Recent developments in Alzheimer's disease therapeutics

Directory of Open Access Journals (Sweden)

Aisen Paul S

2009-02-01

Full Text Available Abstract Alzheimer's disease is a devastating neurological disorder that affects more than 37 million people worldwide. The economic burden of Alzheimer's disease is massive; in the United States alone, the estimated direct and indirect annual cost of patient care is at least $100 billion. Current FDA-approved drugs for Alzheimer's disease do not prevent or reverse the disease, and provide only modest symptomatic benefits. Driven by the clear unmet medical need and a growing understanding of the molecular pathophysiology of Alzheimer's disease, the number of agents in development has increased dramatically in recent years. Truly *disease-modifying' therapies that target the underlying mechanisms of Alzheimer's disease have now reached late stages of human clinical trials. Primary targets include beta-amyloid, whose presence and accumulation in the brain is thought to contribute to the development of Alzheimer's disease, and tau protein which, when hyperphosphorylated, results in the self-assembly of tangles of paired helical filaments also believed to be involved in the pathogenesis of Alzheimer's disease. In this review, we briefly discuss the current status of Alzheimer's disease therapies under study, as well the scientific context in which they have been developed.

[Calcium hypothesis of Alzheimer disease].

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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.

Advancing frontiers in Alzheimer's disease research

International Nuclear Information System (INIS)

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

The application of lipidomics to biomarker research and pathomechanisms in Alzheimer's disease.

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Wong, Matthew W; Braidy, Nady; Poljak, Anne; Sachdev, Perminder S

2017-03-01

Alzheimer's disease is the most common cause of dementia. There are still no disease modifying treatments that can cure or slow disease progression. Recently, Alzheimer's disease researchers have attempted to improve early detection and diagnostic criteria for Alzheimer's disease, with the rationale that treatment of disease, or even prevention, may be more successful during the early preclinical stages of Alzheimer's disease when neurodegenerative damage is not as widespread. As the brain has a high lipid content, lipidomics may offer novel insights into the underlying pathogenesis of Alzheimer's disease. This review reports on recent developments in the relatively unexplored field of lipidomics in Alzheimer's disease, including novel biomarkers and pathomechanisms of Alzheimer's disease. Numerous biomarker panels involving phospholipids and sphingolipids have been proposed, indicating perturbed lipid metabolism in early stages of Alzheimer's disease. Future strategies targeting these metabolic changes through dietary supplementation could have therapeutic benefits in at-risk individuals. Dysregulated lipid metabolism could reflect pathological changes in synaptic function and neuronal membranes, leading to cognitive decline. However, extensive validation in large independent cohorts is required before lipid biomarkers can be used clinically to assess Alzheimer's disease risk and progression.

[Biomarkers of Alzheimer disease].

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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.

Validation study of the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) for the Portuguese patients with mild cognitive impairment and Alzheimer's disease.

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Nogueira, Joana; Freitas, Sandra; Duro, Diana; Almeida, Jorge; Santana, Isabel

2018-03-23

The Alzheimer's disease assessment scale-Cognitive Subscale (ADAS-Cog) is a battery to assess cognitive performance in Alzheimer's disease (AD) and was developed according to the core characteristics of cognitive decline in AD: memory, language, praxis, constructive ability, and orientation. The aim of this study was to explore the diagnostic accuracy and discriminative capacity of the ADAS-Cog for Mild Cognitive Impairment (MCI) and AD, using cut-off points for the Portuguese population. The European Portuguese version of the ADAS-Cog was administrated to 650 participants, divided into a control group (n = 210), an MCI group (n = 240), and an AD group (n = 200). The clinical groups fulfilled standard international diagnostic criteria. Controls were healthy cognitive participants actively integrated in the community. The neuropsychological assessment protocol included the ADAS-Cog, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Adults and Older Adults Functional Assessment Inventory (IAFAI). The ADAS-Cog revealed good psychometric indicators, and the total scores were significantly different between the three groups (p  9 points (AUC = .835; sensitivity = 58% and specificity = 91%) and AD > 12 points (AUC = .996; sensitivity = 94% and specificity = 98%). Our findings confirmed the capacity of the ADAS-Cog total score to identify cognitive impairment in AD patients, with poor sensitivity for MCI, in a Portuguese cohort.

Level of understanding of Alzheimer disease among caregivers and the general population.

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Jorge, C; Cetó, M; Arias, A; Blasco, E; Gil, M P; López, R; Dakterzada, F; Purroy, F; Piñol-Ripoll, G

2018-05-11

Understanding of Alzheimer disease is fundamental for early diagnosis and to reduce caregiver burden. The objective of this study is to evaluate the degree of understanding of Alzheimer disease among informal caregivers and different segments of the general population through the Alzheimer's Disease Knowledge Scale. We assessed the knowledge of caregivers in different follow-up periods (less than one year, between 1 and 5 years, and over 5 years since diagnosis) and individuals from the general population. Alzheimer's Disease Knowledge Scale scores were grouped into different items: life impact, risk factors, symptoms, diagnosis, treatment, disease progression, and caregiving. A total of 419 people (215 caregivers and 204 individuals from the general population) were included in the study. No significant differences were found between groups for overall Alzheimer's Disease Knowledge Scale score (19.1 vs. 18.8, P = .9). There is a scarce knowledge of disease risk factors (49.3%) or the care needed (51.2%), while symptoms (78.6%) and course of the disease (77.2%) were the best understood aspects. Older caregiver age was correlated with worse Alzheimer's Disease Knowledge Scale scores overall and for life impact, symptoms, treatment, and disease progression (P < .05). Time since diagnosis improved caregivers' knowledge of Alzheimer disease symptoms (P = .00) and diagnosis (P = .05). Assessing the degree of understanding of Alzheimer disease is essential to the development of health education strategies both in the general population and among caregivers. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium

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Frisoni, G.B.; Henneman, W.J.; Weiner, M.W.

2008-01-01

BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). METHODS: Seven...... academic sites of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic resonance imaging (MRI) scans, cerebrospinal fluid...

Efficacy of psychosocial intervention in patients with mild Alzheimer's disease: the multicentre, rater blinded, randomised Danish Alzheimer Intervention Study (DAISY)

DEFF Research Database (Denmark)

Waldorff, F.B.; Buss, D.V.; Eckermann, A.

2012-01-01

To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers.......To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers....

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

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

2009-01-01

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

TREM2 Variants in Alzheimer's Disease

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Guerreiro, Rita; Wojtas, Aleksandra; Bras, Jose; Carrasquillo, Minerva; Rogaeva, Ekaterina; Majounie, Elisa; Cruchaga, Carlos; Sassi, Celeste; Kauwe, John S.K.; Younkin, Steven; Hazrati, Lilinaz; Collinge, John; Pocock, Jennifer; Lashley, Tammaryn; Williams, Julie; Lambert, Jean-Charles; Amouyel, Philippe; Goate, Alison; Rademakers, Rosa; Morgan, Kevin; Powell, John; St. George-Hyslop, Peter; Singleton, Andrew; Hardy, John

2013-01-01

BACKGROUND Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia. METHODS We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice. RESULTS We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P = 0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P = 0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease. CONCLUSIONS Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.) PMID:23150934

A light therapy for treating Alzheimer's disease

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Wang, Xue; Han, Mengmeng; Wang, Qiyan; Zeng, Yuhui; Meng, Qingqiang; Zhang, Jun; Wei, Xunbin

2017-02-01

It is generally believed that there are some connections between Alzheimer's disease and amyloid protein plaques in the brain. The typical symptoms of Alzheimer's disease are memory loss, language disorders, mood swings, loss of motivation and behavioral issues. Currently, the main therapeutic method is pharmacotherapy, which may temporarily reduce symptoms, but has many side effects. Infrared light therapy has been studied in a range of single and multiple irradiation protocols in previous studies and was found beneficial for neuropathology. In our research we have studied the effect of infrared light on Alzheimer's disease through transgenic mouse model. We designed an experimental apparatus for treating mice, which primarily included a therapeutic box and a LED array, which emitted infrared light. After the treatment, we assessed the effects of infrared light by performing two tests: cognitive performance of mice in Morris water maze, and plaque load by immunofluorescence analysis. Immunofluorescence analysis was based on measuring the quantity of plaques in mouse brain slices. Our results show that infrared therapy is able to improve cognitive performance in the mouse model. It might provide a novel and safe way to treat Alzheimer's disease.

Alzheimer's Disease Facts and Figures

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Full Text Available ... THE 10 SIGNS Alzheimer's Disease Facts in Each State The 2018 Alzheimer's Disease Facts and Figures report ... on the impact of this disease in every state across the nation. Click below to see the ...

Amyloid beta peptide immunotherapy in Alzheimer disease.

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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.

The clinical use of structural MRI in Alzheimer disease

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Frisoni, G.B.; Fox, N.C.; Jack, C.R.; Scheltens, P.; Thompson, P.M.

2010-01-01

Structural imaging based on magnetic resonance is an integral part of the clinical assessment of patients with suspected Alzheimer dementia. Prospective data on the natural history of change in structural markers from preclinical to overt stages of Alzheimer disease are radically changing how the

Nutritional supplementation for Alzheimer's disease?

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Shea, Thomas B; Remington, Ruth

2015-03-01

Evidence for the benefit of nutrition in Alzheimer's disease continues to accumulate. Many studies with individual vitamins or supplements show marginal, if any, benefit. However, new findings with combinatorial formulations demonstrate improvement in cognitive performance and behavioral difficulties that accompany Alzheimer's disease. Herein, we review some of the most recent clinical advances and summarize supportive preclinical studies. We present novel positive effects on Alzheimer's disease derived from diet, trace elements, vitamins and supplements. We discuss the inherent difficulty in conducting nutritional studies because of the variance in participants' nutritional history, versus pharmacological interventions in which participants are naive to the intervention. We examine the evidence that epigenetics play a role in Alzheimer's disease and how nutritional intervention can modify the key epigenetic events to maintain or improve cognitive performance. Overall consideration of the most recent collective evidence suggests that the optimal approach for Alzheimer's disease would seem to combine early, multicomponent nutritional approaches (a Mediterranean-style diet, multivitamins and key combinatorial supplements), along with lifestyle modifications such as social activity and mental and physical exercise, with ultimate addition of pharmacological agents when warranted.

The biological substrates of Alzheimer's disease

International Nuclear Information System (INIS)

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

1986-01-01

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

Discrepancy between self- and proxy-rated pain in Alzheimer's disease: results from the danish Alzheimer intervention study

DEFF Research Database (Denmark)

Jensen-Dahm, C.; Vogel, A.; Waldorff, F.B.

2012-01-01

OBJECTIVES: To investigate the prevalence of self- and proxy-reported pain in a cohort with Alzheimer's disease (AD) and to identify characteristics of individuals with AD reporting pain. DESIGN: Data were collected at the baseline visit of the Danish Alzheimer Intervention Study. SETTING......: Community. PARTICIPANTS: Three hundred twenty-one community-living individuals with AD (MMSE >/= 20) and their primary caregivers. MEASUREMENTS: Pain was assessed as part of the EuroQol EQ-5D (caregiver- and self-rated). The Cornell Scale for Depression in Dementia, Quality of Life in Alzheimer's Disease...

Language impairment in Alzheimer's disease and benefits of acetylcholinesterase inhibitors

Directory of Open Access Journals (Sweden)

Ferris SH

2013-08-01

Full Text Available Steven H Ferris,1 Martin Farlow21Alzheimer's Disease Center, Comprehensive Center on Brain Aging, New York University Langone Medical Center, New York, NY, 2Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USAAbstract: Alzheimer's disease is characterized by progressively worsening deficits in several cognitive domains, including language. Language impairment in Alzheimer's disease primarily occurs because of decline in semantic and pragmatic levels of language processing. Given the centrality of language to cognitive function, a number of language-specific scales have been developed to assess language deficits throughout progression of the disease and to evaluate the effects of pharmacotherapy on language function. Trials of acetylcholinesterase inhibitors, used for the treatment of clinical symptoms of Alzheimer's disease, have generally focused on overall cognitive effects. However, in the current report, we review data indicating specific beneficial effects of acetylcholinesterase inhibitors on language abilities in patients with Alzheimer’s disease, with a particular focus on outcomes among patients in the moderate and severe disease stages, during which communication is at risk and preservation is particularly important.Keywords: Alzheimer's disease, donepezil, cognition, language, communication, clinical trials

[Proceeding memory in Alzheimer's disease].

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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.

Rivastigmine in Alzheimer's disease and Parkinson's disease dementia: an ADAS-cog factor analysis.

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Weintraub, Daniel; Somogyi, Monique; Meng, Xiangyi

2011-09-01

Rivastigmine treatment is associated with significant improvements on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) in patients with mild-to-moderate Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Both AD and PDD are purported to have different profiles of cognitive impairment, which may respond differentially to rivastigmine treatment. This was a retrospective analysis of 3 randomized, double-blind, rivastigmine trial databases (Investigation of transDermal Exelon in ALzheimer's disease [IDEAL; AD], EXelon in PaRkinson's disEaSe dementia Study [EXPRESS; PDD], and Alzheimer's Disease with ENA 713 [ADENA; AD]). Factor analyses of the 11 baseline ADAS-cog items derived the same factors in the 2 diseases, that is, "memory" and "language". Rivastigmine-treated AD and PDD patients showed significant improvements (P < .0001 versus placebo) on both factors. For both AD and PDD, rivastigmine had a numerically greater effect on memory than language. Treatment effect sizes were numerically greater in PDD compared with AD. Rivastigmine treatment is associated with improvement in memory and language in AD and PDD. The numerically greater response in PDD is consistent with greater cholinergic deficits in this disease state.

Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer`s disease

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Lannfelt, L; Lilius, L; Viitanen, M; Winblad, B; Basun, H [Huddinge Hospital, Karolinska Institute, Dept. of Geriatric Medicine, (Sweden); Houlden, H; Rossor, M [St. Mary` s Hospital, Dept. of Neurology, Medical School, London (United Kingdom); Hardy, J [University of South Florida, Suncoast Alzheimer` s Disease Research Labs, Department of Psychiatry, Tampa (United States)

1995-02-01

Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer`s disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid presursor protein gene involvement in Alzheimer`s disease families, as it is closely linked to the gene. Most cases of Alzheimer`s disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer`s disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. (au) (26 refs.).

Efficacy of language assessment in Alzheimer's disease: comparing in-person examination and telemedicine.

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Vestal, Lindsey; Smith-Olinde, Laura; Hicks, Gretchen; Hutton, Terri; Hart, John

2006-01-01

With the large number of aging individuals requiring screening of cognitive functions for dementing illnesses, there is a necessity for innovative evaluation approaches. One domain that should allow for online, at a distance, examination is speech and language dysfunction, if the auditory and visual transmission is of sufficient quality to allow adequate patient participation and reliable, valid interpretation of signs and symptoms (Duffy et al 1997). Examine the effectiveness of language assessment in mild Alzheimer's patients using telemedicine (TM) compared with traditional in-person (IP) assessment. Ten patients with mild Alzheimer's disease, enrolled at a Geriatric Memory Clinic received a battery of standard language tests under two conditions: face-to-face and via satellite TM. Comparison of TM and IP testing conditions were assessed within each for scores on each test in the two conditions. On each of the five language tasks, the Wilcoxon signed ranks test indicated no significant difference on performance between the TM and IP conditions for each participant. Overall acceptance of the TM evaluation in an elderly population was rated at a high level except for one individual. Telemedicine can improve access to speech and language evaluation services which is relevant to both dementia and other neurological diseases of the elderly. In particular, this specific assessment tool can be used to provide evaluations in under-served rural areas.

Epidemiology of Alzheimer disease.

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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.

Comparing Clinical Profiles in Alzheimer's Disease and Parkinson's Disease Dementia

Directory of Open Access Journals (Sweden)

Martin R. Farlow

2013-09-01

Full Text Available Background: Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD and Parkinson's disease dementia (PDD may improve the interpretation of drug effects and the design of future studies. Methods: This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD. Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog, Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL scale, 10-item Neuropsychiatric Inventory (NPI-10 and the ADCS-Clinical Global Impression of Change (CGIC was compared [standardized difference (Cohen's d, similar if Results: Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47 and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58 were higher in AD; PDD patients were more impaired in the language (0.23 and praxis (0.34 domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14 and improvement on the NPI-10 (0.11 compared with patients with PDD. Conclusion: Differing patterns of impairment occur in AD and PDD.

Comparing clinical profiles in Alzheimer's disease and Parkinson's disease dementia.

Science.gov (United States)

Farlow, Martin R; Schmitt, Frederick; Aarsland, Dag; Grossberg, George T; Somogyi, Monique; Meng, Xiangyi

2013-01-01

Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) may improve the interpretation of drug effects and the design of future studies. This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD). Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, 10-item Neuropsychiatric Inventory (NPI-10) and the ADCS-Clinical Global Impression of Change (CGIC) was compared [standardized difference (Cohen's d), similar if <0.1]. Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47) and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58) were higher in AD; PDD patients were more impaired in the language (0.23) and praxis (0.34) domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14) and improvement on the NPI-10 (0.11) compared with patients with PDD. Differing patterns of impairment occur in AD and PDD.

Assessing neuronal networks: understanding Alzheimer's disease.

LENUS (Irish Health Repository)

Bokde, Arun L W

2012-02-01

Findings derived from neuroimaging of the structural and functional organization of the human brain have led to the widely supported hypothesis that neuronal networks of temporally coordinated brain activity across different regional brain structures underpin cognitive function. Failure of integration within a network leads to cognitive dysfunction. The current discussion on Alzheimer\\'s disease (AD) argues that it presents in part a disconnection syndrome. Studies using functional magnetic resonance imaging, positron emission tomography and electroencephalography demonstrate that synchronicity of brain activity is altered in AD and correlates with cognitive deficits. Moreover, recent advances in diffusion tensor imaging have made it possible to track axonal projections across the brain, revealing substantial regional impairment in fiber-tract integrity in AD. Accumulating evidence points towards a network breakdown reflecting disconnection at both the structural and functional system level. The exact relationship among these multiple mechanistic variables and their contribution to cognitive alterations and ultimately decline is yet unknown. Focused research efforts aimed at the integration of both function and structure hold great promise not only in improving our understanding of cognition but also of its characteristic progressive metamorphosis in complex chronic neurodegenerative disorders such as AD.

Alzheimer's Disease Facts and Figures

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Full Text Available ... of death among those age 65 and older. It also is a leading cause of disability and ... development of biomarkers for Alzheimer's disease is making it possible to detect Alzheimer's disease and provide an ...

The clinical use of structural MRI in Alzheimer disease

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Frisoni, Giovanni B.; Fox, Nick C.; Jack, Clifford R.; Scheltens, Philip; Thompson, Paul M.

2010-01-01

Structural imaging based on magnetic resonance is an integral part of the clinical assessment of patients with suspected Alzheimer dementia. Prospective data on the natural history of change in structural markers from preclinical to overt stages of Alzheimer disease are radically changing how the disease is conceptualized, and will influence its future diagnosis and treatment. Atrophy of medial temporal structures is now considered to be a valid diagnostic marker at the mild cognitive impairment stage. Structural imaging is also included in diagnostic criteria for the most prevalent non-Alzheimer dementias, reflecting its value in differential diagnosis. In addition, rates of whole-brain and hippocampal atrophy are sensitive markers of neurodegeneration, and are increasingly used as outcome measures in trials of potentially disease-modifying therapies. Large multicenter studies are currently investigating the value of other imaging and nonimaging markers as adjuncts to clinical assessment in diagnosis and monitoring of progression. The utility of structural imaging and other markers will be increased by standardization of acquisition and analysis methods, and by development of robust algorithms for automated assessment. PMID:20139996

Various MRS application tools for Alzheimer disease and mild cognitive impairment.

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Gao, F; Barker, P B

2014-06-01

MR spectroscopy is a noninvasive technique that allows the detection of several naturally occurring compounds (metabolites) from well-defined regions of interest within the human brain. Alzheimer disease, a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. During the past 20 years, multiple studies have been performed on MR spectroscopy in patients with both mild cognitive impairment and Alzheimer disease. Generally, MR spectroscopy studies have found decreased N-acetylaspartate and increased myo-inositol in both patients with mild cognitive impairment and Alzheimer disease, with greater changes in Alzheimer disease than in mild cognitive impairment. This review summarizes the information content of proton brain MR spectroscopy and its related technical aspects, as well as applications of MR spectroscopy to mild cognitive impairment and Alzheimer disease. While MR spectroscopy may have some value in the differential diagnosis of dementias and assessing prognosis, more likely its role in the near future will be predominantly as a tool for monitoring disease response or progression in treatment trials. More work is needed to evaluate the role of MR spectroscopy as a biomarker in Alzheimer disease and its relationship to other imaging modalities. © 2014 by American Journal of Neuroradiology.

Alzheimer's Disease Assessment: A Review and Illustrations Focusing on Item Response Theory Techniques.

