegenerative processes.

  13. Blood transcriptomic biomarkers of Alzheimer's disease patients treated with EHT 0202.

    PubMed

    Désiré, Laurent; Blondiaux, Elodie; Carrière, Jennifer; Haddad, Raphael; Sol, Olivier; Fehlbaum-Beurdeley, Pascale; Einstein, Rich; Zhou, Weiyin; Pando, Matthew P

    2013-01-01

    Monitoring the genomic expression of patients in clinical trials for Alzheimer's disease (AD) can assist trial design and treatment response analysis. Here, we report on the identification in AD patients of blood-based transcriptomic signatures associated with treatment response of EHT 0202, a new compound with potential disease-modifying and symptomatic properties, in a 3-month, placebo-controlled, Phase IIA study aimed at determining the clinical safety, tolerability, and exploratory efficacy of EHT 0202 (40 and 80 mg bid) as adjunctive therapy to one cholinesterase inhibitor in mild to moderate AD patients. Genome-wide transcriptomic profiling was performed on blood samples taken prior to treatment and at study completion in a subpopulation of 60 AD patients selected as either the 10 worst disease decliners or the 10 best improvers of each treatment group, using ADAS-Cog scores as measure of disease severity. In the patients responding to EHT 0202, a pre-treatment (baseline) transcriptomic signature showed activation of pathways related to AD, CNS disorders, diabetes, inflammation, and autoimmunity, while a post-treatment signature indicated reduced activation of these pathways with induced metabolic and transcription stimulation. This pilot study demonstrates the utility of blood transcriptomic signatures used as biomarkers for predicting patient response or monitoring efficacy, for an administered therapeutic drug in a complex disease such as AD. For EHT 0202 or other AD drugs, such biomarkers may help to improve strategies to better identify appropriate patient populations for treatment, understand the drug mechanism of efficacy, and/or clarify the inherent subjectivity in most clinical endpoints used in this disease.

  14. Prediction of probable Alzheimer's disease in memory-impaired patients: A prospective longitudinal study.

    PubMed

    Tierney, M C; Szalai, J P; Snow, W G; Fisher, R H; Nores, A; Nadon, G; Dunn, E; St George-Hyslop, P H

    1996-03-01

    We determined whether a battery of neuropsychological tests could predict who would develop Alzheimer's disease (AD) in a group of 123 memory-impaired nondemented patients. Patients were followed longitudinally for 2 years with a research battery of neuropsychological tests. After 2 years, 29 developed probable AD, and 94 did not develop dementia. We used logistic regression analyses to examine the classification accuracy of subjects' performance at entry to the study on the research battery. The logistic regression model was significant with an accuracy of 89%, sensitivity of 76%, and specificity of 94%. Two tests contributed significantly to this model: the delayed recall from the Rey Auditory Verbal Learning Test and the Mental Control subtest of the Wechsler Memory Scale. These two tests alone produced the same accuracy, sensitivity, and specificity as the larger model. These results demonstrate that probable AD can be predicted with a high degree of accuracy and with a relatively brief battery of neuropsychological tests.

  15. MR diffusion tensor imaging (DTI) and neuropsychological testing for neuronal connectivity in Alzheimer's disease (AD) patients

    NASA Astrophysics Data System (ADS)

    Zhong, Jianhui; Ni, Hongyan; Zhu, Tong; Ekholm, Sven; Kavcic, Voyko

    2004-04-01

    We have used MR DTI to identify relevant brain structures involved in visuospatial processing, in an attempt to link perceptual and attentional impairments to WM changes in Alzheimer's disease (AD) patients. Correlation of DTI measured parameters with results of several neuropsychological tests will be reported here. Several issues related to quantitation of DTI parameters in ROI analysis are addressed. In spite of only a small number of subjects were studied so far, we found not only that AD patients showed significant decrease of white matter (WM) integrity in corpus callosum (CC), most prominent at the posterior portion, but also found significant correlations between the DTI parameters and scores from several neuropsychological tests. Our preliminary results suggest that DTI help to improve the overall accuracy rate in distinguishing between early AD onset and age-related functional decline, and potentially may improve efficiency in differentiating between different types of dementia.

  16. Vibrational spectroscopic analysis of peripheral blood plasma of patients with Alzheimer's disease.

    PubMed

    Carmona, Pedro; Molina, Marina; López-Tobar, Eduardo; Toledano, Adolfo

    2015-10-01

    Using Raman and infrared spectroscopy, we monitored spectral changes occurring in the blood plasma of patients with Alzheimer's disease (AD) in relation to healthy controls. The protein secondary structure as reflected by amide I band involves β-sheet enrichment, which may be attributable to Aβ peptide formation and to increasing proportion of the globulins that are β-sheet rich. Likewise, the behavior of the infrared 1200-1000-cm(-1) region and the Raman 980-910- and 450-400-cm(-1) regions can be explained in terms of the said plasma composition change. Further, the 744-cm(-1) Raman band from healthy control plasma shows frequency upshifting in the course of AD, which may be generated by the platelets collected in blood plasma. Linear discrimination analysis and receiver operating characteristic (ROC) analysis have been used to distinguish between patients with AD and age-matched healthy controls with a diagnostic accuracy of about 94%.

  17. Oxidative Stress in Patients with Alzheimer's Disease: Effect of Extracts of Fermented Papaya Powder

    PubMed Central

    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

  18. Contact Heat Evoked Potentials (CHEPs) in Patients with Mild-Moderate Alzheimer's Disease and Matched Control--A Pilot Study.

    PubMed

    Jensen-Dahm, Christina; Madsen, Caspar Skau; Waldemar, Gunhild; Ballegaard, Martin; Hejl, Anne-Mette; Johnsen, Birger; Jensen, Troels Staehelin

    2016-04-01

    Clinical studies have found that patients with Alzheimer's disease report pain of less intensity and with a lower affective response, which has been thought to be due to altered pain processing. The authors wished to examine the cerebral processing of non-painful and painful stimuli using somatosensory evoked potentials and contact heat evoked potentials in patients with Alzheimer's disease and in healthy elderly controls. Case-control study Twenty outpatients with mild-moderate Alzheimer's disease and in 17 age- and gender-matched healthy controls were included Contact heat evoked potentials and somatosensory evoked potentials were recorded in all subjects. Furthermore, warmth detection threshold and heat pain threshold were assessed. Patients and controls also rated quality and intensity of the stimuli. The authors found no difference on contact heat evoked potential amplitude (P = 0.59) or latency of N2 or P2 wave (P = 0.62 and P = 0.75, respectively) between patients and controls. In addition, there was no difference in regard to pain intensity scores or pain quality. The patients and controls had similar warmth detection threshold and heat pain threshold. Somatosensory evoked potentials, amplitude, and latency were within normal range and similar for the two groups. The findings suggest that the processing of non-painful and painful stimuli is preserved in patients with mild to moderate Alzheimer's disease. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Assessment of Health-Related Quality of Life for Caregivers of Alzheimer's Disease Patients

    PubMed Central

    Papadopoulos, Angelos A.; Panagiotakos, Demosthenes B.

    2016-01-01

    Background. Alzheimer's disease (AD) dementia is a chronic neurodegenerative disorder that results in total cognitive impairment and functional decline. Family members are the most usual caregivers worldwide, resulting in a subsequent degradation of their quality of life. Methods. During November 2013–March 2014 in Athens, Greece, 155 AD patients' family caregivers' Health-Related Quality of Life and existence of depressive symptomatology were assessed. Results. A strong negative correlation between the dimensions of HRQoL and the scores of the depression scale was revealed. AD patients' caregivers have a lower HRQoL almost in all dimensions compared to the Greek urban general population. The caregivers' social role, the existence of emotional problems, and their mental health status led to this result. Furthermore significantly important differences in caregivers' total HRQoL and depressive symptomatology were indicated in relation to their gender, hypertension existence, patient care frequency, cohabitation with the patient, disease aggravation, and economic status. Conclusions. Caring for relatives with AD strongly correlates with negative caregivers' HRQoL scores and adversely affects their depressive symptomatology. This negative correlation is enhanced in the later stages of the disease, in greater frequency of care, through living with a patient, in poor financial status, and with the existence of a chronic illness. PMID:28083154

  20. [Psychoneuroimmunological predictors for burden in older caregivers of patients with Alzheimer's disease].

    PubMed

    Corazza, Danilla I; Pedroso, Renata V; Andreatto, Carla A A; Scarpari, Lais; Garuffi, Marcelo; Costa, José L R; Santos-Galduróz, Ruth F

    2014-01-01

    The responsibility of giving care to patients with Alzheimer's disease (AD) may result in health changes in the older caregiver. It is important to explore the factors which influence the presence of care burden and to create strategies to face this condition. In this context, the aims of present study were to investigate the relationships between psychoneuroimmunological parameters and determine the predictors to burden in older caregivers of patients with AD. A total of 30 AD older caregivers participating in the «Cognitive and Functional Kinesiotherapy Program in Elderly with Alzheimer's disease«(PRO-CDA)», de Rio Claro, SP-Brazil, were submitted to an assessment protocol to evaluate the psychoneuroimmunological parameters. A descriptive statistical analysis, Pearson correlation and multiple linear regressions were performed. The mean age of caregivers was 71.3 (±9.3), and predominantly are first-grade relatives. The caregiver burden was associated with depressive symptoms (r=0.60, P<.001), caregiver distress (r=0.68, P<.001), and neuropsychiatric disorders of AD patients (r=0.53, P<.001). The multiple regression analysis confirmed depressive symptoms and neuropsychiatric disturbances as predictors of caregiver burden. Caregiver burden is associated with, and influenced by parameters related to the caregiver psychological suffering and to characteristics inherent to AD. Thus, it is important to find strategies and implement non-pharmacological programs to provide support to older caregivers, and to assist in the treatment of patients with AD, in order to improve the integral health of this population. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

  1. Amyloid imaging in prodromal Alzheimer's disease

    PubMed Central

    2011-01-01

    Patients with mild cognitive impairment are at an increased risk of progression to Alzheimer's disease. However, not all patients with mild cognitive impairment progress, and it is difficult to accurately identify those patients who are in the prodromal stage of Alzheimer's disease. In a recent paper, Koivunen and colleagues report that Pittsburgh compound-B, an amyloid-beta positron emission tomography ligand, predicts the progression of patients with mild cognitive impairment to Alzheimer's disease. Of 29 subjects with mild cognitive impairment, 21 (72%) had a positive Pittsburgh compound-B positron emission tomography baseline scan. In their study, 15 of these 21 (71%) patients progressed to Alzheimer's disease, whilst only 1 out of 8 (12.5%) Pittsburgh compound-B-negative patients with mild cognitive impairment did so. Moreover, in these mild cognitive impairment patients, the overall amyloid burden increased approximately 2.5% during the follow-up period. This is consistent with other longitudinal amyloid imaging studies that found a similar increase in amyloid deposition over time in patients with mild cognitive impairment. These studies together challenge current theories that propose a flattening of the increase of brain amyloid deposition already in the preclinical stage of Alzheimer's disease. These findings may have important implications for the design of future clinical trials aimed at preventing progression to Alzheimer's disease by lowering the brain amyloid-beta burden in patients with mild cognitive impairment. PMID:21936965

  2. 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.

  3. 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.

  4. 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.

  5. Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease.

    PubMed

    Mattsson, Niklas; Andreasson, Ulf; Zetterberg, Henrik; Blennow, Kaj

    2017-05-01

    Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration. In this prospective case-control study, an ultrasensitive assay was used to measure plasma NFL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative. The study dates were September 7, 2005, to February 13, 2012. The plasma NFL analysis was performed in September 2016. Associations were tested between plasma NFL and diagnosis, Aβ pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism. Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P < .001). Plasma NFL was increased in patients with MCI (mean, 42.8 ng/L) and patients with AD dementia (mean, 51.0 ng/L) compared with controls (mean, 34.7 ng/L) (P < .001) and had high diagnostic accuracy for patients with AD with dementia vs controls (area under the receiver operating characteristic curve, 0.87, which is comparable to established CSF biomarkers). Plasma NFL was particularly high in patients with MCI and patients with AD dementia with Aβ pathologic features. High plasma NFL correlated with poor cognition and AD-related atrophy (at baseline and longitudinally) and with brain hypometabolism (longitudinally). Plasma NFL is associated with AD diagnosis and with

  6. 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. Copyright © 2015. Published by Elsevier Inc.

  7. Dopamine differently modulates central cholinergic circuits in patients with Alzheimer disease and CADASIL.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Thomschewski, Aljosha; Kunz, Alexander Baden; Lochner, Piergiorgio; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco

    2014-10-01

    Short-latency afferent inhibition (SAI) technique gives the opportunity to non-invasively test an inhibitory circuit in the human cerebral motor cortex that depends mainly on central cholinergic activity. Important SAI abnormalities have been reported in both patients with Alzheimer disease (AD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a model of "pure" vascular dementia (VD). Interestingly, a normalization of SAI was observed in AD after levo-dopa (L-dopa) administration. We aimed to determine whether the pharmacological manipulation of the dopaminergic system can also interfere with SAI test in CADASIL patients, compared with AD patients and healthy controls. SAI was found to be significantly reduced in both patient groups. L-Dopa significantly increased SAI in the AD patients, while it failed to restore SAI abnormality in CADASIL patients. Therefore, L-dopa-mediated changes on SAI in AD patients seem to be a specific effect. The present study supports the notion that relationship between acetylcholine and dopamine systems may be specifically abnormal in AD. L-Dopa challenge may thus be able to differentiate the patients with AD or a mixed form of dementia from those with "pure" VD.

  8. Frontal lobe function in elderly patients with Alzheimer's disease and caregiver burden.

    PubMed

    Hashimoto, Akiko; Matsuoka, Kiwamu; Yasuno, Fumihiko; Takahashi, Masato; Iida, Junzo; Jikumaru, Kiyoko; Kishimoto, Toshifumi

    2017-07-01

    Understanding of the relationship between caregiver burden and the degree of behavioural deficits in patients with Alzheimer's disease (AD) is relatively limited. Therefore, it is worthwhile to examine the correlations between the various relevant factors to improve the efficacy of care for patients with AD. The aim of this study was to investigate the specific contributions of frontal lobe dysfunction in AD patients to caregiver burden, while controlling for other predictor variables. Participants included 30 pairs of caregivers and patients with AD. The Zarit Burden Interview and Frontal Assessment Battery were used to measure the caregiver burden and patients' frontal lobe function, respectively. To investigate the effects of frontal lobe dysfunction on caregiver burden, hierarchical regression equations with steps incorporating additional predictor variables were fitted. We also performed a correlation analysis between the individual subdomains of the Zarit Burden Interview and the predictor variables. Our study suggests that the degree of frontal lobe dysfunction in AD patients predicts their caregiver burden, when other factors of daily functional limitations and neuropsychiatric symptoms are controlled. Daily functional limitations and neuropsychiatric symptoms affected caregivers' psychosocial burden, whereas frontal lobe dysfunction affected caregivers' burden due to the increase in the dependency of the patients. Our findings indicate that to ameliorate the disabilities of patients and reduce caregiver burden, there is a need for interventions that focus on psychosocial burdens, as shown in previous studies, as well as on excessive dependency due to frontal lobe dysfunction. © 2017 Japanese Psychogeriatric Society.

  9. Nutritional Status of Patients with Alzheimer's Disease and Their Caregivers.

    PubMed

    Tombini, Mario; Sicari, Maura; Pellegrino, Giovanni; Ursini, Francesca; Insardá, Pasqualina; Di Lazzaro, Vincenzo

    2016-10-18

    Malnutrition is one of the most important conditions that negatively affects the health of elder people, particularly in patients with dementia. To provide an assessment of nutritional status of patients affected by Alzheimer's disease (AD) living at home and of their caregivers by means of Mini Nutritional Assessment (MNA), and to explore the influence of different factors on nutrition. 90 patients affected by AD living at home and 90 age- and sex-matched caregivers were enrolled. Patients and caregivers, coming from an urban-rural fringe of Southern Italy, were assessed using full MNA, Mini-Mental State Examination, Geriatric Depression Scale- short form, Activity of Daily Living, and Instrumental Activities of Daily Living scales. Malnutrition was found with high prevalence in patients affected by AD of different severity (more than 95% of patients were malnourished or at risk of malnutrition), and associated with reduced functional status. An altered nutrition was also recognized with high rate in the group of caregivers (23.3% were malnourished and 41.1% at risk of malnutrition) and the worse nutritional condition was correlated with higher age and lower functional and cognitive status and education. A positive correlation between MNA score of AD patients and caregivers was found. Corrective measures should be taken in order to early identify nutritional deficiencies and risk of malnutrition observed with high rate in both groups of AD patients and their caregivers; in these subjects a nutrition education program and intervention policies are mandatory to restore nutritional status.

  10. Galantamine for Alzheimer's disease.

    PubMed

    Olin, J; Schneider, L

    2001-01-01

    Galantamine (also called galanthamine, marketed as Reminyl (Janssen)) was isolated from several plants, including daffodil bulbs, but is now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer's disease (AD), and recently several multicenter clinical trials have been published with positive findings. Galantamine has received regulatory approval in 29 counties: Argentina, Australia, Canada, Czechia, the European Union (except for The Netherlands), Iceland, Korea, Mexico, Norway, Poland, Singapore, South Africa, Switzerland, Thailand, and the United States. The objective of this overview is to assess the clinical effects of galantamine in patients with probable AD, and to investigate potential moderators of an effect. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 4 July 2001 using the terms galantamine and Reminyl. The Specialized Register at that time contained records from the following databases: CCTR/Central:April 2001 (issue 2); Medline: 1966 to June 2001; Embase: 1980 to April 2001; PsycLit: 1887 to April 2001; Cinahl: 1982 to March 2001; SIGLE (Grey Literature in Europe): 1980 to December 2000; ISTP (Index to Scientific and Technical Proceedings): to May 2000; INSIDE (BL database of Conference Proceedings and Journals): to June 2000; Aslib Index to Theses (UK and Ireland theses): 1970 to June 2001; Dissertation Abstract (USA): 1861 to June 2001; ADEAR (Alzheimer's Disease Clinical Trials Database): to June 2001; National Research Register (including the MRC Clinical Trials Directory): April 2001 (issue 2) Alzheimers Society Trials Database: to June 2001; Glaxo-Wellcome Trials Database: to June 2001

  11. Alzheimer disease in 2020.

    PubMed

    Holtzman, David M; Mandelkow, Eckhard; Selkoe, Dennis J

    2012-11-01

    Remarkable advances in unraveling the biological underpinnings of Alzheimer disease (AD) have occurred during the last 25 years. Despite this, we have made only the smallest of dents in the development of truly disease-modifying treatments. What will change over the next 10 years? While the answer is not clear, we make several predictions on the state of the field in 2020, based on the rich knowledge described in the other contributions in this collection. As such, our predictions represent some of the principal unresolved questions that we believe deserve special investigative attention in the coming decade.

  12. Cerebrospinal fluid levels of transition metals in patients with Alzheimer's disease.

    PubMed

    Molina, J A; Jiménez-Jiménez, F J; Aguilar, M V; Meseguer, I; Mateos-Vega, C J; González-Muñoz, M J; de Bustos, F; Porta, J; Ortí-Pareja, M; Zurdo, M; Barrios, E; Martínez-Para, M C

    1998-01-01

    We compared CSF and serum levels of iron, copper, manganese, and zinc, measured by atomic absorption spectrophotometry, in 26 patients patients with Alzheimer's disease (AD) without major clinical signs of undernutrition, and 28 matched controls. CSF zinc levels were significantly decreased in AD patients as compared with controls (p < 0.05). The serum levels of zinc, and the CSF and serum levels of iron, copper, and manganese, did not differ significantly between AD-patient and control groups. These values were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination in the AD group. Weight and body mass index were significantly lower in AD patients than in controls. Because serum zinc levels were normal, the possibility that low CSF zinc levels were due to a deficiency of dietary intake seems unlikely. However, it is possible that they might be related to the interaction of beta-amyloid and/or amyloid precursor protein with zinc, that could result in a depletion of zinc levels.

  13. Applicability of the abbreviated neuropsychologic battery (NEUROPSI) in Alzheimer disease patients.

    PubMed

    Abrisqueta-Gomez, Jacqueline; Ostrosky-Solis, Feggy; Bertolucci, Paulo H F; Bueno, Orlando F A

    2008-01-01

    NEUROPSI is a brief neuropsychologic battery developed to briefly assess a wide spectrum of cognitive functions. The aim of this study was to examine the applicability of a Portuguese version of this battery and verify the efficacy in detecting cognitive impairment in Alzheimer disease (AD) patients. NEUROPSI was applied to 75 elderly people, 25 patients with probable AD in mild stage (AD1), 25 patients in moderate stage (AD2), and 25 healthy elderly persons (control group), matched with the AD patients for age and schooling. Before testing all participants were applied the Mini-Mental State Examination. Results showed significant differences in total scores of the tests; NEUROPSI (P<0.001) and Mini-Mental State Examination (P<0.001), and the control group scored highest in both of the tests followed by groups AD1 and AD2. Differences were also found between the initial phase and the moderate phase. Results indicate that NEUROPSI is an efficient instrument for detecting AD patients in the initial stage of the disease.

  14. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer's disease.

    PubMed

    An, Seong Soo; Park, Sun Ah; Bagyinszky, Eva; Bae, Sun Oh; Kim, Yoon-Jeong; Im, Ji Young; Park, Kyung Won; Park, Kee Hyung; Kim, Eun-Joo; Jeong, Jee Hyang; Kim, Jong Hun; Han, Hyun Jeong; Choi, Seong Hye; Kim, SangYun

    2016-01-01

    Early-onset Alzheimer's disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer's disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer's disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16-17), PSEN1 (exons 3-12), and PSEN2 (exons 3-12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We

  15. Visual signs and symptoms in patients with the visual variant of Alzheimer disease.

    PubMed

    Kaeser, Pierre-François; Ghika, Joseph; Borruat, François-Xavier

    2015-06-30

    Prominent visual symptoms can present in the visual variant of Alzheimer's disease (VVAD). Ophthalmologists have a significant role to play in the early diagnosis of VVAD. We retrospectively reviewed the files of ten consecutive patients diagnosed with VVAD. All patients had a full neuro-ophthalmologic examination, a formal neurological and neuro-psychological testing, and cerebral MRI to confirm diagnosis. In addition, functional neuroimaging was obtained in seven patients. The common primary symptom at presentation with all patients was difficulty with near vision (reading difficulty n = 8, "visual blur" in near vision n = 2), and difficulty writing (n = 3). Following assessment, impaired reading and writing skills were evident in 9/10 and 8/10 patients respectively. Median distance visual acuity was 20/25 and at near the median visual acuity was J6. Partial homonymous visual field defect was detected in 80 % (8/10) of the patients. Color vision was impaired in all patients when tested with Ishihara pseudoisochromatic plates, but simple color naming was normal in 8/9 tested patients. Simultanagnosia was present in 8/10 patients. Vision dysfunction corresponded with cerebral MRI findings where parieto-occipital cortical atrophy was observed in all patients. PET scan (5 patients) or SPECT (2 patients) revealed parieto-occipital dysfunction (hypometabolism or hypoperfusion) in all 7 tested patients Visual difficulties are prominent in VVAD. Dyslexia, incomplete homonymous hemianopia, preserved color identification with abnormal color vision on Ishihara, and simultanagnosia were all symptoms observed frequently in this patient series. Ophthalmologists should be aware of the possibility of neurodegenerative disorders such as VVAD in patients with unexplained visual complaints, in particular reading difficulties.

  16. Risk factors for delusion of theft in patients with Alzheimer's disease showing mild dementia in Japan.

    PubMed

    Murayama, N; Iseki, E; Endo, T; Nagashima, K; Yamamoto, R; Ichimiya, Y; Arai, H; Sato, K

    2009-07-01

    The mechanism underlying delusion in Alzheimer's disease patients has not been fully clarified; however, the occurrence of delusion is a critical issue for dementia patients and their caregivers. In Japan, delusion of theft is the most frequent delusion in AD patients. We examined the risk factors for delusion of theft in AD patients showing mild dementia. Fifty-six AD patients were administered HDS-R, MMSE and COGNISTAT, including the 'speech sample', to assess their neuropsychological and social cognitive functions. The age, years of education, presence of cohabiting family members and premorbid personality traits were obtained from family members. About 25.0% of AD patients showed delusion of theft (D-group), and 75% did not (non-D-group). About 33.3% of female patients and 5.9% of male patients were included in the D-group (p < 0.05). About 13.6% of patients who were cohabiting with family members and 66.7% of patients who were living alone were included in the D-group (p < 0.05). About 35.1% of patients who had a neurotic personality and 5.3% of patients who did not were included in the D-group (p < 0.05). There were no significant differences in scores on HDS-R, MMSE and COGNISTAT sub-scales, except for 'speech sample', between the two groups. In the 'speech sample', 38.7% of patients who understood a relationship between two boys and 12.0% of patients who did not were included in the D-group (p < 0.05). These results indicated that delusion of theft in AD patients was related to female gender, absence of cohabiting family members, neurotic personality and retained social cognitive function.

  17. Health service utilization among Alzheimer's disease patients: evidence from managed care.

    PubMed

    Frytak, Jennifer R; Henk, Henry J; Zhao, Yang; Bowman, Lee; Flynn, Jennifer A; Nelson, Michael

    2008-09-01

    The objective of this study was to assess the disease burden of Alzheimer's disease (AD) in a commercial managed care setting by comparing direct health care costs and adverse event outcomes between patients with AD and without AD. The study design used eligibility, medical, and pharmacy claims data from a large, national, geographically diverse, fee-for-service U.S. managed health plan. Commercially insured patients aged 65 years and older with a pharmacy benefit with evidence of AD (n = 4,450) and a control group without AD (n = 13,650) were matched by age, gender, plan location, and length of enrollment. Adverse event outcomes, comorbid conditions, and annualized health care costs were compared. Incremental costs were calculated by using a two-part model to estimate the burden of illness; incremental cost confidence intervals were estimated by bootstrap analysis. Patients with AD had generally higher health care costs and higher risk of acute adverse outcomes than the control cohort. Annual adjusted total health care costs per patient were approximately $1,418 greater for the AD cohort. Patients with AD had an unadjusted fracture risk of 14.6% versus 6.2% in the matched cohort and accidental injury/falls risk of 27.4% versus 11.4%. Few studies have examined the disease burden of AD in commercial managed care settings. Similar to results of comparative studies with Medicare data, the disease burden is greater for patients with AD compared with a matched control cohort, with a different mix and a greater number of comorbid health care conditions partially accounting for this difference. As membership in commercial and Medicare managed care plans increases, plans will need to develop effective mechanisms to manage the health care of high-risk, high-cost patients with AD.

  18. The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study.

    PubMed

    Bosco, Paolo; Redolfi, Alberto; Bocchetta, Martina; Ferrari, Clarissa; Mega, Anna; Galluzzi, Samantha; Austin, Mark; Chincarini, Andrea; Collins, D Louis; Duchesne, Simon; Maréchal, Bénédicte; Roche, Alexis; Sensi, Francesco; Wolz, Robin; Alegret, Montserrat; Assal, Frederic; Balasa, Mircea; Bastin, Christine; Bougea, Anastasia; Emek-Savaş, Derya Durusu; Engelborghs, Sebastiaan; Grimmer, Timo; Grosu, Galina; Kramberger, Milica G; Lawlor, Brian; Mandic Stojmenovic, Gorana; Marinescu, Mihaela; Mecocci, Patrizia; Molinuevo, José Luis; Morais, Ricardo; Niemantsverdriet, Ellis; Nobili, Flavio; Ntovas, Konstantinos; O'Dwyer, Sarah; Paraskevas, George P; Pelini, Luca; Picco, Agnese; Salmon, Eric; Santana, Isabel; Sotolongo-Grau, Oscar; Spiru, Luiza; Stefanova, Elka; Popovic, Katarina Surlan; Tsolaki, Magda; Yener, Görsev G; Zekry, Dina; Frisoni, Giovanni B

    2017-09-01

    Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, (18)F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively). There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  19. Alterations of membrane protein expression in red blood cells of Alzheimer's disease patients.

    PubMed

    Várady, György; Szabó, Edit; Fehér, Ágnes; Németh, Adrienn; Zámbó, Boglárka; Pákáski, Magdolna; Janka, Zoltán; Sarkadi, Balázs

    2015-09-01

    Preventive measures, prognosis, or selected therapy in multifactorial maladies, including Alzheimer's disease (AD), require the application of a wide range of diagnostic assays. There is a large unmet need for relatively simple, blood-based biomarkers in this regard. We have recently developed a rapid and reliable flow cytometry and antibody-based method for the quantitative measurement of various red blood cell (RBC) membrane proteins from a drop of blood. Here, we document that the RBC expression of certain membrane proteins, especially that of the GLUT1 transporter and the insulin receptor (INSR), is significantly higher in AD patients than in age-matched healthy subjects. The observed differences may reflect long-term metabolic alterations relevant in the development of AD. These findings may pave the way for a diagnostic application of RBC membrane proteins as relatively stable and easily accessible personalized biomarkers in AD.

  20. Evaluating associations between 5-HTTLPR polymorphism and Alzheimer's disease for Korean patients.

    PubMed

    Ha, Tae Min; Cho, Deuk Man; Park, Sung Woo; Joo, Myung Jin; Lee, Bong Ju; Kong, Bo Geum; Kim, Jae Min; Yoon, Jin Sang; Kim, Young Hoon

    2005-01-01

    There has been growing evidence that the serotonin (5-HT) system is important in the regulation of memory and thus might be associated with Alzheimer's disease (AD), while research results on this issue have been inconsistent. The 5-HT system has also been suggested to be responsible for a significant portion of the behavioural aspects of AD. This study aimed to investigate the associations of the 5-HT transporter gene linked polymorphic region (5-HTTLPR) polymorphism with AD and delusional/aggressive symptoms of AD in Korean samples of 65 patients and 43 controls. The 5-HTTLPR polymorphism was neither associated with AD nor with delusional/aggressive symptoms of AD. It was suggested that phenotypic expression of the 5-HTTLPR polymorphism might be varied according to ethnic differences. Copyright (c) 2005 S. Karger AG, Basel.

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

    PubMed

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

    2010-01-01

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

  2. Predictive Factors of Rapid Cognitive Decline in Patients with Alzheimer Disease

    PubMed Central

    Barbe, Coralie; Morrone, Isabella; Novella, J.L.; Dramé, Moustapha; Wolak-Thierry, Aurore; Aquino, Jean-Pierre; Ankri, Joël; Jolly, Damien; Mahmoudi, Rachid

    2016-01-01

    Aim To determine predictive factors associated with rapid cognitive decline (RCD) in elderly patients suffering from Alzheimer disease (AD). Methods Patients suffering from mild to moderate AD were included. RCD was defined as the loss of at least 3 points on the Mini-Mental State Examination (MMSE) over 12 months. Factors associated with RCD were identified by logistic regression. Results Among 123 patients included, 61 were followed up until 12 months. RCD occurred in 46% of patients (n = 28). Polymedication (p < 0.0001), the fact that the caregiver was the child or spouse of the patient (p < 0.0001) and autonomy for washing (p < 0.0001) were protective factors against RCD, while the presence of caregiver burden (p < 0.0001) was shown to be a risk factor for RCD. Conclusion Early detection of the RCD risk in AD patients could make it possible to anticipate the patient's medical needs and adjust the care plan for caregiver burden. PMID:28101101

  3. Alzheimer's disease in the United Kingdom: developing patient and carer support strategies to encourage care in the community.

    PubMed

    Hunter, R; McGill, L; Bosanquet, N; Johnson, N

    1997-09-01

    Alzheimer's disease is a growing challenge for care providers and purchasers. With the shift away from the provision of long term institutional care in most developed countries, there is a growing tendency for patients with Alzheimer's disease to be cared for at home. In the United Kingdom, this change of direction contrasts with the policies of the 1980s and 90s which focused more attention on controlling costs than on assessment of the needs of the patient and carer and patient management. In recent years, the resources available for management of Alzheimer's disease have focused on institutional care, coupled with drug treatment to control difficult behaviour as the disease progresses. For these reasons, the current system has led to crisis management rather than preventive support--that is, long term care for a few rather than assistance in the home before the crises occur and institutional care is needed. Despite recent innovations in the care of patients with Alzheimer's disease, the nature of the support that patients and carers receive is poorly defined and sometimes inadequate. As a result of the shift towards care in the community, the informal carer occupies an increasingly central role in the care of these patients and the issue of how the best quality of care may be defined and delivered is an issue which is now ripe for review. The objective of this paper is to redefine the type of support that patients and carers should receive so that the disease can be managed more effectively in the community. The needs of patients with Alzheimer's disease and their carers are many and this should be taken into account in defining the quality and structure of healthcare support. This paper shows how new initiatives, combined with recently available symptomatic drug treatment, can allow patients with Alzheimer's disease to be maintained at home for longer. This will have the dual impact of raising the quality of care for patients and improving the quality of life

  4. The missing link between faces and names: evidence from Alzheimer's disease patients.

    PubMed

    Calabria, Marco; Sabio, Alicia; Martin, Clara; Hernández, Mireia; Juncadella, Montserrat; Gascón-Bayarri, Jordi; Reñé, Ramon; Ortiz-Gil, Jordi; Ugas, Lidia; Costa, Albert

    2012-11-01

    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. Specifically, it is unknown whether this deficit is due to a degradation of the links between faces and proper names, or due to deficits in intentionally accessing and retrieving proper names from faces. Here, we aim to investigate the integrity of the links between famous faces and proper names in AD while minimizing the impact of the explicit retrieval. We compare the performances of AD patients and elderly controls in a face-name priming task. We assess the integrity of the link between faces and names at two different levels: identity level - the name and face belong to the same person; and semantic level - the name and face belong to the same category (e.g., politicians). Our results reveal that AD patients compared with controls show intact semantic priming but reduced priming for person identity. This suggests that the deficits in intentionally retrieving proper names in AD are the result of a partial disruption of the network at the identity level, i.e., the links between known faces and proper names. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Patients' diagnosis decisions in Alzheimer's disease: the influence of family factors.

    PubMed

    Rapp, Thomas

    2014-10-01

    It is surprising to observe that the number of patients receiving a late diagnosis for Alzheimer's disease (AD) remains high even in countries promoting early diagnosis campaigns. We explore the impact of family history and family support on the risks of receiving a delayed diagnosis. We use French data of 1131 patients diagnosed between 1991 and 2005. We find that the presence of AD history in the family increased the risks of receiving a delayed diagnosis. This was true especially when AD history involved brothers, sisters and other relatives (uncles or cousins). The presence of an informal caregiver at the time of the first warning signs reduced the risks of receiving a late diagnosis, regardless of the informal caregiver concerned (spouse, son, daughter etc.). We identify several opportunities for early detection campaigns. Families with history of disease should be targeted. Campaigns should also target isolated patients, who do not benefit from informal care. Our results underline the importance of improving the diagnosis access for old patients and for men. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Cerebrospinal fluid substance P concentrations are elevated in patients with Alzheimer's disease.

    PubMed

    Johansson, Per; Almqvist, Erik G; Wallin, Anders; Johansson, Jan-Ove; Andreasson, Ulf; Blennow, Kaj; Zetterberg, Henrik; Svensson, Johan

    2015-11-16

    The neuropeptides substance P, orexin A (hypocretin-1) and neurotensin are signaling molecules that influence brain activity. We examined their cerebrospinal fluid (CSF) levels in a study population consisting of Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), other dementias (n=15), and healthy controls (n=20). CSF substance P level was increased in AD patients compared to patients with other dementias and healthy controls (P<0.05 and P<0.01, respectively). Patients with other dementia or SMCI had lower CSF orexin A level than AD patients (both P<0.05) and marginally lower level than healthy controls (both P=0.05). CSF neurotensin level was similar in all groups. In the total study population (n=80), CSF substance P level correlated positively with CSF levels of T-tau and P-tau, and in AD patients (n=32), CSF substance P level correlated positively with CSF Aβ1-42 level. In conclusion, CSF substance P level was elevated in AD patients and correlated with CSF Aβ1-42 level, a well established marker of senile plaque pathology. The role of low CSF orexin A level in other dementias or SMCI needs to be explored in further studies.

  7. Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer Disease: A Systematic Review.

    PubMed

    Li, Jun; Cesari, Matteo; Liu, Fei; Dong, Birong; Vellas, Bruno

    2017-02-01

    Basic and clinical research support a link between diabetes mellitus and Alzheimer disease (AD). However, the relationship with AD progression is unclear. This review focuses on the association between diabetes and cognitive decline in patients with AD. The literature published through May 2015 was searched in 3 databases: PubMed, Embase and Cochrane. Studies evaluating the effects of diabetes on patients with AD or cognitive decline were included, and extracted data were analyzed. A total of 10 articles met the inclusion criteria for review. The results of these studies were inconsistent in terms of the association between diabetes and cognitive decline. Only 2 studies demonstrated that the presence of diabetes was independently related to the progression of cognitive decline in the patients with AD, and 3 studies suggested that histories of diabetes were not correlated with the changes in cognitive function in patients with AD. Half of the included studies even indicated that histories of diabetes were associated with lesser declines in cognitive function in patients with AD. Current evidence indicates that the link between diabetes and cognitive decline in patients with AD is uncertain. Further clinical studies are needed, with larger samples, long-term follow up and an extended battery of cognitive assessments.

  8. 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

  9. Relationship between eating disturbance and dementia severity in patients with Alzheimer's disease.

    PubMed

    Kai, Kyoko; Hashimoto, Mamoru; Amano, Koichiro; Tanaka, Hibiki; Fukuhara, Ryuji; Ikeda, Manabu

    2015-01-01

    Eating is one of the most important daily activities in managing patients with dementia. Although various eating disturbance occur as dementia progresses, to our knowledge, most of the studies focused on a part of eating disturbance such as swallowing and appetite. There have been few comprehensive studies including eating habits and food preference in patients with Alzheimer's disease (AD). The aims of this study were to investigate almost all eating disturbance and to examine the relationship of eating disturbance to dementia stage in AD. A total of 220 patients with AD and 30 normal elderly (NE) subjects were recruited. Eating disturbance was assessed by a comprehensive questionnaire that had been previously validated. Potential relationships between the characteristics of eating disturbance and dementia stage as classified by the Clinical Dementia Rating (CDR) were assessed. Overall, 81.4% of patients with AD showed some eating and swallowing disturbance, whereas only 26.7% of the NE subjects had such a disturbance. Even in an early stage, patients with AD had many types of eating disturbance; "Appetite change" was shown in nearly half of the mild AD patients (49.5%). In the moderate stage, the scores of "change of eating habits and food preference" were highest, and in the severe stage "swallowing disturbance" became critical. In AD, the relationship of dementia stage to eating disturbance differs according to the type of eating disturbance. The relationships between various eating disturbance and the severity of dementia should be considered.

  10. Screening for Patients with Mild Alzheimer Disease Using Frequency Doubling Technology Perimetry

    PubMed Central

    Aykan, Umit; Akdemir, M. Orcun; Yildirim, Ozlem; Varlibas, Figen

    2013-01-01

    Abstract We compared the visual field performances of patients with mild Alzheimer disease (AD) with normal subjects and detected visual field impairment attributable to the magnocellular pathway using frequency doubling technology—Matrix (FDT-Matrix). We recruited 43 patients with mild AD (mean age: 68.0 ± 7.2 years) and 33 controls who are visually and cognitively normal (mean age: 64.1 ± 6.4 years). All participants had at least two reliable FDT-Matrix 30-2 tests. Reliability indices, global indices (mean deviation and pattern standard deviation), and glaucoma hemifield test results were measured with FDT-Matrix. The mean test duration was significantly longer in patient group compared with controls (p = 0.002). Among the reliability indices, false negatives were higher in patient group than controls (p = 0.003). There were statistically significant differences in mean deviation and pattern standard deviation values (p < 0.0001 and p < 0.0001, respectively) and glaucoma hemifield test results (p < 0.001) between the patient and the control group. Our results imply that the pathogenesis of cognitive deterioration may not only be confined to the cortical area but also to the magnocellular pathway. We underline that FDT testing can be useful for the identification of early impairment and the follow-up of patients with AD. PMID:28167993

  11. Pharmacological modulation of cognitive and behavioral symptoms in patients with dementia due to Alzheimer's disease.

    PubMed

    de Oliveira, Fabricio Ferreira; Bertolucci, Paulo Henrique Ferreira; Chen, Elizabeth Suchi; Smith, Marilia de Arruda Cardoso

    2014-01-15

    To evaluate correlations of pharmacological treatment with cognitive and behavioral symptoms in patients with dementia due to Alzheimer's disease with low schooling, subjects were assessed for demographic features, neuropsychiatric symptoms, cognitive decline, functionality, caregiver burden, APOE haplotypes and pharmacological treatment. Among 217 patients, use of cholinesterase inhibitors with or without Memantine was associated with less neuropsychiatric symptoms, while anti-psychotics and/or anti-epileptic drugs were associated with lower instrumental functionality. Anti-psychotics were also associated with more neuropsychiatric symptoms in moderately impaired patients, possibly reflecting the greater need for such treatment when behavioral symptoms are present. Patients receiving more medications were usually younger, obese, married, with higher schooling and more neuropsychiatric symptoms. APOE4+ haplotypes were correlated with earlier dementia onset, but not with pharmacological treatment. Higher caregiver burden was associated with more psychotropic drugs. A trend was found for treatment with cholinesterase inhibitors and Memantine to be associated with longer lengths of dementia for moderately impaired but not for severely impaired patients, regardless of APOE haplotypes, translating into a synergistic effect among such medications for slowing cognitive decline but not for prolonging survival. Further longitudinal studies may be required to assess dose-response relationships regarding treatment with psychotropics for patients with dementia.

  12. Serum calreticulin is a negative biomarker in patients with Alzheimer's disease.

    PubMed

    Lin, Qiao; Cao, Yunpeng; Gao, Jie

    2014-11-25

    Calreticulin is down-regulated in the cortical neurons of patients with Alzheimer's disease (AD) and may be a potential biomarker for the diagnosis of AD. A total of 128 AD patients were randomly recruited from May 2012 to July 2013. The mRNA levels of calreticulin were measured from the serum of tested subjects using real-time quantitative reverse transcriptase-PCR (real-time qRT-PCR). Serum levels of calreticulin were determined by ELISA and Western Blot. Serum levels of calreticulin in AD patients were significantly lower than those from a healthy group (p < 0.01). The baseline characters indicated that sample size, gender, mean age, diabetes and BMI (body mass index) were not major sources of heterogeneity. The serum levels of mRNA and protein of calreticulin were lower in AD patients than those from a healthy group, and negatively associated with the progression of AD according to CDR scores (p < 0.01). Thus, there is a trend toward decreased serum levels of calreticulin in the patients with progression of AD. Serum levels of calreticulin can be a negative biomarker for the diagnosis of AD patients.

  13. Characteristics of sleep disturbance in community-dwelling Alzheimer's disease patients.

    PubMed

    McCurry, S M; Logsdon, R G; Teri, L; Gibbons, L E; Kukull, W A; Bowen, J D; McCormick, W C; Larson, E B

    1999-01-01

    This study examined the frequency, predictors, and impact of sleep problems in a population-based sample of 205 Alzheimer's disease (AD) patients. Sleeping more than usual and early morning awakenings were the most common sleep problems reported but were the least disturbing behaviors for caregivers. Night-time awakenings were less common but were most disturbing to caregivers. Using logistic regression analyses, the factors most strongly associated with night awakenings among patients were male gender, greater memory problems, and decreased functional status. Patient depression increased the risk for caregivers to rate patient sleep problems as more disturbing overall. Cluster analyses revealed three characteristic groups of patients who awakened caregivers: one group was inactive during the day but had few other behavior problems; one group had increased levels of fearfulness, fidgeting, and occasional sadness; and the third group had multiple behavior problems, including frequent episodes of sadness, fearfulness, inactivity, fidgeting, and hallucinations. These findings indicate that the nature of sleep problems in AD is multifaceted; future research on the occurrence and treatment of sleep disturbance in dementia patients should consider the patterns of individual differences that may influence its development.

  14. Donepezil 23 mg in Asian patients with moderate-to-severe Alzheimer's disease.

    PubMed

    Han, S-H; Lee, J-H; Kim, S Y; Park, K W; Chen, C; Tripathi, M; Dash, A; Kubota, N

    2017-02-01

    Ethnic diversity between different populations may affect treatment safety and efficacy. A subanalysis to a global trial (study 326) was carried out to ascertain the safety and efficacy of donepezil 23 mg/day compared with donepezil 10 mg/day in Asian patients with moderate-to-severe Alzheimer's disease. Changes in cognition and global functioning were measured by the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), respectively, at week 24. Cognitive improvement measured by SIB score was greater with donepezil 23 mg than with donepezil 10 mg (+1.36 vs -1.56]; difference, 2.92). There was no difference between the groups in global function measured by the CIBIC-Plus (3.94 and 3.95, respectively). Overall, 119 patients (82.1%) receiving donepezil 23 mg and 56 (71.8%) receiving donepezil 10 mg experienced ≥1 treatment emergent adverse events (TEAEs). In the donepezil 23 mg group, the incidence of TEAEs was higher among patients of lower weight (<55 kg) at baseline than in those of higher weight (64 of 75 patients [85.3%] vs 55 of 70 patients [78.5%]). The benefits and risks associated with donepezil 23 mg in Asian patients are comparable to those of the global study population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. What do Alzheimer's disease patients know about animals? It depends on task structure and presentation format.

    PubMed

    Rich, Jill B; Park, Norman W; Dopkins, Stephen; Brandt, Jason

    2002-01-01

    Deficits on tasks requiring semantic memory in Alzheimer's disease (AD) may be due to storage loss, a retrieval deficit, or both. To address this question, we administered multiple tasks involving 9 exemplars of the category "animals," presented as both words and pictures, to 12 AD patients and 12 nondemented individuals. Participants made semantic judgments by class (sorting task), similarity (triadic comparison task), and dimensional attributes (ordering task). Relative to control participants, AD patients were impaired on an unstructured sorting task, but did not differ on a constrained sorting task. On the triadic comparison task, the patients were as likely to make judgments based on size as domesticity attributes, whereas control participants made judgments based primarily on domesticity. The patients' judgments were also less consistent across tasks than those of control participants. On the ordering tasks, performance was generally comparable between groups with pictures but not words, suggesting that pictures enable AD patients to access information from semantic memory that is less accessible with lexical stimuli. These results suggest that AD patients' semantic judgments are impaired when the retrieval context is unstructured, but perform normally under supportive retrieval conditions.

  16. Prosocial capabilities in Alzheimer's patients.

    PubMed

    Bosch-Domènech, Antoni; Nagel, Rosemarie; Sánchez-Andrés, Juan V

    2010-01-01

    To examine the decision making of Alzheimer's patients in a simple, classic game focusing on their capabilities to implement social norms and common social preferences. Patients with Stage I (very mild and mild) Alzheimer's disease (AD) were asked to participate in a dictator game, a type of game in which a subject has to decide how to allocate a certain amount of money between himself and another person. When we compared the results of treatments involving AD patients (at an early stage) with those of identical treatments involving patients with mild cognitive impairment or healthy elderly controls, with similar ages and social backgrounds, we did not find statistically significant differences. This finding suggests that Stage I AD patients are as capable of making decisions involving basic social norms and preferences as other individuals of their age. Whatever brain structures are affected by the disease, they do not appear to influence, at this early stage, the neural basis for cooperation-enhancing social interactions.

  17. Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the brains of patients with Alzheimer's disease.

    PubMed

    Yumoto, Sakae; Kakimi, Shigeo; Ohsaki, Akihiro; Ishikawa, Akira

    2009-11-01

    Aluminum (Al) exposure has been reported to be a risk factor for Alzheimer's disease (senile dementia of Alzheimer type), although the role of Al in the etiology of Alzheimer's disease remains controversial. We examined the presence of Al in the Alzheimer's brain using energy-dispersive X-ray spectroscopy combined with transmission electron microscopy (TEM-EDX). TEM-EDX analysis allows simultaneous imaging of subcellular structures with high spatial resolution and analysis of small quantities of elements contained in the same subcellular structures. We identified senile plaques by observation using TEM and detected Al in amyloid fibers in the cores of senile plaques located in the hippocampus and the temporal lobe by EDX. Phosphorus and calcium were also present in the amyloid fibers. No Al could be detected in the extracellular space in senile plaques or in the cytoplasm of nerve cells. In this study, we demonstrated colocalization of Al and beta-amyloid (Abeta) peptides in amyloid fibers in the cores of senile plaques. The results support the following possibilities in the brains of patients with Alzheimer's disease: Al could be involved in the aggregation of Abeta peptides to form toxic fibrils; Al might induce Abeta peptides into the beta-sheet structure; and Al might facilitate iron-mediated oxidative reactions, which cause severe damage to brain tissues.

  18. Lower lean mass and higher percent fat mass in patients with Alzheimer's disease.

    PubMed

    Buffa, R; Mereu, E; Putzu, P; Mereu, R M; Marini, E

    2014-10-01

    In this study we analyzed body composition in relation to cognitive and functional status, in a cross-sectional sample of patients with Alzheimer's disease (AD). Seventy individuals (27 men, 78.1±6.5years; 43 women, 80.4±5.6years) with mild-moderate stages of AD (clinical dementia ratings 1 and 2) were selected from the Alzheimer Center, SS. Trinità Hospital, ASL 8 of Cagliari (Italy). Cognitive and psycho-functional status was evaluated using mini-mental state examination (MMSE), activities of daily living (ADL) scale, and geriatric depression scale (GDS). Mini-nutritional assessment (MNA) was applied. Anthropometric measurements were taken and body mass index (BMI) was calculated. Body composition was assessed by means of specific bioelectrical impedance vector analysis (BIVA), using the references for the elderly. In comparison with the reference group, patients with AD showed similar BMI and MNA, but peculiar bioelectrical characteristics: lower phase angles and longer vectors (p<0.05). According to specific BIVA, this bioelectrical pattern is indicative of a reduction of lean tissue mass and an increase of percent fat mass (FM%). A more accentuated lean mass reduction (p < 0.05) was observed in women with worse cognitive status and a FM% increase (p < 0.01) in women with worse functional status. In conclusion, patients with AD had lower lean tissue mass and higher percent fat mass than healthy elderly individuals. In women, this pattern was associated with cognitive and functional decline, as indicated by MMSE and ADL values. Specific BIVA showed to be a suitable technique in the elderly, that could enhance BMI and MNA information in the evaluation of nutritional status. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Pharmacogenomics in Alzheimer's disease.