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Balsis, Steve; Choudhury, Tabina K; Geraci, Lisa; Benge, Jared F; Patrick, Christopher J

2018-04-01

Alzheimer's disease (AD) affects neurological, cognitive, and behavioral processes. Thus, to accurately assess this disease, researchers and clinicians need to combine and incorporate data across these domains. This presents not only distinct methodological and statistical challenges but also unique opportunities for the development and advancement of psychometric techniques. In this article, we describe relatively recent research using item response theory (IRT) that has been used to make progress in assessing the disease across its various symptomatic and pathological manifestations. We focus on applications of IRT to improve scoring, test development (including cross-validation and adaptation), and linking and calibration. We conclude by describing potential future multidimensional applications of IRT techniques that may improve the precision with which AD is measured.

Machine learning for the assessment of Alzheimer's disease through DTI

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Lella, Eufemia; Amoroso, Nicola; Bellotti, Roberto; Diacono, Domenico; La Rocca, Marianna; Maggipinto, Tommaso; Monaco, Alfonso; Tangaro, Sabina

2017-09-01

Digital imaging techniques have found several medical applications in the development of computer aided detection systems, especially in neuroimaging. Recent advances in Diffusion Tensor Imaging (DTI) aim to discover biological markers for the early diagnosis of Alzheimer's disease (AD), one of the most widespread neurodegenerative disorders. We explore here how different supervised classification models provide a robust support to the diagnosis of AD patients. We use DTI measures, assessing the structural integrity of white matter (WM) fiber tracts, to reveal patterns of disrupted brain connectivity. In particular, we provide a voxel-wise measure of fractional anisotropy (FA) and mean diffusivity (MD), thus identifying the regions of the brain mostly affected by neurodegeneration, and then computing intensity features to feed supervised classification algorithms. In particular, we evaluate the accuracy of discrimination of AD patients from healthy controls (HC) with a dataset of 80 subjects (40 HC, 40 AD), from the Alzheimer's Disease Neurodegenerative Initiative (ADNI). In this study, we compare three state-of-the-art classification models: Random Forests, Naive Bayes and Support Vector Machines (SVMs). We use a repeated five-fold cross validation framework with nested feature selection to perform a fair comparison between these algorithms and evaluate the information content they provide. Results show that AD patterns are well localized within the brain, thus DTI features can support the AD diagnosis.

Semantic Memory in the Clinical Progression of Alzheimer Disease.

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Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

2017-09-01

Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

Cognitive rehabilitation for elderly people with early-stage Alzheimer?s disease

OpenAIRE

Kim, Seyun

2015-01-01

[Purpose] The purpose of this study was to investigate the effect of cognitive rehabilitation including tasks of cognitive training on performance of everyday activities in elderly people with early-stage Alzheimer?s disease. [Subjects and Methods] Forty-three elderly people (15 men, 28 women) with a diagnosis of Alzheimer?s disease who had a Mini-Mental State Examination (MMSE) score of 18 or above were randomly assigned to two groups: the cognitive rehabilitation group (experimental) and co...

Is α‐T catenin (VR22) an Alzheimer's disease risk gene?

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Bertram, Lars; Mullin, Kristina; Parkinson, Michele; Hsiao, Monica; Moscarillo, Thomas J; Wagner, Steven L; Becker, K David; Velicelebi, Gonul; Blacker, Deborah; Tanzi, Rudolph E

2007-01-01

Background Recently, conflicting reports have been published on the potential role of genetic variants in the α‐T catenin gene (VR22; CTNNA3) on the risk for Alzheimer's disease. In these papers, evidence for association is mostly observed in multiplex families with Alzheimer's disease, whereas case–control samples of sporadic Alzheimer's disease are predominantly negative. Methods After sequencing VR22 in multiplex families with Alzheimer's disease linked to chromosome 10q21, we identified a novel non‐synonymous (Ser596Asn; rs4548513) single nucleotide polymorphism (SNP). This and four non‐coding SNPs were assessed in two independent samples of families with Alzheimer's disease, one with 1439 subjects from 437 multiplex families with Alzheimer's disease and the other with 489 subjects from 217 discordant sibships. Results A weak association with the Ser596Asn SNP in the multiplex sample, predominantly in families with late‐onset Alzheimer's disease (p = 0.02), was observed. However, this association does not seem to contribute substantially to the chromosome 10 Alzheimer's disease linkage signal that we and others have reported previously. No evidence was found of association with any of the four additional SNPs tested in the multiplex families with Alzheimer's disease. Finally, the Ser596Asn change was not associated with the risk for Alzheimer's disease in the independent discordant sibship sample. Conclusions This is the first study to report evidence of an association between a potentially functional, non‐synonymous SNP in VR22 and the risk for Alzheimer's disease. As the underlying effects are probably small, and are only seen in families with multiple affected members, the population‐wide significance of this finding remains to be determined. PMID:17209133

Epidemiology of Alzheimer Disease

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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

Alzheimer's Disease Facts and Figures

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Full Text Available ... Mortality Alzheimer's disease is the only top 10 cause of death in the United States that cannot be prevented, ... even slowed. Alzheimer's disease is the sixth-leading cause of death in the United States, and the fifth-leading ...

Alzheimer's Disease Facts and Figures

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Full Text Available ... health and long-term care costs. worried about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts ... Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, ...

Vitamin D and the risk of dementia and Alzheimer disease.

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Littlejohns, Thomas J; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Fried, Linda; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Kos, Katarina; Soni, Maya; Llewellyn, David J

2014-09-02

To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions. © 2014 American Academy of Neurology.

Insulin and Alzheimer disease: type 3 diabetes?

Directory of Open Access Journals (Sweden)

Andrés Jagua Gualdrón

2007-01-01

Full Text Available Alzheimer Disease is a neurodegenerative disease of central nervous system whose incidence will increase in next years. Recent investigations relate alzheimer with insulin signaling defects in neurons. Is alzheimer Disease a type 3 diabetes? In this communication write a brief article about evidences from this alzheimer‘s disease model.

Disrupting beta-amyloid aggregation for Alzheimer disease treatment.

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Estrada, L D; Soto, C

2007-01-01

Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment. Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (Abeta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse Abeta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural Abeta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with Abeta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.

Neuroinflammation in Alzheimer's Disease

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Heneka, Michael T.; Carson, Monica J.; El Khoury, Joseph; Landreth, Gary E.; Brosseron, Frederik; 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, Stephane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A.; Breitner, John C.; Cole, Greg M.; Golenbock, Douglas T.; Kummer, Markus P.

2018-01-01

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment but strongly interacts with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on micro- and astroglia and trigger an innate immune response, characterized by the release of inflammatory mediators, which contribute to disease progression and severity. Genome wide analysis suggests that several genes, which increase the risk for sporadic Alzheimer's disease en-code for factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity are likely to interfere with the immunological processes of the brain and further promote disease progression. This re-view provides an overview on the current knowledge and focuses on the most recent and exciting findings. Modulation of risk factors and intervention with the described immune mechanisms are likely to lead to future preventive or therapeutic strategies for Alzheimer's disease. PMID:25792098

Cognitive, functional and behavioral assessment: Alzheimer's disease

Directory of Open Access Journals (Sweden)

Márcia L.F. Chaves

Full Text Available Abstract A review of the evidence on cognitive, functional and behavioral assessment for the diagnosis of dementia due to Alzheimer's disease (AD is presented with revision and broadening of the recommendations on the use of tests and batteries in Brazil for the diagnosis of dementia due to AD. A systematic review of the literature (MEDLINE, LILACS and SCIELO database was carried out by a panel of experts. Studies on the validation and/or adaptation of tests, scales and batteries for the Brazilian population were analyzed and classified according to level of evidence. There were sufficient data to recommend the IQCODE, DAFS-R, DAD, ADL-Q and Bayer scale for the evaluation of instrumental activities of daily living, and the Katz scale for the assessment of basic activities of daily living. For the evaluation of neuropsychiatric symptoms, the Neuropsychiatric Inventory (NPI and the CAMDEX were found to be useful, as was the Cornell scale for depression in dementia. The Mini-Mental State Examination has clinical utility as a screening test, as do the multifunctional batteries (CAMCOG-R, ADAS-COG, CERAD and MDRS for brief evaluations of several cognitive domains. There was sufficient evidence to recommend the CDR scale for clinical and severity assessment of dementia. Tests for Brazilian Portuguese are recommended by cognitive domain based on available data.

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

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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.

Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

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Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian; Zhou, Juan

2017-11-01

Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our

Microprobe PIXE analysis and EDX analysis on the brain of patients with Alzheimer`s disease

Energy Technology Data Exchange (ETDEWEB)

Yumoto, S. [Tokyo Univ. (Japan). Faculty of Medicine; Horino, Y.; Mokuno, Y.; Fujii, K.; Kakimi, S.; Mizutani, T.; Matsushima, H.; Ishikawa, A.

1996-12-31

To investigate the cause of Alzheimer`s disease (senile dementia of Alzheimer`s disease type), we examined aluminium (Al) in the brain (hippocampus) of patients with Alzheimer`s disease using heavy ion (5 MeV Si{sup 3+}) microprobe particle-induced X-ray emission (PIXE) analysis. Heavy ion microprobes (3 MeV Si{sup 2+}) have several times higher sensitivity for Al detection than 2 MeV proton microprobes. We also examined Al in the brain of these patients by energy dispersive X-ray spectroscopy (EDX). (1) Al was detected in the cell nuclei isolated from the brain of patients with Alzheimer`s disease using 5 MeV Si{sup 3+} microprobe PIXE analysis, and EDX analysis. (2) EDX analysis demonstrated high levels of Al in the nucleolus of nerve cells in frozen sections prepared from the brain of these patients. Our results support the theory that Alzheimer`s disease is caused by accumulation of Al in the nuclei of brain cells. (author)

Alzheimer's Disease Facts and Figures

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Full Text Available ... get Alzheimer's disease were diagnosed in the mild cognitive impairment (MCI) stage — before dementia — it would collectively save $7 trillion to $7.9 trillion in health and long-term care costs. worried about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts ...

A rivastigmine patch for the treatment of Alzheimer's disease and Parkinson's disease dementia.

Science.gov (United States)

Cummings, Jeffrey; Winblad, Bengt

2007-11-01

Rivastigmine patch is the first transdermal treatment to be approved for Alzheimer's disease (AD) and Parkinson's disease dementia in the USA and for AD in Europe. It provides smooth, continuous drug delivery, and has the potential to maintain rivastigmine concentrations within an optimal therapeutic window while avoiding the peaks and troughs associated with oral drug delivery. The target dose, rivastigmine 9.5 mg/24 h patch (a 10 cm(2) patch), is given once daily and requires a simple one-step dose titration to the therapeutic dose. In a 24-week study in 1195 AD patients, the rivastigmine 9.5 mg/24 h patch provided similar efficacy to the highest dose range of capsules, with approximately three-times fewer reports of nausea and vomiting. Patients in the 9.5 mg/24 h patch and 12 mg/day capsule groups evidenced significant improvements versus placebo on both primary outcome measures: the Alzheimer's Disease Assessment Scale-Cognitive subscale; and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change; in addition to the following secondary outcome measures: Alzheimer's Disease Cooperative Study-Activities of Daily Living scale; Mini-Mental State Examination; and Trail Making Test Part A for assessment of attention, visual tracking and motor processing speed. Treatment differences on the Neuropsychiatric Inventory and Ten Point Clock-drawing Test did not reach statistical significance in this study. The patch may be the optimal way to treat dementia patients with rivastigmine.

Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer's disease and vascular dementia.

Science.gov (United States)

Thomas, Taya; Miners, Scott; Love, Seth

2015-04-01

Perfusion is reduced in the cerebral neocortex in Alzheimer's disease. We have explored some of the mechanisms, by measurement of perfusion-sensitive and disease-related proteins in post-mortem tissue from Alzheimer's disease, vascular dementia and age-matched control brains. To distinguish physiological from pathological reduction in perfusion (i.e. reduction exceeding the decline in metabolic demand), we measured the concentration of vascular endothelial growth factor (VEGF), a protein induced under conditions of tissue hypoxia through the actions of hypoxia-inducible factors, and the myelin associated glycoprotein to proteolipid protein 1 (MAG:PLP1) ratio, which declines in chronically hypoperfused brain tissue. To evaluate possible mechanisms of hypoperfusion, we also measured the levels of amyloid-β40, amyloid-β42, von Willebrand factor (VWF; a measure of microvascular density) and the potent vasoconstrictor endothelin 1 (EDN1); we assayed the activity of angiotensin I converting enzyme (ACE), which catalyses the production of another potent vasoconstrictor, angiotensin II; and we scored the severity of arteriolosclerotic small vessel disease and cerebral amyloid angiopathy, and determined the Braak tangle stage. VEGF was markedly increased in frontal and parahippocampal cortex in Alzheimer's disease but only slightly and not significantly in vascular dementia. In frontal cortex the MAG:PLP1 ratio was significantly reduced in Alzheimer's disease and even more so in vascular dementia. VEGF but not MAG:PLP1 increased with Alzheimer's disease severity, as measured by Braak tangle stage, and correlated with amyloid-β42 and amyloid-β42: amyloid-β40 but not amyloid-β40. Although MAG:PLP1 tended to be lowest in cortex from patients with severe small vessel disease or cerebral amyloid angiopathy, neither VEGF nor MAG:PLP1 correlated significantly with the severity of structural vascular pathology (small vessel disease, cerebral amyloid angiopathy or VWF

Active Vaccines for Alzheimer Disease Treatment.

Science.gov (United States)

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.

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

Science.gov (United States)

2017-05-11

Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

Deconstructing Mitochondrial Dysfunction in Alzheimer Disease

Directory of Open Access Journals (Sweden)

Vega García-Escudero

2013-01-01

Full Text Available There is mounting evidence showing that mitochondrial damage plays an important role in Alzheimer disease. Increased oxygen species generation and deficient mitochondrial dynamic balance have been suggested to be the reason as well as the consequence of Alzheimer-related pathology. Mitochondrial damage has been related to amyloid-beta or tau pathology or to the presence of specific presenilin-1 mutations. The contribution of these factors to mitochondrial dysfunction is reviewed in this paper. Due to the relevance of mitochondrial alterations in Alzheimer disease, recent works have suggested the therapeutic potential of mitochondrial-targeted antioxidant. On the other hand, autophagy has been demonstrated to play a fundamental role in Alzheimer-related protein stress, and increasing data shows that this pathway is altered in the disease. Moreover, mitochondrial alterations have been related to an insufficient clearance of dysfunctional mitochondria by autophagy. Consequently, different approaches for the removal of damaged mitochondria or to decrease the related oxidative stress in Alzheimer disease have been described. To understand the role of mitochondrial function in Alzheimer disease it is necessary to generate human cellular models which involve living neurons. We have summarized the novel protocols for the generation of neurons by reprogramming or direct transdifferentiation, which offer useful tools to achieve this result.

Cognitive Assessment of Patients With Alzheimer's Disease by Telemedicine: Pilot Study

Science.gov (United States)

Carotenuto, Anna; Rea, Raffaele; Ricci, Giovanna; Fasanaro, Angiola Maria; Amenta, Francesco

2018-01-01

Background Approximately 46.8 million people are living with dementia worldwide and their number will grow in the next years. Any potential treatment should be administered as early as possible because it is important to provide an early cognitive assessment and to regularly monitor the mental function of patients. Information and communication technologies can be helpful to reach and follow patients without displacing them, but there may be doubts about the reliability of cognitive tests performed by telemedicine. Objective The purpose of this study was to evaluate the reliability of the Mini Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog) tests administered in hospital by videoconference to patients with mild to moderate Alzheimer's disease. Methods The tests were administered to 28 Alzheimer's disease outpatients (8 male, mean age 73.88, SD 7.45 years; 20 female mean age 76.00, SD 5.40 years) recruited and followed in the Alzheimer’s Unit of the A Cardarelli National Hospital (Naples, Italy) at baseline and after 6, 12, 18, and 24 months of observation. Patients were evaluated first face-to-face by a psychologist and then, after 2 weeks, by another psychologist via videoconference in hospital. Results This study showed no differences in the MMSE and ADAS-cog scores when the tests were administered face-to-face or by videoconference, except in patients with more pronounced cognitive deficits (MMSE<17), in which the assessment via videoconference overestimated the cognitive impairment (face to face, MMSE mean 13.9, SD 4.9 and ADAS-cog mean 9.0, SD 3.8; videoconference, MMSE mean 42.8, SD 12.5 and ADAS-cog mean 56.9, SD 5.5). Conclusions We found that videoconferencing is a reliable approach to document cognitive stability or decline, and to measure treatment effects in patients with mild to moderate dementia. A more extended study is needed to confirm these results. PMID:29752254

Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial.

Science.gov (United States)

Scheltens, Philip; Kamphuis, Patrick J G H; Verhey, Frans R J; Olde Rikkert, Marcel G M; Wurtman, Richard J; Wilkinson, David; Twisk, Jos W R; Kurz, Alexander

2010-01-01

To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD). A total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale-revised, and the 13-item modified Alzheimer's Disease Assessment Scale-cognitive subscale at week 12. At 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale-cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study-Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated. Supplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials. 2010 The Alzheimer's Association. All rights reserved.

[Anesthesia and Alzheimer disease - Current perceptions].

Science.gov (United States)

Marques, Ana Filipa Vieira da Silva Ferreira; Lapa, Teresa Alexandra Santos Carvalho

It has been speculated that the use of anesthetic agents may be a risk factor for the development of Alzheimer disease. The objective of this review is to describe and discuss pre-clinical and clinical data related to anesthesia and this disease. Alzheimer disease affects about 5% of the population over 65 years old, with age being the main risk factor and being associated with a high morbidity. Current evidence questions a possible association between anesthesia, surgery, and long-term cognitive effects, including Alzheimer disease. Although data from some animal studies suggest an association between anesthesia and neurotoxicity, this link remains inconclusive in humans. We performed a review of the literature in which we selected scientific articles in the PubMed database, published between 2005 and 2016 (one article from 1998 due to its historical relevance), in English, which address the possible relationship between anesthesia and Alzheimer disease. 49 articles were selected. The possible relationship between anesthetic agents, cognitive dysfunction, and Alzheimer disease remains to be clarified. Prospective cohort studies or randomized clinical trials for a better understanding of this association will be required. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Sex differences in cognitive impairment and Alzheimer's disease.

Science.gov (United States)

Li, Rena; Singh, Meharvan

2014-08-01

Studies have shown differences in specific cognitive ability domains and risk of Alzheimer's disease between the men and women at later age. However it is important to know that sex differences in cognitive function during adulthood may have their basis in both organizational effects, i.e., occurring as early as during the neuronal development period, as well as in activational effects, where the influence of the sex steroids influence brain function in adulthood. Further, the rate of cognitive decline with aging is also different between the sexes. Understanding the biology of sex differences in cognitive function will not only provide insight into Alzheimer's disease prevention, but also is integral to the development of personalized, gender-specific medicine. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of sex differences in cognitive function from young to old, and examines the effects of sex hormone treatments on Alzheimer's disease in men and women. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical Application of 18F-FDG PET in Alzheimer's Disease

International Nuclear Information System (INIS)

Ryu, Young Hoon

2008-01-01

PET of the cerebral metabolic rate of glucose is increasingly used to support the clinical diagnosis in the examination of patients with suspected major neurodegenerative disorders, such as Alzheimer's disease. 18 F-FDG PET has been reported to have high diagnostic performance, especially, very high sensitivity in the diagnosis and clinical assessment of therapeutic efficacy. According to clinical research data hitherto, 18 F-FDG PET is expected to be an effective diagnostic tool in early and differential diagnosis of Alzheimer's disease. Since 2004, Medicare covers 18 F-FDG PET scans for the differential diagnosis of fronto-temporal dementia (FTD) and Alzheimer's disease (AD) under specific requirements; or, its use in a CMS approved practical clinical trial focused on the utility of 18 F-FDG PET in the diagnosis or treatment of dementing neurodegenerative diseases

Specific deficit of colour-colour short-term memory binding in sporadic and familial Alzheimer's disease.