    PubMed

    Cacabelos, Ramón

    2008-01-01

    Pharmacological treatment in Alzheimer's disease (AD) accounts for 10-20% of direct costs, and fewer than 20% of AD patients are moderate responders to conventional drugs (donepezil, rivastigmine, galantamine, memantine), with doubtful cost-effectiveness. Both AD pathogenesis and drug metabolism are genetically regulated complex traits in which hundreds of genes cooperatively participate. Structural genomics studies demonstrated that more than 200 genes might be involved in AD pathogenesis regulating dysfunctional genetic networks leading to premature neuronal death. The AD population exhibits a higher genetic variation rate than the control population, with absolute and relative genetic variations of 40-60% and 0.85-1.89%, respectively. AD patients also differ in their genomic architecture from patients with other forms of dementia. Functional genomics studies in AD revealed that age of onset, brain atrophy, cerebrovascular hemodynamics, brain bioelectrical activity, cognitive decline, apoptosis, immune function, lipid metabolism dyshomeostasis, and amyloid deposition are associated with AD-related genes. Pioneering pharmacogenomics studies also demonstrated that the therapeutic response in AD is genotype-specific, with apolipoprotein E (APOE) 4/4 carriers the worst responders to conventional treatments. About 10-20% of Caucasians are carriers of defective cytochrome P450 (CYP) 2D6 polymorphic variants that alter the metabolism and effects of AD drugs and many psychotropic agents currently administered to patients with dementia. There is a moderate accumulation of AD-related genetic variants of risk in CYP2D6 poor metabolizers (PMs) and ultrarapid metabolizers (UMs), who are the worst responders to conventional drugs. The association of the APOE-4 allele with specific genetic variants of other genes (e.g., CYP2D6, angiotensin-converting enzyme [ACE]) negatively modulates the therapeutic response to multifactorial treatments affecting cognition, mood, and behavior

  20. Changes in cognitive domains during three years in patients with Alzheimer's disease treated with donepezil

    PubMed Central

    Persson, Cecilia M; Wallin, Åsa K; Levander, Sten; Minthon, Lennart

    2009-01-01

    Background The objective was to identify separate cognitive domains in the standard assessment tools (MMSE, ADAS-Cog) and analyze the process of decline within domains during three years in Alzheimer's disease (AD) patients with donepezil treatment. Method AD patients (n = 421) were recruited from a clinical multi-centre study program in Sweden. Patients were assessed every six months during three years. All patients received donepezil starting directly after study entry. After dropouts, 158 patients remained for analyses over three years. Data for the other patients were analysed until they dropped out (4 groups based on length in study). Results Factor analyses of all items suggested that there were three intercorrelated factors: a General, a Memory and a Spatial factor for which we constructed corresponding domains. Overall there was a cognitive improvement at six months followed by a linear drop over time for the three domains. Some group and domain differences were identified. Patients who remained longer in the study had better initial performance and a slower deterioration rate. The early dropouts showed no improvement at six months and many dropped out due to side effects. The other groups displayed a performance improvement at six months that was less pronounced in the Memory domain. Before dropping out, deterioration accelerated, particularly in the Spatial domain. Conclusion The course of illness in the three domains was heterogeneous among the patients. We were not able to identify any clinically relevant correlates of this heterogeneity. As an aid we constructed three algorithms corresponding to the cognitive domains, which can be used to characterize patients initially, identify rapid decliners and follow the course of the disease. PMID:19208247

  1. Machine learning methods for anticipating the psychological distress in patients with Alzheimer's disease.

    PubMed

    Zhou, Xiaolin; Xu, Jie; Zhao, Yongbo

    2006-12-01

    Recent studies proved that psychological distress is an accelerator of Alzheimer disease (AD). However, the factors that affect the psychological distress of AD patients are still unknown. The aim of this study was to predict the incidence and identify the risk factors of psychological distress in AD patients. Artificial neural networks and Machine learning models were used to predict the incidence of psychological distress in AD patients. Linear regression and decision tree models were used to identify the factors of psychological distress in AD patients. Among all models for predicting the incidence of psychological distress in AD patients, the artificial neural networks with 8 hidden neurons achieved the highest predictive accuracy of 81.92%. In the five machine learning models, the ADTree algorithm made the highest Predictive Accuracy of 77.94%. As for risk factor analysis, the Linear Regression and Decision Tree models reported similar sets of variables that affect the psychological distress of AD patients. Three variables were reported by Linear Regression to be in negative correlation with psychological distress: the use of professional care service, caregiver consuming cigarette, and caregiver consuming alcohol. The incidence of psychological distress in AD patients can be predicted by artificial neural networks with an accuracy of 81.92%. There are four main risk factors for psychological distress of AD patients: "Caregiver experiencing psychological distress", "Caregiver suffering from chronic disease or cancer", "Care recipient's health status being serious or getting worse", and "Lack of professional care service". These findings are potentially helpful for the prediction, prevention and intervention of psychological distress in AD patients.

  2. Antioxidant therapies for Alzheimer's disease.

    PubMed

    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.

  3. [Therapy of Alzheimer disease].

    PubMed

    Kovács, Tibor

    2009-03-01

    Dementia is one of the most important health problems in the aging populations. The most frequent cause of it is Alzheimer's disease (AD) which is characterized by intracellular neuro-fibrillary tangles (NFT) and the extracellular senile plaques. The NFTs are mainly formed by the hyperphosphorylated microtubule-binding protein, the tau, while the senile plaques are composed of beta-amyloid protein cleaved from the amyloid precursor protein (APP) by the beta- and gamma-secretases. The pharmacotherapy of AD consists of symptomatic and disease-modifying therapies. The most frequently used therapeutic agents are the nootropic drugs supported by personal rather evidence based experiences. The leading-edge therapy of AD at present is the inhibition of the acetylcholine-esterase enzyme (AChEI) with mainly cognitive symptomatic and weak disease-modifying effects; they are licensed in the mild and middle stages of AD (MMSE 26-10), but their effect is proved in the severe stage of the disease and they are effective in the management of the neuropsychiatric symptoms too. Memantine (which is an inhibitor of the N-metil-D-aspartate receptor) is used in the middle and severe stages of AD and it can be effectively combined with AChEIs. The future therapy of AD will possibly be a "causative" therapy. The most frequent directions are therapies aiming to decrease the production or the deposition of beta-amyloid peptide. The active vaccination study of AN-1792 was terminated because of immunological side-effects, but several active and passive immunisation therapies are in development nowadays. It is also possible to inhibit the aggregation of the beta-amyloid peptide with peptide fragments or with Cu2+ and Zn2+ ion chelators. A promising direction is the inhibition of the enzymes responsible for the production of the beta-amyloid peptide: beta-secretase inhibitors with low molecular weight and penetrability through the blood-brain barrier are developed while the inhibitors of the

  4. Detergent-insoluble EAAC1/EAAT3 aberrantly accumulates in hippocampal neurons of Alzheimer's disease patients.

    PubMed

    Duerson, Kevin; Woltjer, Randall L; Mookherjee, Paramita; Leverenz, James B; Montine, Thomas J; Bird, Thomas D; Pow, David V; Rauen, Thomas; Cook, David G

    2009-04-01

    Disturbed glutamate homeostasis may contribute to the pathological processes involved in Alzheimer's disease (AD). Once glutamate is released from synapses or from other intracellular sources, it is rapidly cleared by glutamate transporters. EAAC1 (also called EAAT3 or SLC1A1) is the primary glutamate transporter in forebrain neurons. In addition to transporting glutamate, EAAC1 plays other roles in regulating GABA synthesis, reducing oxidative stress in neurons, and is important in supporting neuron viability. Currently, little is known about EAAC1 in AD. To address whether EAAC1 is disturbed in AD, immunohistochemistry was performed on tissue from hippocampus and frontal cortex of AD and normal control subjects matched for age and gender. While EAAC1 immunostaining in cortex appeared comparable to controls, in the hippocampus, EAAC1 aberrantly accumulated in the cell bodies and proximal neuritic processes of CA2-CA3 pyramidal neurons in AD patients. Biochemical analyses showed that Triton X-100-insoluble EAAC1 was significantly increased in the hippocampus of AD patients compared to both controls and Parkinson's disease patients. These findings suggest that aberrant glutamate transporter expression is associated with AD-related neuropathology and that intracellular accumulation of detergent-insoluble EAAC1 is a feature of the complex biochemical lesions in AD that include altered protein solubility.

  5. Analysis of the magnetoencephalogram background activity in Alzheimer's disease patients with auto-mutual information.

    PubMed

    Gómez, Carlos; Hornero, Roberto; Abásolo, Daniel; Fernández, Alberto; Escudero, Javier

    2007-09-01

    The aim of the present study was to analyse the magnetoencephalogram (MEG) background activity in patients with Alzheimer's disease (AD), one of the most frequent disorders among elderly population. For this pilot study, we recorded the MEGs with a 148-channel whole-head magnetometer in 20 patients with probable AD and 21 age-matched control subjects. Artefact-free epochs of 3392 samples were analysed with auto-mutual information (AMI). Average AMI decline rates were lower for the AD patients' recordings than for control subjects' ones. Statistically significant differences were found using a Student's t-test (p<0.01) in 144 channels. Mean AMI values were analysed with a receiver operating characteristic curve. Sensitivity, specificity and accuracy values of 75%, 90.5% and 82.9% were obtained. Our results show that AMI estimations of the magnetic brain activity are different in both groups, hence indicating an abnormal type of dynamics associated with AD. This study suggests that AMI might help medical doctors in the diagnosis of the disease.

  6. Predictors of patient self-ratings of quality of life in Alzheimer disease: cross-sectional results from the Canadian Alzheimer's Disease Quality of Life Study.

    PubMed

    Naglie, Gary; Hogan, David B; Krahn, Murray; Beattie, B Lynn; Black, Sandra E; Macknight, Chris; Freedman, Morris; Patterson, Christopher; Borrie, Michael; Bergman, Howard; Byszewski, Anna; Streiner, David; Irvine, Jane; Ritvo, Paul; Comrie, Janna; Kowgier, Matthew; Tomlinson, George

    2011-10-01

    To assess whether the core symptoms of Alzheimer disease (AD) consistently predict patient self-rated quality of life (QOL) as assessed by a variety of QOL measures in a large national sample of AD patients. Cross-sectional. Fifteen dementia and geriatric clinics across Canada. Community-living patients with AD (n = 370) with Mini-Mental State Exam (MMSE) scores greater than 10. Patients rated their QOL by using two utility indexes, the European QOL-5 Dimensions and the Quality of Well-Being Scale, a global QOL Visual Analog Scale, and the disease-specific QOL-AD instrument. Cognition was assessed with the AD Assessment Scale-Cognitive subscale and MMSE, function with the Disability Assessment for Dementia, and behavioral and psychological symptoms with the Neuropsychiatric Inventory and the Geriatric Depression Scale (GDS). One-way analysis of variance and fully adjusted multiple linear regression were used to assess the relationship between core dementia symptoms and QOL ratings. The QOL measures had only small-to-moderate correlations with each other. For all QOL measures, patient ratings were significantly lower among patients with more depressive symptoms. In multivariable analyses, the GDS score was the only significant independent predictor of patient self-ratings for all four QOL measures. Self-rated symptoms of depression were a consistent independent predictor of patient-rated QOL across diverse QOL measures, while performance-based measures of cognition and informant-based functional status were not. These findings confirm the importance of identifying and treating depression in patients with AD and endorse the use of measures of self-rated depressive symptoms and QOL as outcomes in AD clinical trials.

  7. Direct visualization of fungal infection in brains from patients with Alzheimer's disease.

    PubMed

    Pisa, Diana; Alonso, Ruth; Juarranz, Angeles; Rábano, Alberto; Carrasco, Luis

    2015-01-01

    Recently, we have reported the presence of fungal infections in patients with Alzheimer's disease (AD). Accordingly, fungal proteins and DNA were found in brain samples, demonstrating the existence of infection in the central nervous system. In the present work, we raised antibodies to specific fungal species and performed immunohistochemistry to directly visualize fungal components inside neurons from AD patients. Mice infected with Candida glabrata were initially used to assess whether yeast can be internalized in mammalian tissues. Using polyclonal rabbit antibodies against C. glabrata, rounded immunopositive cells could be detected in the cytoplasm of cells from liver, spleen, and brain samples in infected, but not uninfected, mice. Immunohistochemical analyses of tissue from the frontal cortex of AD patients revealed the presence of fungal material in a small percentage (~10%) of cells, suggesting the presence of infection. Importantly, this immunopositive material was absent in control samples. Confocal microscopy indicated that this fungal material had an intracellular localization. The specific morphology of this material varied between patients; in some instances, disseminated material was localized to the cytoplasm, whereas small punctate bodies were detected in other patients. Interestingly, fungal material could be revealed using different anti-fungal antibodies, suggesting multiple infections. In summary, fungal infection can only be observed using specific anti-fungal antibodies and only a small percentage of cells contain fungi. Our findings provide an explanation for the hitherto elusive detection of fungi in AD brains, and are consistent with the idea that fungal cells are internalized inside neurons.

  8. MRI volume of the medial frontal cortex predicts financial capacity in patients with mild Alzheimer's disease.

    PubMed

    Stoeckel, Luke E; Stewart, Christopher C; Griffith, H Randall; Triebel, Kristen; Okonkwo, Ozioma C; den Hollander, Jan A; Martin, Roy C; Belue, Katherine; Copeland, Jacquelynn N; Harrell, Lindy E; Brockington, John C; Clark, David G; Marson, Daniel C

    2013-09-01

    Persons with mild Alzheimer's disease (AD) have significant deficits in financial abilities. This study examined the relationship between brain structure volumes, cognition, and financial capacity in patients with mild AD. Sixteen mild AD patients and 16 older adult comparisons completed the Financial Capacity Instrument (FCI), a psychometric measure of financial abilities, and also underwent magnetic resonance imaging (MRI) to obtain volumes of the bilateral hippocampi, angular gyri, precunei, and medial and dorsolateral frontal cortices. Mild AD patients performed significantly below comparisons on the FCI and had significantly smaller hippocampi. Among mild AD patients, FCI performance was moderately correlated with frontal (medial and dorsolateral frontal cortex) and posterior (angular gyri and precunei) cortical volumes. Stepwise regression demonstrated that medial frontal cortex volume predicted FCI score. The relationship between medial frontal cortex volume and overall FCI score was partially mediated by two measures of simple attention (DRS Attention, DRS Construction). The findings suggest that medial frontal cortex atrophy and associated declines in simple attention play an increasingly important role in declining financial skills in patients with mild AD.

  9. The relation of patient dependence to home health aide use in Alzheimer's disease.

    PubMed

    Scherer, Rachel K; Scarmeas, Nikolaos; Brandt, Jason; Blacker, Deborah; Albert, Marilyn S; Stern, Yaakov

    2008-09-01

    Although there has been much research devoted to understanding the predictors of nursing home placement (NHP) in Alzheimer's disease (AD) patients, there is currently a lack of research concerning the predictors of home health care. The objective of this study was to examine whether the Dependence Scale can predict home health aide (HHA) use. The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States. Markov analyses (n=75) were used to calculate annual transition probabilities for the "new onset" of HHA use (instances where an HHA was absent at the previous visit, but present at the next visit) as a function of HHA presence at the preceding year's visit and dependence level at that preceding year's visit. The dependence level at the previous year's visit was a significant predictor of HHA use at the next year's visit. Three specific items of the Dependence Scale (needing household chores done for oneself, needing to be watched or kept company when awake, and needing to be escorted when outside) were significant predictors of the presence of an HHA. The Dependence Scale is a valuable tool for predicting HHA use in AD patients. Obtaining a better understanding of home health care in AD patients may help delay NHP and have a positive impact on the health and well-being of both the caregiver and the patient.

  10. FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer's disease.

    PubMed

    Paroni, Giulia; Seripa, Davide; Fontana, Andrea; D'Onofrio, Grazia; Gravina, Carolina; Urbano, Maria; Cascavilla, Leandro; Pellegrini, Fabio; Greco, Antonio; Pilotto, Alberto

    2014-01-01

    Acetylcholinesterase inhibitors (AChEIs) may reduce the oxidative stress in brain of Alzheimer's disease (AD) patients. Forkhead box O1 (FOXO1) protein has been reported as the link between oxidative stress and AD. We evaluated a potential association between FOXO1 gene locus and the response to AChEI treatment in patients with sporadic AD. In this prospective study, 109 Caucasian AD patients were treated with standard doses of donepezil, galantamine, or rivastigmine for 6 months. Functional and cognitive status were evaluated at baseline and after treatment. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Genotype analyses, including the APOE polymorphism, were made in blinded fashion. A significantly higher frequency of FOXO1 rs7981045 G/G genotype was observed in nonresponders compared with responders (17.14% versus 2.70%, P=0.010). Age, sex, and APOE-adjusted logistic regression analysis confirmed that patients with the G/G genotype had a significantly higher risk of poor response to AChEI treatment (odds ratio =10.310; 95% confidence interval, 1.510-70.362). Haplotype analysis revealed significant differences in haplotype frequency distribution between these groups. FOXO1 may influence the clinical response to AChEIs in AD patients.

  11. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Increased CSF APPs-α levels in patients with Alzheimer disease treated with acitretin.

    PubMed

    Endres, Kristina; Fahrenholz, Falk; Lotz, Johannes; Hiemke, Christoph; Teipel, Stefan; Lieb, Klaus; Tüscher, Oliver; Fellgiebel, Andreas

    2014-11-18

    We investigated induction of α-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoid acitretin (Neotigason; Actavis, München-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of α-secretase-derived amyloid precursor protein (APPs-α). Twenty-one patients clinically diagnosed with mild to moderate AD received acitretin (30 mg per day) or placebo in a 4-week double-blind study. Primary endpoint was the difference of CSF APPs-α ratios calculated from the APPs-α levels after treatment and at baseline. We monitored safety and tolerability of the treatment. In addition, we assessed biomarkers such as β-amyloid 42 (Aβ42) under treatment conditions. The acitretin group showed a significant increase in CSF APPs-α levels compared with the placebo group (difference 0.38, 95% confidence interval 0.03-0.72, p = 0.035) within this rather short treatment period. The synthetic retinoid acitretin was overall safe and well tolerated. Our pilot study highlights that acitretin is able to enhance the nonamyloidogenic APP processing in human patients. Clinical consequences of this regulation should be investigated in larger and longer trials in patients with AD to evaluate acitretin's potential to serve as a novel therapeutic drug. This study provides Class III evidence that in patients with AD, oral acitretin increases CSF APPs-α levels. © 2014 American Academy of Neurology.

  13. Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer's disease.

    PubMed

    Kessler, H; Pajonk, F-G; Meisser, P; Schneider-Axmann, T; Hoffmann, K-H; Supprian, T; Herrmann, W; Obeid, R; Multhaup, G; Falkai, P; Bayer, T A

    2006-11-01

    Increasing evidence links Alzheimer's disease (AD) with misbalanced Cu homeostasis. Recently, we have shown that dietary Cu supplementation in a transgenic mouse model for AD increases bioavailable brain Cu levels, restores Cu, Zn-super oxide-1 activity, prevents premature death, and lowers A beta levels. In the present report we investigated AD patients with normal levels of A beta 42, Tau and Phospho-Tau in the cerebrospinal fluid (CSF) in comparison with AD patients exhibiting aberrant levels in these CSF biomarkers. The influence of these cerebrospinal fluid (CSF) diagnostic markers with primary dependent variables blood Cu, Zn and ceruloplasmin (CB) and secondary with CSF profiles of Cu, Zn and neurotransmitters was determined. Multivariate tests revealed a significant effect of factor diagnostic group (no AD diagnosis in CSF or AD diagnosis in CSF) for variables plasma Cu and CB (F=4.80; df=2, 23; p=0.018). Subsequent univariate tests revealed significantly reduced plasma Cu (-12.7%; F=7.05; df=1, 25; p=0.014) and CB (-14.1%; F=9.44; df=1, 24; p=0.005) levels in patients with aberrant CSF biomarker concentrations. Although only AD patients were included, the reduced plasma Cu and CB levels in patients with a CSF diagnosis of advanced AD supports previous observations that a mild Cu deficiency might contribute to AD progression.

  14. 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.

  15. Alzheimer's disease biomarker discovery in symptomatic and asymptomatic patients: experimental approaches and future clinical applications.

    PubMed

    Ho, Lap; Fivecoat, Hayley; Wang, Jun; Pasinetti, Giulio Maria

    2010-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly. Current treatments for AD are not as effective as needed, nor is there any definitive antemortem diagnostic. Understanding the biological processes that occur during AD onset and/or progression will improve disease diagnosis and treatment. Recent applications of microarray technologies for analysis of messenger (m) RNA expression profiles have elucidated distinct changes in the brain as a function of AD dementia initiation and progression. However, mRNA analysis underestimates post-transcriptional modifications and therefore provides only a partial view of the molecular changes in the AD brain. Combining mRNA studies with protein expression analysis may provide a more global picture of the biological processes associated with AD dementia. Information gathered could lead to the development of select biological indices (biomarkers) for guiding AD diagnosis and therapy. We will provide a brief background on AD, followed by a review on the applications of microarray, proteomics, as well as microRNA expression profile analysis to develop novel diagnostic strategies that may be useful for the diagnosis AD and for monitoring disease progression. The availability of biomarkers that promote early disease diagnosis, particularly among asymptomatic patients, will lead to the application of personalized medicine in AD.

  16. 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

  17. 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

  18. Genetic aspects of Alzheimer disease.

    PubMed

    Bird, Thomas D

    2008-04-01

    Alzheimer disease is the most common cause of dementia and represents a major public health problem. The neuropathologic findings of amyloid-beta plaques and tau containing neurofibrillary tangles represent important molecular clues to the underlying pathogenesis. Genetic factors are well recognized, but complicated. Three rare forms of autosomal-dominant early-onset familial Alzheimer disease have been identified and are associated with mutations in amyloid precursor protein, presenilin 1, and presenilin 2 genes. The more common late-onset form of Alzheimer disease is assumed to be polygenic/multifactorial. However, thus far the only clearly identified genetic risk factor for Alzheimer disease is Apo lipoprotein E. The epsilon4 allele of Apo lipoprotein E influences age at onset of Alzheimer disease, but is neither necessary nor sufficient for the disease. The search continues for the discovery of additional genetic influences.

  19. 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

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

    PubMed

    Leidinger, Petra; Backes, Christina; Deutscher, Stephanie; Schmitt, Katja; Mueller, Sabine C; Frese, Karen; Haas, Jan; Ruprecht, Klemens; Paul, Friedemann; Stähler, Cord; Lang, Christoph J G; Meder, Benjamin; Bartfai, Tamas; Meese, Eckart; Keller, Andreas

    2013-07-29

    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. 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. The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases.

  1. Prediction of Incipient Alzheimer's Disease Dementia in Patients with Mild Cognitive Impairment.

    PubMed

    Ardekani, Babak A; Bermudez, Elaine; Mubeen, Asim M; Bachman, Alvin H

    2017-01-01

    Mild cognitive impairment (MCI) is a transitional stage from normal aging to Alzheimer's disease (AD) dementia. It is extremely important to develop criteria that can be used to separate the MCI subjects at imminent risk of conversion to Alzheimer-type dementia from those who would remain stable. We have developed an automatic algorithm for computing a novel measure of hippocampal volumetric integrity (HVI) from structural MRI scans that may be useful for this purpose. To determine the utility of HVI in classification between stable and progressive MCI patients using the Random Forest classification algorithm. We used a 16-dimensional feature space including bilateral HVI obtained from baseline and one-year follow-up structural MRI, cognitive tests, and genetic and demographic information to train a Random Forest classifier in a sample of 164 MCI subjects categorized into two groups [progressive (n = 86) or stable (n = 78)] based on future conversion (or lack thereof) of their diagnosis to probable AD. The overall accuracy of classification was estimated to be 82.3% (86.0% sensitivity, 78.2% specificity). The accuracy in women (89.1%) was considerably higher than that in men (78.9%). The prediction accuracy achieved in women is the highest reported in any previous application of machine learning to AD diagnosis in MCI. The method presented in this paper can be used to separate stable MCI patients from those who are at early stages of AD dementia with high accuracy. There may be stronger indicators of imminent AD dementia in women with MCI as compared to men.

  2. Is sertraline treatment or depression remission in depressed Alzheimer patients associated with improved caregiver well being? Depression in Alzheimer's Disease Study 2.

    PubMed

    Flynn Longmire, Crystal V; Drye, Lea T; Frangakis, Constantine E; Martin, Barbara K; Meinert, Curtis L; Mintzer, Jacobo E; Munro, Cynthia A; Porsteinsson, Anton P; Rabins, Peter V; Rosenberg, Paul B; Schneider, Lon S; Weintraub, Daniel; Lyketsos, Constantine G

    2014-01-01

    We wanted to assess if sertraline treatment (versus placebo) or remission of depression at 12 weeks (versus nonremission) in Alzheimer patients is associated with improved caregiver well being. We conducted a randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of sertraline for the treatment of depression in individuals with Alzheimer disease in five clinical research sites across the United States. Participants were caregivers of patients enrolled in the Depression in Alzheimer's Disease Study 2 (N = 131). All caregivers received standardized psychosocial support throughout the study. Caregiver outcome measures included depression (Beck Depression Inventory), distress (Neuropsychiatric Inventory), burden (Zarit Burden Interview), and quality of life (Medical Outcomes Study Short Form Health Survey). Fifty-nine percent of caregivers were spouses, 63.4% were women, and 64.1% were white. Caregivers of patients in both treatment groups had significant reductions in distress scores over the 24-week study period, but there was not a greater benefit for caregivers of patients taking sertraline. However, caregivers of patients whose depression was in remission at week 12 had greater declines in distress scores over the 24 weeks than caregivers of patients whose depression did not remit by week 12. Patient treatment with sertraline was not associated with significantly greater reductions in caregiver distress than placebo treatment. Distress but not level of depression or burden lessened for all caregivers regardless of remission status and even more so for those who cared for patients whose depression remitted. Results imply an interrelationship between caregiver distress and patient psychiatric outcomes. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Language background in early life may be related to neuropsychiatry symptoms in patients with Alzheimer disease.