Science.gov (United States)

Parra, Mario A; Sala, Sergio Della; Abrahams, Sharon; Logie, Robert H; Méndez, Luis Guillermo; Lopera, Francisco

2011-06-01

Short-term memory binding of visual features which are processed across different dimensions (shape-colour) is impaired in sporadic Alzheimer's disease, familial Alzheimer's disease, and in asymptomatic carriers of familial Alzheimer's disease. This study investigated whether Alzheimer's disease also impacts on within-dimension binding processes. The study specifically explored whether visual short-term memory binding of features of the same type (colour-colour) is sensitive to Alzheimer's disease. We used a neuropsychological battery and a short-term memory binding task to assess patients with sporadic Alzheimer's disease (Experiment 1), familial Alzheimer's disease (Experiment 2) due to the mutation E280A of the Presenilin-1 gene and asymptomatic carriers of the mutation. The binding task assessed change detection within arrays of unicoloured objects (Colour Only) or bicoloured objects the colours of which had to be remembered separately (Unbound Colours) or together (Bound Colours). Performance on the Bound Colours condition (1) explained the largest proportion of variance between patients (sporadic and familial Alzheimer's disease), (2) combined more sensitivity and specificity for the disease than other more traditional neuropsychological tasks, (3) identified asymptomatic carriers of the mutation even when traditional neuropsychological measures and other measures of short-term memory did not and, (4) contrary to shape-colour binding, correlated with measures of hippocampal functions. Colour-colour binding and shape-colour binding both appear to be sensitive to AD even though they seem to rely on different brain mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Preclinical MRI and NMR Bio-markers of Alzheimer's Disease: Concepts and Applications

International Nuclear Information System (INIS)

Dhenain, M.; Dhenain, M.; Dhenain, M.

2008-01-01

Alzheimer's disease is an important social and economic issue for our societies. The development of therapeutics against this severe dementia requires assessing the effects of new drugs in animal models thanks to dedicated bio-markers. This review first overviews Alzheimer's disease and its models as well as the concept of bio-markers. It then focuses on MRI and NMR bio-markers of Alzheimer's disease in animals. Anatomical markers such as atrophy and angiography are useful to phenotype newly developed models of Alzheimer's disease, even if the alterations in these animals are not as severe as in humans. Amyloid plaques imaging is a promising marker of the pathology in animals, and is a rapidly evolving field of MRI. Functional methods such as perfusion and diffusion imaging or spectroscopy are able to detect alterations in transgenic mice mimicking Alzheimer and also to show similar alterations than in humans. They can thus be good translational markers of the disease. Manganese-Enhanced MRI shows a reduction of neuronal transportation in transgenic models of Alzheimer and it allows monitoring improvements induced by treatments of the disease. It is thus a promising bio-marker of the pathology in animals. (authors)

Alzheimer's disease: studies of diagnosis and therapy

NARCIS (Netherlands)

J.J. Claus (Jules Johan)

1993-01-01

textabstractDespite tremendous recent advances in the clinical neurology, neurobiology and epidemiology of Alzheimer's disease, the cause as well as its treatment remains as much a mystery today as when it was first described in 1907 by Alois Alzheimer.' Alzheimer's disease, the most common type

beta. -Amyloid gene dosage in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E

1988-01-11

The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

Synaptic changes in Alzheimer's disease in vivo

International Nuclear Information System (INIS)

Mueller-Gaertner, H.W.

1994-01-01

The article describes the current knowledge on biochemical changes in Alzheimer's disease. Following a summary on post mortem findings, results from positron emission tomography will be focused on. This synopsis shows that patients with Alzheimer's disease show very consistently changes in the cholinergic transmission. In addition to this, changes of the dopaminergic, noradrenergic and serotonergic system are observed. It is possible, that clinical, pathological and functional differences in Alzheimer's disease between different patients reflect variations of a single disease process. It is also thinkable, that there are subclassifications in Alzheimer's disease which are reflected in the above described biochemical abnormalities. In this case it is important in therapeutical terms to investigate these subtypes. (orig.) [de

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

Science.gov (United States)

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

2016-01-01

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

Alzheimer's Disease Facts and Figures

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Full Text Available ... Join the Cause alz.org >> Alzheimer's & Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: Download the Infographic: English Spanish Share the ...

Recruitment of subjects into clinical trials for Alzheimer disease.

Science.gov (United States)

Knebl, Janice A; Patki, Deepti

2010-09-01

Alzheimer disease is a devastating neurodegenerative disorder affecting millions of Americans. It reduces the ability of the individual to remain independent, places a burden on caregivers, and substantially increases healthcare costs. New treatments are being tested in numerous clinical trials with the goal of preventing or delaying the onset of Alzheimer disease, slowing or modifying the disease's course, or finding a cure for patients with the disease. Alzheimer disease research can successfully proceed only if individuals who have this illness are willing to participate in clinical trials. However, recruitment and retention of subjects in clinical trials for Alzheimer disease is a challenging task. Furthermore, because of reductions in decision-making capacities of individuals with Alzheimer disease, clinical trials also need to involve caregivers. The present article delineates unique hurdles encountered in the recruitment process for Alzheimer disease clinical trials. The article also identifies strategies for effective recruitment of subjects in Alzheimer disease clinical trials, including guidelines to help principal investigators and clinical research coordinators reach recruitment goals.

Alzheimer's Disease Facts and Figures

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Full Text Available ... of Alzheimer's. Today, someone in the United States develops Alzheimer's every 65 seconds. By mid-century, someone in the United States will develop the disease every 33 seconds. GET INVOLVED. Join ...

Alzheimer's Disease Facts and Figures

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... Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of the help ...

Alzheimer's Disease Facts and Figures

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Full Text Available ... existing cases of Alzheimer's. Today, someone in the United States develops Alzheimer's every 65 seconds. By mid-century, someone in the United States will develop the disease every 33 seconds. GET ...

Asbestos exposure and Alzheimer disease

Energy Technology Data Exchange (ETDEWEB)

Bianchi, C; Bittesini, L; Brollo, A

1986-02-01

10 cases in which an asbestos-related disease (malignant pleural mesothelioma or asbestosis) was associated with severe Alzheimer type lesions in the brain are reported. The patients, all males aged between 67 and 78 years, had been occupationally exposed to asbestos in the shipbuilding industry. The hypothesis that asbestos is a favoring factor in the genesis of Alzheimer disease is discussed.

Down Syndrome and Alzheimer's Disease

Science.gov (United States)

... 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 ...

Melanopsin retinal ganglion cell loss in Alzheimer's disease

DEFF Research Database (Denmark)

La Morgia, Chiara; Ross-Cisneros, Fred N; Koronyo, Yosef

2015-01-01

OBJECTIVE: Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer's disease (AD). We investigated mRGCs in AD, hypothesizing their contribution to circadian dysfunction. METHODS: We assessed retinal nerve...

Perception of Alzheimer Disease in Iranian Traditional Medicine.

Science.gov (United States)

Saifadini, Rostam; Tajadini, Haleh; Choopani, Rasool; Mehrabani, Mitra; Kamalinegad, Mohamad; Haghdoost, Aliakbar

2016-03-01

Alzheimer disease (AD) is the most common cause of dementia. In regards to the world's aging population, control and treatment of AD will be one of the major concerns of global public health in the next century. Alzheimer disease was not mentioned with the same phrase or its equivalent in traditional medical texts. The main of present paper was to investigate symptoms and causes of alzheimer disease from the view point of Iranian traditional medicine. In this qualitative study, we searched reliable sources of Iranian traditional medicine such as Canon of Medicide by Avicenna (Al-Quanon fi- tibb), Aghili cure by Aghili's (Molajat-E-aghili), Tib-E-Akbari, Exire -E-Aazam and Sharh-E-Asbab and some reliable resources of neurology were probed base on keywords to find a disease that had the most overlap in terms of symptoms with alzheimer disease. By taking from the relevant materials, the extracted texts were compared and analyzed. Findings showed that alzheimer disease has the most overlap with Nesyan (fisad-e-zekr, fisad-e-fekr and fisad-e-takhayol) symptoms in Iranian traditional medicine. Although this is not a perfect overlap and there are causes, including coldness and dryness of the brain or coldness and wetness that could also lead to alzheimer disease according to Iranian traditional medicine. According to Iranian traditional medicine, The brain dystemperement is considered the main causes of alzheimer disease. By correcting the brain dystemperement, alzheimer can be well managed. This study helps to suggest a better strategy for preventing and treating alzheimer in the future.

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

Science.gov (United States)

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…

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.

Science.gov (United States)

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

Alzheimer's Disease Facts and Figures

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Full Text Available ... Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of the help ...

Alzheimer's Disease Facts and Figures

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Full Text Available ... Help | Join the Cause alz.org >> Alzheimer's & Dementia >> Home Text size: A A A 2018 Alzheimer's Disease ... people who receive adult day services and nursing home care. Take action. Become an advocate SPECIAL REPORT: ...

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

Science.gov (United States)

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.

Galantamine for Alzheimer's disease.

Science.gov (United States)

Olin, J; Schneider, L

2001-01-01

Galantamine (also called galanthamine, marketed as Reminyl (Janssen)) can be isolated from several plants, including daffodil bulbs, and 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, and recently several multicentre clinical trials have been published with positive findings. Galantamine has received regulatory approval in Sweden, is available in Austria, and awaits marketing approval in the United States, Europe, and other countries. The objective of this review is to assess the clinical effects of galantamine in patients with probable Alzheimer's disease, and to investigate potential moderators of an effect. The Cochrane Dementia Group specialized register of clinical trials was searched using the terms 'galantamine,' and 'galanthamine' (15 February 2000) as was the Cochrane Controlled Trials Register (2000, Issue 2). These terms were also used to search the following databases: EMBASE, MEDLINE, PsychLit; Combined Health Information Database, NRR (National Research Register), ADEAR (Alzheimer's Disease Education and Referral Centre clinical database, BIOMED (Biomedicine and Health), Glaxo-Wellcome Clinical Trials Register, National Institutes of Health Clinical Trials Databases, Current Controlled Trials, Dissertation Abstracts (mainly North American dissertations) 1961-1994, Index to UK Theses (British dissertations) 1970-1994. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. Trials selected were randomized, double-blind, parallel-group, and unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in people with Alzheimer

Modern approach in the therapy of Alzheimer's disease

Directory of Open Access Journals (Sweden)

D. I. Rodin

2014-01-01

Full Text Available Alzheimer's disease is a well-known neurodegenerative disorder. One of its main risk factors is age. Due to a worldwide increase of human longevity Alzheimer's disease became the most common form of dementia. The disease has been studied in different countries for many decades but still its etiology remains unclear. By now there is no cure for Alzheimer's, moreover there are no that can at least slow down the disease progression. In this review we made an attempt to summarize all current studies of the most advanced drugs for Alzheimer's.

7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine

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... of this page please turn Javascript on. Feature: Alzheimer's Disease 7 Warning Signs of Alzheimer's Past Issues / Fall 2010 Table of Contents The ... Suncoast Gerontology Center, University of South Florida. How Alzheimer's Changes the Brain The only definite way to ...

Alzheimer's Disease Facts and Figures

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Full Text Available ... SPECIAL REPORT: FINANCIAL AND PERSONAL BENEFITS OF EARLY DIAGNOSIS Early diagnosis of Alzheimer's provides a number of important benefits ... to detect Alzheimer's disease and provide an accurate diagnosis earlier than at any other time in history. ...

Alzheimer's Disease Facts and Figures

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Full Text Available ... health and long-term care costs. worried about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts ... is a not-for-profit 501(c)(3) organization. Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our ...

CT study in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Arai, Heii; Kobayashi, Kazunari; Ikeda, Kenji; Nagao, Yoshiko; Ogihara, Ryuji; Kosaka, Kenji [Tokyo Metropolitan Matsuzawa Hospital (Japan)

1983-01-01

Cerebral atrophy on CT was studied in 18 patients with clinically diagnosed Alzheimer's disease and in 14 healthy age-matched subjects as the control. The patients with Alzheimer's disease were divided into three groups of Stages I, II and III, according to their clinical symptoms. The study of the measurement method disclosed that the computerized measurement involving calculation of the number of pixels contained within the range of the designated CT numbers is liable to produce errors for the determination of the subarachnoid spaces and the ventricles with calcified colloid plexus. Therefore, for the present study was the method adopted, in which the subarachnoid spaces and the ventricles are measured based on the number of pixels contained in the region of interest by tracing them on the display monitor. Then, both Subarachnoid Space Volume Index (SVI) and Ventricle Volume Index (VVI) were calculated as the indices for cortical atrophy and ventricular dilatation in a slice through the level of the foramen interventriculare Monroi and other three successive ones through upper regions. Cerebral atrophy observed on CT in Alzheimer patients is attributable to Alzheimer's disease processes, rather than to physiological aging of the brain. The degree of the atrophy increases in proportion to the clinical stage, and cortical atrophy is apparent even at Stage I, whereas ventricular dilatation becomes pronounced at later stage. CT is one of effective clinical tests for the diagnosis of Alzheimer's disease.

CT study in Alzheimer's disease

International Nuclear Information System (INIS)

Arai, Heii; Kobayashi, Kazunari; Ikeda, Kenji; Nagao, Yoshiko; Ogihara, Ryuji; Kosaka, Kenji

1983-01-01

Cerebral atrophy on CT was studied in 18 patients with clinically diagnosed Alzheimer's disease and in 14 healthy age-matched subjects as the control. The patients with Alzheimer's disease were divided into three groups of Stages I, Ii and III, according to their clinical symptoms. The study of the measurement method disclosed that the computerized measurement involving calculation of the number of pixels contained within the range of the designated CT numbers is liable to produce errors for the determination of the subarachnoid spaces and the ventricles with calcified colloid plexus. Therefor, for the present study was the method adopted, in which the subarachnoid spaces and the ventricles are measured based on the number of pixels contained in the region of interest by tracing them on the display monitor. Then, both Subarachnoid Space Volume Index (SVI) and Ventricle Volume Index (VVI) were calculated as the indices for cortical atrophy and ventricular dilatation in a slice through the level of the foramen interventriculare Monroi and other three successive ones through upper regions. Cerebral atrophy observed on CT in Alzheimer patients is attributable to Alzheimer's disease processes, rather than to physiological aging of the brain. The degree of the atrophy increases in proportion to the clinical stage, and cortical atrophy is apparent even at Stage I, whereas ventricular dilatation becomes pronounced at later stage. CT is one of effective clinical tests for the diagnosis of Alzheimer's disease. (J.P.N.)

[Nutritional approaches to modulate oxidative stress that induce Alzheimer's disease. Nutritional approaches to prevent Alzheimer's disease].

Science.gov (United States)

Lara, Humberto Herman; Alanís-Garza, Eduardo Javier; Estrada Puente, María Fernanda; Mureyko, Lucía Liliana; Alarcón Torres, David Alejandro; Ixtepan Turrent, Liliana

2015-01-01

Alzheimer's disease is the most common cause of dementia in the world; symptoms first appear after age 65 and have a progressive evolution. Expecting an increase on its incidence and knowing there is currently no cure for Alzheimer's disease, it is a necessity to prevent progression. The change in diet due to globalization may explain the growth of the incidence in places such as Japan and Mediterranean countries, which used to have fewer incidences. There is a direct correlation between disease progression and the increased intake of alcohol, saturated fats, and red meat. Therefore, we find obesity and higher serum levels in cholesterol due to saturated fat as a result. A way to decrease the progression of Alzheimer's is through a diet rich in polipheno/es (potent antioxidants), unsaturated fats (monounsaturated and polyunsaturated), fish, vegetable fa t, fruits with low glycemic index, and a moderate consumption of red wine. Through this potent antioxidant diet we accomplish the prevention of dementia and the progression of Alzheimer's disease. This article emphasizes the food and other components that have been demonstrated to decrease the oxidative stress related to these progressive diseases.

Estrogen and early-onset Alzheimer's disease

NARCIS (Netherlands)

A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cornelia); J.C.M. Witteman (Jacqueline)

1999-01-01

textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of

Inflammatory mechanisms in Alzheimer's disease

NARCIS (Netherlands)

Eikelenboom, P.; Zhan, S. S.; van Gool, W. A.; Allsop, D.

1994-01-01

Alzheimer's disease is aetiologically heterogeneous, but the pathogenesis is often considered to be initiated by the deposition of amyloid fibrils, followed by neuritic tau pathology and neuronal death. A variety of inflammatory proteins has been identified in the brains of patients with Alzheimer's

Memory binding and white matter integrity in familial Alzheimer's disease.

Science.gov (United States)

Parra, Mario A; Saarimäki, Heini; Bastin, Mark E; Londoño, Ana C; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

2015-05-01

Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to

A disease state fingerprint for evaluation of Alzheimer's disease

DEFF Research Database (Denmark)

Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho

2011-01-01

Diagnostic processes of Alzheimer's disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization...... interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease...

Serotonin 6 receptor controls alzheimer?s disease and depression

OpenAIRE

Yun, Hyung-Mun; Park, Kyung-Ran; Kim, Eun-Cheol; Kim, Sanghyeon; Hong, Jin Tae

2015-01-01

Alzheimer?s disease (AD) and depression in late life are one of the most severe health problems in the world disorders. Serotonin 6 receptor (5-HT6R) has caused much interest for potential roles in AD and depression. However, a causative role of perturbed 5-HT6R function between two diseases was poorly defined. In the present study, we found that a 5-HT6R antagonist, SB271036 rescued memory impairment by attenuating the generation of A? via the inhibition of ?-secretase activity and the inact...

Developing novel blood-based biomarkers for Alzheimer's disease

DEFF Research Database (Denmark)

Snyder, Heather M; Carrillo, Maria C; Grodstein, Francine

2014-01-01

Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue...... of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant...

Assessment of socioemotional processes facilitates the distinction between frontotemporal lobar degeneration and Alzheimer's disease.

Science.gov (United States)

Narme, Pauline; Mouras, Harold; Roussel, Martine; Devendeville, Agnès; Godefroy, Olivier

2013-01-01

We explored the value of a battery of socioemotional tasks for differentiating between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Patients with FTLD (n = 13) or AD (n = 13) and healthy controls (n = 26) underwent a neuropsychological assessment and the socioemotional battery (an empathy questionnaire, an emotion recognition task, and theory of mind tasks). Socioemotional processes were markedly impaired in FTLD but relatively unaffected in mild AD. The computed Socioemotional Index discriminated more accurately between FTLD from AD than behavioral and executive assessments did. Furthermore, impairments in socioemotional processes were correlated with indifference to others.

Homocysteine, antioxidant vitamins and lipids as biomarkers of neurodegeneration in Alzheimer's disease versus non-Alzheimer's dementia.

Science.gov (United States)

Raszewski, Grzegorz; Chwedorowicz, Roman; Chwedorowicz, Agnieszka; Gustaw Rothenberg, Katarzyna

2016-01-01

Evidence for the benefit of antioxidants' based therapeutic intervention in dementia are inconsistent. Parallel studies in disease forms of dementia different than Alzheimer's are even less conclusive. In this study, the role of serum levels of homocysteine (tHcy), lipids and antioxidants in predicting the risk of cognitive decline in Alzheimer's disease (AD) versus non-Alzheimer's dementias (n-AD). The objective was to add to the ongoing cumulative research to establish the biochemical baseline for potential nutri-therapeutic intervention in different forms of dementia. 65 participants with dementia (DP-s) were divided into two groups: ADP--patients with Alzheimer's disease and n-ADP--patients with dementia of a different etiology than primary neurodegenerative dementia in the course of Alzheimer's disease. Cognitive function was assessed by Mini-Mental State Examination (MMSE) and related to plasma levels of tHcy, folate, vitamins B-6, B-12, lipids and vitamins A and E for both groups. Also examined were associations between cognitive impairment and several variables (age, education, duration of dementia) that might confound nutrition-cognition associations. A significant reduction in serum vitamin A levels and elevation of total cholesterol levels were shown for the DP-s group compared to those in the control group. Moreover, significant differences were found in MMSE data and serum vitamin E and tHcy levels between patients with ADP and n-ADP. The scores for MMSE showed a correlation with the vitamin E levels and duration of dementia in the ADP group and/or correlation with tHcy, levels of vitamins A and/or E, and duration of dementia in the n-ADP group. The results obtained suggest that elevated serum tHcy and decreased levels of vitamins A and E are associated with an increased risk of non-Alzheimer's dementias, although further studies involving a larger cohort are now needed to verify these results.

Small vessel disease is linked to disrupted structural network covariance in Alzheimer's disease.

Science.gov (United States)

Nestor, Sean M; Mišić, Bratislav; Ramirez, Joel; Zhao, Jiali; Graham, Simon J; Verhoeff, Nicolaas P L G; Stuss, Donald T; Masellis, Mario; Black, Sandra E

2017-07-01

Cerebral small vessel disease (SVD) is thought to contribute to Alzheimer's disease (AD) through abnormalities in white matter networks. Gray matter (GM) hub covariance networks share only partial overlap with white matter connectivity, and their relationship with SVD has not been examined in AD. We developed a multivariate analytical pipeline to elucidate the cortical GM thickness systems that covary with major network hubs and assessed whether SVD and neurodegenerative pathologic markers were associated with attenuated covariance network integrity in mild AD and normal elderly control subjects. SVD burden was associated with reduced posterior cingulate corticocortical GM network integrity and subneocorticocortical hub network integrity in AD. These findings provide evidence that SVD is linked to the selective disruption of cortical hub GM networks in AD brains and point to the need to consider GM hub covariance networks when assessing network disruption in mixed disease. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Mitophagy and Alzheimer's Disease

DEFF Research Database (Denmark)

Kerr, Jesse S.; Adriaanse, Bryan A.; Greig, Nigel H.

2017-01-01

Neurons affected in Alzheimer's disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged...

Turning principles into practice in Alzheimer's disease

NARCIS (Netherlands)

Lindesay, J.; Bullock, R.; Daniels, H.; Emre, M.; Foerstl, H.; Froelich, L.; Gabryelewicz, T.; Martinez-Lage, P.; Monsch, A. U.; Tsolaki, M.; van Laar, T.

P>The prevalence of dementia is reaching epidemic proportions globally, but there remain a number of issues that prevent people with dementia, their families and caregivers, from taking control of their condition. In 2008, Alzheimer's Disease International (ADI) launched a Global Alzheimer's Disease

Unraveling Alzheimer?s: Making Sense of the Relationship between Diabetes and Alzheimer?s Disease 1

OpenAIRE

Schilling, Melissa A.

2016-01-01

Numerous studies have documented a strong association between diabetes and Alzheimer?s disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intra...

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.

Science.gov (United States)

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.

Knowledge and pharmacological management of Alzheimer's disease by managing community pharmacists: a nationwide study.

Science.gov (United States)

Zerafa, Natalie; Scerri, Charles

2016-12-01

Background Managing community pharmacists can play a leading role in supporting community dwelling individuals with Alzheimer's disease and their caregivers. Objective The main purpose of this study was to assess knowledge of managing community pharmacists towards Alzheimer's disease and its pharmacological management. Setting Community pharmacies in the Maltese islands. Method A nationwide survey was conducted with full-time managing community pharmacists in possession of a tertiary education degree in pharmacy studies. The level of knowledge was investigated using the Alzheimer's Disease Knowledge Scale and the Alzheimer's Disease Pharmacotherapy Measure. Participants were also asked to rate a number of statements related to disease management. Results Maltese managing community pharmacists (57 % response rate) had inadequate knowledge on risk factors, caregiving issues and pharmacological management of Alzheimer's disease. Age and number of years working in a community pharmacy setting were found to be negatively correlated with increased knowledge. Conclusion The findings highlight the need of providing training and continued educational support to managing community pharmacists in order to provide quality advice to individuals with dementia and their caregivers in the community.

Ophthalmic examination in early diagnosis of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Xin Li

2018-02-01

Full Text Available Alzheimer's disease is a progressive neurodegenerative disorder causing irreversible deterioration in memory and loss of self-care ability, which is seriously affecting the quality of life. There is no cure for Alzheimer's disease. Medication only can control the progression of the disease. Early diagnosis and control of disease progress is of great significance in improving the quality of life of the patients and reducing the burden of family and society. Ophthalmic examination is seen as a window which can “see” brain directly, and some changes in the eye can reflect the changes of the brain most directly. This paper reviews the ophthalmic examination of Alzheimer's disease, including optical coherence tomography(OCT, visual field, contrast sensitivity and eye movements, et al. We hope to provide a new idea for the early diagnosis of Alzheimer's disease.

Computational representation of Alzheimer's disease evolution applied to a cooking activity.

Science.gov (United States)

Serna, Audrey; Rialle, Vincent; Pigot, Hélène

2006-01-01

This article presents a computational model and a simulation of the decrease of activities of daily living performances due to Alzheimer's disease. The disease evolution is simulated thanks to the cognitive architecture ACT-R. Activities are represented according to the retrieval of semantic units in declarative memory and the trigger of rules in procedural memory. The simulation of Alzheimer's disease decrease is simulated thanks to the variation of subsymbolic parameters. The model is applied to a cooking activity. Simulation of 100 hundred subjects shows results similar to those realised in a standardized assessment with human subjects.

Risk profiles of Alzheimer disease.

Science.gov (United States)

Bilbul, Melanie; Schipper, Hyman M

2011-07-01

Alzheimer disease (AD) is a dementing, neurodegenerative disorder that affects approximately 500,000 Canadians and its prevalence is expected to double over the next 30 years. Although several medications may temporarily augment cognitive abilities in AD, there presently exists no proven method to avoid the inevitable clinical deterioration in this devastating condition. The delineation of risk factors for the development of AD offers hope for the advent of effective prevention or interventions that might retard the onset of symptoms. In this article, we provide a comprehensive review of midlife risk factors implicated in the etiopathogenesis of sporadic AD. Although some risk factors are heritable and largely beyond our control, others are determined by lifestyle or environment and are potentially modifiable. In a companion paper, we introduce the concept of an Alzheimer Risk Assessment Clinic for ascertainment and mitigation of these and other putative dementia risk factors in middle-aged adults.

Neuroinflammation and Alzheimer disease: clinical and therapeutic implications

NARCIS (Netherlands)

Eikelenboom, P.; Rozemuller, A. J.; Hoozemans, J. J.; Veerhuis, R.; van Gool, W. A.

2000-01-01

In Alzheimer disease brains, the amyloid plaques are closely associated with a locally induced, nonimmune-mediated, chronic inflammatory response without any apparent influx of leukocytes from the blood. The present findings indicate that in cerebral A beta diseases (Alzheimer disease, Down

[Anti-ageing therapies in Alzheimer's disease].

Science.gov (United States)

Alonso Abreu, Gara S; Brito Armas, José M; Castro Fuentes, Rafael

Alzheimer's disease is the most common cause of dementia in the elderly population. Currently, there are no effective treatments to prevent or delay the natural course of the disease. Numerous studies have provided information about the molecular processes underlying biological ageing and, perhaps more importantly, potential interventions to slow ageing and promote healthy longevity in laboratory model systems. The main issue addressed in this review is whether an intervention that has anti-ageing properties can alter the appearance and/or progression of Alzheimer's disease, a disease in which age is the biggest risk factor. Different anti-ageing interventions have been shown to prevent (and in some cases possibly restore) several parameters recognised as central symptoms to the development of Alzheimer's disease. In addition, they are taking the first steps towards translating these laboratory discoveries into clinical applications. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Science.gov (United States)

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

Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

Science.gov (United States)

Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

2017-09-01

Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

Developing injectable immunoglobulins to treat cognitive impairment in Alzheimer's disease.

Science.gov (United States)

Steinitz, Michael

2008-05-01

Alzheimer's disease is a devastating disorder, clinically characterized by a comprehensive cognitive decline. The novel strategy of anti-amyloid-beta immunotherapy has been suggested following encouraging results obtained in murine models of Alzheimer's disease, in non-human primates, and in small-scale clinical trials. To examine the choice between active or passive anti-amyloid-beta immunization and the choice of the molecule to which the immune machinery should be targeted, which are central issues in future immune therapy of Alzheimer's disease. Research into the new area of Alzheimer's disease immune therapy is primarily based on in vivo and in vitro studies of murine models of Alzheimer's disease. The studies are hence limited to defined genetic deficiencies. In humans, infusion of anti-amyloid-beta antibodies is considered a safer approach than active anti-amyloid-beta vaccination. Alzheimer's-disease-protective anti-amyloid-beta monoclonal antibodies should target specific epitopes within the amyloid beta(1 42) peptide, avoiding possibly harmful binding to the ubiquitous normal amyloid precursor protein. Since Alzheimer's disease immunotherapy requires repeated infusion of antibodies over a prolonged period of time, Alzheimer's disease patients will tolerate such antibodies provided the latter are exclusively of human origin. Human monoclonal antibodies that correspond to ubiquitous anti-amyloid-beta, present in all healthy humans, might bear important protective characteristics.

Alzheimer’s Disease Deaths

Centers for Disease Control (CDC) Podcasts

2017-05-25

Dr. Christopher Taylor of CDC’s Alzheimer’s Disease and Healthy Aging Program describes Alzheimer’s disease, the fifth leading cause of death in Americans 65 years and older.  Created: 5/25/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/25/2017.

Parkinson's disease and Alzheimer's disease: hypersensitivity to X-rays in cultured cell lines

Energy Technology Data Exchange (ETDEWEB)

Robbins, J H; Otsuka, Fujio; Tarone, R E; Polinsky, R J; Nee, L E; Brumback, R A

1985-09-01

Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death.

Parkinson's disease and Alzheimer's disease: hypersensitivity to X-rays in cultured cell lines

International Nuclear Information System (INIS)

Robbins, J.H.; Otsuka, Fujio; Tarone, R.E.; Polinsky, R.J.; Nee, L.E.; Brumback, R.A.

1985-01-01

Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death. (author)

FKBP immunophilins and Alzheimer's disease: A chaperoned affair

Indian Academy of Sciences (India)

2011-07-08

Jul 8, 2011 ... FKBP immunophilins and Alzheimer's disease: A chaperoned affair. Weihuan Cao Mary ... Keywords. Alzheimer's disease; amyloid precursor protein; beta amyloid; FKBP; FK506; immunophilins; tau ... 43 | Issue 1. March 2018.

Preclinical MRI and NMR Bio-markers of Alzheimer's Disease: Concepts and Applications

Energy Technology Data Exchange (ETDEWEB)

Dhenain, M. [CEA, DSV, I2BM, SHFJ, F-91401 Orsay (France); Dhenain, M. [CNRS, URA 2210, F-91401 Orsay (France); Dhenain, M. [CEA, DSV, I2BM, Neurospin, F-91191 Gif sur Yvette(France)

2008-07-01

Alzheimer's disease is an important social and economic issue for our societies. The development of therapeutics against this severe dementia requires assessing the effects of new drugs in animal models thanks to dedicated bio-markers. This review first overviews Alzheimer's disease and its models as well as the concept of bio-markers. It then focuses on MRI and NMR bio-markers of Alzheimer's disease in animals. Anatomical markers such as atrophy and angiography are useful to phenotype newly developed models of Alzheimer's disease, even if the alterations in these animals are not as severe as in humans. Amyloid plaques imaging is a promising marker of the pathology in animals, and is a rapidly evolving field of MRI. Functional methods such as perfusion and diffusion imaging or spectroscopy are able to detect alterations in transgenic mice mimicking Alzheimer and also to show similar alterations than in humans. They can thus be good translational markers of the disease. Manganese-Enhanced MRI shows a reduction of neuronal transportation in transgenic models of Alzheimer and it allows monitoring improvements induced by treatments of the disease. It is thus a promising bio-marker of the pathology in animals. (authors)

Short-term memory binding deficits in Alzheimer's disease

OpenAIRE

Parra, Mario; Abrahams, S.; Fabi, K.; Logie, R.; Luzzi, S.; Della Sala, Sergio

2009-01-01

Alzheimer's disease impairs long term memories for related events (e.g. faces with names) more than for single events (e.g. list of faces or names). Whether or not this associative or ‘binding’ deficit is also found in short-term memory has not yet been explored. In two experiments we investigated binding deficits in verbal short-term memory in Alzheimer's disease. Experiment 1 : 23 patients with Alzheimer's disease and 23 age and education matched healthy elderly were recruited. Participants...

Early neurovascular dysfunction in a transgenic rat model of Alzheimer?s disease

OpenAIRE

Joo, Illsung L.; Lai, Aaron Y.; Bazzigaluppi, Paolo; Koletar, Margaret M.; Dorr, Adrienne; Brown, Mary E.; Thomason, Lynsie A. M.; Sled, John G.; McLaurin, JoAnne; Stefanovic, Bojana

2017-01-01

Alzheimer?s disease (AD), pathologically characterized by amyloid-? peptide (A?) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some A?-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease p...

Neuroinflammation in Alzheimer's disease and prion disease

NARCIS (Netherlands)

Eikelenboom, P.; Bate, C.; van Gool, W. A.; Hoozemans, J. J. M.; Rozemuller, J. M.; Veerhuis, R.; Williams, A.

2002-01-01

Alzheimer's disease (AD) and prion disease are characterized neuropathologically by extracellular deposits of Abeta and PrP amyloid fibrils, respectively. In both disorders, these cerebral amyloid deposits are co-localized with a broad variety of inflammation-related proteins (complement factors,

Prevalence and incidence of Alzheimer's disease in Europe: A meta-analysis.

Science.gov (United States)

Niu, H; Álvarez-Álvarez, I; Guillén-Grima, F; Aguinaga-Ontoso, I

2017-10-01

A disease of unknown aetiology, Alzheimer's disease (AD) is the most common type of dementia. As the elderly population grows worldwide, the number of patients with AD also increases rapidly. The aim of this meta-analysis is to evaluate the prevalence and incidence of AD in Europe. We conducted a literature search on Medline, Scopus, and CINAHL Complete using the keywords «Alzheimer», «Alzheimer's disease», and «AD» combined with «prevalence», «incidence», and «epidemiology». A Bayesian random effects model with 95% credible intervals was used. The I 2 statistic was applied to assess heterogeneity. The prevalence of Alzheimer's disease in Europe was estimated at 5.05% (95% CI, 4.73-5.39). The prevalence in men was 3.31% (95% CI, 2.85-3.80) and in women, 7.13% (95% CI, 6.56-7.72), and increased with age. The incidence of Alzheimer's disease in Europe was 11.08 per 1000 person-years (95% CI, 10.30-11.89). Broken down by sex, it was 7.02 per 1000 person-years (95% CI, 6.06-8.05) in men and 13.25 per 1000 person-years (95% CI, 12.05-14.51) in women; again these rates increased with age. The results of our meta-analysis allow a better grasp of the impact of this disease in Europe. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Alzheimer's disease and other neurological disorders.

Science.gov (United States)

Henderson, V W

2007-10-01

Menopausal status and estrogen-containing hormone therapy may influence several neurological disorders, including Alzheimer's disease, epilepsy, migraine headache, multiple sclerosis, Parkinson's disease, sleep disorders, and stroke. For most of these illnesses, evidence on hormone therapy is insufficient to guide practice decisions. For stroke, clinical trial evidence indicates that hormone therapy increases risk of cerebral infarction. For women with Alzheimer's disease, estrogen treatment trials have tended to be small and of short duration. Most suggest that estrogen started after the onset of dementia symptoms does not meaningfully improve cognition or slow disease progression. Hormone therapy initiated after age 64 increased all-cause dementia in the Women's Health Initiative Memory Study. Many observational studies, however, report protective associations between hormone use and Alzheimer risk. Apparent risk reduction may represent a bias toward hormone therapy, since hormones are more often prescribed to healthier women. However, when compared to the Women's Health Initiative Memory Study, estrogen exposures in many observational studies reflect hormone initiation at a younger age, closer to the time of menopause. One intriguing hypothesis is that hormone therapy initiated or used during an early critical window may reduce later Alzheimer incidence. Public health implications of this hypothesis are important, but current data are inadequate to decide the issue.

Computed tomography study of Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Arai, H; Kobayashi, K; Ikeda, Y; Nagao, Y; Ogihara, R; Kosaka, K

1983-01-01

Computed tomography (CT) was used to study cerebral atrophy in 18 patients with clinically diagnosed Alzheimer's disease of presenile type and in 14 healthy age-matched subjects as controls. Using the computerized planimetric method, Subarachnoid Space Volume Index and Ventricle Volume Index were calculated as the measure of cortical atrophy and ventricular dilatation respectively. From the results the following conclusions were drawn: 1. The cerebral atrophy in Alzheimer patients could be attributable to the disease processes rather than to physiological aging of the brain. 2. The degree of atrophy increases in parallel with the progress of the clinical stage, and the cortical atrophy is already apparent at an early stage, whereas the ventricular dilatation becomes pronounced at later stages. 3. CT could be one of the most useful clinical tests available for the diagnosis of Alzheimer's disease.

Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials.

Directory of Open Access Journals (Sweden)

Guoyan Yang

Full Text Available Huperzine A is a Chinese herb extract used for Alzheimer's disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer's disease.We searched for randomized clinical trials (RCTs of Huperzine A for Alzheimer's disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249.20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS and Wechsler Memory Scale (WMS at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR. One trial demonstrated no significant change in cognitive function as measured by Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog and activity of daily living as measured by Alzheimer's disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A.Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer's disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials.

Glaucoma and Alzheimer Disease: A Single Age-Related Neurodegenerative Disease of the Brain.

Science.gov (United States)

Mancino, Raffaele; Martucci, Alessio; Cesareo, Massimo; Giannini, Clarissa; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

2017-12-06

Open Angle Glaucoma is one of the leading causes of irreversible blindness worldwide. Elevated intraocular pressure is considered an important risk factor for glaucoma, however a subset of patients experience disease progression even in presence of normal intraocular pressure values. This implies that risk factors other than intraocular pressure are involved in the pathogenesis of glaucoma. A possible relationship between glaucoma and neurodegenerative diseases such as Alzheimer Disease has been suggested. In this regard, we have recently described a high prevalence of alterations typical of glaucoma, using Heidelberg Retinal Tomograph-3 (HRT-3), in a group of patients with Alzheimer Disease. Interestingly, these alterations were not associated with elevated intraocular pressure or abnormal Central Corneal Thickness values. Alzheimer Disease is the most common form of dementia associated with progressive deterioration of memory and cognition. Complaints related to vision are common among Alzheimer Disease patients. Features common to both diseases, including risk factors and pathophysiological mechanisms, gleaned from the recent literature do suggest that Alzheimer Disease and glaucoma can be considered age-related neurodegenerative diseases that may co-exist in the elderly. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Harmonized diagnostic criteria for Alzheimer's disease

DEFF Research Database (Denmark)

Morris, J C; Blennow, K; Froelich, L

2014-01-01

BACKGROUND: Two major sets of criteria for the clinical diagnosis of Alzheimer's disease (AD) recently have been published, one from an International Working Group (IWG) and the other from working groups convened by the National Institute on Aging (NIA) and the Alzheimer's Association (AA...

The usefulness of CT scanning in clinical observation on the patients with Alzheimer`s disease; Znaczenie tomografii komputerowej w obserwacji klinicznej pacjentow z choroba Alzheimera

Energy Technology Data Exchange (ETDEWEB)

Golebiowski, M; Barcikowska, M; Pfeffer-Baczuk, A; Luczywek, E [Akademia Medyczna, Warsaw (Poland)

1994-12-31

On the basis of brain CT studies of 150 patients of the clinic for persons with Alzheimer`s disease the diagnostic utility of measurement of hippocampal fissure and craniocerebral ratios was assessed. In analyzed group hippocampal fissure measurements greater than 4 mm occurred only in patients with symptoms of Alzheimer`s type dementia. The measurement showed 90% sensitivity and 70% specificity as the prognostic factor of clinical course, especially at the first part of the disease. The evaluation of the hippocampal fissure in conjunction with detailed analysis of CT picture of the atrophic brain allowed for precise final diagnosis. (author). 14 refs, 4 refs.

Volume changes in Alzheimer's disease and mild cognitive impairment: cognitive associations

International Nuclear Information System (INIS)

Evans, Matthew C.; Barnes, Josephine; Nielsen, Casper; Clegg, Shona L.; Blair, Melanie; Douiri, Abdel; Boyes, Richard G.; Fox, Nick C.; Kim, Lois G.; Leung, Kelvin K.; Ourselin, Sebastien

2010-01-01

To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer's disease (AD), mild cognitive impairment (MCI) and control subjects. In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period. Brain atrophy rates and ventricular enlargement differed between subject groups (p < 0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects. Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers. (orig.)

Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.

LENUS (Irish Health Repository)

Hampel, Harald

2012-02-01

OBJECTIVE: Lithium, a first-line drug for the treatment of bipolar depression, has recently been shown to regulate glycogen synthase kinase-3 (GSK-3), a kinase that is involved in the phosphorylation of the tau protein. Since hyperphosphorylation of tau is a core pathological feature in Alzheimer\\'s disease, lithium-induced inhibition of GSK-3 activity may have therapeutic effects in Alzheimer\\'s disease. In the current study, we tested the effect of short-term lithium treatment in patients with Alzheimer\\'s disease. METHOD: A total of 71 patients with mild Alzheimer\\'s disease (Mini-Mental State Examination score > or = 21 and < or = 26) were successfully randomly assigned to placebo (N = 38) or lithium treatment (N = 33) at 6 academic expert memory clinics. The 10-week treatment included a 6-week titration phase to reach the target serum level of lithium (0.5-0.8 mmol\\/L). The primary outcome measures were cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) and GSK-3 activity in lymphocytes. Secondary outcome measures were CSF concentration of total tau and beta-amyloid(1-42) (Abeta(1-42)), plasma levels of Abeta(1-42), Alzheimer\\'s Disease Assessment Scale (ADAS)-Cognitive summary scores, MMSE, and Neuropsychiatric Inventory (NPI). Patients were enrolled in the study from November 2004 to July 2005. RESULTS: No treatment effect on GSK-3 activity or CSF-based biomarker concentrations (P > .05) was observed. Lithium treatment did not lead to change in global cognitive performance as measured by the ADAS-Cog subscale (P = .11) or in depressive symptoms. CONCLUSIONS: The current results do not support the notion that lithium treatment may lead to reduced hyperphosphorylation of tau protein after a short 10-week treatment in the Alzheimer\\'s disease target population. TRIAL REGISTRATION: (Controlled-Trials.com) Identifier: ISRCTN72046462.

Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI.

Science.gov (United States)

Caroli, Anna; Prestia, Annapaola; Wade, Sara; Chen, Kewei; Ayutyanont, Napatkamon; Landau, Susan M; Madison, Cindee M; Haense, Cathleen; Herholz, Karl; Reiman, Eric M; Jagust, William J; Frisoni, Giovanni B

2015-01-01

The aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI). Magnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography markers, and Alzheimer's Disease Assessment Scale-cognitive subscale were compared in terms of effect size and statistical power over different follow-up periods in 2 MCI groups, selected from Alzheimer's Disease Neuroimaging Initiative data set based on cerebrospinal fluid (abnormal cerebrospinal fluid Aβ1-42 concentration-ABETA+) or magnetic resonance imaging evidence of Alzheimer disease (positivity to hippocampal atrophy-HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms. Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency. These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials.

Effect and mechanism of acupuncture on Alzheimer's disease.

Science.gov (United States)

Zeng, Bai-Yun; Salvage, Sarah; Jenner, Peter

2013-01-01

Alzheimer's disease is the most common form of dementia diagnosed in the aging population worldwide. The cause of Alzheimer's is still not clear. There is no cure for the disease and current treatments are only symptomatic relieve. The search for new treatment is made ever more urgent due to increasing population aging. Acupuncture has been in practice in China for more than 3000 years and used to treat a wide variety of conditions including cardiovascular and psychiatric diseases, acute, and chronic pain. In this chapter, we review recent development on the effects and mechanisms of acupuncture on Alzheimer's disease. In Alzheimer's animal models, acupuncture stimulation at acupoints enhances cholinergic neurotransmission, trophic factor releasing, reduces apoptotic and oxidative damages, improves synaptic plasticity and decreases the levels of Aβ proteins in the hippocampus and relevant brain regions. The biochemical modulations by acupuncture in the brains of Alzheimer's models are correlated with the cognitive improvement. In Alzheimer's patients, functional brain images demonstrated that acupuncture increased in the activity in the temporal lobe and prefrontal lobe which are related to the memory and cognitive function. Although only a few acupuncture clinical studies with a small number of participants are reported, they represent an important step forward in the research of both acupuncture and Alzheimer's. Translation of acupuncture research in animal model studies into the human subjects will undoubtedly enhance acupuncture efficacy in clinical study and treatment which could eventually lead to a safer, well-tolerated and inexpensive form of care for Alzheimer's patients. © 2013 Elsevier Inc. All rights reserved.

A disease state fingerprint for evaluation of Alzheimer's disease

DEFF Research Database (Denmark)

Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho

2011-01-01

Diagnostic processes of Alzheimer's disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization...... interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease......'s degree of similarity to previously diagnosed disease population. A summary of patient data and results of the computation are displayed in a succinct Disease State Fingerprint (DSF) visualization. The visualization clearly discloses how patient data contributes to the AD state, facilitating rapid...

Music Enhances Autobiographical Memory in Mild Alzheimer's Disease

Science.gov (United States)

El Haj, Mohamad; Postal, Virginie; Allain, Philippe

2012-01-01

Studies have shown that the "Four Seasons" music may enhance the autobiographical performance of Alzheimer's disease (AD) patients. We used a repeated measures design in which autobiographical recall of 12 mild AD patients was assessed using a free narrative method under three conditions: (a) in "Silence," (b) after being exposed to the opus "Four…

Vaccination against Alzheimer disease: an update on future strategies.

Science.gov (United States)

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

2014-01-01

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

Aluminium in brain tissue in familial Alzheimer's disease.

Science.gov (United States)

Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

2017-03-01

The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Clinical utility of color-form naming in Alzheimer's disease: preliminary evidence

DEFF Research Database (Denmark)

Nielsen, Niels Peter; Wiig, Elisabeth H; Warkentin, Siegbert

2004-01-01

Performances on Alzheimer's Quick Test color-form naming and Mini-Mental State Examination were compared for 38 adults with Alzheimer's disease and 38 age- and sex-matched normal controls. Group means differed significantly and indicated longer naming times by adults with Alzheimer's disease...... associated with Alzheimer's disease, are preliminary given the relatively small sample....

Retinal nerve fiber layer and ganglion cell complex thickness assessment in patients with Alzheimer disease and mild cognitive impairment. Preliminary results

Directory of Open Access Journals (Sweden)

A. S. Tiganov

2014-07-01

Full Text Available Purpose: to investigate the retinal nerve fiber layer (RNFL and the macular ganglion cell complex (GCC in patients with Alzheimer`s disease and mild cognitive impairment.Methods: this study included 10 patients (20 eyes with Alzheimer`s disease, 10 patients with mild cognitive impairment and 10 age- and sex-matched healthy controls that had no history of dementia. All the subjects underwent psychiatric examination, including the Mini-Mental State Examination (MMSE, and complete ophthalmological examination, comprising optical coherence tomography and scanning laser polarimetry.Results: there was a significant decrease in GCC thickness in patients with Alzheimer`s disease compared to the control group, global loss volume of ganglion cells was higher than in control group. there was no significant difference among the groups in terms of RNFL thickness. Weak positive correlation of GCC thickness and MMSE results was observed.Conclusion: Our data confirm the retinal involvement in Alzheimer`s disease, as reflected by loss of ganglion cells. Further studies will clear up the role and contribution of dementia in pathogenesis of optic neuropathy.

How close is the stem cell cure to the Alzheimer's disease

OpenAIRE

Tang, Jun

2012-01-01

Alzheimer's disease, a progressive neurodegenerative illness, is the most common form of dementia. So far, there is neither an effective prevention nor a cure for Alzheimer's disease. In recent decades, stem cell therapy has been one of the most promising treatments for Alzheimer's disease patients. This article aims to summarize the current progress in the stem cell treatments for Alzheimer's disease from an experiment to a clinical research.

Alzheimer's Disease Facts and Figures

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Full Text Available ... 2018 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease in every ... with third parties. Please read our security and privacy policy . Plan ahead Get help and support I ...

Alzheimer's Disease Facts and Figures

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Full Text Available ... home care. Take action. Become an advocate SPECIAL REPORT: FINANCIAL AND PERSONAL BENEFITS OF EARLY DIAGNOSIS Early ... State The 2018 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease ...

Alzheimer's Disease Facts and Figures

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Full Text Available ... 323 BILLION. BETWEEN 2000 AND 2015 DEATHS FROM HEART DISEASE HAVE DECREASED 11% WHILE DEATHS FROM ALZHEIMER'S ... deaths from the number one cause of death (heart disease) decreased 11 percent. Among people age 70, ...

Alzheimer's Disease Facts and Figures

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Full Text Available ... disease is the only top 10 cause of death in the United States that cannot be prevented, ... Alzheimer's disease is the sixth-leading cause of death in the United States, and the fifth-leading ...

The neuropsychological profile of Alzheimer disease.

Science.gov (United States)

Weintraub, Sandra; Wicklund, Alissa H; Salmon, David P

2012-04-01

Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from "normal," age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease.

Predictors of sustained response to rivastigmine in patients with Alzheimer's disease: a retrospective analysis.

Science.gov (United States)

Sadowsky, Carl H; Grossberg, George T; Somogyi, Monique; Meng, Xiangyi

2011-01-01

The cholinesterase inhibitor rivastigmine is approved for the treatment of mild to moderate Alzheimer's disease. However, it is not possible to predict which individuals will benefit from treatment. This retrospective analysis of an international, 24-week, randomized, double-blind trial aimed to identify the percentage of persons with Alzheimer's disease who have a sustained response with rivastigmine patch, rivastigmine capsules, or placebo; to determine the magnitude of the sustained treatment response; and to investigate baseline patient characteristics predictive of the observed sustained response. Patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) at week 16 and maintained at least the week 16 improvement at week 24 were identified as sustained responders. Treatment differences and baseline predictive factors were assessed in patients demonstrating a 1-, 2-, 3-, 4-, or 5-point sustained improvement. The first patient was screened in November 2003 and the last patient completed the study in January 2006. More persons with Alzheimer's disease had sustained improvements on the ADAS-cog and ADCS-ADL with rivastigmine versus placebo. Sustained improvements of 4 or 5 points on the ADAS-cog or ADCS-ADL were demonstrated in the 9.5-mg/24-h rivastigmine patch (24% and 36% of patients, respectively) and 12-mg/d capsule groups (28% on both outcome measures). Factors predictive of a sustained response to treatment included baseline Mini-Mental State Examination, ADAS-cog, and ADCS-ADL scores and treatment, country of treatment, and time since first symptom was diagnosed by a physician. Understanding factors predictive of sustained cholinesterase inhibitor treatment response should help to optimize Alzheimer's disease management and encourage compliance by allowing more realistic expectations of treatment effects.

An image processing technique for diagnosis of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Massoud Mahmoudian

2009-08-01

Full Text Available

• BACKGROUND: Patients with Alzheimer's disease (AD reportedly hibit hypersensitivity to much diluted tropicam solution (0.005%, a M4 muscarinic receptor antagonist. Therefore aocular application of 0.005% tropicamide ma be useful for screening dementia. The aim of this study was to simplify the pupil response test by using a new image analyzing system, which consists of a cheap, simple, and easy to use web-camera and a computer.
• METHODS: Intraocular tropicamide of 0.005% concentration was administered in 3 groups: Alzheimer's disease patients (n = 8, average age = 76 ± 5, non-Alzheimer's disease elderly (n = 6, average age = 65 ± 7, and young subjects (n = 8, average age = 28 ± 5. Every 5 minutes for 60 minutes, image of the eye's shape were taken, and the diameter of the pupils was measured.
• RESULTS: The results showed that differences in pupil dilation rate between Alzheimer's disease and non-Alzheimer's disease subjects were statistically significant. ROC analysis showed that after 35 minutes the sensitivity and specificity of the test were 100%.
• CONCLUSIONS: Based on our results, we concluded that this recording system might be an appropriate and reliable tool for pupil response diagnosis test of Alzheimer's disease.
• KEYWORDS: Alzheimer’s Disease, Tropicamide, Pupil.

New scoring methodology improves the sensitivity of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials.

Science.gov (United States)

Verma, Nishant; Beretvas, S Natasha; Pascual, Belen; Masdeu, Joseph C; Markey, Mia K

2015-11-12

As currently used, the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) has low sensitivity for measuring Alzheimer's disease progression in clinical trials. A major reason behind the low sensitivity is its sub-optimal scoring methodology, which can be improved to obtain better sensitivity. Using item response theory, we developed a new scoring methodology (ADAS-CogIRT) for the ADAS-Cog, which addresses several major limitations of the current scoring methodology. The sensitivity of the ADAS-CogIRT methodology was evaluated using clinical trial simulations as well as a negative clinical trial, which had shown an evidence of a treatment effect. The ADAS-Cog was found to measure impairment in three cognitive domains of memory, language, and praxis. The ADAS-CogIRT methodology required significantly fewer patients and shorter trial durations as compared to the current scoring methodology when both were evaluated in simulated clinical trials. When validated on data from a real clinical trial, the ADAS-CogIRT methodology had higher sensitivity than the current scoring methodology in detecting the treatment effect. The proposed scoring methodology significantly improves the sensitivity of the ADAS-Cog in measuring progression of cognitive impairment in clinical trials focused in the mild-to-moderate Alzheimer's disease stage. This provides a boost to the efficiency of clinical trials requiring fewer patients and shorter durations for investigating disease-modifying treatments.

New cardiovascular targets to prevent late onset Alzheimer disease.

Science.gov (United States)

Claassen, Jurgen A H R

2015-09-15

The prevalence of dementia rises to between 20% and 40% with advancing age. The dominant cause of dementia in approximately 70% of these patients is Alzheimer disease. There is no effective disease-modifying pharmaceutical treatment for this neurodegenerative disease. A wide range of Alzheimer drugs that appeared effective in animal models have recently failed to show clinical benefit in patients. However, hopeful news has emerged from recent studies that suggest that therapeutic strategies aimed at reducing cardiovascular disease may also reduce the prevalence of dementia due to Alzheimer disease. This review summarizes the evidence for this link between cardiovascular disease and late onset Alzheimer dementia. Only evidence from human research is considered here. Longitudinal studies show an association between high blood pressure and pathological accumulation of the protein amyloid-beta42, and an even stronger association between vascular stiffness and amyloid accumulation, in elderly subjects. Amyloid-beta42 accumulation is considered to be an early marker of Alzheimer disease, and increases the risk of subsequent cognitive decline and development of dementia. These observations could provide an explanation for recent observations of reduced dementia prevalence associated with improved cardiovascular care. Copyright © 2015 Elsevier B.V. All rights reserved.

Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt-Jakob disease.

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Podlesniy, Petar; Llorens, Franc; Golanska, Ewa; Sikorska, Beata; Liberski, Pawel; Zerr, Inga; Trullas, Ramon

2016-05-01

Low content of cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker of early stage Alzheimer's disease (AD), but whether mtDNA is altered in a rapid neurodegenerative dementia such as Creutzfeldt-Jakob disease is unknown. CSF mtDNA was measured using digital polymerase chain reaction (dPCR) in two independent cohorts comprising a total of 112 patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD), probable AD, or non-Alzheimer's type dementia. Patients with AD exhibit low mtDNA content in CSF compared with patients diagnosed with sCJD or with non-Alzheimer's type dementias. The CSF concentration of mtDNA does not correlate with Aβ, t-tau, p-tau, and 14-3-3 protein levels in CSF. Low-CSF mtDNA is not a consequence of brain damage and allows the differential diagnosis of AD from sCJD and other dementias. These results support the hypothesis that mtDNA in CSF is a pathophysiological biomarker of AD. Copyright © 2015 Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

[Development of anti-Alzheimer's disease drug based on beta-amyloid hypothesis].

Science.gov (United States)

Sugimoto, Hachiro

2010-04-01

Currently, there are five anti-Alzheimer's disease drugs approved. These are tacrine, donepezil, rivastigmine, galantamine, and memantine. The mechanism of the first four drugs is acetylcholinesterase inhibition, while memantine is an NMDA-receptor antagonist. However, these drugs do not cure Alzheimer's, but are only symptomatic treatments. Therefore, a cure for Alzheimer's disease is truly needed. Alzheimer's disease is a progressive neurodegenerative disease characterized by cognitive deficits. The cause of the disease is not well understood, but research indicates that the aggregation of beta-amyloid is the fundamental cause. This theory suggests that beta-amyloid aggregation causes neurotoxicity. Therefore, development of the next anti-Alzheimer's disease drug is based on the beta-amyloid theory. We are now studying natural products, such as mulberry leaf extracts and curcumin derivatives, as potential cure for Alzheimer's disease. In this report, we describe some data about these natural products and derivatives.

Alzheimer's Disease Facts and Figures

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Full Text Available ... ALZHEIMER'S DISEASE IS THE 6TH LEADING CAUSE OF DEATH IN THE UNITED STATES. 16.1 MILLION AMERICANS ... AT OVER $323 BILLION. BETWEEN 2000 AND 2015 DEATHS FROM HEART DISEASE HAVE DECREASED 11% WHILE DEATHS ...

Epigenetics in Alzheimer's Disease: Perspective of DNA Methylation.

Science.gov (United States)

Qazi, Talal Jamil; Quan, Zhenzhen; Mir, Asif; Qing, Hong

2018-02-01

Research over the years has shown that causes of Alzheimer's disease are not well understood, but over the past years, the involvement of epigenetic mechanisms in the developing memory formation either under pathological or physiological conditions has become clear. The term epigenetics represents the heredity of changes in phenotype that are independent of altered DNA sequences. Different studies validated that cytosine methylation of genomic DNA decreases with age in different tissues of mammals, and therefore, the role of epigenetic factors in developing neurological disorders in aging has been under focus. In this review, we summarized and reviewed the involvement of different epigenetic mechanisms especially the DNA methylation in Alzheimer's disease (AD), late-onset Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and autosomal dominant Alzheimer's disease (ADAD). Down to the minutest of details, we tried to discuss the methylation patterns like mitochondrial DNA methylation and ribosomal DNA (rDNA) methylation. Additionally, we mentioned some therapeutic approaches related to epigenetics, which could provide a potential cure for AD. Moreover, we reviewed some recent studies that validate DNA methylation as a potential biomarker and its role in AD. We hope that this review will provide new insights into the understanding of AD pathogenesis from the epigenetic perspective especially from the perspective of DNA methylation.

Anti-amyloid treatments in Alzheimer's disease.

Science.gov (United States)

Sapra, Mamta; Kim, Kye Y

2009-06-01

Alzheimer's disease is one of the most challenging threats to the healthcare system in society. One of the main characteristic of Alzheimer's disease (AD) pathology is formation of amyloid plaques from accumulation of amyloid beta peptide. The therapeutic agents that are currently available for AD including acetylcholinesterase inhibitors (AchEIs) and the N-methyl-D-aspartate (NMDA) antagonist are focused on improving the symptoms and do not revert the progression of the disease. This limitation coupled with the burgeoning increase in the prevalence of AD and resultant impact on healthcare economics calls for more substantial treatments for AD. According to the leading amyloid hypothesis, cleavage of amyloid precursor protein to release amyloid beta peptide is the critical event in pathogenesis of Alzheimer's disease. Recently treatment strategies have been focused on modifying the formation, clearance and accumulation of neurotoxic amyloid beta peptide. This article reviews different therapeutic approaches that have been investigated to target amyloid beta ranging from secretase modulators, antiaggregation agents to amyloid immunotherapy. Authors review the different novel drugs which are in clinical trials.

Drawing Disorders in Alzheimer's Disease and Other Forms of Dementia.

Science.gov (United States)

Trojano, Luigi; Gainotti, Guido

2016-04-21

Drawing is a multicomponential process that can be impaired by many kinds of brain lesions. Drawing disorders are very common in Alzheimer's disease and other forms of dementia, and can provide clinical information for the distinction of the different dementing diseases. In our review we started from an overview of the neural and cognitive bases of drawing, and from a recollection of the drawing tasks more frequently used for assessing individuals with dementia. Then, we analyzed drawing disorders in dementia, paying special attention to those observed in Alzheimer's disease, from the prodromal stages of the amnesic mild cognitive impairment to the stages of full-blown dementia, both in the sporadic forms with late onset in the entorhino-hippocampal structures and in those with early onset in the posterior neocortical structures. We reviewed the drawing features that could differentiate Alzheimer's disease from vascular dementia and from the most frequent forms of degenerative dementia, namely frontotemporal dementia and Lewy body disease. Finally, we examined some peculiar aspects of drawing disorders in dementia, such as perseverations, rotations, and closing-in. We argue that a careful analysis of drawing errors helps to differentiate the different forms of dementia more than overall accuracy in drawing.

Social participation in home-living patients with mild Alzheimer's disease

DEFF Research Database (Denmark)

Sørensen, Lisbeth Villemoes; Waldorff, Frans Boch; Waldemar, Gunhild

2007-01-01

The purpose of this study was to investigate social participation in home-living patients with mild Alzheimer's disease (AD) and to identify predictors for low social participation. The study was based on baseline data from 330 home-living patients with mild AD who participated in The Danish...... Alzheimer Intervention Study (DAISY). Proxy-obtained information from primary caregiver assessed patients' social participation. The result showed that low social participation was present in mild AD. Significant independent predictors of low social participation were impairment in activities of daily...

Accelerating stem cell trials for Alzheimer's disease.

Science.gov (United States)

Hunsberger, Joshua G; Rao, Mahendra; Kurtzberg, Joanne; Bulte, Jeff W M; Atala, Anthony; LaFerla, Frank M; Greely, Henry T; Sawa, Akira; Gandy, Sam; Schneider, Lon S; Doraiswamy, P Murali

2016-02-01

At present, no effective cure or prophylaxis exists for Alzheimer's disease. Symptomatic treatments are modestly effective and offer only temporary benefit. Advances in induced pluripotent stem cell (iPSC) technology have the potential to enable development of so-called disease-in-a-dish personalised models to study disease mechanisms and reveal new therapeutic approaches, and large panels of iPSCs enable rapid screening of potential drug candidates. Different cell types can also be produced for therapeutic use. In 2015, the US Food and Drug Administration granted investigational new drug approval for the first phase 2A clinical trial of ischaemia-tolerant mesenchymal stem cells to treat Alzheimer's disease in the USA. Similar trials are either underway or being planned in Europe and Asia. Although safety and ethical concerns remain, we call for the acceleration of human stem cell-based translational research into the causes and potential treatments of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occupational Therapy Interventions for People With Alzheimer's Disease.