    PubMed

    Liu, Yi-Chien; Hsu, Jung-Lung; Wang, Shuu-Jin; Yip, Ping-Keung; Meguro, Kenichi; Fuh, Jong-Ling

    2017-02-10

    The relationship between early life experience and the occurrence of neuropsychiatry symptoms (NPSs) in patients with Alzheimer disease (AD) is unclear. From 2012 to 2014, we prospectively recruited 250 patients with probable AD from the memory clinic of Taipei Veterans General Hospital. All patients underwent standard assessments, including brain magnetic resonance imaging or computed tomography, neuropsychological tests, neuropsychiatry inventory (NPI-Q) and related blood tests. A linear regression analysis was performed to investigate the relationship between NPSs and age, gender, disease severity, depression, language background (with or without Japanese education). Among the 250 participants, 113 (45.2%) were women. Their average age was 82.6 years. Of all the participants, 93 (37.2%) had received formal Japanese education, whereas 157 (62.8%) did not receive Japanese education. The participants with Japanese education were slightly younger (83.1 ± 3.6 vs. 81.4 ± 3.4, P = 0.006), with a higher proportion of them were women (30.5% vs. 69.8%, P < 0.001) and fewer years of total education (10.8 ± 4.5 vs. 7.7 ± 3.2, P < 0.001), compared to the participants without Japanese education. NPI-Q scores significantly differed between the two groups (15.8 vs. 24.1, P = 0.024). Both disease severity and language background predicted NPI-Q scores. Language background in early life may be related to NPSs in patients with AD, and this effect is more significant in patients with a lower education level than in those with a higher education level. More NPSs may be the result of negative effects on dominant language or early life experiences.

  4. Predictors of physician referral for patient recruitment to Alzheimer disease clinical trials.

    PubMed

    Galvin, James E; Meuser, Thomas M; Boise, Linda; Connell, Cathleen M

    2009-01-01

    Inadequate recruitment into Alzheimer disease clinical trials is an important threat to the validity and generalizability of the studies. The majority of dementia patients are first evaluated by community-based physicians; however, physician perceptions of clinical research are largely unknown. A survey was distributed to 3123 physicians in 3 states; 370 were returned. Survey items assessed attitudes, perceived benefits of and barriers to referral to clinical research, and physicians use of the internet for medical information. The mean age of the respondents was 50.6+/-10.8 years; 70% were male, 78% white, 61% were primary care providers; 63% used the internet > or =3 times/week. No demographic or medical specialty differences existed between those who were likely (n=193) and unlikely (n=162) to refer patients to clinical trials. Differences were discovered in perceived benefits reported by physicians who were more likely to refer, whereas differences in perceived barriers existed in primary care compared with specialists. Referral to clinical trials is predicted by close proximity to a research center [odds ratio (OR): 4.0; 95% confidence interval (CI), 1.1-15.6] and availability of internet information regarding diagnostic evaluation (OR: 2.3; 95% CI, 1.1-4.7). Primary barriers included concerns about exposure of patients to uncomfortable procedures (OR: 4.7; 95% CI, 1.2-18.7) and lack of time to discuss research participation (OR: 6.8; 95% CI, 1.4-32.3). Proximity to a research center and availability of diagnostic clinical tools are strong predictors of clinical trial referral. Concern over risks to patients and lack of time are strong barriers. These results suggest that dementia outreach education targeted to physicians should emphasize the importance of clinical trials with a focus on discussing research participation in a time-efficient manner and increasing awareness of risk reduction and the safety of research protocols. Providing easy access to up

  5. Fungal Enolase, β-Tubulin, and Chitin Are Detected in Brain Tissue from Alzheimer's Disease Patients.

    PubMed

    Pisa, Diana; Alonso, Ruth; Rábano, Alberto; Horst, Michael N; Carrasco, Luis

    2016-01-01

    Recent findings provide evidence that fungal structures can be detected in brain tissue from Alzheimer's disease (AD) patients using rabbit polyclonal antibodies raised against whole fungal cells. In the present work, we have developed and tested specific antibodies that recognize the fungal proteins, enolase and β-tubulin, and an antibody that recognizes the fungal polysaccharide chitin. Consistent with our previous studies, a number of rounded yeast-like and hyphal structures were detected using these antibodies in brain sections from AD patients. Some of these structures were intracellular and, strikingly, some were found to be located inside nuclei from neurons, whereas other fungal structures were detected extracellularly. Corporya amylacea from AD patients also contained enolase and β-tubulin as revealed by these selective antibodies, but were devoid of fungal chitin. Importantly, brain sections from control subjects were usually negative for staining with the three antibodies. However, a few fungal structures can be observed in some control individuals. Collectively, these findings indicate the presence of two fungal proteins, enolase and β-tubulin, and the polysaccharide chitin, in CNS tissue from AD patients. These findings are consistent with our hypothesis that AD is caused by disseminated fungal infection.

  6. Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus

    PubMed Central

    Biessels, G J; De Leeuw, F‐E; Lindeboom, J; Barkhof, F; Scheltens, P

    2006-01-01

    Background The risk of Alzheimer's disease (AD) is increased in type 2 diabetes (DM2). This increased risk has been attributed to vascular comorbidity, but other mechanisms, such as accelerated ageing of the brain, have also been implicated. Objective To determine whether AD in patients with DM2 is associated with an increased occurrence of vascular lesions in the brain, by increased cerebral atrophy, or a combination of both. Methods In total, 29 patients with AD and DM2 and 58 patients with AD and without DM2 were included in the study. Clinical characteristics were recorded, and a neuropsychological examination and magnetic resonance imaging (MRI) scan were performed. MRI scans were rated for cortical and subcortical atrophy, medial temporal lobe atrophy, white matter lesions, and infarcts. Results The neuropsychological profiles of the two groups were identical. Patients with AD and DM2 had increased cortical atrophy on MRI (p<0.05) compared with the non‐DM2 group. In addition, infarcts were more common (odds ratio 2.4; 95% CI 0.8 to 7.8), but this effect did not account for the increased atrophy. The other MR measures did not differ between the groups. Conclusion The results suggest that non‐vascular mechanisms, leading to increased cortical atrophy, are also involved in the increased risk of AD in DM2. PMID:16484636

  7. Predicting rapid cognitive decline in Alzheimer's disease patients using quantitative EEG markers and neuropsychological test scores.

    PubMed

    Reyes-Coronel, Carmina; Waser, Markus; Garn, Heinrich; Deistler, Manfred; Dal-Bianco, Peter; Benke, Thomas; Ransmayr, Gerhard; Grossegger, Dieter; Schmidt, Reinhold

    2016-08-01

    Alzheimer's Disease (AD) can take different courses: some patients remain relatively stable while others decline rapidly within a given period of time. Losing more than 3 Mini-Mental State Examination (MMSE) points in one year is classified as rapid cognitive decline (RCD). This study used neuropsychological test scores and quantitative EEG (QEEG) markers obtained at a baseline examination to identify if an AD patient will be suffering from RCD. Data from 68 AD patients of the multi-centric cohort study PRODEM-Austria were applied. 15 of the patients were classified into the RCD group. RCD versus non-RCD support vector machine (SVM) classifiers using QEEG markers as predictors obtained 72.1% and 77.9% accuracy ratings based on leave-one-out validation. Adding neuropsychological test scores of Boston Naming Test improved the classifier to 80.9% accuracy, 80% sensitivity, and 81.1% specificity. These results indicate that QEEG markers together with neuropsychological test scores can be used as RCD predictors.

  8. 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

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

    PubMed

    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.

  10. Oral reading fluency analysis in patients with Alzheimer disease and asymptomatic control subjects.

    PubMed

    Martínez-Sánchez, F; Meilán, J J G; García-Sevilla, J; Carro, J; Arana, J M

    2013-01-01

    Many studies highlight that an impaired ability to communicate is one of the key clinical features of Alzheimer disease (AD). To study temporal organisation of speech in an oral reading task in patients with AD and in matched healthy controls using a semi-automatic method, and evaluate that method's ability to discriminate between the 2 groups. A test with an oral reading task was administered to 70 subjects, comprising 35 AD patients and 35 controls. Before speech samples were recorded, participants completed a battery of neuropsychological tests. There were no differences between groups with regard to age, sex, or educational level. All of the study variables showed impairment in the AD group. According to the results, AD patients' oral reading was marked by reduced speech and articulation rates, low effectiveness of phonation time, and increases in the number and proportion of pauses. Signal processing algorithms applied to reading fluency recordings were shown to be capable of differentiating between AD patients and controls with an accuracy of 80% (specificity 74.2%, sensitivity 77.1%) based on speech rate. Analysis of oral reading fluency may be useful as a tool for the objective study and quantification of speech deficits in AD. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  11. Electroencephalogram background activity characterization with approximate entropy and auto mutual information in Alzheimer's disease patients.

    PubMed

    Abásolo, Daniel; Hornero, Roberto; Espino, Pedro; Escudero, Javier; Gómez, Carlos

    2007-01-01

    The aim of this study was to analyze the electroencephalogram (EEG) background activity in Alzheimer's disease (AD) with two non-linear methods: Approximate Entropy (ApEn) and Auto Mutual Information (AMI). ApEn quantifies the regularity in data, while AMI detects linear and non-linear dependencies in time series. EEGs were recorded from the 19 scalp loci of the international 10-20 system in 11 AD patients and 11 age-matched controls. ApEn was significantly lower in AD patients at electrodes O1, O2, P3 and P4 (p<0.01). The AMI of the AD patients decreased significantly more slowly with time delays than the AMI of normal controls at electrodes T5, T6, O1, O2, P3 and P4 (p<0.01). Furthermore, we observed a strong correlation between the results obtained with both non-linear methods, suggesting that the AMI rate of decrease can be used to estimate the regularity in time series. The decreased irregularity found in AD patients suggests that EEG analysis with ApEn and AMI could help to increase our insight into brain dysfunction in AD.

  12. 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.

  13. Identification of CHCHD10 Mutation in Chinese Patients with Alzheimer Disease.

    PubMed

    Xiao, Tingting; Jiao, Bin; Zhang, Weiwei; Pan, Chuzheng; Wei, Jingya; Liu, Xiaoyan; Zhou, Yafang; Zhou, Lin; Tang, Beisha; Shen, Lu

    2017-09-01

    CHCHD10 gene has been identified to be associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Considering the clinical phenotype and pathology characterization were overlapped between FTD and Alzheimer disease (AD), and so far, no systematic analysis of CHCHD10 mutation was conducted in patients with AD in Asian population. Therefore, we screened of all exons in CHCHD10 in a cohort of 484 AD patients (60 with family history) from Mainland China. A heterozygous variant p.A35D (c.104C>A), previously reported in a patient with FTD in Italian population, was identified in a female patient with sporadic LOAD. The age at onset of mutation carrier was 86, presented as typical amnestic dementia. The mutation was found to be deleterious according to in silico predictions and excluded in 500 ethnically and geographically matched controls. Our finding revealed the clinical manifestations of variant p.A35D (c.104C>A) in a LOAD case and indicated that CHCHD10 mutation was presented in different types of dementia.

  14. Wrist actigraphy for measuring sleep in intervention studies with Alzheimer's disease patients: application, usefulness, and challenges.

    PubMed

    Camargos, Einstein F; Louzada, Fernando M; Nóbrega, Otávio T

    2013-12-01

    Sleep disorders are common in patients with Alzheimer's disease (AD). An important aspect of intervention studies in patients with sleep disorders is the choice of assessment strategy. This paper presents a literature review concerning assessment strategies for measuring sleep in intervention studies with AD patients, with a focus on actigraphy. Thirty-seven articles were selected for this review, having analysis of sleep/nocturnal rhythm disturbances by actigraphy as the primary or secondary outcome. The advantages and limitations of actigraphy were discussed vis-à-vis polysomnography and subjective interventions. The following methodological aspects were addressed: impact of experimental design and patient setting, inclusion and exclusion criteria, placement of the actigraphy device, adherence to the regimen, duration of recordings and the choice of sleep parameters. Our analyses suggest that the methods used in intervention studies encompassing sleep disorders and dementia could be improved by increasing accuracy of diagnosis, categorization of sleep disturbances, adherence to actigraphy, and by clearly defining the variables and endpoints in each study. Also, controlling variables that could interfere with sleep and describing the data processing and analysis might improve interpretation of results.

  15. Spared emotional perception in patients with Alzheimer's disease is associated with negative caregiver outcomes.

    PubMed

    Daley, Ryan T; Sugarman, Michael A; Shirk, Steven D; O'Connor, Maureen K

    2017-02-17

    Caregivers (CGs) for patients with Alzheimer's disease (AD) often experience negative mental health and relationship outcomes. Additionally, emotional perception abilities are often compromised in early AD; the relationships between these deficits and CG outcomes are unclear. The present study investigated the relationship between emotional perception abilities in AD participants and CG well-being. Participants included 28 individuals with AD, their spousal CGs, and 30 older controls (OCs). Patients and controls completed the Montreal Cognitive Assessment and Advanced Clinical Solutions: Social Perception subtest. CGs completed questionnaires related to relationship satisfaction, burden, depression, and patient neuropsychiatric symptoms and activities of daily living. The patient group performed significantly worse than OCs on measures of cognition and emotional perception. Several significant relationships emerged between AD participant emotional perception and CG outcomes. Higher CG depression was associated with greater overall emotional perception abilities (r = .39, p = .041). Caregiver burden was positively correlated with AD participants' ability to label the emotional tones of voices (r = .47, p = .015). Relationship satisfaction was not significantly correlated with emotional perception. This study replicated earlier findings of impaired emotional perception abilities in AD participants. However, preserved abilities in emotional perception were associated greater CG depression and burden. Interestingly, the CGs satisfaction with the marital relationship did not appear to be influenced by changes in emotional perception. Higher emotional engagement among couples in which one spouse has cognitive impairment may contribute to increased negative interactions and in turn a greater sense of burden and depression, while leaving the marital relationship preserved.

  16. Alzheimer's Disease Beyond Abeta.

    PubMed

    Town, Terrence

    2010-05-01

    Many of the Alzheimer's disease (AD) clinical trials have made it far enough down the pipeline to allow conclusions about targeting the amyloid-beta peptide (Abeta) as a therapeutic approach. Based on these results, it is becoming clear that a multifocal approach to AD treatment is probably necessary. However, critical discussion beyond Abeta is necessary to enable the next wave of AD therapeutic targets. For this reason, the 2010 Keystone Symposium, 'Alzheimer's Disease Beyond Abeta', was organized by JoAnne McLaurin and Tony Wyss-Coray to spark topical discussion and debate. While researchers struggled to get beyond that ever-present pathognomonic feature of AD, new and exciting evidence was presented that raised our awareness of what is around the corner for next-generation AD therapeutics beyond Abeta. This report will describe some of the highlights from Copper Mountain Resort throughout the meeting period of 10-15 January 2010 in Colorado (USA). Despite illuminating scientific presentations and intense discussions, a number of important questions remain concerning the best biomarkers and targets to focus on, and when and how to therapeutically intervene.

  17. Alzheimer's Patients' Use of Painkilling Patches Cause for Concern

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_162442.html Alzheimer's Patients' Use of Painkilling Patches Cause for Concern Researchers ... opioid painkillers may be common among Alzheimer's disease patients and could be a cause for concern, researchers ...

  18. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Restless legs syndrome in a group of patients with Alzheimer's disease.

    PubMed

    Talarico, Giuseppina; Canevelli, M; Tosto, G; Vanacore, N; Letteri, F; Prastaro, M; Troili, F; Gasparini, M; Lenzi, G L; Bruno, G

    2013-03-01

    Restless legs syndrome (RLS) is a neurological disorder characterized by the urge to move the legs associated with peculiar unpleasant sensations during periods of rest and inactivity that are relieved by movement. A few studies analyzed RLS in neurodegenerative diseases such as Alzheimer's Disease (AD). The aim of our study was to assess the prevalence and the clinical characteristics of RLS in a cohort of AD patients. Three hundred and thirty-nine subjects with a diagnosis of AD were recruited. Cognitive, functional, and neuropsychiatric measures were collected at baseline and six-monthly for a 2-years follow-up Fourteen subjects met the RLS criteria. RLS subjects were more frequently male (p:0,006) and younger than AD subject without RLS (p:0,029). MMSE, ADL and IADL were not significantly different. NPI total scores did not differ significantly, however, AD patients with RLS were found to be more apathetic (p:0,001) than AD subjects without RLS. RLS prevalence in our AD cohort was estimated to be about 4%. RLS appeared to be associated with neuropsychiatric symptoms such as apathy. RLS and apathy might share a common pathophysiological basis represented by a dysfunction of the central dopaminergic system.

  20. [Key points of the follow-up plan in the care of Alzheimer's disease patients].

    PubMed

    Hein, C; Sourdet, S; Piau, A; Villars, H; Nourhashemi, F; Vellas, B

    2011-03-01

    The following article presents the main points of the follow-up plan of Alzheimer's disease (AD) and related syndromes patients. The general objective of this follow-up plan is to improve the quality of live of these subjects and their family. The key points are assessments of cognitive decline, functional decline and complications such as behavioural and psychological symptoms of dementia (BPSD), malnutrition and gait and balance disorders. In clinical practice, different tools are available, but frequency of evaluation is not consensual. However, the aim of this follow-up is to detect, prevent and treat complications and to improve the use of residual functional abilities in basic activities of daily living. The physician also needs to detect and prevent caregiver's exhaustion and to consider the ethical issues raised by the disease. The care plan is based on non pharmacological and pharmacological measures. The non pharmacological approach must be implemented first. The place of anti-dementia drugs is considered. Lastly, this follow-up plan aims to limit iterative admissions to emergency room and to increase the access to geriatric units. Communication and collaboration between specialist, family practitioner and caregivers are needed in order to reach the objective of quality of life improvement in AD patients.

  1. Patients with mild Alzheimer's disease produced shorter outgoing saccades when reading sentences.

    PubMed

    Fernández, Gerardo; Schumacher, Marcela; Castro, Liliana; Orozco, David; Agamennoni, Osvaldo

    2015-09-30

    In the present work we analyzed forward saccades of thirty five elderly subjects (Controls) and of thirty five mild Alzheimer's disease (AD) during reading regular and high-predictable sentences. While they read, their eye movements were recorded. The pattern of forward saccade amplitudes as a function of word predictability was clearly longer in Controls. Our results suggest that Controls might use stored information of words for enhancing their reading performance. Further, cloze predictability increased outgoing saccades amplitudes, as this increase stronger in high-predictable sentences. Quite the contrary, patients with mild AD evidenced reduced forward saccades even at early stages of the disease. This reduction 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. Our findings might be relevant for expanding the options for the early detection and monitoring of in the early stages of AD. Furthermore, eye movements during reading could provide a new tool for measuring a drug's impact on patient's behavior. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Active Vaccines for Alzheimer Disease Treatment.

    PubMed

    Sterner, Rosalie M; Takahashi, Paul Y; Yu Ballard, Aimee C

    2016-09-01

    Vaccination against peptides specific to Alzheimer disease may generate an immune response that could help inhibit disease and symptom progression. PubMed and Scopus were searched for clinical trial articles, review articles, and preclinical studies relevant to the field of active Alzheimer disease vaccines and raw searches yielded articles ranging from 2016 to 1973. ClinicalTrials.gov was searched for active Alzheimer disease vaccine trials. Manual research and cross-referencing from reviews and original articles was performed. First generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease resulted in cases of meningoencephalitis in 6% of patients, so next generation vaccines are working to target more specific epitopes to induce a more controlled immune response. Difficulty in developing these vaccines resides in striking a balance between providing a vaccine that induces enough of an immune response to actually clear protein sustainably but not so much of a response that results in excess immune activation and possibly adverse effects such as meningoencephalitis. Although much work still needs to be done in the field to make this a practical possibility, the enticing allure of being able to treat or even prevent the extraordinarily impactful disease that is Alzheimer disease makes the idea of active vaccination for Alzheimer disease very appealing and something worth striving toward. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  3. Relationship of physical and functional independence and perceived quality of life of veteran patients with Alzheimer disease.

    PubMed

    Yeaman, Paul A; Kim, Dong-Yun; Alexander, Jeffrey L; Ewing, Helen; Kim, Kye Y

    2013-08-01

    Alzheimer disease not only affects the cognitive function but also impacts one's abilities to perform daily tasks. This study evaluated for correlation between the quality of life of patients with Alzheimer disease (QoL-AD) and the level of independence and to evaluate the statistical difference between patients' quality of life and proxy perception of quality of life by utilizing the Katz activities of daily living and QoL-AD on patients and QoL-AD on caregivers. There was a small positive correlation (r = .13) between the levels of physical and functional independence and the perceived QoL. Also, patient consistently had higher QoL-AD than their caregiver counterparts. These findings provide some insight into our need to acknowledge factors that may influence QoL and illustrate the importance of monitoring for executive dysfunction and the safety risk.

  4. Haloperidol disrupts, clozapine reinstates the circadian rest-activity cycle in a patient with early-onset Alzheimer disease.

    PubMed

    Wirz-Justice, A; Werth, E; Savaskan, E; Knoblauch, V; Gasio, P F; Müller-Spahn, F

    2000-01-01

    Measurement of the circadian rest-activity cycle in a patient with early-onset Alzheimer disease for 555 days revealed marked changes in the timing and amount of nocturnal activity. After neuroleptic medication was changed to haloperidol, the rest-activity cycle became completely arrhythmic for two months, concomitant with a marked worsening of cognitive state. Circadian integrity returned together with clinical improvement when the patient was subsequently treated with clozapine. This observation suggests that the known tendency for patients with Alzheimer disease to develop sleep-wake cycle disturbances may be aggravated by a classic neuroleptic; in contrast, the atypical neuroleptic clozapine may consolidate it. Similar observations in schizophrenic patients indicate that this chronobiological finding is drug- and not illness-related.

  5. Tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells.

    PubMed

    Woerman, Amanda L; Aoyagi, Atsushi; Patel, Smita; Kazmi, Sabeen A; Lobach, Iryna; Grinberg, Lea T; McKee, Ann C; Seeley, William W; Olson, Steven H; Prusiner, Stanley B

    2016-12-13

    Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP). Extracts from AGD, CBD, and PSP patient samples, which contain four-repeat (4R) tau prions, were transmitted to HEK293 cells expressing 4R tau fused to YFP. These studies demonstrated that prion propagation in HEK cells requires isoform pairing between the infecting prion and the recipient substrate. Interestingly, tau aggregates in AD and CTE, containing both 3R and 4R isoforms, were unable to robustly infect either 3R- or 4R-expressing cells. However, AD and CTE prions were able to replicate in HEK293T cells expressing both 3R and 4R tau. Unexpectedly, increasing the level of 4R isoform expression alone supported the propagation of both AD and CTE prions. These results allowed us to determine the levels of tau prions in AD and CTE brain extracts.

  6. 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…

  7. 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…

  8. Plasma nutrient status of patients with Alzheimer's disease: Systematic review and meta-analysis.

    PubMed

    Lopes da Silva, Sofia; Vellas, Bruno; Elemans, Saskia; Luchsinger, José; Kamphuis, Patrick; Yaffe, Kristine; Sijben, John; Groenendijk, Martine; Stijnen, Theo

    2014-07-01

    Alzheimer disease (AD) patients are at risk of nutritional insufficiencies because of physiological and psychological factors. Nutritional compounds are postulated to play a role in the pathophysiological processes that are affected in AD. We here provide the first systematic review and meta-analysis that compares plasma levels of micronutrients and fatty acids in AD patients to those in cognitively intact elderly controls. A secondary objective was to explore the presence of different plasma nutrient levels between AD and control populations that did not differ in measures of protein/energy nourishment. We screened literature published after 1990 in the Cochrane Central Register of Controlled Trials, Medline, and Embase electronic databases using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for AD patients, controls, micronutrient, vitamins, and fatty acids, resulting in 3397 publications, of which 80 met all inclusion criteria. Status of protein/energy malnutrition was assessed by body mass index, mini nutritional assessment score, or plasma albumin. Meta-analysis, with correction for differences in mean age between AD patients and controls, was performed when more than five publications were retrieved for a specific nutrient. We identified five or more studies for folate, vitamin A, vitamin B12, vitamin C, vitamin D, vitamin E, copper, iron, and zinc but fewer than five studies for vitamins B1 and B6, long-chain omega-3 fatty acids, calcium, magnesium, manganese, and selenium (the results of the individual publications are discussed). Meta-analysis showed significantly lower plasma levels of folate and vitamin A, vitamin B12, vitamin C, and vitamin E (P < .001), whereas nonsignificantly lower levels of zinc (P = .050) and vitamin D (P = .075) were found in AD patients. No significant differences were observed for plasma levels of copper and iron. A meta-analysis that was limited to studies reporting no differences in

  9. 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

  10. Detecting signs of dysphagia in patients with Alzheimer's disease with oral feeding in daily life.

    PubMed

    Sato, Emiko; Hirano, Hirohiko; Watanabe, Yutaka; Edahiro, Ayako; Sato, Kazumichi; Yamane, Genyuki; Katakura, Akira

    2014-07-01

    It is important to understand dysphagia in patients with dementia, as it is associated with malnutrition and aspiration pneumonia. Particularly in patients with Alzheimer's disease (AD), mortality from pneumonia is high and accounts for 70% of the causes of death. However, the standard swallowing tests are often difficult to use for patients with dementia, and methods to assess daily swallowing function are required. Therefore, the purpose of the present study was to identify signs of dysphagia in AD patients in daily life. A total of 155 AD patients underwent evaluation of their swallowing function (modified water swallowing test), oral status (residual teeth, occlusal contacts), oral functions (lips function, tongue function, rinsing and gargling ability), vital functions (Barthel Index, Vitality Index), nutritional status (serum albumin, body mass index), cognitive function and neurological signs (Mini-Mental State Examination, Clinical Dementia Rating, limb contractures), and diet-related assessments (storing food in the mouth, stuffing food into the mouth, appetite, caloric intake). The severity of AD was significantly associated with swallowing function (P < 0.001). According to logistic regression analysis, the factor most significantly associated with dysphagia was "rinsing ability" (P = 0.001, odds ratio 4.8, 95% confidence interval 1.9-12.1). The factors that affect swallowing function in AD patients were examined. The swallowing function of severe AD patients was poor, and an association between AD and dysphagia was shown. Defective rinsing ability was identified as a risk factor for dysphagia. Therefore, observation of daily rinsing ability appears to be useful to identify signs of dysphagia in AD patients. © 2013 Japan Geriatrics Society.