Science.gov (United States)

Piersol, Catherine Verrier; Jensen, Lou; Lieberman, Deborah; Arbesman, Marian

Evidence Connection articles provide a clinical application of systematic reviews developed in conjunction with the American Occupational Therapy Association's (AOTA's) Evidence-Based Practice Project. In this Evidence Connection article, we describe a case report of a person with Alzheimer's disease. The occupational therapy assessment and intervention process in the home setting is described. Findings from the systematic reviews on this topic were published in the November/December 2017 issue of the American Journal of Occupational Therapy and in AOTA's Occupational Therapy Practice Guidelines for Adults With Alzheimer's Disease and Related Major Neurocognitive Disorders. Each article in this series summarizes the evidence from the published reviews on a given topic and presents an application of the evidence to a related clinical case. Evidence Connection articles illustrate how the research evidence from the reviews can be used to inform and guide clinical reasoning. Copyright © 2018 by the American Occupational Therapy Association, Inc.

Multimodal PET Imaging of Amyloid and Tau Pathology in Alzheimer Disease and Non-Alzheimer Disease Dementias.

Science.gov (United States)

Xia, Chenjie; Dickerson, Bradford C

2017-07-01

Biomarkers of the molecular pathology underpinning dementia syndromes are increasingly recognized as crucial for diagnosis and development of disease-modifying treatments. Amyloid PET imaging is an integral part of the diagnostic assessment of Alzheimer disease. Its use has also deepened understanding of the role of amyloid pathology in Lewy body disorders and aging. Tau PET imaging is an imaging biomarker that will likely play an important role in the diagnosis, monitoring, and treatment in dementias. Using tau PET imaging to examine how tau pathology relates to amyloid and other markers of neurodegeneration will serve to better understand the pathophysiologic cascade that leads to dementia. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease.

Science.gov (United States)

Herrmann, Nathan; Gauthier, Serge

2008-12-02

The management of severe Alzheimer disease often presents difficult choices for clinicians and families. The disease is characterized by a need for full-time care and assistance with basic activities of daily living. We outline an evidence-based approach for these choices based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of severe Alzheimer disease. Subsequent to the conference, we searched for additional articles published from January 2006 to March 2008 using the same search terms. We graded the strength of the evidence using the criteria of the Canadian Task Force on Preventive Health Care. We identified 940 articles, of which 838 were selected for further study. Thirty-four articles were judged to be of at least good or fair quality and were used to generate 17 recommendations. Assessment of severe Alzheimer disease should include the measurement of cognitive function and the assessment of behaviour, function, medical status, nutrition, safety and caregiver status. Management could include treatment with a cholinesterase inhibitor or memantine, or both. Treatment of neuropsychiatric symptoms begins with nonpharmacologic approaches to addressing behavioural problems. Severe agitation, aggression and psychosis, which are potentially dangerous to the patient, the caregiver and others in the environment, can be treated with atypical antipsychotics, with consideration of their increased risk of cerebrovascular events and death. All pharmacologic approaches require careful monitoring and periodic reassessment to determine whether continued treatment is necessary. Caregiver support and use of community

The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

NARCIS (Netherlands)

McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack, C.R.; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R.; Mohs, R.C.; Morris, J.C.; Rossor, M.N.; Scheltens, P.; Carrillo, M.C.; Thies, B.; Weintraub, S.; Phelps, C.H.

2011-01-01

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers

Auditory post-processing in a passive listening task is deficient in Alzheimer's disease.

Science.gov (United States)

Bender, Stephan; Bluschke, Annet; Dippel, Gabriel; Rupp, André; Weisbrod, Matthias; Thomas, Christine

2014-01-01

To investigate whether automatic auditory post-processing is deficient in patients with Alzheimer's disease and is related to sensory gating. Event-related potentials were recorded during a passive listening task to examine the automatic transient storage of auditory information (short click pairs). Patients with Alzheimer's disease were compared to a healthy age-matched control group. A young healthy control group was included to assess effects of physiological aging. A bilateral frontal negativity in combination with deep temporal positivity occurring 500 ms after stimulus offset was reduced in patients with Alzheimer's disease, but was unaffected by physiological aging. Its amplitude correlated with short-term memory capacity, but was independent of sensory gating in healthy elderly controls. Source analysis revealed a dipole pair in the anterior temporal lobes. Results suggest that auditory post-processing is deficient in Alzheimer's disease, but is not typically related to sensory gating. The deficit could neither be explained by physiological aging nor by problems in earlier stages of auditory perception. Correlations with short-term memory capacity and executive control tasks suggested an association with memory encoding and/or overall cognitive control deficits. An auditory late negative wave could represent a marker of auditory working memory encoding deficits in Alzheimer's disease. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Head-to-Head Visual Comparison between Brain Perfusion SPECT and Arterial Spin-Labeling MRI with Different Postlabeling Delays in Alzheimer Disease.

Science.gov (United States)

Kaneta, T; Katsuse, O; Hirano, T; Ogawa, M; Yoshida, K; Odawara, T; Hirayasu, Y; Inoue, T

2017-08-01

Arterial spin-labeling MR imaging has been recently developed as a noninvasive technique with magnetically labeled arterial blood water as an endogenous contrast medium for the evaluation of CBF. Our aim was to compare arterial spin-labeling MR imaging and SPECT in the visual assessment of CBF in patients with Alzheimer disease. In 33 patients with Alzheimer disease or mild cognitive impairment due to Alzheimer disease, CBF images were obtained by using both arterial spin-labeling-MR imaging with a postlabeling delay of 1.5 seconds and 2.5 seconds (PLD 1.5 and PLD 2.5 , respectively) and brain perfusion SPECT. Twenty-two brain regions were visually assessed, and the diagnostic confidence of Alzheimer disease was recorded. Among all arterial spin-labeling images, 84.9% of PLD 1.5 and 9% of PLD 2.5 images showed the typical pattern of advanced Alzheimer disease (ie, decreased CBF in the bilateral parietal, temporal, and frontal lobes). PLD 1.5 , PLD 2.5 , and SPECT imaging resulted in obviously different visual assessments. PLD 1.5 showed a broad decrease in CBF, which could have been due to an early perfusion. In contrast, PLD 2.5 did not appear to be influenced by an early perfusion but showed fewer pathologic findings than SPECT. The distinctions observed by us should be carefully considered in the visual assessments of Alzheimer disease. Further studies are required to define the patterns of change in arterial spin-labeling-MR imaging associated with Alzheimer disease. © 2017 by American Journal of Neuroradiology.

Reliability of the Alzheimer's disease assessment scale (ADAS-Cog) in longitudinal studies.

Science.gov (United States)

Khan, Anzalee; Yavorsky, Christian; DiClemente, Guillermo; Opler, Mark; Liechti, Stacy; Rothman, Brian; Jovic, Sofija

2013-11-01

Considering the scarcity of longitudinal assessments of reliability, there is need for a more precise understanding of cognitive decline in Alzheimer's Disease (AD). The primary goal was to assess longitudinal changes in inter-rater reliability, test retest reliability and internal consistency of scores of the ADAS-Cog. 2,618 AD subjects were enrolled in seven randomized, double-blind, placebo-controlled, multicenter-trials from 1986 to 2009. Reliability, internal-consistency and cross-sectional analysis of ADAS-Cog and MMSE across seven visits were examined. Intra-class correlation (ICC) for ADAS-Cog was moderate to high supporting their reliability. Absolute Agreement ICCs 0.392 (Visit-7) to 0.806 (Visit-2) showed a progressive decrease in correlations across time. Item analysis revealed a decrease in item correlations, with the lowest correlations for Visit 7 for Commands (ICC=0.148), Comprehension (ICC=0.092), Spoken Language (ICC=0.044). Suitable assessment of AD treatments is maintained through accurate measurement of clinically significant outcomes. Targeted rater education ADAS-Cog items over-time can improve ability to administer and score the scale.

The Neuropsychological Profile of Alzheimer Disease

Science.gov (United States)

Weintraub, Sandra; Wicklund, Alissa H.; Salmon, David P.

2012-01-01

Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from “normal,” age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease. PMID:22474609

Neuroinflammation in Alzheimer's disease

NARCIS (Netherlands)

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, Stephane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A.; Breitner, John C.; Cole, Greg M.; Golenbock, Douglas T.; Kummer, Markus P.

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

Neuroinflammation in Alzheimer's disease

NARCIS (Netherlands)

Heneka, M.T.; Carson, M.J.; Khoury, J. El; Landreth, G.E.; Brosseron, F.; Feinstein, D.L.; Jacobs, A.H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R.M.; Herrup, K.; Frautschy, S.A.; Finsen, B.; Brown, G.C.; Verkhratsky, A.; Yamanaka, K.; Koistinaho, J.; Latz, E.; Halle, A.; Petzold, G.C.; Town, T.; Morgan, D.; Shinohara, M.L.; Perry, V.H.; Holmes, C.; Bazan, N.G.; Brooks, D.J.; Hunot, S.; Joseph, B.; Deigendesch, N.; Garaschuk, O.; Boddeke, E.; Dinarello, C.A.; Breitner, J.C.; Cole, G.M.; Golenbock, D.T.; Kummer, M.P.

2015-01-01

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

A study of the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) in an Icelandic elderly population.

Science.gov (United States)

Hannesdóttir, Kristin; Snaedal, Jón

2002-01-01

The Alzheimer's Disease Assessment Scale (ADAS) is designed for screening of cognitive and non-cognitive dysfunctions characteristic of persons with probable Alzheimer's disease (AD). The cognitive part of the scale (ADAS-Cog) is both convenient for screening of probable AD and as a measure of cognitive functioning during drug intervention. The aim of this study was to translate the ADAS-Cognitive sub-test (ADAS-Cog) into Icelandic and to study its application in an elderly Icelandic population. The Mini-Mental State Examination (MMSE) and the ADAS-Cog were administered to 20 AD patients and 20 controls. Each patient was also rated on the Global Deterioration Scale (GDS). The probable AD patients were divided into two groups based on their GDS: 3-4 and 5-6 points. The patients were also divided into two groups based on their MMSE score: very mild to mild (23-30 points) and mild to moderate (15-22 points). Furthermore, the subjects were divided into two age groups: 65-76 and 77-92 years. Results revealed a highly significant difference on MMSE (22.3 +/- 3.4; 26.8 +/- 1.6; P ADAS-Cog (18.4 +/- 7.7; 7.3 +/- 3.5; P ADAS-Cog plays an important role in the diagnostic makeup of AD along with other detailed investigations, such as neuropsychological assessment.

Disease-modifying drugs in Alzheimer's disease

Directory of Open Access Journals (Sweden)

Ghezzi L

2013-12-01

Full Text Available Laura Ghezzi, Elio Scarpini, Daniela Galimberti Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy Abstract: Alzheimer's disease (AD is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathology is characterized by deposition of amyloid beta peptide (so-called senile plaques and tau protein in the form of neurofibrillary tangles. Currently, two classes of drugs are licensed by the European Medicines Agency for the treatment of AD, ie, acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N-methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment with acetylcholinesterase inhibitors or memantine aims at slowing progression and controlling symptoms, whereas drugs under development are intended to modify the pathologic steps leading to AD. Herein, we review the clinical features, pharmacologic properties, and cost-effectiveness of the available acetylcholinesterase inhibitors and memantine, and focus on disease-modifying drugs aiming to interfere with the amyloid beta peptide, including vaccination, passive immunization, and tau deposition. Keywords: Alzheimer's disease, acetylcholinesterase inhibitors, memantine, disease-modifying drugs, diagnosis, treatment

Efficacy of a medical food on cognition in Alzheimer's disease: results from secondary analyses of a randomized, controlled trial

NARCIS (Netherlands)

Kamphuis, P.J.G.H.; Verhey, F.R.; Olde Rikkert, M.G.; Twisk, J.W.; Swinkels, S.H.; Scheltens, P.

2011-01-01

Objective: To investigate the extent that baseline cognitive impairment and intake adherence affected the 13-item Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) intervention response of a medical food in Alzheimer's Disease (AD) patients. Desigrt/setting/participants

Efficacy of a medical food on cognition in Alzheimer's disease: results from secondary analyses of a randomized, controlled trial

NARCIS (Netherlands)

Kamphuis, P.J.; Verhey, F.R.J.; Olde Rikkert, M.G.M.; Twisk, J.W.R.; Swinkels, S.H.N.; Scheltens, P.

2011-01-01

OBJECTIVE: To investigate the extent that baseline cognitive impairment and intake adherence affected the 13-item Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) intervention response of a medical food in Alzheimer's Disease (AD) patients. DESIGN/SETTING/PARTICIPANTS

Bilingualism delays clinical manifestation of Alzheimer's disease

OpenAIRE

Woumans, Evy; Santens, Patrick; Sieben, Anne; Versijpt, Jan; Stevens, Michaël; Duyck, Wouter

2015-01-01

The current study investigated the effects of bilingualism on the clinical manifestation of Alzheimer's disease (AD) in a European sample of patients. We assessed all incoming AD patients in two university hospitals within a specified timeframe. Sixty-nine monolinguals and 65 bilinguals diagnosed with probable AD were compared for time of clinical AD manifestation and diagnosis. The influence of other potentially interacting variables was also examined. Results indicated a significant delay f...

Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms.

Science.gov (United States)

Epperly, Ted; Dunay, Megan A; Boice, Jack L

2017-06-15

Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

In situ hybridization of nucleus basalis neurons shows increased β-amyloid mRNA in Alzheimer disease

International Nuclear Information System (INIS)

Cohen, M.L.; Golde, T.E.; Usiak, M.F.; Younkin, L.H.; Younkin, S.G.

1988-01-01

To determine which cells within the brain produce β-amyloid mRNA and to assess expression of the β-amyloid gene in Alzheimer disease, the authors analyzed brain tissue from Alzheimer and control patients by in situ hybridization. The results demonstrate that β-amyloid mRNA is produced by neurons in the nucleus basalis of Meynert and cerebral cortex and that nuclues basalis perikarya from Alzheimer patients consistently hybridize more β-amyloid probe than those from controls. These observations support the hypothesis that increased expression of the β-amyloid gene plays an important role in the deposition of amyloid in the brains of patients with Alzheimer disease

Body mass index and risk of Alzheimer's disease

DEFF Research Database (Denmark)

Nordestgaard, Liv Tybjærg; Tybjærg-Hansen, Anne; Nordestgaard, Børge G.

2017-01-01

between low BMI and high risk of Alzheimer's disease. Design, Setting, and Participants: Using a Mendelian randomization approach, we studied 95,578 individuals from the Copenhagen General Population Study (CGPS) with up to 36 years of follow-up and consortia data on 303,958 individuals from the Genetic...... Investigation of Anthropometric Traits (GIANT) and the International Genomics of Alzheimer's Project (IGAP). Main Outcome Measure: Risk of Alzheimer's disease. Results: The causal odds ratio for a 1-kg/m2 genetically determined lower BMI was 0.98 [95% confidence interval (CI), 0.77 to 1.23] for a weighted...... allele score in the CGPS. Using 32 BMIdecreasing variants from GIANT and IGAP the causal odds ratio for Alzheimer's disease for a 1-standard deviation (SD) lower genetically determined BMI was 1.02 (95% CI, 0.86 to 1.22). Corresponding observational hazard ratios from the CGPS were 1.07 (95% CI, 1...

A study on knowledge, attitudes and health behaviours regarding Alzheimer's disease among community residents in Tianjin, China.

Science.gov (United States)

Yang, H-F; Cong, J-Y; Zang, X-Y; Jiang, N; Zhao, Y

2015-11-01

What is known on the subject? Several studies have measured the general public's knowledge and attitudes towards Alzheimer's disease; however, much of this work is based on western samples. Due to cultural differences, the western findings may be difficult to generalize to the Chinese general public. In addition, the few studies conducted in China were often restricted to a relatively narrow range of knowledge and attitudes. What this paper adds to existing knowledge? The general public had little knowledge of Alzheimer's disease, especially on the causes, symptoms and risk factors. In terms of attitudes, although the general public held positive attitudes towards persons with Alzheimer's disease, most of them were not sure whether or not to share a diagnosis of Alzheimer's disease with the patient. In daily life, only a low proportion of people kept mentally active. What are the implications for practice? A popularization of a wide range of knowledge about Alzheimer's disease needs to be undertaken, especially focusing on persons with low educational level and emphasizing the causes, symptoms and risk factors. Besides, there is a significant need to draw up evidence-based dietary and lifestyle guidelines for Alzheimer's disease risk reduction. Moreover, health promotion agencies should identify priority groups for Alzheimer's disease risk reduction initiatives, especially those with lower income, a lower level of knowledge on Alzheimer's disease and with chronic diseases. The purpose of this descriptive correlational cross-sectional study was to assess the current level of knowledge, attitudes and health behaviours regarding Alzheimer's disease among community residents in Tianjin, China and to identify factors related to these attributes. A convenience sample of 140 community-dwelling adults aged 20-75 years was selected to complete a researcher-designed questionnaire about Alzheimer's disease-related knowledge, attitudes and health behaviours. The findings

Comparison of CSF Distribution between Idiopathic Normal Pressure Hydrocephalus and Alzheimer Disease.

Science.gov (United States)

Yamada, S; Ishikawa, M; Yamamoto, K

2016-07-01

CSF volumes in the basal cistern and Sylvian fissure are increased in both idiopathic normal pressure hydrocephalus and Alzheimer disease, though the differences in these volumes in idiopathic normal pressure hydrocephalus and Alzheimer disease have not been well-described. Using CSF segmentation and volume quantification, we compared the distribution of CSF in idiopathic normal pressure hydrocephalus and Alzheimer disease. CSF volumes were extracted from T2-weighted 3D spin-echo sequences on 3T MR imaging and quantified semi-automatically. We compared the volumes and ratios of the ventricles and subarachnoid spaces after classification in 30 patients diagnosed with idiopathic normal pressure hydrocephalus, 10 with concurrent idiopathic normal pressure hydrocephalus and Alzheimer disease, 18 with Alzheimer disease, and 26 control subjects 60 years of age or older. Brain to ventricle ratios at the anterior and posterior commissure levels and 3D volumetric convexity cistern to ventricle ratios were useful indices for the differential diagnosis of idiopathic normal pressure hydrocephalus or idiopathic normal pressure hydrocephalus with Alzheimer disease from Alzheimer disease, similar to the z-Evans index and callosal angle. The most distinctive characteristics of the CSF distribution in idiopathic normal pressure hydrocephalus were small convexity subarachnoid spaces and the large volume of the basal cistern and Sylvian fissure. The distribution of the subarachnoid spaces in the idiopathic normal pressure hydrocephalus with Alzheimer disease group was the most deformed among these 3 groups, though the mean ventricular volume of the idiopathic normal pressure hydrocephalus with Alzheimer disease group was intermediate between that of the idiopathic normal pressure hydrocephalus and Alzheimer disease groups. The z-axial expansion of the lateral ventricle and compression of the brain just above the ventricle were the common findings in the parameters for differentiating

Inflammation and Alzheimer's disease

NARCIS (Netherlands)

Akiyama, H.; Barger, S.; Barnum, S.; Bradt, B.; Bauer, J.; Cole, G. M.; Cooper, N. R.; Eikelenboom, P.; Emmerling, M.; Fiebich, B. L.; Finch, C. E.; Frautschy, S.; Griffin, W. S.; Hampel, H.; Hull, M.; Landreth, G.; Lue, L.; Mrak, R.; Mackenzie, I. R.; McGeer, P. L.; O'Banion, M. K.; Pachter, J.; Pasinetti, G.; Plata-Salaman, C.; Rogers, J.; Rydel, R.; Shen, Y.; Streit, W.; Strohmeyer, R.; Tooyoma, I.; van Muiswinkel, F. L.; Veerhuis, R.; Walker, D.; Webster, S.; Wegrzyniak, B.; Wenk, G.; Wyss-Coray, T.

2000-01-01

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical

A computed tomography study of Alzheimer's disease

International Nuclear Information System (INIS)

Arai, H.; Kobayashi, K.; Juntendo Univ. School of Medicine, Tokyo; Ikeda, Y.; Nagao, Y.; Ogihara, R.; Kosaka, K.; Psychiatric Research Inst. of Tokyo

1983-01-01

Computed tomography (CT) was used to study cerebral atrophy in 18 patients with clinically diagnosed Alzheimer's disease of presenile type and in 14 healthy age-matched subjects as controls. Using the computerized planimetric method, Subarachnoid Space Volume Index and Ventricle Volume Index were calculated as the measure of cortical atrophy and ventricular dilatation respectively. From the results the following conclusions were drawn: 1. The cerebral atrophy in Alzheimer patients could be attributable to the disease processes rather than to physiological aging of the brain. 2. The degree of atrophy increases in parallel with the progress of the clinical stage, and the cortical atrophy is already apparent at an early stage, whereas the ventricular dilatation becomes pronounced at later stages. 3. CT could be one of the most useful clinical tests available for the diagnosis of Alzheimer's disease. (orig.) [de

[A preliminary study of low dosage zuclopenthixol depot in Alzheimer's disease].