  11. How to calculate an MMSE score from a MODA score (and vice versa) in patients with Alzheimer's disease.

    PubMed

    Cazzaniga, R; Francescani, A; Saetti, C; Spinnler, H

    2003-11-01

    The aim of the present study was to provide a statistically sound way of reciprocally converting scores of the mini-mental state examination (MMSE) and the Milan overall dementia assessment (MODA). A consecutive series of 182 patients with "probable" Alzheimer's disease patients was examined with both tests. MODA and MMSE scores proved to be highly correlated. A formula for converting MODA and MMSE scores was generated.

  12. Prevalence and clinicoradiological analyses of patients with Alzheimer disease coexisting multiple microbleeds.

    PubMed

    Nagasawa, Junpei; Kiyozaka, Tetsuhito; Ikeda, Ken

    2014-10-01

    Pathologic findings of cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) coexist frequently. Both diseases are associated with β-amyloid deposition and dementia. We aimed to evaluate frequency and clinicoradiological profile of AD patients with multiple microbleeds (MBs). We reviewed clinical records and magnetic resonance imaging (MRI) findings in patients with probable AD diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria from 2009 to 2012. Brain MRI was performed at 1.5-T superconducting system, including T2*-weighted gradient-echo imaging. MBs were defined as rounded, hypointense foci less than or equal to 10 mm in size in the brain parenchyma. MBs topography was divided into the lobar (L) and the deep/infratentorial (D/I) region. Multiple MBs were defined as the number greater than or equal to 8 in the L and the D/I territory, respectively. White matter hyperintensities (WMHs) were assessed using the age-related white matter changes scale. Clinicoradiological findings were examined for 1 year. Prevalence and clinicoradiological profiles were studied in patients with multiple L or D/I MBs. Five hundred fifty patients (238 men and 312 women) participated in the present study. Mean age (standard deviation) was 78.4 (7.7) years, 78.3 (8.1) years in men and 78.6 (7.5) years in women. A total of 132 patients (55 men and 78 women) had at least 1 MB. Prevalence of MB ≥ 1 was 24%, 23 in men and 25 in women. The ratio of L and D/I MBs were 1.1, .6 in men and 1.8 in women. Multiple MBs were detected in 93 patients (17%), 38 (16%) men and 55 (17%) in women. L distribution was found in 49 patients (9%), 15 men (6%) and 34 women (11%), and D/I distribution in 44 patients (8%), 23 men (10%) and 21 women (7%). Multiple L MBs was associated with faster

  13. The Effects of Donepezil on 15-Item Geriatric Depression Scale Structure in Patients with Alzheimer Disease

    PubMed Central

    Yang, Youngsoon; Kwak, Yong Tae

    2016-01-01

    Background/Aims In Alzheimer disease (AD), depression is among the most common accompanying neuropsychiatric symptoms and has different clinical manifestations when compared with early-life depression. In patients with drug-naïve AD, we tried to explore the structure of the 15-item Geriatric Depression Scale (GDS15) and the effect of donepezil on these substructures. Methods GDS15, cognitive function, and activities of daily living function tests were administered to 412 patients with probable AD who had not been medicated before visiting the hospital. Using principal component analysis, three factors were identified. The patients with AD who received only donepezil were retrospectively analyzed and we compared the change of cognition and GDS15 subgroup after donepezil medication. Results Our study identified three factors and revealed that the GDS15 may be comprised of a heterogeneous scale. The Barthel index was significantly correlated with factor 1 (positively) and factor 2 (negatively). The Korean version of the MMSE (K-MMSE) was significantly correlated with factor 2 and factor 3. Compared to the baseline state, K-MMSE and GDS15 showed significant improvement after taking donepezil. Among GDS15 subgroups, factor 2 and factor 3 showed significant improvement after donepezil treatment. Conclusions These results suggest that the GDS15 may be comprised of a heterogeneous scale and donepezil differentially affects the GDS15 subgroup in AD. PMID:27790242

  14. Biomarkers of inflammation and amyloid-β phagocytosis in patients at risk of Alzheimer disease

    PubMed Central

    Fiala, Milan; Veerhuis, Robert

    2010-01-01

    The ultimate goal of diagnostic research is a blood test detecting the risk of Alzheimer disease (AD) before neuronal damage develops. Current amyloid-β (Aβ) tests do not detect the process leading to neurodegeneration. Novel immunologic and proteomics tests are based on aberrant appearance of inflammatory cytokines in the CSF and other protein biomarkers in the CSF or blood, and immune biomarkers of peripheral blood mononuclear cells (PBMC's). Cytokines, chemokines, complement factors, serum amyloid P component, and signaling proteins in the CSF or blood may be a rich source of diagnostic biomarkers, but the power of these tests will need to be examined in prospective studies. Recently-described flow cytometric test of defective Aβ phagocytosis detects patients with AD with a high sensitivity and specificity in distinct populations (confirmed AD patients vs. active University professors), but further experience is necessary for its use in general population at risk of AD. The analysis of the transcriptome of peripheral blood mononuclear cells “stressed” by Aβ is beginning to unravel the relations between specific pathways and AD. Thus novel diagnostic tests may provide biomarkers for pre-clinical detection, clarification of progression from MCI to AD, and follow-up of patients in clinical trials of immunostimulating therapies. PMID:19699791

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

    PubMed Central

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

    2015-01-01

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

  16. Characteristics of number transcoding errors of Chinese- versus English-speaking Alzheimer's disease patients.

    PubMed

    Ting, Simon Kang Seng; Chia, Pei Shi; Kwek, Kevin; Tan, Wilnard; Hameed, Shahul

    2016-10-01

    Number processing disorder is an acquired deficit in mathematical skills commonly observed in Alzheimer's disease (AD), usually as a consequence of neurological dysfunction. Common impairments include syntactic errors (800012 instead of 8012) and intrusion errors (8 thousand and 12 instead of eight thousand and twelve) in number transcoding tasks. This study aimed to understand the characterization of AD-related number processing disorder within an alphabetic language (English) and ideographical language (Chinese), and to investigate the differences between alphabetic and ideographic language processing. Chinese-speaking AD patients were hypothesized to make significantly more intrusion errors than English-speaking ones, due to the ideographical nature of both Chinese characters and Arabic numbers. A simplified number transcoding test derived from EC301 battery was administered to AD patients. Chinese-speaking AD patients made significantly more intrusion errors (p = 0.001) than English speakers. This demonstrates that number processing in an alphabetic language such as English does not function in the same manner as in Chinese. The impaired inhibition capability likely contributes to such observations due to its competitive lexical representation in brain for Chinese speakers.

  17. Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease

    PubMed Central

    1996-01-01

    In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies: a previously described polyclonal and two new monoclonal antibodies. Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD. PMID:8879214

  18. Impact of Nutritional Supplementation and a Psychomotor Program on Patients With Alzheimer's Disease.

    PubMed

    Vicente de Sousa, Odete; Soares Guerra, Rita; Sousa, Ana Sofia; Pais Henriques, Bebiana; Pereira Monteiro, Anabela; Amaral, Teresa Freitas

    2017-09-01

    This study aims to evaluate the impact of oral nutritional supplementation (ONS) and a psychomotor rehabilitation program on nutritional and functional status of community-dwelling patients with Alzheimer's disease (AD). A 21-day prospective randomized controlled trial was conducted and third intervention group performed a psychomotor rehabilitation program. Patients were followed up for 180 days. Mean (standard deviation) score of Mini Nutritional Assessment (MNA) increased both in the nutritional supplementation group (NSG; n = 25), 0.4 (0.8), and in the nutritional supplementation psychomotor rehabilitation program group (NSPRG; n = 11), 1.5 (1.0), versus -0.1 (1.1) in the control group (CG; n = 43), P < .05. Further improvements at 90-day follow-up for MNA in NSG: 1.3 (1.2) and NSPRG: 1.6 (1.0) versus 0.3 (1.7) in CG ( P < .05) were observed. General linear model analysis showed that the NSG and NSPRG ▵MNA score improved after intervention, at 21 days and 90 days, was independent of the MNA and Mini-Mental State Examination scores at baseline ( Ps > .05). The ONS and a psychomotor rehabilitation program have a positive impact on long-term nutritional and functional status of patients with AD.

  19. An assessesment of telephone assistance systems for caregivers of patients with Alzheimer's disease.

    PubMed

    Garzón-Maldonado, F J; Gutiérrez-Bedmar, M; Serrano-Castro, V; Requena-Toro, M V; Padilla-Romero, L; García-Casares, N

    2016-06-09

    Telephone assistance is a common practice in neurology, although there are only a few studies about this type of healthcare. We have evaluated a Telephone Assistance System (TAS) for caregivers of patients with Alzheimer's disease (AD) from 2 points of view: financially and according to the level of satisfaction of the caregiver. 97 patients with a diagnosis of AD according to NINCDS-ADRDA criteria and their 97 informal caregivers were selected. We studied cost differences between on-site assistance and telephone assistance (TAS) for 12 months. We used a self-administered questionnaire to assess the level of satisfaction of caregivers at the end of the study period. TAS savings amounted to 80.05 ± 27.07 euros per user. 73.6% of the caregivers consider TAS a better or much better system than on-site assistance, while only 2.6% of the caregivers considered TAS a worse or much worse system than on-site assistance. Telephone assistance systems are an efficient healthcare resource for monitoring patients with AD in neurology departments. Furthermore, the level of user satisfaction was high. We therefore consider that telephone assistance service should be offered by healthcare services. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  20. 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.

  1. [Clinical stages of patients with Alzheimer disease treated in specialist clinics in Spain. The EACE study].

    PubMed

    Alom Poveda, J; Baquero, M; González-Adalid Guerreiro, M

    2013-10-01

    The diagnostic paradigm of Alzheimer disease (AD) is changing; there is a trend toward diagnosing the disease in its early stages, even before the complete syndrome of dementia is apparent. The clinical stage at which AD is usually diagnosed in our area is unknown. Therefore, the purpose of this study is to describe the clinical stages of AD patients at time of diagnosis. Multicentre, observational and cross-sectional study. Patients with probable AD according to NINCDS-ARDRA criteria, attended in specialist clinics in Spain, were included in the study. We recorded the symptom onset to evaluation and symptom onset to diagnosis intervals and clinical status of AD (based on MMSE, NPI questionnaire, and CDR scale). Participants in this study included 437 specialists representing all of Spain's autonomous communities and a total of 1,707 patients, of whom 1,694 were included in the analysis. Mean MMSE score was 17.6±4.8 (95% CI:17.4-17.9). Moderate cognitive impairment (MMSE between 10 and 20) was detected in 64% of the patients, and severe cognitive impairment (MMSE<10) in 6%. The mean interval between symptom onset and the initial primary care visit was 10.9±17.2 months (95% CI:9.9-11.8), and the interval between symptom onset and diagnosis with AD was 28.4±21.3 months. Results from the EACE show that most AD patients in our area have reached a moderate clinical stage by the time they are evaluated in a specialist clinic. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  2. Alzheimer-type neuropathology in a 28 year old patient with iatrogenic Creutzfeldt-Jakob disease after dural grafting.

    PubMed

    Preusser, M; Ströbel, T; Gelpi, E; Eiler, M; Broessner, G; Schmutzhard, E; Budka, H

    2006-03-01

    We report the case of a 28 year old man who had received a cadaverous dura mater graft after a traumatic open skull fracture with tearing of the dura at the age of 5 years. A clinical suspicion of Creutzfeldt-Jakob disease (CJD) was confirmed by a brain biopsy 5 months prior to death and by autopsy, thus warranting the diagnosis of iatrogenic CJD (iCJD) according to WHO criteria. Immunohistochemistry showed widespread cortical depositions of disease associated prion protein (PrP(sc)) in a synaptic pattern, and western blot analysis identified PrP(sc) of type 2A according to Parchi et al. Surprisingly, we found Alzheimer-type senile plaques and cerebral amyloid angiopathy in widespread areas of the brain. Plaque-type and vascular amyloid was immunohistochemically identified as deposits of beta-A4 peptide. CERAD criteria for diagnosis of definite Alzheimer's disease (AD) were met in the absence of neurofibrillar tangles or alpha-synuclein immunoreactive inclusions. There was no family history of AD, CJD, or any other neurological disease, and genetic analysis showed no disease specific mutations of the prion protein, presenilin 1 and 2, or amyloid precursor protein genes. This case represents (a) the iCJD case with the longest incubation time after dural grafting reported so far, (b) the youngest documented patient with concomitant CJD and Alzheimer-type neuropathology to date, (c) the first description of Alzheimer-type changes in iCJD, and (d) the second case of iCJD in Austria. Despite the young patient age, the Alzheimer-type changes may be an incidental finding, possibly related to the childhood trauma.

  3. Body Mass Index and Mortality Rate in Korean Patients with Alzheimer's Disease.

    PubMed

    Jang, Hyemin; Kim, Jong Hun; Choi, Seong Hye; Lee, Yunhwan; Hong, Chang Hyung; Jeong, Jee Hyang; Han, Hyun Jeong; Moon, So Young; Park, Kyung Won; Han, Seol-Hee; Park, Kee Hyung; Kim, Hee Jin; Na, Duk L; Seo, Sang Won

    2015-01-01

    A relationship between body weight, cognitive impairment, and the onset of Alzheimer's disease (AD) was recently reported. However, to our knowledge, no studies have investigated the relationship between body weight and mortality in Asian AD patients. We evaluated the relationship between body mass index (BMI) and mortality rate in Korean AD cohorts. Participants were consecutively included from two Korean representative registries: 579 AD patients from Samsung Medical Center and 1911 AD patients from the Clinical Research Center for Dementia of South Korea study. We combined these two AD cohorts to evaluate the association between BMI and mortality. BMI was used to categorize the participants into underweight, normal-weight, overweight, and obesity subgroups. All deaths were confirmed through the nationwide mortality database of Statistics Korea. 53 of 181 (29.3%), 208 of 1,127 (18.5%), 88 of 626 (14.1%), and 115 of 556 (20.7%) patients died in the underweight, normal-weight, overweight, and obese subgroups during 43.7 months of follow-up. The time-dependent cox proportional hazards model showed that, relative to the normal-weight subgroup, the underweight group had higher mortality (HR 1.82 (95% CI, 1.07-3.09)) while overweight group had lower mortality rate (HR 0.60 (95% CI, 0.38-0.95)) The effects of underweight and overweight were prominent in younger and older elderly group, respectively. However, there were no interactive effects of dementia severity or gender and BMI on survival rate. Relative to AD patients of normal weight, those who were underweight had an increased mortality rate, and overweight predicted decreased mortality in AD patients. Furthermore, our findings may help facilitate mortality stratification in AD patients by using baseline BMI.

  4. Declining financial capacity in patients with mild Alzheimer disease: a one-year longitudinal study.

    PubMed

    Martin, Roy; Griffith, H Randall; Belue, Katherine; Harrell, Lindy; Zamrini, Edward; Anderson, Britt; Bartolucci, Alfred; Marson, Daniel

    2008-03-01

    The objective of this study was to investigate change over time in financial abilities in patients with mild Alzheimer disease (AD). The authors conducted a prospective 1-year longitudinal study at a large southern U.S. metropolitan-area medical school university. Participants included healthy older adults (N=63) and patients with mild AD (N=55). The authors conducted a standardized performance measure of financial capacity. Performance was assessed on 18 financial tasks, nine domains of financial activity, and overall financial capacity. Capacity outcomes classifications (capable, marginally capable, or incapable) for domains and overall performance were made using cut scores referenced to comparison group performance. At baseline, patients with mild AD performed significantly below healthy older adults on 16 of 18 tasks, on all nine domains, and on overall financial capacity. At one-year follow up, comparison group performance was stable on all variables. In contrast, patients with mild AD showed substantial declines in overall financial capacity, on eight of nine domains, and on 12 of 18 tasks. Similarly, the proportion of the mild AD group classified as marginally capable and incapable increased substantially over one year for the two overall scores and for five financial domains. Financial capacity is already substantially impaired in patients with mild AD at baseline and undergoes rapid additional decline over one year. Relative to the comparison group, overall financial capacity performance in the AD group declined 10%, from approximately 80% of the comparison group performance at baseline to 70% at follow up. Financial skills showed differential rates of decline on both simple and complex tasks. Of clinical and public policy interest was the declining judgment of patients with mild AD regarding simple fraud schemes. The study supports the importance of prompt financial supervision and planning for patients newly diagnosed with AD.

  5. 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

  6. Antibodies in Cerebrospinal Fluid of Some Alzheimer Disease Patients Recognize Cholinergic Neurons in the Rat Central Nervous System

    NASA Astrophysics Data System (ADS)

    McRae-Degueurce, Amanda; Booj, Serney; Haglid, Kenneth; Rosengren, Lars; Karlsson, Jan Erik; Karlsson, Ingvar; Wallin, Anders; Svennerholm, Lars; Gottfries, Carl-Gerhard; Dahlstrom, Annica

    1987-12-01

    The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.

  7. [Molecular basics of Alzheimer's disease].

    PubMed

    Grigorenko, A P; Rogaev, E I

    2007-01-01

    Studies of molecular mechanisms for Alzheimer's Disease have led to the two major achievements. First, genes with mutations causing Alzheimer's Disease (presenilin genes PSI, PS2 and APP) or bearing a risk factor polymorphism (ApoE) for Alzheimer's Disease were described. Second, the new type of proteases and mechanisms of regulation of cellular differentiation and development by processes of intramembrane proteolysis were identified. These mechanisms, apparently, are universal for various cell types and organisms. Presenilin is a catalytic component of tetra-protein complex (epsilon-/gamma-secretase) cleaving type I transmembrane proteins. Other recently discovered aspartate proteases, IMPAS/SPP, cleave type II transmembrane proteins. Processing of transmembrane proteins by cellular intramembrane proteases results in production of signal peptides, transcriptional factors and short hydrophobic proteins (fragments of transmembrane domains), which may have a physiological function or play a key role in patogenic events associated with ageing (e.g., beta-amyloid formation in Alzheimer's Disease). To date approximately 160 mutations in PSI gene, more than 10 mutations in PS2 gene and 21 mutations in APP gene were described. Early preclinical diagnostics of some early forms of Alzheimer's Disease became possible. Since patogeneses of early and late onset forms of Alzheimer's Disease are similar, identification of molecular or epigenetic factors affecting primary molecular mechanisms (intramembrane or membrane associated proteolysis) underlying the disease may ultimately contribute to development of rational therapy for Alzheimer's Disease.

  8. 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.

  9. Induced pluripotent stem cells from familial Alzheimer's disease patients differentiate into mature neurons with amyloidogenic properties.

    PubMed

    Mahairaki, Vasiliki; Ryu, Jiwon; Peters, Ann; Chang, Qing; Li, Tong; Park, Tea Soon; Burridge, Paul W; Talbot, Conover C; Asnaghi, Laura; Martin, Lee J; Zambidis, Elias T; Koliatsos, Vassilis E

    2014-12-15

    Although the majority of Alzheimer's disease (AD) cases are sporadic, about 5% of cases are inherited in an autosomal dominant pattern as familial AD (FAD) and manifest at an early age. Mutations in the presenilin 1 (PSEN1) gene account for the majority of early-onset FAD. Here, we describe the generation of virus-free human induced pluripotent stem cells (hiPSCs) derived from fibroblasts of patients harboring the FAD PSEN1 mutation A246E and fibroblasts from healthy age-matched controls using nonintegrating episomal vectors. We have differentiated these hiPSC lines to the neuronal lineage and demonstrated that hiPSC-derived neurons have mature phenotypic and physiological properties. Neurons from mutant hiPSC lines express PSEN1-A246E mutations themselves and show AD-like biochemical features, that is, amyloidogenic processing of amyloid precursor protein (APP) indicated by an increase in β-amyloid (Aβ)42/Aβ40 ratio. FAD hiPSCs harboring disease properties can be used as humanized models to test novel diagnostic methods and therapies and explore novel hypotheses for AD pathogenesis.

  10. Color perception differentiates Alzheimer's Disease (AD) from Vascular Dementia (VaD) patients.

    PubMed

    Arnaoutoglou, N A; Arnaoutoglou, M; Nemtsas, P; Costa, V; Baloyannis, S J; Ebmeier, K P

    2017-08-01

    Alzheimer's Disease (AD) and Vascular Dementia (VaD) are the most common causes of dementia in older people. Both diseases appear to have similar clinical symptoms, such as deficits in attention and executive function, but specific cognitive domains are affected. Current cohort studies have shown a close relationship between αβ deposits and age-related macular degeneration (Johnson et al., 2002; Ratnayaka et al., 2015). Additionally, a close link between the thinning of the retinal nerve fiber (RNFL) and AD patients has been described, while it has been proposed that AD patients suffer from a non-specific type of color blindness (Pache et al., 2003). Our study included 103 individuals divided into three groups: A healthy control group (n = 35), AD (n = 32) according to DSM-IV-TR, NINCDS-ADRDA criteria, and VaD (n = 36) based on ΝΙΝDS-AIREN, as well as Magnetic Resonance Imaging (MRI) results. The severity of patient's cognitive impairment, was measured with the Mini-Mental State Examination (MMSE) and was classified according to the Reisberg global deterioration scale (GDS). Visual perception was examined using the Ishihara plates: "Ishihara Color Vision Test - 38 Plate." The three groups were not statistically different for demographic data (age, gender, and education). The Ishihara color blindness test has a sensitivity of 80.6% and a specificity of 87.5% to discriminate AD and VaD patients when an optimal (32.5) cut-off value of performance is used. Ishihara Color Vision Test - 38 Plate is a promising potential method as an easy and not time-consuming screening test for the differential diagnosis of dementia between AD and VaD.

  11. Reduced Cerebrospinal Fluid Concentration of Apolipoprotein A-I in Patients with Alzheimer's Disease.

    PubMed

    Johansson, Per; Almqvist, Erik G; Bjerke, Maria; Wallin, Anders; Johansson, Jan-Ove; Andreasson, Ulf; Blennow, Kaj; Zetterberg, Henrik; Svensson, Johan

    2017-01-01

    Apolipoprotein E (ApoE) has been extensively studied in Alzheimer's disease (AD), but little is known of apolipoprotein A-I (ApoA-I) in cerebrospinal fluid (CSF). Plasma lipids as well as ApoA-I and ApoE in plasma and CSF were determined and related to Mini-Mental State Examination (MMSE) score, APOE genotype, and CSF AD biomarkers. Consecutive patients with AD (n = 29), stable mild cognitive impairment (n = 13), other dementias (n = 14), and healthy controls (n = 18) were included at a single center. AD patients had higher plasma triglycerides and lower CSF ApoA-I concentration than controls (both p < 0.05). CSF ApoE concentration was reduced in other dementias (p < 0.01). In AD as well as other dementias, the ratios between CSF and plasma concentrations of both ApoA-I and ApoE were lower than those in the controls. ApoA-I and ApoE in plasma and CSF were not influenced by APOEɛ4 allele distribution. In the total study population (n = 74), CSF ApoA-I correlated positively with MMSE score (r = 0.26, p < 0.05) and negatively with CSF P-tau (r = -0.25, p < 0.05). CSF ApoE correlated positively with CSF concentrations of T-tau and P-tau in the total study population and in AD patients. CSF ApoA-I was reduced in AD patients and associated with measures of cognitive function and AD disease status. The mechanisms underlying the decreased CSF:plasma ratios of ApoA-I and ApoE in AD and other dementias need to be explored in further studies.

  12. Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial.

    PubMed

    Hoffmann, Kristine; Sobol, Nanna A; Frederiksen, Kristian S; Beyer, Nina; Vogel, Asmus; Vestergaard, Karsten; Brændgaard, Hans; Gottrup, Hanne; Lolk, Annette; Wermuth, Lene; Jacobsen, Søren; Laugesen, Lars P; Gergelyffy, Robert G; Høgh, Peter; Bjerregaard, Eva; Andersen, Birgitte B; Siersma, Volkert; Johannsen, Peter; Cotman, Carl W; Waldemar, Gunhild; Hasselbalch, Steen G

    2016-01-01

    Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent. To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms. The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: -3.5, 95% confidence interval (CI) -5.8 to -1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition. This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.

  13. The effects of patient function and dependence on costs of care in Alzheimer's disease.

    PubMed

    Zhu, Carolyn W; Leibman, Christopher; McLaughlin, Trent; Scarmeas, Nikolaos; Albert, Marilyn; Brandt, Jason; Blacker, Deborah; Sano, Mary; Stern, Yaakov

    2008-08-01

    To estimate incremental effects of patients' dependence and function on costs of care during the early stages of Alzheimer's disease (AD) and to compare strengths of their relationships with different cost components. Multicenter, cross-sectional, observational study. Three university hospitals in the United States. One hundred seventy-nine community-living patients with probable AD, with modified Mini-Mental State Examination scores of 30 or higher. Patients' dependence was measured using the Dependence Scale (DS). Functional capacity was measured using the Blessed Dementia Rating Scale (BDRS). Total cost was measured by summing direct medical costs and informal costs. Direct medical costs included costs of hospitalization, outpatient treatment and procedures, assistive devices, and medications. Informal costs were estimated from time spent helping with basic and instrumental activities of daily living for up to three caregivers per patient using national average hourly earnings as wage rate. DS and BDRS were associated with higher total cost; a 1-point increase in DS was associated with a $1,832 increase in total cost, and a 1-point increase in BDRS was associated with a $3,333 increase. Examining component costs separately identified potential differences between DS and BDRS. A 1-point increase in BDRS was associated with a $1,406 increase in direct medical cost. A 1-point increase in DS was associated with a $1,690 increase in informal cost. Patients' dependence and function related differently to direct medical and informal cost, suggesting that measures of function and dependence provided unique information for explaining variations in cost of care for patients with AD, highlighting the value in measuring both constructs.