Science.gov (United States)

Robles, A; Rodríguez Navarrete, F J; Taboada, O; Docasar, L; Páramo, M; Noya, M

1996-03-01

Persistent psychomotor agitation and psychotic ideation in patients with Alzheimer's disease are normally treated orally with antipsychotic drugs and are occasionally treated with other drugs. Neuroleptics administered intramuscularly at very low doses are an alternative, especially when the patient rejects medicine as a results of his or her anosognosia or of paranoid manifestations. We present the results we obtained after observing the effects of depot zuclopenthixol in six patients with probable Alzheimer's disease (based upon NINCDS-ADRDA criteria). Psychic abnormalities were assessed as per the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). Possible extrapyramidal side effects were evaluated by means of the Abnormal Involuntary Movement Scale (AIMS). Initially 60 mg (0.3 ml) were administered intramuscularly and successive doses could be modified by +/-20 mg (0.1 ml) according to results seen on the various scales. During the first six weeks of treatment progressive improvement was noted on all three psychic functions scales in all patients. Between the sixth and twelfth weeks improvement continued although without significant change. The AIMS did not show significant changes in the twelve weeks of follow-up. We consider depot zuclopenthixol at low doses as efficacious in treating persistent psychomotor agitation and/or psychotic manifestations of Alzheimer's disease. No undesired side effects were observed in our group after a twelve week follow-up.

Evaluating Recall and Recognition Memory Using the Montreal Cognitive Assessment: Applicability for Alzheimer's and Huntington's Diseases.

Science.gov (United States)

Van Liew, Charles; Santoro, Maya S; Goldstein, Jody; Gluhm, Shea; Gilbert, Paul E; Corey-Bloom, Jody

2016-12-01

We sought to investigate whether the Montreal Cognitive Assessment (MoCA) could provide a brief assessment of recall and recognition using Huntington disease (HD) and Alzheimer disease (AD) as disorders characterized by different memory deficits. This study included 80 participants with HD, 64 participants with AD, and 183 community-dwelling control participants. Random-effects hierarchical logistic regressions were performed to assess the relative performance of the normal control (NC), participants with HD, and participants with AD on verbal free recall, cued recall, and multiple-choice recognition on the MoCA. The NC participants performed significantly better than participants with AD at all the 3 levels of assessment. No difference existed between participants with HD and NC for cued recall, but NC participants performed significantly better than participants with HD on free recall and recognition. The participants with HD performed significantly better than participants with AD at all the 3 levels of assessment. The MoCA appears to be a valuable, brief cognitive assessment capable of identifying specific memory deficits consistent with known differences in memory profiles. © The Author(s) 2016.

Predicting cognitive decline in Alzheimer's disease: an integrated analysis

DEFF Research Database (Denmark)

Lopez, Oscar L; Schwam, Elias; Cummings, Jeffrey

2010-01-01

Numerous patient- and disease-related factors increase the risk of rapid cognitive decline in patients with Alzheimer's disease (AD). The ability of pharmacological treatment to attenuate this risk remains undefined.......Numerous patient- and disease-related factors increase the risk of rapid cognitive decline in patients with Alzheimer's disease (AD). The ability of pharmacological treatment to attenuate this risk remains undefined....

The effect of red grape juice on Alzheimer's disease in rats.

Science.gov (United States)

Siahmard, Zahra; Alaei, Hojjatollah; Reisi, Parham; Pilehvarian, Ali Asghar

2012-01-01

Alzheimer's disease is a neurodegenerative disease appearing as a result of free radicals and oxidative stress. Antioxidants agents boost memory and control Alzheimer's disease. Since red grape juice contains antioxidant agents, its effects on speed of learning and improvement of memory was studied in Alzheimer's rats. Alzheimer's model was induced by bilateral infusion of streptozocine into lateral ventricles of brain of male rats. Rats drank 10% red grape juice for 21 days. Passive avoidance learning test was used for measuring memory and learning in rats. Our results showed that learning and memory in STZ-group decreased significantly compared to Sham group. However, intake of red grape juice increased speed of learning and improvement of memory in Alzheimer's rats. Our results suggest that there are active ingredients in red grape juice, which probably have therapeutic and preventive effects on cognitive impairments in Alzheimer's disease.

Validation of Alzheimer's disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer's Disease Neuroimaging Initiative (E-ADNI)

DEFF Research Database (Denmark)

Buerger, Katharina; Frisoni, Giovanni; Uspenskaya, Olga

2009-01-01

BACKGROUND: Alzheimer's Disease Neuroimaging Initiatives ("ADNI") aim to validate neuroimaging and biochemical markers of Alzheimer's disease (AD). Data of the pilot European-ADNI (E-ADNI) biological marker programme of cerebrospinal fluid (CSF) and plasma candidate biomarkers are reported. METHO...

Software tool for improved prediction of Alzheimer's disease

DEFF Research Database (Denmark)

Soininen, Hilkka; Mattila, Jussi; Koikkalainen, Juha

2012-01-01

Diagnostic criteria of Alzheimer's disease (AD) emphasize the integration of clinical data and biomarkers. In practice, collection and analysis of patient data vary greatly across different countries and clinics.......Diagnostic criteria of Alzheimer's disease (AD) emphasize the integration of clinical data and biomarkers. In practice, collection and analysis of patient data vary greatly across different countries and clinics....

Telomere shortening reduces Alzheimer's disease amyloid pathology in mice

NARCIS (Netherlands)

Rolyan, Harshvardhan; Scheffold, Annika; Heinrich, Annette; Begus-Nahrmann, Yvonne; Langkopf, Britta Heike; Hoelter, Sabine M.; Vogt-Weisenhorn, Daniela M.; Liss, Birgit; Wurst, Wolfgang; Lie, Dieter Chichung; Thal, Dietmar Rudolf; Biber, Knut; Rudolph, Karl Lenhard

Alzheimer's disease is a neurodegenerative disorder of the elderly and advancing age is the major risk factor for Alzheimer's disease development. Telomere shortening represents one of the molecular causes of ageing that limits the proliferative capacity of cells, including neural stem cells.

An approach for estimating item sensitivity to within-person change over time: An illustration using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog).

Science.gov (United States)

Dowling, N Maritza; Bolt, Daniel M; Deng, Sien

2016-12-01

When assessments are primarily used to measure change over time, it is important to evaluate items according to their sensitivity to change, specifically. Items that demonstrate good sensitivity to between-person differences at baseline may not show good sensitivity to change over time, and vice versa. In this study, we applied a longitudinal factor model of change to a widely used cognitive test designed to assess global cognitive status in dementia, and contrasted the relative sensitivity of items to change. Statistically nested models were estimated introducing distinct latent factors related to initial status differences between test-takers and within-person latent change across successive time points of measurement. Models were estimated using all available longitudinal item-level data from the Alzheimer's Disease Assessment Scale-Cognitive subscale, including participants representing the full-spectrum of disease status who were enrolled in the multisite Alzheimer's Disease Neuroimaging Initiative. Five of the 13 Alzheimer's Disease Assessment Scale-Cognitive items demonstrated noticeably higher loadings with respect to sensitivity to change. Attending to performance change on only these 5 items yielded a clearer picture of cognitive decline more consistent with theoretical expectations in comparison to the full 13-item scale. Items that show good psychometric properties in cross-sectional studies are not necessarily the best items at measuring change over time, such as cognitive decline. Applications of the methodological approach described and illustrated in this study can advance our understanding regarding the types of items that best detect fine-grained early pathological changes in cognition. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

In vivo target bio-imaging of Alzheimer's disease by fluorescent zinc oxide nanoclusters.

Science.gov (United States)

Lai, Lanmei; Zhao, Chunqiu; Su, Meina; Li, Xiaoqi; Liu, Xiaoli; Jiang, Hui; Amatore, Christian; Wang, Xuemei

2016-07-21

Alzheimer's disease (AD) is an irreversible neurodegenerative disease which is difficult to cure. When Alzheimer's disease occurs, the level of zinc ions in the brain changes, and the relevant amount of zinc ions continue decreasing in the cerebrospinal fluid and plasma of Alzheimer's patients with disease exacerbation. In view of these considerations, we have explored a new strategy for the in vivo rapid fluorescence imaging of Alzheimer's disease through target bio-labeling of zinc oxide nanoclusters which were biosynthesized in vivo in the Alzheimer's brain via intravenous injection of zinc gluconate solution. By using three-month-old and six-month-old Alzheimer's model mice as models, our observations demonstrate that biocompatible zinc ions could pass through the blood-brain barrier of the Alzheimer's disease mice and generate fluorescent zinc oxide nanoclusters (ZnO NCs) through biosynthesis, and then the bio-synthesized ZnO NCs could readily accumulate in situ on the hippocampus specific region for the in vivo fluorescent labeling of the affected sites. This study provides a new way for the rapid diagnosis of Alzheimer's disease and may have promising prospects in the effective diagnosis of Alzheimer's disease.

Impaired awareness of deficits and neuropsychiatric symptoms in early Alzheimer's disease: the Danish Alzheimer Intervention Study (DAISY)

DEFF Research Database (Denmark)

Vogel, A.; Waldorff, Frans Boch; Waldemar, G.

2010-01-01

Impaired awareness may be associated with increased neuropsychiatric symptoms in moderate to severe Alzheimer's disease, but relatively little is known about the association in early Alzheimer's disease. The aim of this study was to investigate if impaired awareness was associated with a higher...... frequency of neuropsychiatric symptoms in early Alzheimer's disease. In a Danish multicenter study, 321 patients with MMSE score > or =20 were evaluated. Patients with poor insight had significantly more neuropsychiatric symptoms than patients with full insight. When patients had increasing neuropsychiatric...

Role of neuropsychological assessment in the differential diagnosis of Alzheimer's disease and vascular dementia

Directory of Open Access Journals (Sweden)

Érica Maria Lima Pimentel

Full Text Available Abstract The prevalence of dementia increases significantly from the age of 65 years, doubling every five years thereafter. Alzheimer's disease (AD and vascular dementia (VaD constitute the two main dementia types. Differentiating them encompasses anamnesis, neurological examination, laboratory and neuroimaging exams and neuropsychological assessment. Neuropsychological assessment produces different findings for each dementia type, and reveals those areas most impaired as well as those most preserved. The aim of the present article was to describe the role of neuropsychology in diagnosing dementia and achieving a differential diagnosis between AD and VaD. A general overview follows of the most widely known instruments used to assess cognitive function in dementia, and the cognitive changes seen in AD and VaD. The conclusion drawn was that there is significant overlap in cognitive changes between both these dementia types, while each type has its own specific characteristics which are identifiable and quantifiable on neuropsychological assessments and provide the basis for reaching a differential diagnosis.

Alzheimer's Disease Facts and Figures

Medline Plus

Full Text Available ... Argentina ADNI Amyloid Imaging Task Force Alzheimer’s Association Business Consortia (AABC) Biomarker Consortium GBSC Working Groups Global Alzheimer’s Association Interactive Network International Alzheimer's Disease Research ...

Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

Science.gov (United States)

Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

2006-02-01

Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

Inter-observer variation of diagnosis of Alzheimer's disease by SPECT

International Nuclear Information System (INIS)

Oshima, Motoo; Machida, Kikuo; Koizumi, Kiyoshi

2001-01-01

SPECT shows characteristic distribution in Alzheimer's disease. The purpose of this study is to define inter-observer variations in the diagnosis of Alzheimer's disease. Fifty-seven patients, included 19 Alzheimer's disease were collected from four institutions. Five-graded score was used to interprete SPECT in 18 regions. Ten nuclear medicine physicians interpreted SPECT referred with MMSE and clinical information. Among 57 cases 19 Alzheimer's disease were selected in this study. Statistics were performed between SPECT score and MMSE score. In conclusion, inter-observer variation is present in SPECT interpretation. There was a good correlation SPECT and MMSE with proper brain SPECT physicians. They are superior to in the interpretation not only resident, but other specialists. Education in the interpretation of brain SPECT looks important. (author)

A culture-brain link: Negative age stereotypes predict Alzheimer's disease biomarkers.

Science.gov (United States)

Levy, Becca R; Ferrucci, Luigi; Zonderman, Alan B; Slade, Martin D; Troncoso, Juan; Resnick, Susan M

2016-02-01

Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease. (c) 2016 APA, all rights reserved).

Science Signaling Podcast for 10 May 2016: PKCα in Alzheimer's disease.

Science.gov (United States)

Newton, Alexandra C; Tanzi, Rudolph E; VanHook, Annalisa M

2016-05-10

This Podcast features an interview with Alexandra Newton and Rudolph Tanzi, authors of a Research Article that appears in the 10 May 2016 issue of Science Signaling, about activating mutations in protein kinase Cα that may promote the type of neural defects that characterize Alzheimer's disease. Alzheimer's disease is a progressive neurodegenerative disorder that causes cognitive loss and, eventually, death. Alzheimer's disease is characterized by the accumulation of amyloid-β (Aβ), synaptic depression, and synaptic degeneration. Alfonso et al found activating mutations in the gene encoding protein kinase Cα (PKCα) in some families with inherited Alzheimer's disease. Loss of PKCα function prevented Aβ-induced synaptic depression in brain tissue from mice, suggesting that activated forms of PKCα may contribute to Alzheimer's disease in some patients.Listen to Podcast. Copyright © 2016, American Association for the Advancement of Science.

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

NARCIS (Netherlands)

Ossenkoppele, R.; Pijnenburg, Y.A.L.; Perry, D.C.; Cohn-Sheehy, B.I.; Scheltens, N.M.E.; Vogel, J.W.; Kramer, J.H.; van der Vlies, A.E.; La Joie, R.; Rosen, H.J.; van der Flier, W.M.; Grinberg, L.T.; Rozemuller, A.J.M.; Huang, E.J.; van Berckel, B.N.M.; Miller, B.L.; Barkhof, F.; Jagust, W.J.; Scheltens, P.; Seeley, W.W.; Rabinovici, G.D.

2015-01-01

A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical,

Global issues in drug development for Alzheimer's disease.

Science.gov (United States)

Doody, Rachelle S; Cole, Patricia E; Miller, David S; Siemers, Eric; Black, Ronald; Feldman, Howard; Schindler, Rachel; Graham, Stephen; Heath, Theresa; Khachaturian, Ara S; Evans, Rebecca; Carrillo, Maria C

2011-03-01

The number of clinical trials for Alzheimer's disease conducted outside the United States in a broad array of countries is increasing. As the number of compounds ready for clinical testing increases, and as trials become longer and more complex, this trend is expected to grow. The cultural and ethical context of global clinical trials, potential benefits for those involved, and practical approaches to obstacles generated by these global trials were discussed at a meeting of the Alzheimer's Association Research Roundtable. Regulatory issues, including regional differences in study registration procedures, rules for collecting and reporting serious adverse events, requirements for national identity of study populations, and regulatory audits were also discussed by individuals who are knowledgeable about global clinical trials for Alzheimer's disease. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Proxy-rated quality of life in Alzheimer's disease

DEFF Research Database (Denmark)

Vogel, Asmus; Bhattacharya, Suvosree; Waldorff, Frans Boch

2012-01-01

The study investigated the change in proxy rated quality of life (QoL) of a large cohort of home living patients with Alzheimer's disease (AD) over a period of 36 months.......The study investigated the change in proxy rated quality of life (QoL) of a large cohort of home living patients with Alzheimer's disease (AD) over a period of 36 months....

Effect Size Analyses of Souvenaid in Patients with Alzheimer?s Disease

OpenAIRE

Cummings, Jeffrey; Scheltens, Philip; McKeith, Ian; Blesa, Rafael; Harrison, John E.; Bertolucci, Paulo H.F.; Rockwood, Kenneth; Wilkinson, David; Wijker, Wouter; Bennett, David A.; Shah, Raj C.

2016-01-01

Background: Souvenaid? (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes. Objective: To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm. Methods: Data from all three reported randomized controlled trials of Souvenaid in Alzheimer?s disease (...

The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer?s disease

OpenAIRE

Yang, Shuang-shuang; Zhang, Rui; Wang, Gang; Zhang, Yong-fang

2017-01-01

Alzheimer?s disease (AD) is a chronic neurodegenerative disease, which is associated with learning and memory impairment in the elderly. Recent studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic regimen. In a number of recent studies, inhibitors of histone deacetylase (HDACs) have been found to be a novel promising therapeutic?agents for neurological disorders, particularly for AD and other neurodegenerative diseases. Alth...

Evidence for brain glucose dysregulation in Alzheimer's disease.

Science.gov (United States)

An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

2018-03-01

It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

Genetic defect causing familial Alzheimer's disease maps on chromosome 21

Energy Technology Data Exchange (ETDEWEB)

St. George-Hyslop, P.H.; Tanzi, R.E.; Polinsky, R.J.; Haines, J.L.; Nee, L.; Watkins, P.C.; Myers, R.H.; Feldman, R.G.; Pollen, D.; Drachman, D.; Growdon, J.

1987-02-20

Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

Risk factors for Alzheimer's disease : a genetic-epidemiologic study

NARCIS (Netherlands)

C.M. van Duijn (Cornelia)

1992-01-01

textabstractThe work presented in this thesis has been motivated by the Jack of knowledge of risk factors for Alzheimer's disease. It has been long recognised that genetic factors are implicated, in particular in early-onset Alzheimer's disease.4 But to what extent are genetic factors involved?

The Alzheimer's Disease Knowledge Scale: Development and Psychometric Properties

Science.gov (United States)

Carpenter, Brian D.; Balsis, Steve; Otilingam, Poorni G.; Hanson, Priya K.; Gatz, Margaret

2009-01-01

Purpose: This study provides preliminary evidence for the acceptability, reliability, and validity of the new Alzheimer's Disease Knowledge Scale (ADKS), a content and psychometric update to the Alzheimer's Disease Knowledge Test. Design and Methods: Traditional scale development methods were used to generate items and evaluate their psychometric…

Bihemispheric cerebral FDG PET correlates of cognitive dysfunction as assessed by the CERAD in Alzheimer's disease.

Science.gov (United States)

Schönknecht, Oskar Dieter Peter; Hunt, Aoife; Toro, Pablo; Guenther, Thomas; Henze, Marcus; Haberkorn, Uwe; Schröder, Johannes

2011-04-01

Alzheimer's disease (AD) is characterized by a variety of cognitive deficits which can be reliably assessed by the neuropsychological test battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), but the cerebral changes underlying the respective cognitive deficits are only partly understood. Measures of severity of dementia in AD as well as delayed episodic memory performance in mild cognitive impairment significantly correlated with bihemispheric cerebral glucose hypometabolism. We therefore hypothesized that the CERAD cognitive battery may represent cerebral dysfunction of both hemispheres in patients with AD. In 32 patients with AD, cerebral glucose metabolism was investigated using positron-emission-tomography with 18Fluorodeoxyglucose (FDG PET) and associated with the test scores of the CERAD cognitive battery by statistical parametric mapping. Episodic memory scores significantly correlated with temporopari etal glucose metabolism of both hemispheres while delayed episodic memory significantly was correlated with the right frontotemporal cortices. Verbal fluency and naming scores significantly correlated with glucose metabolism in left temporoparietal and right frontal cortices, whereas constructional praxis predominantly correlated significantly with the bilateral precuneus. In conclusion, the results of our study demonstrate that not only memory function but also functions of language and constructional praxis in AD are associated with glucose metabolism as revealed by FDG PET in subsets of uni- and bilateral brain areas. The findings of our study for the first time demonstrate that in AD neuropsychological deficits as assessed by the CERAD refer to different cerebral sites of both hemispheres.

Therapeutics of Neurotransmitters in Alzheimer's Disease.

Science.gov (United States)

Kandimalla, Ramesh; Reddy, P Hemachandra

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by the loss of memory, multiple cognitive impairments and changes in the personality and behavior. Several decades of intense research have revealed that multiple cellular changes are involved in disease process, including synaptic damage, mitochondrial abnormalities and inflammatory responses, in addition to formation and accumulation of amyloid-β (Aβ) and phosphorylated tau. Although tremendous progress has been made in understanding the impact of neurotransmitters in the progression and pathogenesis of AD, we still do not have a drug molecule associated with neurotransmitter(s) that can delay disease process in elderly individuals and/or restore cognitive functions in AD patients. The purpose of our article is to assess the latest developments in neurotransmitters research using cell and mouse models of AD. We also updated the current status of clinical trials using neurotransmitters' agonists/antagonists in AD.

Detecting Treatment Group Differences in Alzheimer's Disease Clinical Trials: A Comparison of Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) and the Clinical Dementia Rating - Sum of Boxes (CDR-SB).