  14. Serum Uric Acid Levels in Patients with Alzheimer's Disease: A Meta-Analysis

    PubMed Central

    Chen, Xueping; Guo, Xiaoyan; Huang, Rui; Chen, Yongping; Zheng, Zhenzhen; Shang, Huifang

    2014-01-01

    Background Serum uric acid (UA) could exert neuro-protective effects against Alzheimer's disease (AD) via its antioxidant capacities. Many studies investigated serum UA levels in AD patients, but to date, results from these observational studies are conflicting. Methods We conducted a meta-analysis to compare serum UA levels between AD patients and healthy controls by the random-effects model. Studies were identified by searching PubMed, ISI Web of Science, EMBASE, and the Cochrane library databases from 1966 through July 2013 using the Medical Subject Headings and keywords without restriction in languages. Only case-control studies were included if they had data on serum UA levels in AD patients and healthy controls. Begg's funnel plot and Egger's regression test were applied to assess the potential publication bias. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Results A total of 11 studies met the inclusion criteria including 2708 participants were abstracted. Serum UA levels were not significantly different in AD patients compared to healthy controls (standardized mean difference (SMD) = −0.50; 95% confidence interval (CI): −1.23 to 0.22). Little evidence of publication bias was observed. Sensitivity analyses showed that the combined SMD was consistent every time omitting any one study, except only one study which greatly influenced the overall results. Meta-regression showed that year of publication, race, sample size, and mean age were not significant sources of heterogeneity. Conclusion Our meta-analysis of case-control studies suggests that serum UA levels do not differ significantly in AD patients, but there may be a trend toward decreased UA in AD after an appropriate interpretation. More well-designed investigations are needed to demonstrate the potential change of serum UA levels in AD patients. PMID:24714617

  15. The influence of vascular risk factors on cognitive decline in patients with Alzheimer's disease.

    PubMed

    Blom, Kim; Vaartjes, Ilonca; Peters, Sanne A E; Koek, Huiberdina L

    2014-09-01

    The influence of vascular risk factors (VRFs) on the rate of cognitive decline in patients with established dementia is unclear. This study aims to examine the association between VRFs and the rate of cognitive decline in patients with Alzheimer's disease (AD). Data were obtained from patients visiting a memory clinic between 2004 and 2012. VRFs were determined at baseline and included hypertension, hypercholesterolemia, diabetes mellitus, overweight and smoking. Continuous values of blood pressure, total cholesterol, glucose level and body mass index were also obtained. Mini-Mental State Exam (MMSE) scores were obtained at baseline and during follow-up visits. The association between VRFs and the annual change in MMSE scores was analysed with a multivariable linear mixed model adjusted for age, sex and the aforementioned VRFs. From 174 patients (mean age 78.3 years), with a follow-up time up to 5.8 years (mean 1.1 year), in total 447 MMSE scores were obtained. The multivariable analyses showed an association between age as well as systolic blood pressure and a decline in annual rates of change in MMSE scores of -0.05 (95% confidence interval (CI): -0.09 to 0.00) and -0.01 (CI: -0.03 to 0.00), respectively. For all other VRFs, including sex, patients did not show a significant difference. This study did not find an association between preventable vascular risk factors and cognitive decline in patients with AD, except for systolic blood pressure. As the association between systolic blood pressure and decline in MMSE was small, clinical relevance may be limited. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Differences in nutritional status between very mild Alzheimer's disease patients and healthy controls.

    PubMed

    Olde Rikkert, Marcel G M; Verhey, Frans R; Sijben, John W C; Bouwman, Femke H; Dautzenberg, Paul L J; Lansink, Mirian; Sipers, Walther M W; van Asselt, Dieneke Z B; van Hees, Anneke M J; Stevens, Martijn; Vellas, Bruno; Scheltens, Philip

    2014-01-01

    Studies on the systemic availability of nutrients and nutritional status in Alzheimer's disease (AD) are widely available, but the majority included patients in a moderate stage of AD. This study compares the nutritional status between mild AD outpatients and healthy controls. A subgroup of Dutch drug-naïve patients with mild AD (Mini-Mental State Examination (MMSE) ≥20) from the Souvenir II randomized controlled study (NTR1975) and a group of Dutch healthy controls were included. Nutritional status was assessed by measuring levels of several nutrients, conducting the Mini Nutritional Assessment (MNA®) questionnaire and through anthropometric measures. In total, data of 93 healthy cognitively intact controls (MMSE 29.0 [23.0-30.0]) and 79 very mild AD patients (MMSE = 25.0 [20.0-30.0]) were included. Plasma selenium (p < 0.001) and uridine (p = 0.046) levels were significantly lower in AD patients, with a similar trend for plasma vitamin D (p = 0.094) levels. In addition, the fatty acid profile in erythrocyte membranes was different between groups for several fatty acids. Mean MNA screening score was significantly lower in AD patients (p = 0.008), but not indicative of malnutrition risk. No significant differences were observed for other micronutrient or anthropometric parameters. In non-malnourished patients with very mild AD, lower levels of some micronutrients, a different fatty acid profile in erythrocyte membranes and a slightly but significantly lower MNA screening score were observed. This suggests that subtle differences in nutrient status are present already in a very early stage of AD and in the absence of protein/energy malnutrition.

  17. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab.

    PubMed

    Ostrowitzki, Susanne; Deptula, Dennis; Thurfjell, Lennart; Barkhof, Frederik; Bohrmann, Bernd; Brooks, David J; Klunk, William E; Ashford, Elizabeth; Yoo, Kisook; Xu, Zhi-Xin; Loetscher, Hansruedi; Santarelli, Luca

    2012-02-01

    Gantenerumab is a fully human anti-Aβ monoclonal antibody in clinical development for the treatment of Alzheimer disease (AD). To investigate whether treatment with gantenerumab leads to a measurable reduction in the level of Aβ amyloid in the brain and to elucidate the mechanism of amyloid reduction. A multicenter, randomized, double-blind, placebo-controlled, ascending-dose positron emission tomographic study. Additionally, ex vivo studies of human brain slices from an independent sample of patients who had AD were performed. Three university medical centers. Patients with mild-to-moderate AD. Two consecutive cohorts of patients received 2 to 7 infusions of intravenous gantenerumab (60 or 200 mg) or placebo every 4 weeks. Brain slices from patients who had AD were coincubated with gantenerumab at increasing concentrations and with human microglial cells. Percent change in the ratio of regional carbon 11-labeled Pittsburgh Compound B retention in vivo and semiquantitative assessment of gantenerumab-induced phagocytosis ex vivo. Sixteen patients with end-of-treatment positron emission tomographic scans were included in the analysis. The mean (95% CI) percent change from baseline difference relative to placebo (n = 4) in cortical brain amyloid level was -15.6% (95% CI, -42.7 to 11.6) for the 60-mg group (n = 6) and -35.7% (95% CI, -63.5 to -7.9) for the 200-mg group (n = 6). Two patients in the 200-mg group showed transient and focal areas of inflammation or vasogenic edema on magnetic resonance imaging scans at sites with the highest level of amyloid reduction. Gantenerumab induced phagocytosis of human amyloid in a dose-dependent manner ex vivo. Gantenerumab treatment resulted in a dose-dependent reduction in brain amyloid level, possibly through an effector cell-mediated mechanism of action.

  18. Plasma tau in Alzheimer disease.

    PubMed

    Mattsson, Niklas; Zetterberg, Henrik; Janelidze, Shorena; Insel, Philip S; Andreasson, Ulf; Stomrud, Erik; Palmqvist, Sebastian; Baker, David; Tan Hehir, Cristina A; Jeromin, Andreas; Hanlon, David; Song, Linan; Shaw, Leslie M; Trojanowski, John Q; Weiner, Michael W; Hansson, Oskar; Blennow, Kaj

    2016-10-25

    To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, (18)fluorodeoxyglucose-PET, and cognition. Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD. © 2016 American Academy of Neurology.

  19. Plasma tau in Alzheimer disease

    PubMed Central

    Zetterberg, Henrik; Janelidze, Shorena; Insel, Philip S.; Andreasson, Ulf; Stomrud, Erik; Palmqvist, Sebastian; Baker, David; Tan Hehir, Cristina A.; Jeromin, Andreas; Hanlon, David; Song, Linan; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Hansson, Oskar; Blennow, Kaj

    2016-01-01

    Objective: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. Methods: This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18fluorodeoxyglucose-PET, and cognition. Results: Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Conclusions: Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD. PMID:27694257

  20. Visuomotor integration is compromised in Alzheimer's disease patients reaching for remembered targets.

    PubMed

    Tippett, William J; Krajewski, Adam; Sergio, Lauren E

    2007-01-01

    This study examined the ability of neurologically healthy individuals and individuals with Alzheimer's disease (AD) to successfully complete procedures involving short-term spatial visuomotor memory tasks, and tasks involving increasingly complex visuomotor transformations. Participants made sliding finger movements over a clear touch-sensitive screen on two separate spatial planes (vertical and horizontal), to visually constant and remembered target positions. Significant main effects were observed between participant groups on reaction time and movement time measures. As well, significant changes in reaction time and movement time were observed within the patient group over the different of any experimental procedures. In addition, as task increased in complexity significant increases in errors were observed in the AD group. Overall, the results reveal that AD patients show substantial declines in their ability to process and integrate visual information to produce motor responses. Therefore, we believe that this psychophysical research provides further evidence that AD, even early stages of AD, can affect anatomical regions supporting vision for action.

  1. Systemic oxidative stress in older patients with mild cognitive impairment or late onset Alzheimer's disease.

    PubMed

    Cervellati, Carlo; Cremonini, Eleonora; Bosi, Cristina; Magon, Stefania; Zurlo, Amedeo; Bergamini, Carlo M; Zuliani, Giovanni

    2013-05-01

    A large body of evidences obtained in human and animal brain tissue suggest a role of oxidative stress (OxS) in the pathogenesis of late onset Alzheimer's disease (LOAD); on the contrary, data on peripheral markers of OxS in LOAD are still controversial. We evaluated the serum levels of products of lipid peroxidation, hydroperoxides, advanced oxidation protein products, total and residual antioxidant power, thiols, and uric acid in a sample of 334 older individuals: 101 LOAD patients, 134 patients with mild cognitive impairment (MCI), and 99 controls. At univariate analysis, serum hydroperoxides were higher while residual antioxidant power was lower in MCI and LOAD compared with in controls. By multivariate logistic regression analysis we found that, compared with controls, high levels (over median value) of serum hydroperoxides were independently associated with an increase in the likehood of having MCI (Odd Ratio: 2.59, 95% Confidence Interval: 1.08-6.21) or LOAD (OR: 4.09, 95%CI: 1.36-11.81). Furthermore, low levels of residual antioxidant power (below the median value) were associated with increased risk of having MCI (OR: 3.97, 95% CI: 1.62-9.72), but not dementia (OR: 2.31, 95%CI: 0.83-6.63). Our study suggests that a systemic redox-imbalance leading to OxS might be associated not only with LOAD but also with MCI.

  2. Cholinesterase inhibitors are compatible with psychosocial intervention for Alzheimer disease patients suggested by neuroimaging findings.

    PubMed

    Meguro, Kenichi

    2017-01-30

    We previously reported that the frontal lobe was stimulated by psychosocial intervention for dementia patients, and that the parietal lobe was associated with logical judgment. We hypothesized that the combined therapeutic approach with symptomatic drug treatment can directly stimulate not only attention function but also judgment function indirectly to observing other participants' behaviors. Fifty-two patients with Alzheimer disease underwent the group reminiscence approach with reality orientation, as well as the donepezil treatment. The cerebral blood flow (CBF) was assessed with (99m)Tc-ECD SPECT. Two analyses were performed: Analysis 1 was to compare Responders vs. Non-responders as shown by MMSE scores, whereas Analysis 2 was to compare Good vs. Poor reminders of the intervention content. We found that the CBF in the frontal lobe was significantly higher in Responders (vs. Non-responders). The CBF in the parietal lobe, especially the left side, was significantly higher in the Good reminders (vs. Poor reminders). The donepezil stimulated the areas similar to where the psychosocial intervention was previously found to be stimulated directly, thus the drug was thought to be compatible for psychosocial intervention. The parietal lobe was stimulated indirectly, suggesting that the indirect effect of the intervention may be based on logical judgment function.

  3. Antidepressant use in Alzheimer's disease patients: results of the REAL.FR cohort.

    PubMed

    Arbus, Christophe; Gardette, Virginie; Bui, Eric; Cantet, Christelle; Andrieu, Sandrine; Nourhashémi, Fati; Schmitt, Laurent; Vellas, Bruno

    2010-02-01

    Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription. REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI). A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression. The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.

  4. Reduced sulfotransferase SULT2A1 activity in patients with Alzheimer's disease.

    PubMed

    Vaňková, M; Hill, M; Velíková, M; Včelák, J; Vacínová, G; Lukášová, P; Vejražková, D; Dvořáková, K; Rusina, R; Holmerová, I; Jarolímová, E; Vaňková, H; Bendlová, B

    2015-01-01

    Steroids are important components in the pathophysiology of Alzheimer's disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5alpha-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD.

  5. 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

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

    PubMed

    Pivi, Glaucia A K; da Silva, Rosimeire V; Juliano, Yara; Novo, Neil F; Okamoto, Ivan H; Brant, César Q; Bertolucci, Paulo H F

    2011-09-26

    Weight loss in patients with Alzheimer's disease (AD) is a common clinical manifestation that may have clinical significance. To evaluate if there is a difference between nutrition education and oral nutritional supplementation on nutritional status in patients with AD. 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. 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). Oral nutritional supplementation is more effective compared to nutrition education in improving nutritional status.

  7. Information content versus relational knowledge: semantic deficits in patients with Alzheimer's disease.

    PubMed

    Aronoff, Justin M; Gonnerman, Laura M; Almor, Amit; Arunachalam, Sudha; Kempler, Daniel; Andersen, Elaine S

    2006-01-01

    Studies of semantic impairment in Alzheimer's disease (AD) have yielded conflicting results, some finding evidence of considerable deficits, others finding that semantic knowledge is relatively intact. How do we reconcile findings from picture naming tasks that seem to indicate semantic impairment in AD with results from certain sorting tasks that suggest intact semantics? To investigate the basis of the contradictory results described above, we conducted a study using two types of tasks: (1) picture naming; and (2) board sorting. The board sorting task we used is a simultaneous similarity judgment task, in which participants are asked to place more similar concepts closer together and less similar ones farther apart. We compared the performance of AD patients on these two tasks, using a number of different analyses that yield very different patterns of results. Our results indicate that whether patients show impairment or not depends on both the nature of the task and the subsequent analysis chosen. Specifically, tasks and analyses that focus on relational knowledge (e.g., dog is more related to cat than to camel) lead to different conclusions than those based on specific information about individual items. These findings suggest that the board sorting method, when coupled with multiple analyses, provides a more complete picture of the underlying semantic deficit in AD than previous studies have shown.

  8. Methylation analysis of SST and SSTR4 promoters in the neocortex of Alzheimer's disease patients.

    PubMed

    Grosser, Christian; Neumann, Lisa; Horsthemke, Bernhard; Zeschnigk, Michael; van de Nes, Johannes

    2014-04-30

    Several observations have pointed to a major pathogenic role of somatostatin depletion with respect to amyloid accumulation, which is often thought to be the crucial event in a cascade leading to Alzheimer's disease (AD). As methylation of CpG islands plays an important role in gene silencing, we studied the methylation status of the CpG islands in the promoters of somatostatin (SST) and in that of its receptor subtype in the cerebral cortex, SSTR4, in tissue samples from the middle temporal (Brodmann area 22) and superior frontal gyrus (Brodmann area 9) of 5 severely affected AD patients aged 72-94 years (Braak stages V-C or VI-C) and 5 non-demented controls aged 50-92 years. Bisulfite sequencing of DNA from cortical gray and infracortical white matter showed that the DNA methylation status at the promoters of SST and SSTR4 did not significantly differ between AD and control samples in any of the regions analyzed. We confirmed these results using deep bisulfite sequencing of PCR products from the SST promoter amplified from DNA from the cortical gray of the superior frontal gyrus of all AD patients and non-demented controls. We observed a trend toward increased DNA methylation with increasing age. In conclusion, deregulated somatostatin signaling in the AD cortices studied cannot be explained by hypermethylation of the SST or SSTR4 promoter CpG islands. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Knowledge of the definition of euthanasia: study with doctors and caregivers of Alzheimer's disease patients.

    PubMed

    Vilela, Luciana Pricoli; Caramelli, Paulo

    2009-01-01

    Euthanasia is an increasingly debated subject among specialized professionals and also among lay people, even in countries such as Brazil where it is not authorized. It is questionable, however, if the concept of euthanasia is well known by these persons. The goal of this study was to investigate knowledge about the definition of euthanasia by family caregivers of patients with dementia and by specialized physicians and also to investigate their personal opinion on this topic. We prospectively interviewed 30 physicians from three different medical specialties and 40 family caregivers of patients with Alzheimer's disease using a structured questionnaire. Two clinical vignettes were also presented to the physicians in order to ascertain their personal opinion about euthanasia. Among the caregivers, 10 (25.0%) knew the correct definition of euthanasia. Regarding their personal view, nine (22.5%) were in favor, while 20 (50.0%) were against. The remaining 11 (27.5%) caregivers were unable to define their position. Among the physicians, 19 (63.3%) gave a coherent answer regarding the definition of euthanasia. When they were presented with the clinical vignettes, less than 50% of them were in favor of euthanasia. The definition of euthanasia was unknown by most of the lay individuals and also by one third of the physicians. Although it is not officially approved in Brazil, a small proportion of family caregivers and also of specialized physicians would be in favor of the practice of euthanasia.

  10. [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.

  11. Context Memory in Alzheimer's Disease

    PubMed Central

    El Haj, Mohamad; Kessels, Roy P.C.

    2013-01-01

    Background Alzheimer's disease (AD) is a neurodegenerative disease characterized by a gradual loss of memory. Specifically, context aspects of memory are impaired in AD. Our review sheds light on the neurocognitive mechanisms of this memory component that forms the core of episodic memory function. Summary Context recall, an element of episodic memory, refers to remembering the context in which an event has occurred, such as from whom or to whom information has been transmitted. Key Messages Our review raises crucial questions. For example, (1) which context element is more prone to being forgotten in the disease? (2) How do AD patients fail to bind context features together? (3) May distinctiveness heuristic or decisions based on metacognitive expectations improve context retrieval in these patients? (4) How does cueing at retrieval enhance reinstating of encoding context in AD? By addressing these questions, our work contributes to the understanding of the memory deficits in AD. PMID:24403906

  12. 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

  13. Metals and Alzheimer's disease.

    PubMed

    Adlard, Paul A; Bush, Ashley I

    2006-11-01

    There is increasing evidence to support a role for both the amyloid beta-protein precursor (AbetaPP) and its proteolytic fragment, amyloid beta (Abeta), in metal ion homeostasis. Furthermore, metal ions such as zinc and copper can interact with both AbetaPP and Abeta to potentiate Alzheimer's disease by participating in the aggregation of these normal cellular proteins and in the generation of reactive oxygen species. In addition, metal ions may interact on several other AD-related pathways, including those involved in neurofibrillary tangle formation, secretase cleavage of AbetaPP and proteolytic degradation of Abeta. As such, a dysregulation of metal ion homeostasis, as occurs with both aging and in AD, may foster an environment that can both precipitate and accelerate degenerative conditions such as AD. This offers a broad biochemical front for novel therapeutic interventions.

  14. Memory loss in Alzheimer's disease.

    PubMed

    Jahn, Holger

    2013-12-01

    Loss of memory is among the first symptoms reported by patients suffering from Alzheimer's disease (AD) and by their caretakers. Working memory and long-term declarative memory are affected early during the course of the disease. The individual pattern of impaired memory functions correlates with parameters of structural or functional brain integrity. AD pathology interferes with the formation of memories from the molecular level to the framework of neural networks. The investigation of AD memory loss helps to identify the involved neural structures, such as the default mode network, the influence of epigenetic and genetic factors, such as ApoE4 status, and evolutionary aspects of human cognition. Clinically, the analysis of memory assists the definition of AD subtypes, disease grading, and prognostic predictions. Despite new AD criteria that allow the earlier diagnosis of the disease by inclusion of biomarkers derived from cerebrospinal fluid or hippocampal volume analysis, neuropsychological testing remains at the core of AD diagnosis.

  15. Cross-sectional neurocognitive data do not support a transition from fibrofog to Alzheimer disease in fibromyalgia patients.

    PubMed

    Leavitt, Frank; Katz, Robert S

    2015-03-01

    Cognitive dysfunction is a signature feature of fibromyalgia. Many who develop cognitive problems in their middle years are concerned that it is prodromal to Alzheimer's disease. To determine if deficits in episodic memory and progressive cognitive decline, hallmarks of Alzheimer's disease, are prominent in the cognitive makeup of fibromyalgia patients. In a cross-sectional study, performance on 15 neurocognitive (NC) measures was evaluated in 2 cohorts of fibromyalgia subjects. The first cohort contained 94 subjects with a short duration of cognitive problems (≤12 months). The second cohort contained 55 subjects with a long duration of cognitive problems (≥84 months). The 2 groups were similar in education (14.9 ± 2.3 vs 14.9 ± 2.4), vocabulary scale score (11.2 ± 2.3 vs 11.6 ± 2.7), and depression (17.9 ± 9.8 vs 17.7 ± 9.4). The mean durations of cognitive problems in the short- and long-term group were 7.3 ± 3.9 months and 13.3 ± 7.1 years, respectively. There was no evidence of decline on 14 of 15 measures in the fibromyalgia group with an additional 12.6 years of cognitive dysfunction. Normality of function was in evidence on 4 measures of episodic memory in both cohorts. Fibromyalgia patients' fear of developing Alzheimer's disease was not borne out by the data. The cognitive pattern of fibromyalgia appears distinct from that of Alzheimer's disease. Fibrofog is not associated with either episodic memory loss on standard tests of episodic memory or progressive cognitive decline. Patients with fibrofog remember personally experienced events termed episodic memory at a normal rate in quiet, distraction-free conditions. Patients with Alzheimer's disease do not. They forget the essential elements of short stories just read to them in environments free of distractions. In Alzheimer's disease, the brain mechanisms responsible for encoding personally experienced events into memory are irreversibly impaired. In fibrofog, the encoding mechanisms are intact

  16. Explicit (semantic) 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

    BACKGROUND/STUDY CONTEXT: Explicit memory for music was investigated by using a new test with 24 existing and 3 newly composed pieces. Ten patients with mild cognitive impairment (MCI) and 10 patients with early stage of Alzheimer's disease (AD) were compared with 23 healthy subjects, in terms of verbal memory of music by the identification of familiar music excerpts and the discrimination of distortion and original timbre of musical excerpts. MCI and Alzheimer's patients showed significantly poorer performances in tasks requiring verbal memory of musical excerpts than the healthy participants. For discrimination of musical excerpts, MCI and AD patients surprisingly performed significantly better than the healthy comparison subjects. Our results support the notion of a specialized memory system for music.

  17. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease

    PubMed Central

    Dhikav, Vikas; Duraiswamy, Sharmila; Anand, Kuljeet Singh

    2017-01-01

    Introduction: Hippocampus undergoes atrophy in patients with Alzheimer's disease (AD). Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI) of the brain. Medial temporal lobes atrophy (MTL) can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. Materials and Methods: We screened 84 subjects presented to the Department of Neurology of a Tertiary Care Hospital and enrolled forty subjects meeting the National Institute of Neurological and Communicative Disorders and Stroke, AD related Disease Association criteria. Selected patients underwent MRI brain and T1-weighted images in a plane perpendicular to long axis of hippocampus were obtained. Hippocampal volumes were calculated manually using a standard protocol. The calculated hippocampal volumes were correlated with Scheltens Visual Rating Method for Rating MTL. A total of 32 cognitively normal age-matched subjects were selected to see the same correlation in the healthy subjects as well. Sensitivity and specificity of both methods was calculated and compared. Results: There was an insignificant correlation between the hippocampal volumes and MTL rating scores in cognitively normal elderly (n = 32; Pearson Correlation coefficient = 0.16, P > 0.05). In the AD Group, there was a moderately strong correlation between measured hippocampal volumes and MTL Rating (Pearson's correlation coefficient = −0.54; P < 0.05. There was a moderately strong correlation between hippocampal volume and Mini-Mental Status Examination in the AD group. Manual delineation was superior compared to the visual method (P < 0.05). Conclusions: Good correlation was present between manual hippocampal volume measurements and MTL scores. Sensitivity and specificity of manual measurement of hippocampus was

  18. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease.

    PubMed

    Dhikav, Vikas; Duraiswamy, Sharmila; Anand, Kuljeet Singh

    2017-01-01

    Hippocampus undergoes atrophy in patients with Alzheimer's disease (AD). Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI) of the brain. Medial temporal lobes atrophy (MTL) can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. We screened 84 subjects presented to the Department of Neurology of a Tertiary Care Hospital and enrolled forty subjects meeting the National Institute of Neurological and Communicative Disorders and Stroke, AD related Disease Association criteria. Selected patients underwent MRI brain and T1-weighted images in a plane perpendicular to long axis of hippocampus were obtained. Hippocampal volumes were calculated manually using a standard protocol. The calculated hippocampal volumes were correlated with Scheltens Visual Rating Method for Rating MTL. A total of 32 cognitively normal age-matched subjects were selected to see the same correlation in the healthy subjects as well. Sensitivity and specificity of both methods was calculated and compared. There was an insignificant correlation between the hippocampal volumes and MTL rating scores in cognitively normal elderly (n = 32; Pearson Correlation coefficient = 0.16, P > 0.05). In the AD Group, there was a moderately strong correlation between measured hippocampal volumes and MTL Rating (Pearson's correlation coefficient = -0.54; P < 0.05. There was a moderately strong correlation between hippocampal volume and Mini-Mental Status Examination in the AD group. Manual delineation was superior compared to the visual method (P < 0.05). Good correlation was present between manual hippocampal volume measurements and MTL scores. Sensitivity and specificity of manual measurement of hippocampus was higher compared to visual rating scores for MTL in patients with

  19. CSF markers in Alzheimer disease patients are not related to the different degree of cognitive impairment.

    PubMed

    Stefani, Alessandro; Martorana, Alessandro; Bernardini, Sergio; Panella, Marta; Mercati, Flavio; Orlacchio, Antonio; Pierantozzi, Mariangela

    2006-12-21

    Standard markers in cerebrospinal fluid (CSF), as soluble amyloid beta 1-42 (Abeta1-42) and total tau protein (t-tau), may contribute to dementia subtypes diagnostic accuracy. Yet, their sensitivity to assess the different degree of cognitive deficit is not fully clarified. Our study analyses Abeta1-42 and t-tau CSF levels in different cohorts of Alzheimer's disease (AD) patients, distinguished as early AD (mild cognitively impaired subjects recently converted to AD), mild AD (MMSE<23; > or =18), and moderately advanced AD (MMSE<18). The control group was represented by age-matched patients affected by depressive pseudo-dementia. Reduced Abeta1-42 and increased t-tau CSF levels were confirmed as hallmarks of AD at any disease stage. In early AD patients, Abeta1-42 levels were already significantly low, if compared to the control group (336 vs 867 ng/L; p<0.0001). On the contrary, Abeta1-42 levels did not differ between AD subgroups, and in particular between mild to moderate AD. A significant progressive increase of t-tau concentration was found when comparing early AD (269 ng/L) to more advanced AD stages (468 ng/L and 495 ng/L for mild and moderate AD, respectively). Our findings confirm that the impairment of amyloidogenic cascade is an early, even pre-clinical process, but suggest that soluble Abeta1-42 concentration has a negligible correlation with the clinical progression. Conversely, t-tau concentration correlates with the transition towards marked cognitive impairment.

  20. Three-week nutritional supplementation effect on long-term nutritional status of patients with mild Alzheimer disease.

    PubMed

    de Sousa, Odete Luísa Vicente; Amaral, Teresa F

    2012-01-01

    Short-term nutritional supplements enable an improvement in Alzheimer patients' nutritional status, but it remains to be seen whether they will be sufficient to improve long-term nutritional status. The aim of this study was to evaluate the long-term impact of a 3-week nutritional supplementation on the nutritional status of undernourished patients with probable mild Alzheimer disease. A 21-day prospective randomized nonblinded controlled trial was conducted. Patients were followed-up for an additional period until the 90th day after the beginning of the intervention. Intervention resulted in significant improvements in Mini Nutritional Assessment (MNA) score [Mean=1.4, standard deviation (SD)=0.8 vs. 0.0 (0.1) in the control group, P<0.001] and also in anthropometrical and serum biomarkers of Alzheimer disease (AD) patients' nutritional status. Further improvements in the AD patients' MNA mean score=1.4 (SD=2.3) versus -0.5 (SD=0.6) in the control group (P=0.003) were seen at 90 days follow-up. Data show that a 3-week nutritional supplementation has a positive long-term impact on the nutritional status of undernourished patients with mild probable AD.

  1. Correlations among cognitive and behavioural assessments in patients with dementia due to Alzheimer's disease.

    PubMed

    de Oliveira, Fabricio Ferreira; Wajman, Jose Roberto; Bertolucci, Paulo Henrique Ferreira; Chen, Elizabeth Suchi; Smith, Marilia Cardoso

    2015-08-01

    Primarily, we sought to verify correlations among assessments for cognition, behaviour and functional independence in a sample of patients with dementia due to Alzheimer's disease (AD). Secondarily, impacts of education, APOE haplotypes, length of dementia, age and alcohol use over the neuropsychiatric assessment were estimated. Patients with AD were assessed for demographic features, neuropsychiatric symptoms, cognitive test scores, functional impairment, caregiver burden and APOE haplotypes. Statistical comparisons were undertaken by way of Kruskal-Wallis test, linear regressions and Spearman correlations, significance at ρ < 0.05. A total of 217 patients were included. Mean schooling was 4.21 ± 3.7 years, with significant impacts over cognitive tests. Mean age at examination was 78 ± 6.19 years-old, significantly influencing instrumental functionality. The mean length of the dementia syndrome was 5.4 ± 2.9 years, significantly impacting cognitive decline and functionality. Apathy was the most common behavioural symptom, negatively correlated with anxiety and delusions, and positively correlated with lifetime alcohol load. Patients with previous smoking or drinking habits were more likely to continue smoking or drinking later in life. APOE4+ haplotypes led to earlier dementia onset and significantly lower caregiver burden in mild dementia stages. Most correlations among test results were highly significant, confirming that cognition, behaviour and functionality are usually interrelated in all stages of AD. Caregiver burden was correlated with behaviour, but not with cognition, and was lower for patients with APOE4+ haplotypes in mild dementia stages. Education is a major impact factor for cognitive performance. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Dementia and Nutrition. Intervention study in institutionalized patients with Alzheimer disease.

    PubMed

    Gil Gregorio, P; Ramirez Diaz, S P; Ribera Casado, J M

    2003-01-01

    To know nutritional status of a group of institutionalized patients with moderate Alzheimer's Disease (AD), and to ascertain the effects of an intervention with nutritional supplements on morbidity and mortality after one year follow-up. 99 patients (mean age: 86.5 years), 80 women, with a diagnosis of AD according with NINCDS/ADRDA criteria, were recruited from 8 nursing-homes. 25 were included in an intervention group and received a nutritional supplements along 12 months. Evolution was evaluated according to the Functional Assessment Staging Test (FAST). Patients with FAST levels 5-6 were included. General clinical variables as well as variables reflecting cognitive state and nutritional status: anthropometric, biochemical data and Mini Nutritional Assessment (MNA) were analysed. Statistical analysis was carry out with the SPSS 10.0 package. Mean time since diagnosis was 49 months, with a 20.2 months duration of institutionalization. Mean value of MNA was 20.1 3.5. 16.5% of patients had a BMI equal o lower than 21. After one year the intervention group showed higher levels of albumin (P=05), pre-albumin (P=05), iron (P=01), zinc (P=05), and beta-carotene (P=05) than the control group. The same response in BMI (P=05), MNA (P=05), and triceps skinfold (P=01). Mortality was lower (16% vs. 22.7%), without statistical significance, in the intervention group, as it was the number of infectious events (47% vs. 66% P=05), and the days in bed (7.5 2.1 vs. 17.3 5.6 P=05). Nutritional supplements applied to a group of patients with AD living in nursing-homes can reduce morbidity and mortality after one year follow-up.

  3. Cognitive map in patients with mild Alzheimer's disease: a computer-generated arena study.

    PubMed

    Jheng, Sheng-Siang; Pai, Ming-Chyi

    2009-06-08

    In addition to memory impairment, a tendency to get lost is among the initial symptoms in patients with Alzheimer disease (AD). At least two kinds of wayfinding strategies, egocentric and allocentric, have been proposed. It is believed that people may form a cognitive map after repeated movement in a specific environment, and are able to use it as an aid to navigation. In the present study, we investigated the cognitive maps in early AD patients and their application in a computer-generated arena (CGA). We invited very mild AD (CDR 0.5) patients and normal controls (NCs) to participate in the current study. Hand-drawing tests were used to assess their supposedly previously formed cognitive maps of familiar environments, and CGA was used to measure their new environment learning as well as the application of the old map. Nineteen patients (8 females, mean age 67.6 years old, education 9.7 years, and MMSE 24) and 18 NCs (10 females, mean age 66.4 years old, education 8.8 years, and MMSE 27) completed the study. In the hand-drawing map part, both groups did equally well. In the new environment learning, NCs did better than the AD group on the third of six trials. As for the old environment navigation experiment, the AD group spent more time than the NCs in finding the target, but showed no difference to NC regarding the path traveled in the target quadrant. Early AD patients maintain their ability to use a cognitive map and keep pretty good allocentric representation of their familiar environments as well as NC do, but probably both groups do not routinely use their cognitive map to navigate in everyday life properly.

  4. Frequency-specific alterations of large-scale functional brain networks in patients with Alzheimer's disease.

    PubMed

    Qin, Yuan-Yuan; Li, Ya-Peng; Zhang, Shun; Xiong, Ying; Guo, Lin-Ying; Yang, Shi-Qi; Yao, Yi-Hao; Li, Wei; Zhu, Wen-Zhen

    2015-03-05

    Previous studies have indicated that the cognitive deficits in patients with Alzheimer's disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific. Resting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and "small-world" property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz, and 0.11-0.25 Hz). At lower-frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz), the global efficiency, the CC and the "small-world" properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11-0.25 Hz), the CpL was much longer, and the "small-world" property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD. This study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.

  5. Prediction of vascular dementia and Alzheimer's disease in patients with atrial fibrillation or atrial flutter using CHADS2 score.

    PubMed

    Chou, Ruey-Hsing; Chiu, Chun-Chih; Huang, Chin-Chou; Chan, Wan-Leong; Huang, Po-Hsun; Chen, Yu-Chun; Chen, Tzeng-Ji; Chung, Chia-Min; Lin, Shing-Jong; Chen, Jaw-Wen; Leu, Hsin-Bang

    2016-09-01

    Atrial fibrillation (AF) is associated with an increased risk of dementia. However, limited data are available on the predictors of dementia in patients with AF. This study aimed to evaluate whether the CHADS2 score could be a useful tool for risk stratification with regard to dementia occurrence among patients with AF. AF patients were identified from the National Health Insurance sampling database, which has accumulated a total of 1,000,000 participants since 2000. After excluding patients diagnosed with dementia prior to the index day of enrollment, CHADS2 score was measured to investigate its association with the occurrence of dementia, including vascular dementia and Alzheimer's disease. During the mean follow-up period of 3.71 ± 2.78 years, 1135 dementia cases (7.36%) were identified, including 241 cases of vascular dementia and 894 cases of Alzheimer's disease. In multivariate analysis, an increase of 1 point in the CHADS2 score was independently associated with a 54% increase in the risk of vascular dementia (hazard ratio = 1.54; 95% confidence interval, 1.41-1.69; p < 0.001) and a 40% increase in Alzheimer's disease (hazard ratio = 1.40; 95% confidence interval, 1.34-1.46; p < 0.001). CHADS2 score is a useful predictor for the development of vascular dementia as well as Alzheimer's disease in patients with AF. Copyright © 2016. Published by Elsevier Taiwan LLC.

  6. 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…

  7. 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.

  8. 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.

  9. Microwaves and Alzheimer's disease

    PubMed Central

    Zhang, Xia; Huang, Wen-Juan; Chen, Wei-Wei

    2016-01-01

    Alzheimer's diseases (AD) is the most common type of dementia and a neurodegenerative disease that occurs when the nerve cells in the brain die. The cause and treatment of AD remain unknown. However, AD is a disease that affects the brain, an organ that controls behavior. Accordingly, anything that can interact with the brain may affect this organ positively or negatively, thereby protecting or encouraging AD. In this regard, modern life encompasses microwaves for all issues including industrial, communications, medical and domestic tenders, and among all applications, the cell phone wave, which directly exposes the brain, continues to be the most used. Evidence suggests that microwaves may produce various biological effects on the central nervous system (CNS) and many arguments relay the possibility that microwaves may be involved in the pathophysiology of CNS disease, including AD. By contrast, previous studies have reported some beneficial cognitive effects and that microwaves may protect against cognitive impairment in AD. However, although many of the beneficial effects of microwaves are derived from animal models, but can easily be extrapolated to humans, whether microwaves cause AD is an important issue that is to be addressed in the current review. PMID:27698682

  10. Microwaves and Alzheimer's disease.

    PubMed

    Zhang, Xia; Huang, Wen-Juan; Chen, Wei-Wei

    2016-10-01

    Alzheimer's diseases (AD) is the most common type of dementia and a neurodegenerative disease that occurs when the nerve cells in the brain die. The cause and treatment of AD remain unknown. However, AD is a disease that affects the brain, an organ that controls behavior. Accordingly, anything that can interact with the brain may affect this organ positively or negatively, thereby protecting or encouraging AD. In this regard, modern life encompasses microwaves for all issues including industrial, communications, medical and domestic tenders, and among all applications, the cell phone wave, which directly exposes the brain, continues to be the most used. Evidence suggests that microwaves may produce various biological effects on the central nervous system (CNS) and many arguments relay the possibility that microwaves may be involved in the pathophysiology of CNS disease, including AD. By contrast, previous studies have reported some beneficial cognitive effects and that microwaves may protect against cognitive impairment in AD. However, although many of the beneficial effects of microwaves are derived from animal models, but can easily be extrapolated to humans, whether microwaves cause AD is an important issue that is to be addressed in the current review.

  11. 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

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

    PubMed

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

    2016-07-05

    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. 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. 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 visuoconstructional errors (13

  13. Alzheimer's disease, oral function and nutritional status.

    PubMed

    Nordenram, G; Ryd-Kjellen, E; Johansson, G; Nordstrom, G; Winblad, B

    1996-07-01

    To study differences in nutritional, dental status and oral function between institutionalised patients with Alzheimer's disease and cognitively healthy elderly people living in the community. Comparison was made between two groups. Alzheimer's disease sufferers and healthy controls, using established criteria for anthropometric, mental and dental state. An institution and residential area in Stockholm, Sweden. Forty patients with Alzheimer's disease living in a nursing home and 40 age- and gender-matched control subjects living independently. Dental status and anthropometric variables. Overnutrition was less frequent among the demented than the controls and more demented were undernourished. Dental status was similar in the two groups with few edentulous subjects but only 2 of 7 edentulous subjects with Alzheimer's disease wore dentures. Having natural teeth and many functional oral zones is important for food consistency choice, but not for nutritional status. In the Alzheimer group, the stage of dementia has a strong association to the ability to eat unaided and an association with dental status. There are differences in nutritional status between Alzheimer's patients in institutions and cognitively healthy elderly living at home. The choice of food consistency is correlated to dental status but nutritional status is not shown to be influenced by dental status. However, the ability to eat unaided is strongly correlated to cognitive status.

  14. Verbal fluency in Alzheimer's disease, Parkinson's disease, and major depression

    PubMed Central

    de Araujo, Narahyana Bom; Barca, Maria Lage; Engedal, Knut; Coutinho, Evandro Silva Freire; Deslandes, Andrea Camaz; Laks, Jerson

    2011-01-01

    OBJECTIVE: To compare verbal fluency among Alzheimer's disease, Parkinson's disease, and major depression and to assess the sociodemographic and clinical factors associated with the disease severity. METHODS: Patients from an outpatient university center with a clinical diagnosis of Alzheimer's disease, Parkinson's disease or major depression were studied. Severity was staged using the Hoehn & Yahr scale, the Hamilton Depression scale and the Clinical Dementia Rating for Parkinson's disease, major depression, and Alzheimer's disease, respectively. All subjects were tested with the Mini-Mental State Examination, the digit span test, and the verbal fluency test (animals). We fit four types of regression models for the count variable: Poisson model, negative binomial model, zero-inflated Poisson model, and zero-inflated negative binomial model. RESULTS: The mean digit span and verbal fluency scores were lower in patients with Alzheimer's disease (n = 34) than in patients with major depression (n = 52) or Parkinson's disease (n = 17) (p<0.001). The average number of words listed was much lower for Alzheimer's disease patients (7.2 words) compared to the patients presenting with major depression (14.6 words) or Parkinson's disease (15.7 words) (KW test = 32.4; p<0.01). Major depression and Parkinson's disease groups listed 44% (ROM = 1.44) and 48% (ROM = 1.48) more words, respectively, compared to those patients with Alzheimer's disease; these results were independent of age, education, disease severity and attention. Independently of diagnosis, age, and education, severe disease showed a 26% (ROM = 0.74) reduction in the number of words listed when compared to mild cases. CONCLUSIONS: Verbal fluency provides a better characterization of Alzheimer's disease, major depression, and Parkinson's disease, even at later stages. PMID:21655757

  15. The effect of memantine on sleep architecture and psychiatric symptoms in patients with Alzheimer's disease.

    PubMed

    Ishikawa, Ichiro; Shinno, Hideto; Ando, Nobuo; Mori, Takahiro; Nakamura, Yu

    2016-06-01

    Behavioural and psychological symptoms of dementia (BPSD) are commonly present in patients with Alzheimer's disease (AD). Disturbed sleep quality is also observed in AD patients. However, the effects of memantine on sleep architecture have not been investigated. The purpose of this study was to investigate the effects of memantine on polysomnography (PSG) variables and BPSD. In total, 12 patients with AD (mean age: 79.0±4.1 years old) were enrolled in this study. The following tests were performed: the Neuropsychiatric Inventory for the assessment of BPSD, the Mini-Mental State Examination (MMSE) for cognitive function, and PSG for evaluation of sleep architecture. After baseline examinations, patients were treated with memantine according to a standard prescription protocol. After being treated with 20 mg/day of memantine for 4 weeks, examinations were carried out again. All subjects completed the trial. The mean MMSE and NPI scores were 22.6±3.4 and 13.8±12.9, respectively. Treatment with memantine significantly decreased the NPI score (5.8±4.3, p<0.01). There were significant decreases in the scores of subscales for anxiety (p=0.04) and irritability/lability (p=0.04). PSG demonstrated a longer total sleep time (TST) (p<0.01), increases in sleep efficiency (p<0.01) and time spent in stage II (% TST, p=0.02), and decreases in nocturnal awakening (p<0.01), the periodic limb movement index (p<0.01), and time spent in stage I (% TST, p=0.02). Memantine was effective for reducing fragmented sleep and improving BPSD, and was well tolerated.

  16. Working memory and FDG-PET dissociate early and late onset Alzheimer disease patients.

    PubMed

    Kalpouzos, Grégoria; Eustache, Francis; de la Sayette, Vincent; Viader, Fausto; Chételat, Gaël; Desgranges, Béatrice

    2005-05-01

    The aims of this study were to determine the influence of the onset of Alzheimer's disease (AD) on 1) memory and cerebral glucose metabolism, 2) the relationships between cognitive performance and cerebral glucose metabolism. Brain metabolism was measured by 18FDG-PET in 12 early onset AD patients (age < 65 years) and 26 late onset ones (> 65), with comparable mean MMSE scores. Working memory, semantic memory and episodic memory were assessed. Cognitivo-metabolic correlations (CMC) and complementary interregional correlations were performed in order to identify specific neurocognitive processes within each group. Both AD groups performed poorly on all tasks, except digit span in the late onset group. The early onset group performed more poorly than the late onset one on both the digit span and Brown-Peterson Paradigm (BPP) tasks. Temporo-parietal hypometabolism was found in both groups, the left hemisphere being more affected than the right, especially in the early onset patients, who also showed specific left frontal hypometabolism. For the BPP task, the CMC principally involved left frontal areas in the early onset group, and the cerebellum in the late onset one. For the digit span task, they involved cerebellar and occipital regions in the latter. Regarding the digit span, the occipital and cerebellar involvement may have reflected an effective compensatory mechanism in the late onset patients, while high left supramarginal gyrus hypometabolism in the early onset patients may have explained their failure in this task. In the BPP task, the lower performance of the early onset group may have been due to a frontal lobe dysfunction, as suggested by 1) the hypometabolism of this region, 2) the CMC results, 3) the interregional correlations, which indicated greater disruption of the antero- posterior loop.

  17. Effects of multiple training modalities in patients with Alzheimer's disease: a pilot study.

    PubMed

    Tai, Shu-Yu; Hsu, Chia-Ling; Huang, Shu-Wan; Ma, Tzu-Chiao; Hsieh, Wen-Chien; Yang, Yuan-Han

    2016-01-01

    This pilot study investigated the effects of multiple training modalities on cognition, neuropsychiatric symptoms, caregivers' burden, and quality of life in patients with Alzheimer's disease (AD). This intervention study was conducted in 24 patients with AD aged ≥65 years with a Clinical Dementia Rating (CDR) score of 0.5-1. The patients were assigned to receive multiple training modalities (1 hour for each training: Tai Chi, calligraphy, and drawing) over a 6-week period in either the experimental group (n=14) or the comparison group (n=10). A series of neuropsychological tests - namely the Traditional Chinese version Mini-Mental Status Examination, Cognitive Assessment Screening Instrument (CASI), Neuropsychiatric Inventory and the Neuropsychiatric Inventory Caregiver Distress Scale, and the Clinical Dementia Rating Sum of Boxes scale - were conducted at the baseline and after the intervention. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) and Zarit Caregiver Burden Scale were used to assess the quality of life and caregivers' burden, respectively. Independent sample t-test and paired sample t-test were used to analyze the data. After the intervention, the experimental group reported higher scores in the orientation domain of CASI (P=0.007) and in the psychiatry domain of WHOQOL-BREF (P=0.042) compared with the comparison group. Caregivers' distress was significantly decreased in the experimental group (P=0.035) but not in the comparison group (P=0.430). The multiple training modalities improved scores in the orientation domain of CASI and psychiatry domain of WHOQOL-BREF in patients with AD. Moreover, the intervention reduced caregivers' distress.

  18. LDL density and oxidation are modulated by PON1 promoter genotype in patients with Alzheimer's disease.

    PubMed

    Cagnin, Annachiara; Leon, Alberta; Vianello, Daniela; Colavito, Davide; Favaretto, Silvia; Zarantonello, Giulia; Stecca, Anna; Ermani, Mario; Zambon, Alberto

    2013-01-01

    Cholesterol metabolism alteration is a hot topic in the field of Alzheimer's disease (AD). However, data on plasma lipoproteins cholesterol distribution and oxidation in AD and their possible genetic determinants are lacking. The paraoxonase-1 (PON1) gene -107C/T promoter polymorphisms have been found associated with AD. One of the fundamental functions of PON1 enzyme is the inhibition of low-density lipoproteins (LDL) oxidation. We therefore evaluated plasma lipoprotein profile and LDL density and oxidation in late-onset AD patients and healthy elderly subjects, without neuroimaging evidence of cerebrovascular lesions and not on lipid-lowering treatment, and their interaction with PON1 -107C/T and apolipoprotein E (APOE) genotypes. Mean plasma total cholesterol and LDL levels were higher in AD than controls (p < 0.05). Lipoproteins cholesterol distribution shifted toward a greater prevalence of smaller, denser LDL (sd-LDL, p < 0.05) only in AD patients with PON1 -107TT genotype, who also showed increased plasma levels of oxidized LDL (ox-LDL, p = 0.02). A significant association was observed between sd-LDL and ox-LDL levels (p < 005) in AD patients. APOE genotype did not modulate lipoprotein distribution. Increased levels of sd-LDL and ox-LDL particles in the AD PON1 TT patients could be explained by the combined effect of an AD-related pro-oxidant milieu and an ineffective PON1 gene polymorphism-related antioxidant capacity. The functional correlate of the association between PON1 -107C/T polymorphism and AD may be the abnormal modulation of LDL oxidation. Ox-LDL may amplify the processes of endothelial injury promoted by vascular amyloid deposition, which represents one of the potential pathways explaining the cross-road between vascular and neurodegenerative pathomechanisms in AD.

  19. Molecular imaging of Alzheimer disease pathology.

    PubMed

    Kantarci, K

    2014-06-01

    Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents.

  20. Epidemiology of Alzheimer disease

    PubMed Central

    Reitz, Christiane; Brayne, Carol; Mayeux, Richard

    2012-01-01

    The global prevalence of dementia is estimated to be as high as 24 million, and is predicted to double every 20 years through to 2040, leading to a costly burden of disease. Alzheimer disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive function, which typically begins with deterioration in memory. Before death, individuals with this disorder have usually become dependent on caregivers. The neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques—which are frequently surrounded by dystrophic neurites—and intracellular neurofibrillary tangles. These hallmark pathologies are often accompanied by the presence of reactive microgliosis and the loss of neurons, white matter and synapses. The etiological mechanisms underlying the neuropathological changes in AD remain unclear, but are probably affected by both environmental and genetic factors. Here, we provide an overview of the criteria used in the diagnosis of AD, highlighting how this disease is related to, but distinct from, normal aging. We also summarize current information relating to AD prevalence, incidence and risk factors, and review the biomarkers that may be used for risk assessment and in diagnosis. PMID:21304480

  1. Supporting autobiographical memory in patients with Alzheimer's disease using smart phones.

    PubMed

    De Leo, Gianluca; Brivio, Eleonora; Sautter, Scott W

    2011-01-01

    An estimated 5.1 million Americans suffer from Alzheimer's disease (AD). A symptom of AD is the gradual loss of autobiographical memory. Support services have been shown to slow such loss, thereby improving the quality of life of patients and their caregivers. In this case study, a subject in Stage 4 of AD on the Functional Assessment Staging (FAST) scale carried a smart phone with a lanyard for 4 weeks. The smart phone was programmed to take pictures at 5-minute intervals for 12 hours during the day. The pictures were collected, combined in a video slide show, saved to a DVD, and mailed to the subject on a weekly basis. The subject and his caregiver had to view the DVD. In order to evaluate the subject's memory before and after viewing the DVD, a test concerning the most important events of the week was developed. The subject and his caregiver had to answer a satisfaction questionnaire as well. The results of this case study confirmed that the DVD helped the subject recall recent events significantly better and that carrying the smart phone was not considered intrusive to daily routines. This manuscript illustrates how smart phone technology can assist in exercising autobiographical memory.

  2. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients.

    PubMed

    Damjanovic, Amanda K; Yang, Yinhua; Glaser, Ronald; Kiecolt-Glaser, Janice K; Nguyen, Huy; Laskowski, Bryon; Zou, Yixiao; Beversdorf, David Q; Weng, Nan-ping

    2007-09-15

    Caregivers of Alzheimer's disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-alpha and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.

  3. Pericellular innervation of neurons expressing abnormally hyperphosphorylated tau in the hippocampal formation of Alzheimer's disease patients.

    PubMed

    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.

  4. 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

  5. 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

  6. Source Memory for Self and Other in Patients With Mild Cognitive Impairment due to Alzheimer's Disease.

    PubMed

    Rosa, Nicole M; Deason, Rebecca G; Budson, Andrew E; Gutchess, Angela H

    2016-01-01

    The present study examined the role of enactment in source memory in a cognitively impaired population. As seen in healthy older adults, it was predicted that source memory in people with mild cognitive impairment due to Alzheimer's disease (MCI-AD) would benefit from the self-reference aspect of enactment. Seventeen participants with MCI-AD and 18 controls worked in small groups to pack a picnic basket and suitcase and were later tested for their source memory for each item. For item memory, self-referencing improved corrected recognition scores for both MCI-AD and control participants. The MCI-AD group did not demonstrate the same benefit as controls in correct source memory for self-related items. However, those with MCI-AD were relatively less likely to misattribute new items to the self and more likely to misattribute new items to others when committing errors, compared with controls. The enactment effect and self-referencing did not enhance accurate source memory more than other referencing for patients with MCI-AD. However, people with MCI-AD benefited in item memory and source memory, being less likely to falsely claim new items as their own, indicating some self-reference benefit occurs for people with MCI-AD. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

  7. Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients.

    PubMed

    Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; Lima, Daiane Borba de; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar; Bromberg, Elke

    2016-01-01

    Older familial caregivers of Alzheimer's disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. The cognitive measures of 17 young (31-58 years) and 18 old (63-84 years) caregivers and of 17 young (37-57 years) and 18 old (62-84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.

  8. Possibility of Acetylcholinesterase Overexpression in Alzheimer Disease Patients after Therapy with Acetylcholinesterase Inhibitors.

    PubMed

    Kračmarová, Alžběta; Drtinová, Lucie; Pohanka, Miroslav

    2015-01-01

    Acetylcholinesterase is an enzyme responsible for termination of excitatory transmission at cholinergic synapses by the hydrolyzing of a neurotransmitter acetylcholine. Nowadays, other functions of acetylcholinesterase in the organism are considered, for example its role in regulation of apoptosis. Cholinergic nervous system as well as acetylcholinesterase activity is closely related to pathogenesis of Alzheimer disease. The mostly used therapy of Alzheimer disease is based on enhancing cholinergic function using inhibitors of acetylcholinesterase like rivastigmine, donepezil or galantamine. These drugs can influence not only the acetylcholinesterase activity but also other processes in treated organism. The paper is aimed mainly on possibility of increased expression and protein level of acetylcholinesterase caused by the therapy with acetylcholinesterase inhibitors.

  9. 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.

  10. Gray matter atrophy in patients with mild cognitive impairment/Alzheimer's disease over the course of developing delusions.

    PubMed

    Fischer, Corinne E; Ting, Windsor Kwan-Chun; Millikin, Colleen P; Ismail, Zahinoor; Schweizer, Tom A

    2016-01-01

    We conducted a neuroimaging analysis to understand the neuroanatomical correlates of gray matter loss in a group of mild cognitive impairment and early Alzheimer's disease patients who developed delusions. With data collected as part of the Alzheimer's Disease Neuroimaging Initiative, we conducted voxel-based morphometry to determine areas of gray matter change in the same Alzheimer's Disease Neuroimaging Initiative participants, before and after they developed delusions. We identified 14 voxel clusters with significant gray matter decrease in patient scans post-delusional onset, correcting for multiple comparisons (false discovery rate, p < 0.05). Major areas of difference included the right and left insulae, left precuneus, the right and left cerebellar culmen, the left superior temporal gyrus, the right posterior cingulate, the right thalamus, and the left parahippocampal gyrus. Although contrary to our initial predictions of enhanced right frontal atrophy, our preliminary work identifies several neuroanatomical areas, including the cerebellum and left posterior hemisphere, which may be involved in delusional development in these patients. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Brain Imaging in Alzheimer Disease

    PubMed Central

    Johnson, Keith A.; Fox, Nick C.; Sperling, Reisa A.; Klunk, William E.

    2012-01-01

    Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies. PMID:22474610

  12. Brain imaging in Alzheimer disease.

    PubMed

    Johnson, Keith A; Fox, Nick C; Sperling, Reisa A; Klunk, William E

    2012-04-01

    Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies.

  13. Inhibitory functioning in Alzheimer's disease.

    PubMed

    Amieva, Hélène; Phillips, Louise H; Della Sala, Sergio; Henry, Julie D

    2004-05-01

    We present a comprehensive review of studies assessing inhibitory functioning in Alzheimer's disease. The objectives of this review are: (i) to establish whether Alzheimer's disease affects all inhibitory mechanisms equally, and (ii) where possible, to assess whether any effects of Alzheimer's disease on inhibition tasks might be caused by other cognitive deficits, such as slowed processing. We review inhibitory mechanisms considered to play a crucial role in various domains of cognition, such as inhibition involved in working memory, selective attention and shifting abilities, and the inhibition of motor and verbal responses. It was found that whilst most inhibitory mechanisms are affected by the disorder, some are relatively preserved, suggesting that inhibitory deficits in Alzheimer's disease may not be the result of a general inhibitory breakdown. In particular, the experimental results reviewed showed that Alzheimer's disease has a strong effect on tasks requiring controlled inhibition processes, such as the Stroop task. However, the presence of the disease appears to have relatively little effect on tasks requiring more automatic inhibition, such as the inhibition of return task. Thus, the distinction between automatic, reflexive inhibitory mechanisms and controlled inhibitory mechanisms may be critical when predicting the integrity of inhibitory mechanisms in Alzheimer's disease. Substantial effects of Alzheimer's disease on tasks such as negative priming, which are not cognitively complex but do require some degree of controlled inhibition, support this hypothesis. A meta-analytic review of seven studies on the Stroop paradigm revealed substantially larger effects of Alzheimer's disease on the inhibition condition relative to the baseline condition, suggesting that these deficits do not simply reflect general slowing.

  14. 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.

  15. Executive functions in patients with Alzheimer's disease, type 2 diabetes mellitus patients and cognitively healthy older adults.

    PubMed

    Redondo, María Teresa; Beltrán-Brotóns, José Luís; Reales, José Manuel; Ballesteros, Soledad

    2016-10-01

    The present study investigated whether the performance on executive function tasks of patients with type 2 diabetes mellitus (T2DM) is as impaired as that of Alzheimer's disease (AD) patients and to compare their performance with that of a group of cognitively healthy older adults. We also investigated whether glycosylated hemoglobin levels (HbA1c, a measure of glucose regulation) are related to performance on executive control tasks. Three groups of participants (AD, T2DM, and healthy older adults) completed medical and psychological evaluations and performed a series of computerized tasks, including processing speed (simple and choice reaction time) tasks, verbal and visuospatial working memory (WM) updating (n-back) tasks, and the Wisconsin Card Sorting Test (WCST), to assess processing speed and executive functioning. As expected, the results showed that AD patients performed significantly worse than the healthy older adult group in all tasks. Executive functions deteriorated in the two groups of patients but more in the AD group. The T2DM group differed from healthy older controls but not from AD patients in the percentage of perseverations and the percentage of perseverative errors (WCST). These findings revealed working memory (updating and maintenance) and executive control declines in the T2DM compared to healthy older controls but smaller than that suffered by the AD patients. The impairment of executive processing of T2DM patients despite the glycosylated hemoglobin control suggests that these patients are at risk of developing AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Does retrieval frequency account for the pattern of autobiographical memory loss in early Alzheimer's disease patients?

    PubMed

    De Simone, Maria Stefania; Fadda, Lucia; Perri, Roberta; Aloisi, Marta; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

    2016-01-08

    Episodic autobiographical memory (ABM) has been found to be impaired from the early stage of Alzheimer's disease (AD). Previous works have focused on how ABM decreases over the lifespan, but no study has deeply investigated whether the extent of episodic autobiographical amnesia is mediated by the retrieval frequency of the episodic trace itself. The aim of the present study was to determine whether the frequency of trace retrieval has an effect on the quality of autobiographical incidents recall and whether the extent of this contribution changes over time. For this purpose, the episodic component of ABM was assessed in patients in the early stage of AD through a questionnaire which allowed evaluating memory of past personal incidents as a function of both their age of acquisition and retrieval frequency. We found that both AD patients and healthy controls took advantage of greater retrieval frequency across all time segments, because of their better memory performance on frequently retrieved episodes than less frequently retrieved ones. Although in the AD group the retrieval frequency effect (i.e., higher scores on the episodes rated as more frequently retrieved) was found in all time segments, the extent of its beneficial effect on memory performance was temporally-graded and inversely related to the time course. Our findings provide new evidence that the combined action of both age of memory and retrieval frequency could provide a valuable framework for predicting patterns of ABM loss, at least in early AD patients. In line with the Multiple Trace Theory, we speculated that retrieval frequency protects episodic trace recall against hippocampal damage by reinforcing the neural representation of personal context-rich memories, which consequently are easier to access and recall. Furthermore, the age of memory should change the amplitude of this beneficial effect as a function of the remoteness of the trace.

  17. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression.

    PubMed

    Wang, Lucy Y; Shofer, Jane B; Rohde, Kirsten; Hart, Kim L; Hoff, David J; McFall, Yun H; Raskind, Murray A; Peskind, Elaine R

    2009-09-01

    Agitation/aggression in Alzheimer disease (AD) is a major cause of patient distress, caregiver burden, and institutionalization. Enhanced behavioral responsiveness to central nervous system norepinephrine (NE) release may contribute to the pathophysiology of agitation/aggression in AD. Prazosin, a nonsedating generic medication used for hypertension and benign prostatic hypertrophy, antagonizes NE effects at brain postsynaptic alpha-1 adrenoreceptors. This pilot study examined the efficacy and tolerability of prazosin for behavioral symptoms in patients with agitation/aggression in AD. Double-blind, placebo controlled, parallel group study. A university AD center and a nursing home in Seattle, WA. Twenty-two nursing home and community-dwelling participants with agitation/aggression and probable or possible AD (mean age: 80.6 +/- 11.2). Randomization to placebo (N = 11) or prazosin (N = 11). Medication was initiated at 1 mg/day and increased up to 6 mg/day using a flexible dosing algorithm. The Brief Psychiatric Rating Scale (BPRS) and Neuropsychiatric Inventory (NPI) at Weeks 1, 2, 4, 6, and 8. The Clinical Global Impression of Change (CGIC) at Week 8. Participants taking prazosin (mean dose: 5.7 +/- 0.9 mg/day) had greater improvements than those taking placebo (mean dose: 5.6 +/- 1.2 mg/day) on the NPI (mean change: -19 +/- 21 versus -2 +/- 15, chi = 6.32, df = 1, p = 0.012) and BPRS (mean change: -9 +/- 9 versus -3 +/- 5, chi = 4.42, df = 1, p = 0.036) based on linear mixed effects models and the CGIC (mean: 2.6 +/- 1.0 versus 4.5 +/- 1.6, z = 2.57, p = 0.011 [Mann-Whitney test]). Adverse effects and blood pressure changes were similar between prazosin and placebo groups. Prazosin was well tolerated and improved behavioral symptoms in patients with agitation/aggression in AD.

  18. The "hidden" semantic category dissociation in mild-moderate Alzheimer's disease patients.

    PubMed

    Albanese, Emiliano

    2007-03-02

    In patients manifesting mild-moderate Alzheimer's disease (AD), lexical semantic tasks are known to be influenced by several variables which should be adequately taken into account when studying semantic category dissociations. The following study provides indexes of three new variables (imageability (I), percentage of name agreement (pNA) and number of target alternatives (nTA)) and investigates their role in naming in a group of people with AD and in matched older adults controls. Forty young healthy participants rated I, pNA and nTA of 155 stimuli (including living and non-living items) from and sets. Forty-eight people with mild-moderate AD and 40 older adults were given the two naming tests and their naming ratings were analysed with a two-way ANOVA (two groupsxtwo categories) to assess category specificity and the effect of interaction. The influence of relevant concomitant variables in naming was measured using a multiple regression analysis. Semi-partial correlations were carried out to assess the independent contribution of each variable to naming. We found that living items were more imageable and had fewer lexical alternatives and higher name agreement than non-living items. We also found that controls significantly named better than AD patients (F=37.551, p<.001), whilst the two-way ANOVA showed no significant effect of category (F=.649, p=.423). Notably category effect emerged when assessing its independent contribution performing a semi-partial correlation (beta=-.278, p<.001) which kept the effect of relevant concomitant variables under control. Our results confirm that category dissociation does emerge in mild-moderate AD patients when the effect of relevant concomitant variables is adequately taken into account. The hypothesis that the highly correlated properties of items from biological categories may play a protective effect on living things, making them less prone to impairment in the early stages of AD, is discussed.

  19. Epigenomics of Alzheimer's disease.

    PubMed

    Bennett, David A; Yu, Lei; Yang, Jingyun; Srivastava, Gyan P; Aubin, Cristin; De Jager, Philip L

    2015-01-01

    Alzheimer's disease (AD) is a large and growing public health problem. It is characterized by the accumulation of amyloid β peptides and abnormally phosphorylated tau proteins that are associated with cognitive decline and dementia. Much has been learned about the genomics of AD from linkage analyses and, more recently, genome-wide association studies. Several but not all aspects of the genomic landscape are involved in amyloid β metabolism. The moderate concordance of disease among twins suggests other factors, potentially epigenomic factors, are related to AD. We are at the earliest stages of examining the relation of the epigenome to the clinical and pathologic phenotypes that characterize AD. Our literature review suggests that there is some evidence of age-related changes in human brain methylation. Unfortunately, studies of AD have been relatively small with limited coverage of methylation sites and microRNA, let alone other epigenomic marks. We are in the midst of 2 large studies of human brains including coverage of more than 420,000 autosomal cytosine-guanine dinucleotides with the Illumina Infinium HumanMethylation450 BeadArray, and histone acetylation with chromatin immunoprecipitation sequencing. We present descriptive data to help inform other researchers what to expect from these approaches to better design and power their studies. We then discuss future directions to inform on the epigenomic architecture of AD.

  20. 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

  1. What causes alzheimer's disease?

    PubMed

    Armstrong, R A

    2013-01-01

    Since the earliest descriptions of Alzheimer's disease (AD), many theories have been advanced as to its cause. These include: (1) exacerbation of aging, (2) degeneration of anatomical pathways, including the cholinergic and cortico-cortical pathways, (3) an environmental factor such as exposure to aluminium, head injury, or malnutrition, (4) genetic factors including mutations of amyloid precursor protein (APP) and presenilin (PSEN) genes and allelic variation in apolipoprotein E (Apo E), (5) mitochondrial dysfunction, (6) a compromised blood brain barrier, (7) immune system dysfunction, and (8) infectious agents. This review discusses the evidence for and against each of these theories and concludes that AD is a multifactorial disorder in which genetic and environmental risk factors interact to increase the rate of normal aging ('allostatic load'). The consequent degeneration of neurons and blood vessels results in the formation of abnormally aggregated 'reactive' proteins such as β-amyloid (Aβ) and tau. Gene mutations influence the outcome of age-related neuronal degeneration to cause early onset familial AD (EO-FAD). Where gene mutations are absent and a combination of risk factors present, Aβ and tau only slowly accumulate not overwhelming cellular protection systems until later in life causing late-onset sporadic AD (LO-SAD). Aβ and tau spread through the brain via cell to cell transfer along anatomical pathways, variation in the pathways of spread leading to the disease heterogeneity characteristic of AD.

  2. Neurogenesis in Alzheimer's disease

    PubMed Central

    Rodríguez, José J; Verkhratsky, Alexei

    2011-01-01

    It is widely acknowledged that neural stem cells generate new neurons through the process of neurogenesis in the adult brain. In mammals, adult neurogenesis occurs in two areas of the CNS: the subventricular zone and the subgranular zone of the dentate gyrus of the hippocampus. The newly generated cells display neuronal morphology, generate action potentials and receive functional synaptic inputs, their properties being equivalent to those of mature neurons. Alzheimer's disease (AD) is the widespread cause of dementia, and is an age-related, progressive and irreversible neurodegenerative disease that results in massive neuronal death and deterioration of cognitive functions. Here, we overview the relations between adult neurogenesis and AD, and try to analyse the controversies in the field. We also summarise recent data obtained in the triple transgenic model of AD that show time- and region-specific impairment of neurogenesis, which may account for the early changes in synaptic plasticity and cognitive impairments that develop prior to gross neurodegenerative alterations and that could underlie new rescue therapies. PMID:21323664

  3. Nanotechnology for Alzheimer Disease.

    PubMed

    Leszek, Jerzy; Tse, Wai Hei; Zhang, Jin; Ávila-Rodriguez, Marco Fidel; Tarasov, Vadim V; Barreto, George E; Bachurin, Sergey O; Aliev, Gjumrakch

    2017-02-03

    Dementia of Alzheimer disease (AD) type affects memory, thinking and behavior. Researchers believe that changes in the brain may begin 10-20 years before symptoms appear and AD is diagnosed. The need to diagnose and treat the devastating disease at an early stage is critical to manage and treat AD. Unfortunately, the lack of validated biomarkers limits the possibility of the earlier stages of AD. The advance of nanotechnology could offer huge opportunities in early-stage diagnosis and well treatment of AD. Biocompatible nanoparticles with diameter in the range of 1-100 nm could be used as targeted delivery system for drugs (e.g. Rivastigmine) to overcome the blood-brain barrier (BBB), and to minimize the side effects caused by over-dosage. In addition, biocompatible nanomaterials with enhanced optical and magnetic properties may allow them being excellent alternative contrast agents for early-stage diagnosis. With more studies on using nanomaterials and nanotechnology in complex biochemical environment of the central nervous system, it is most likely that nanomaterials and nanotechnology can be give significant impact on the early-stage diagnosis and treatment of AD. In this review we discuss the challenges of current treatment and diagnosis of AD and the development on biocompatible nanoparticles, and provide the rational and potentials of using nanoparticles for both drug carrier and imaging contrast agent for diagnosis and treatment of AD. . Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Health-Related Quality of Life in Patients with Alzheimer's Disease in Different German Health Care Settings.

    PubMed

    Heßmann, Philipp; Seeberg, Greta; Reese, Jens Peter; Dams, Judith; Baum, Erika; Müller, Matthias J; Dodel, Richard; Balzer-Geldsetzer, Monika

    2016-01-01

    The purpose of this study is to evaluate the health-related quality of life (HrQoL) of patients with Alzheimer's disease (AD) in different care settings (institutionalized versus community-dwelling) across all severity stages of dementia. Patients were consecutively recruited with their primary caregivers (123 inpatients and 272 outpatients), and the impact of patient-related parameters such as behavioral and psychological symptoms of dementia (BPSD) (Geriatric Depression Scale [GDS] and Neuropsychiatric Inventory [NPI]) and functional capacity (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]) on HrQoL was analyzed. Patients' HrQoL was assessed using self-reported and caregiver-rated generic (EuroQoL Instrument) and dementia-specific (Quality of Life-Alzheimer's Disease [Qol-AD]) scales. Patients reported a considerably higher HrQoL than their caregivers on the QoL-AD, EQ-5D, and EQ VAS (p <  0.001). Different dementia severity groups showed significantly worse results in HrQoL for patients with lower MMSE scores. The mean self-reported QoL-AD decreased from 32.3±5.7 in the group with the highest MMSE scores to 27.1±5.5 in patients with the lowest MMSE scores (p <  0.001). A considerably lower HrQoL was shown for institutionalized patients versus participants in outpatient settings (proxy-rated QoL-AD 19.7±4.6 versus 26.0±7.1, p <  0.001). Depressive symptoms (GDS), BPSD (NPI), and reduced functional capacity (ADCS-ADL) were evaluated for their impact on patients' HrQoL. Multivariate models explained between 22% and 54% of the variance in patients' HrQoL. To analyze the causative direction of the reported associations, further longitudinal studies should be conducted.

  5. 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 ...

  6. Urinary homocysteic acid levels correlate with mini-mental state examination scores in Alzheimer's disease patients.

    PubMed

    Hasegawa, Tohru; Ichiba, Masayoshi; Matsumoto, Shin-Ei; Kasanuki, Koji; Hatano, Taku; Fujishiro, Hiroshige; Iseki, Eizo; Hattori, Nobutaka; Yamada, Tatsuo; Tabira, Takeshi

    2012-01-01

    Homocysteic acid (HA) has been suggested as a pathogen in a mouse model of Alzheimer's disease (AD), 3xTg-AD. However, it is not established whether HA is involved in humans. We investigated the relationship between urinary HA levels and Mini-Mental State Examination (MMSE) scores in AD patients (n = 70) and non-AD controls (n = 34). We found a positive, statistically significant relationship between the two variables (the urinary HA level and MMSE score) (r = 0.31, p = 0.0008, n = 70). This relationship was stronger in females than males (r = 0.43, p = 0.005, n = 44 in females; r = 0.48, p = 0.02, n = 22 in males). The urinary HA levels were significantly different in AD patients than controls (AD: 8.7 ± 7.5, n = 70; non-dementia control: 13.3 ± 9.4, n = 34, p < 0.01). In addition, aging and smoking were found as lowering factors for urinary HA levels. Our preliminary study showed a negative, statistically significant relationship between blood HA (micromole) and urine HA levels (r = -0.6, p = 0.007, n = 19), and between blood HA levels and MMSE scores (r = -0.79, p = 0.0000518, n = 19). On the basis of these results, we speculate that reduced urinary excretion induces elevated HA levels in blood, resulting in cognitive dysfunctions. This study also suggests that HA may be a candidate of neurotoxins for uremic encephalopathy. Since amyloid-β increases HA toxicity and HA is an agonist of N-methyl-D-aspartic acid (NMDA) receptor, we speculate that elevated blood HA affects the brain cognitive function through NMDA receptor-mediated toxicity in AD.

  7. 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

  8. Biomarkers for early detection of Alzheimer disease.

    PubMed

    Barber, Robert C

    2010-09-01

    The existence of an effective biomarker for early detection of Alzheimer disease would facilitate improved diagnosis and stimulate therapeutic trials. Multidisciplinary clinical diagnosis of Alzheimer disease is time consuming and expensive and relies on experts who are rarely available outside of specialty clinics. Thus, many patients do not receive proper diagnosis until the disease has progressed beyond stages in which treatments are maximally effective. In the clinical trial setting, rapid, cost-effective screening of patients for Alzheimer disease is of paramount importance for the development of new treatments. Neuroimaging of cortical amyloid burden and volumetric changes in the brain and assessment of protein concentrations (eg, β-amyloid 1-42, total tau, phosphorylated tau) in cerebrospinal fluid are diagnostic tools that are not widely available. Known genetic markers do not provide sufficient discriminatory power between different forms of dementia to be useful in isolation. Recent studies using panels of biomarkers for diagnosis of Alzheimer disease or mild cognitive impairment have been promising, though no such studies have been cross-validated in independent samples of subjects. The ideal biomarker enabling early detection of Alzheimer disease has not yet been identified.

  9. Autotoxicity and Alzheimer disease.

    PubMed

    McGeer, P L; McGeer, E G

    2000-06-01

    I mmunological responses are considered to be either humoral, resulting from cloning of B lymphocytes, or cell mediated, resulting from cloning of T lymphocytes. Autoimmune diseases occur when the cloned products attack host tissue. Inflammation is considered a nonspecific response to injury, characterized by exudation of serum into damaged tissue, and identified by the cardinal signs of rubor, calor, dolor, and tumor. However, these classic mechanisms do not fit pathological observations of Alzheimer disease (AD)-affected brain tissue. Although many of the components prominently associated with peripheral immunological and inflammatory states are present in AD lesions, there are no identifiable B lymphocytes or antibodies, and T cells are sparse. Furthermore, the blood-brain barrier is intact, excluding exudation of exogenous serum proteins. Although "neuroinflammation" is the term commonly used to describe the pathological changes, it fails to define adequately the process that is taking place. The reaction is neither a nonspecific response to injury, as classically implied for inflammatory reactions, nor an autoimmune reaction, despite the directed attack against plaques and extracellular tangles. It is most appropriately defined as an innate immunoreaction. The fact that such a reaction can be mounted by brain, an organ frequently described as being immunologically privileged, suggests that a reevaluation is required of the dimensions of the innate immune system, including how it operates at the tissue level. The innate immune system is primitive, while the adaptive immune system, which is directed by peripheral immune organs, is an invention of vertebrates. Even in vertebrates, however, the innate immune system is the first line of defense. Much more needs to be learned about the operation of the innate immune system in health and disease. Arch Neurol. 2000.

  10. Alzheimer's disease and intelligence.