Science.gov (United States)

Wessels, A M; Dowsett, S A; Sims, J R

2018-01-01

The Alzheimer's Disease Assessment Scale's cognitive subscale (ADAS-Cog) has been widely used as an outcome measure in Alzheimer's Disease (AD) clinical trials. In its original form (ADAS-Cog11), the scale has been used successfully in mild-to-moderate AD dementia populations, but its use is more limited in the study of earlier disease (mild cognitive impairment [MCI] or mild dementia due to AD) owing to lack of appropriate sensitivity of some items. With recent focus on earlier treatment, efforts have focused on the development of more sensitive tools, including the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a global assessment tool to evaluate both cognition and function. The ability of the ADAS-Cog and CDR-SB to detect treatment group differences in the clinical trial environment has not been systematically studied. The aim of this analysis was to compare the utility of these tools in detecting treatment group differences, by reviewing study findings identified through advanced searches of clinicaltrials.gov and Ovid, and press releases and scientific presentations. Findings from placebo-controlled studies of ≥ 6m duration and enrolling >100 participants were included; reporting of both the ADAS-Cog and CDR-SB at endpoint was also a requirement. Of the >300 records identified, 34 studies fulfilled the criteria. There were significant placebo versus active drug group differences based on findings from at least one measure for 14 studies. The ADAS-Cog detected treatment differences more frequently than the CDR-SB. Based on these and previously published findings, the ADAS-Cog appears more useful than the CDR-SB in detecting treatment group differences.

Accumulation of murine amyloid-β mimics early Alzheimer's disease.

Science.gov (United States)

Krohn, Markus; Bracke, Alexander; Avchalumov, Yosef; Schumacher, Toni; Hofrichter, Jacqueline; Paarmann, Kristin; Fröhlich, Christina; Lange, Cathleen; Brüning, Thomas; von Bohlen Und Halbach, Oliver; Pahnke, Jens

2015-08-01

Amyloidosis mouse models of Alzheimer's disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer's families. Although these models made substantial contributions to the current knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer's disease, which accounts for patients with Alzheimer's disease. The inherited form is even regarded a 'rare' disease according to the regulations for funding of the European Union (www.erare.eu). Here, we show that mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid-β-degrading enzyme, and the ABC transporter ABCC1, a major contributor to amyloid-β clearance from the brain, develop various aspects of sporadic Alzheimer's disease mimicking the clinical stage of mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows investigations

Positron emission tomography studies of neuronal activity patterns during sensory and cognitive stimulations in Alzheimer`s disease. A study of cortical attention sites in man

Energy Technology Data Exchange (ETDEWEB)

Johannsen, Peter

1997-12-31

This Ph.D.-thesis describes different subtypes of attention, models for the organization of attention, and the attention deficits in Alzheimer`s disease. The experimental part of the study is based on studies of sustained and divided attention to two different sensory modalities; a visual checkerboard stimulation reversing at 7 Hz, and a 110 Hz vibrotactile stimulation of the right hand in a group of healthy elderly subjects (n = 16) age-matched with a group of patients with mild to moderate Alzheimer`s disease (n = 16). The cortical activations during the attention tasks have been mapped using O-15-water and positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) during rest and during performance of an attention task. After anatomical standardization and averaging over subjects, activation foci were assessed by a t-statistical evaluation of the differences of rCBF maps acquired before and during the execution of the attention tasks. The rCBF deficits in the Alzheimer patients were compared to rCBF pattern in the healthy elderly and assessed statistically on a voxel-by-voxel basis, revealing a distinct and localized pattern of rCBF deficits extending from the hippocampal area along the longitudinal fascicle to the temporo-parietal cortices with further deficits in the frontal regions. The resting rCBF deficits are distributed with the same pattern as described in neuropathological studies of lesions in Alzheimer`s disease. In the healthy elderly, both sustained and divided attention elicited activation of the right inferior parietal lobule (Brodmann Area 19/40) and the right middle frontal gyrus (Brodmann Area 46). Divided attention favored activation of the right middle frontal gyrus and sustained attention activation of the right inferior parietal lobule. Both the frontal and the parietal attention sites were active during attention to both the visual and the vibrotactile stimuli. These results support a network hypothesis of

Caregiving for Alzheimer's Disease or Other Dementia

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... What's this? Submit Button Caregiving for Person with Alzheimer's Disease or a related Dementia Recommend on Facebook Tweet Share Compartir What is Alzheimer’s Disease? Alzheimer’s disease is the most common form ...

Current treatments for patients with Alzheimer disease.

Science.gov (United States)

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.

Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease

Science.gov (United States)

Gargini, Ricardo; García, Esther; Perry, George

2017-01-01

Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer's pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer's patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer's disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients' fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer's fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging. PMID:29201274

Lexical priming in Alzheimer's disease and aphasia.

Science.gov (United States)

Arroyo-Anlló, Eva Maria; Beauchamps, Mireille; Ingrand, Pierre; Neau, Jean Philippe; Gil, Roger

2013-01-01

Lexical priming was examined in patients with Alzheimer's disease and in aphasic patients. Control participants were divided into young and elderly [cf. Arroyo-Anlló et al.: Eur J Cogn Psychol 2004;16:535-553]. For lexical priming, a word-stem completion task was used. Normal elderly participants had lexical priming scores that were significantly lower than those of young individuals. Analysis of covariance with age and educational level as covariates showed that the control participants, aphasic and Alzheimer patients did not differ significantly on the lexical priming task. Our results suggest that performance in the lexical priming task diminishes with physiological aging, but is not significantly affected by mild or moderate Alzheimer's disease or by fluent or non-fluent aphasia. Copyright © 2013 S. Karger AG, Basel.

Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease.

Science.gov (United States)

Rodriguez-Vieitez, Elena; Saint-Aubert, Laure; Carter, Stephen F; Almkvist, Ove; Farid, Karim; Schöll, Michael; Chiotis, Konstantinos; Thordardottir, Steinunn; Graff, Caroline; Wall, Anders; Långström, Bengt; Nordberg, Agneta

2016-03-01

Alzheimer's disease is a multifactorial dementia disorder characterized by early amyloid-β, tau deposition, glial activation and neurodegeneration, where the interrelationships between the different pathophysiological events are not yet well characterized. In this study, longitudinal multitracer positron emission tomography imaging of individuals with autosomal dominant or sporadic Alzheimer's disease was used to quantify the changes in regional distribution of brain astrocytosis (tracer (11)C-deuterium-L-deprenyl), fibrillar amyloid-β plaque deposition ((11)C-Pittsburgh compound B), and glucose metabolism ((18)F-fluorodeoxyglucose) from early presymptomatic stages over an extended period to clinical symptoms. The 52 baseline participants comprised autosomal dominant Alzheimer's disease mutation carriers (n = 11; 49.6 ± 10.3 years old) and non-carriers (n = 16; 51.1 ± 14.2 years old; 10 male), and patients with sporadic mild cognitive impairment (n = 17; 61.9 ± 6.4 years old; nine male) and sporadic Alzheimer's disease (n = 8; 63.0 ± 6.5 years old; five male); for confidentiality reasons, the gender of mutation carriers is not revealed. The autosomal dominant Alzheimer's disease participants belonged to families with known mutations in either presenilin 1 (PSEN1) or amyloid precursor protein (APPswe or APParc) genes. Sporadic mild cognitive impairment patients were further divided into (11)C-Pittsburgh compound B-positive (n = 13; 62.0 ± 6.4; seven male) and (11)C-Pittsburgh compound B-negative (n = 4; 61.8 ± 7.5 years old; two male) groups using a neocortical standardized uptake value ratio cut-off value of 1.41, which was calculated with respect to the cerebellar grey matter. All baseline participants underwent multitracer positron emission tomography scans, cerebrospinal fluid biomarker analysis and neuropsychological assessment. Twenty-six of the participants underwent clinical and imaging follow-up examinations after 2.8 ± 0.6 years. By using linear

Building a roadmap for developing combination therapies for Alzheimer's disease.

Science.gov (United States)

Perry, Daniel; Sperling, Reisa; Katz, Russell; Berry, Donald; Dilts, David; Hanna, Debra; Salloway, Stephen; Trojanowski, John Q; Bountra, Chas; Krams, Michael; Luthman, Johan; Potkin, Steven; Gribkoff, Val; Temple, Robert; Wang, Yaning; Carrillo, Maria C; Stephenson, Diane; Snyder, Heather; Liu, Enchi; Ware, Tony; McKew, John; Fields, F Owen; Bain, Lisa J; Bens, Cynthia

2015-03-01

Combination therapy has proven to be an effective strategy for treating many of the world's most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimer's disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition, the Critical Path Institute and the Alzheimer's Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.

Alzheimer's Disease Facts and Figures

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Full Text Available ... Today, someone in the United States develops Alzheimer's every 65 seconds. By mid-century, someone in the United States will develop the disease every 33 seconds. GET INVOLVED. Join the cause Mortality ...

Memantine Attenuates Alzheimer's Disease-Like Pathology and Cognitive Impairment.

Directory of Open Access Journals (Sweden)

Xiaochuan Wang

Full Text Available Deficiency of protein phosphatase-2A is a key event in Alzheimer's disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer's disease brain. In the present study, we overexpressed I1PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1PP2A in Wistar rats. The I1PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer's disease patients.

Effects of medicinal plants on Alzheimer's disease and memory deficits

Directory of Open Access Journals (Sweden)

Muhammad Akram

2017-01-01

Full Text Available Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper treatment option is still not available. There is no cure for Alzheimer's disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced worldwide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer's disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer's disease and memory deficits using conventional herbal therapy.

Investigation of Genetic Variants Associated with Alzheimer Disease in Parkinson Disease Cognition.

Science.gov (United States)

Barrett, Matthew J; Koeppel, Alexander F; Flanigan, Joseph L; Turner, Stephen D; Worrall, Bradford B

2016-01-01

Meta-analysis of genome-wide association studies have implicated multiple single nucleotide polymorphisms (SNPs) and associated genes with Alzheimer disease. The role of these SNPs in cognitive impairment in Parkinson disease (PD) remains incompletely evaluated. The objective of this study was to test alleles associated with risk of Alzheimer disease for association with cognitive impairment in Parkinson disease (PD). Two datasets with PD subjects accessed through the NIH database of Genotypes and Phenotypes contained both single nucleotide polymorphism (SNP) arrays and mini-mental state exam (MMSE) scores. Genetic data underwent rigorous quality control and we selected SNPs for genes associated with AD other than APOE. We constructed logistic regression and ordinal regression models, adjusted for sex, age at MMSE, and duration of PD, to assess the association between selected SNPs and MMSE score. In one dataset, PICALM rs3851179 was associated with cognitive impairment (MMSE  70 years old (OR = 2.3; adjusted p-value = 0.017; n = 250) but not in PD subjects ≤ 70 years old. Our finding suggests that PICALM rs3851179 could contribute to cognitive impairment in older patients with PD. It is important that future studies consider the interaction of age and genetic risk factors in the development of cognitive impairment in PD.

Delayed-Start Analyses in the Phase 3 Solanezumab EXPEDITION3 Study in Mild Alzheimer's Disease.

Science.gov (United States)

Liu-Seifert, H; Case, M G; Andersen, S W; Holdridge, K C; Aisen, P S; Kollack-Walker, S; Siemers, E

2018-01-01

A delayed-start design has been proposed to assess a potential disease-modifying effect in investigational drugs for Alzheimer's disease that target the underlying disease process. We extended this methodology to recently obtained data from the EXPEDITION3. EXPEDITION3 was a Phase 3, double-blind study with participants randomized to solanezumab (400 mg) or placebo every 4 weeks for 80 weeks, with an optional extension of active treatment. The delayed-start analysis was designed to determine if a statistically significant treatment difference established during the placebo-controlled period is maintained (at predefined level) during the delayed-start period, which would suggest the active drug has a disease-modifying effect. The delayed-start analysis was assessed across multiple efficacy measures, and includes data from baseline in the placebo-controlled period and up to 9 months in the delayed-start period. No significant difference was observed between the placebo and solanezumab treatment groups at the end of the placebo-controlled period for the Alzheimer's Disease Assessment Scale-Cognitive 14-item subscale. A significant treatment difference was observed at the end of the placebo-controlled period for the Alzheimer's Disease Cooperative Study-Activities of Daily Living instrumental items, an effect also seen at 6 months in the delayed-start period, and the noninferiority criterion was met. No other efficacy measures met these criteria. Delayed-start statistical methodology was used to understand the longitudinal outcomes in EXPEDITION3 and its extension. The small treatment differences observed at the end of the placebo-controlled phase prevented adequate assessment of any putative disease modifying effect.

Combined Creutzfeldt-Jakob/ Alzheimer's Disease Cases are Important in Search for Microbes in Alzheimer's Disease.

Science.gov (United States)

Bastian, Frank O

2017-01-01

The question whether Alzheimer's disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer's Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD. Further support for a microbial cause for AD comes from occurrence of mixed CJD/AD cases involving up to 15% of AD brains submitted to brain banks. The association of CJD with AD suggests a common etiology rather than simply being a medical curiosity. A co-infection with the transmissible agent of CJD, which we propose to be a Spiroplasma sp., would explain the diversity of bacteria shown to be associated with cases of AD.

Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

Science.gov (United States)

Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin L; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Chaibub Neto, Elias; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard J B; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Iyappan, Anandhi; Jiang, Qijia; Katsumata, Yuriko; Kauwe, John S K; Klein, Arno; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Ma, Tsung-Wei; Malhotra, Ashutosh; Mangravite, Lara M; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Peters, Mette A; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

2016-06-01

Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Predicting Alzheimer's disease by classifying 3D-Brain MRI images using SVM and other well-defined classifiers

International Nuclear Information System (INIS)

Matoug, S; Abdel-Dayem, A; Passi, K; Gross, W; Alqarni, M

2012-01-01

Alzheimer's disease (AD) is the most common form of dementia affecting seniors age 65 and over. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan. Advanced medical imaging and pattern recognition techniques are good tools to create a learning database in the first step and to predict the class label of incoming data in order to assess the development of the disease, i.e., the conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease, which is the most critical brain disease for the senior population. Advanced medical imaging such as the volumetric MRI can detect changes in the size of brain regions due to the loss of the brain tissues. Measuring regions that atrophy during the progress of Alzheimer's disease can help neurologists in detecting and staging the disease. In the present investigation, we present a pseudo-automatic scheme that reads volumetric MRI, extracts the middle slices of the brain region, performs segmentation in order to detect the region of brain's ventricle, generates a feature vector that characterizes this region, creates an SQL database that contains the generated data, and finally classifies the images based on the extracted features. For our results, we have used the MRI data sets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

Prevention of Alzheimer disease: The roles of nutrition and primary care.

Science.gov (United States)

Bane, Tabitha J; Cole, Connie

2015-05-15

Risk factors for developing Alzheimer disease include hypercholesterolemia, hypertension, obesity, and diabetes. Due to lack of effective treatments for Alzheimer disease, nutrition and primary prevention becomes important.

Alzheimer's Disease Facts and Figures

Medline Plus

Full Text Available ... as well as society as a whole. The development of biomarkers for Alzheimer's disease is making it ... I am a caregiver I am a care professional I am a physician I am a researcher ...

The cell cycle in Alzheimer disease: a unique target for neuropharmacology.

Science.gov (United States)

Webber, Kate M; Raina, Arun K; Marlatt, Michael W; Zhu, Xiongwei; Prat, María I; Morelli, Laura; Casadesus, Gemma; Perry, George; Smith, Mark A

2005-10-01

Several hypotheses have been proposed attempting to explain the pathogenesis of Alzheimer disease including, among others, theories involving amyloid deposition, tau phosphorylation, oxidative stress, metal ion dysregulation and inflammation. While there is strong evidence suggesting that each one of these proposed mechanisms contributes to disease pathogenesis, none of these mechanisms are able to account for all the physiological changes that occur during the course of the disease. For this reason, we and others have begun the search for a causative factor that predates known features found in Alzheimer disease, and that might therefore be a fundamental initiator of the pathophysiological cascade. We propose that the dysregulation of the cell cycle that occurs in neurons susceptible to degeneration in the hippocampus during Alzheimer disease is a potential causative factor that, together with oxidative stress, would initiate all known pathological events. Neuronal changes supporting alterations in cell cycle control in the etiology of Alzheimer disease include the ectopic expression of markers of the cell cycle, organelle kinesis and cytoskeletal alterations including tau phosphorylation. Such mitotic alterations are not only one of the earliest neuronal abnormalities in the disease, but as discussed herein, are also intimately linked to all of the other pathological hallmarks of Alzheimer disease including tau protein, amyloid beta protein precursor and oxidative stress, and even risk factors such as mutations in the presenilin genes. Therefore, therapeutic interventions targeted toward ameliorating mitotic changes would be predicted to have a profound and positive impact on Alzheimer disease progression.

Reduction of Alzheimer's disease beta-amyloid pathology in the absence of gut microbiota

OpenAIRE

Harach, T.; Marungruang, N.; Dutilleul, N.; Cheatham, V.; Coy, K. D. Mc; Neher, J. J.; Jucker, M.; Fåk, F.; T.; Lasser; Bolmont, T.

2015-01-01

Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. We generated a germ-free mouse model of Alzheimer's disease and discovered a drastic reduction of cerebral Ab amyloid pathology when compared to control Alzheimer's disease a...

Aging and Alzheimer's Disease: Lessons from the Nun Study.

Science.gov (United States)

Snowdon, David A.

1997-01-01

Describes a woman who maintained high cognitive test scores until her death at 101 years of age despite anatomical evidence of Alzheimer's disease. The woman was part of a larger "Nun Study" in which 678 sisters donated their brains to teach others about the etiology of aging and Alzheimer's disease. Findings are discussed. (RJM)

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease

DEFF Research Database (Denmark)

Hoffmann, Kristine; Sobol, Nanna A; Frederiksen, Kristian S

2016-01-01

BACKGROUND: Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent. OBJECTIVE: To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. METHODS: In a randomized controlled trial, we recruite...... 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.......BACKGROUND: Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent. OBJECTIVE: To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. METHODS: 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 change from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes...

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

NARCIS (Netherlands)

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

2010-01-01

Background and Purpose-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

Clinically Unsuspected Prion Disease Among Patients With Dementia Diagnoses in an Alzheimer's Disease Database.

Science.gov (United States)

Maddox, Ryan A; Blase, J L; Mercaldo, N D; Harvey, A R; Schonberger, L B; Kukull, W A; Belay, E D

2015-12-01

Brain tissue analysis is necessary to confirm prion diseases. Clinically unsuspected cases may be identified through neuropathologic testing. National Alzheimer's Coordinating Center (NACC) Minimum and Neuropathologic Data Set for 1984 to 2005 were reviewed. Eligible patients had dementia, underwent autopsy, had available neuropathologic data, belonged to a currently funded Alzheimer's Disease Center (ADC), and were coded as having an Alzheimer's disease clinical diagnosis or a nonprion disease etiology. For the eligible patients with neuropathology indicating prion disease, further clinical information, collected from the reporting ADC, determined whether prion disease was considered before autopsy. Of 6000 eligible patients in the NACC database, 7 (0.12%) were clinically unsuspected but autopsy-confirmed prion disease cases. The proportion of patients with dementia with clinically unrecognized but autopsy-confirmed prion disease was small. Besides confirming clinically suspected cases, neuropathology is useful to identify unsuspected clinically atypical cases of prion disease. © The Author(s) 2015.

Computed tomography of the temporal horns at Alzheimer's disease. Computertomographie der Temporalhoerner bei Morbus Alzheimer

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Gerber, U; Vogel, [Allgemeines Krankenhaus Ochsenzoll, Hamburg (Germany, F.R.). Abt. Roentgendiagnostik

1989-06-01

In the literature there are different opinions referring to the involvement of the temporal lobes or horns at Alzheimer's disease. Conventionally computed tomogram of the head does not include the temporal horn in its full length. A simple method to demonstrate the temporal horns after cranial computer tomography is described. It allows the evaluation of temporal lobe and temporal horn if questionable alterations at Alzheimer's disease are to be discussed. (orig.).

Potential of chromatin modifying compounds for the treatment of Alzheimer's disease.

Science.gov (United States)

Karagiannis, Tom C; Ververis, Katherine

2012-01-01

Alzheimer's disease is a very common progressive neurodegenerative disorder affecting the learning and memory centers in the brain. The hallmarks of disease are the accumulation of β-amyloid neuritic plaques and neurofibrillary tangles formed by abnormally phosphorylated tau protein. Alzheimer's disease is currently incurable and there is an intense interest in the development of new potential therapies. Chromatin modifying compounds such as sirtuin modulators and histone deacetylase inhibitors have been evaluated in models of Alzheimer's disease with some promising results. For example, the natural antioxidant and sirtuin 1 activator resveratrol has been shown to have beneficial effects in animal models of disease. Similarly, numerous histone deacetylase inhibitors including Trichostatin A, suberoylanilide hydroxamic acid, valproic acid and phenylbutyrate reduction have shown promising results in models of Alzheimer's disease. These beneficial effects include a reduction of β-amyloid production and stabilization of tau protein. In this review we provide an overview of the histone deacetylase enzymes, with a focus on enzymes that have been identified to have an important role in the pathobiology of Alzheimer's disease. Further, we discuss the potential for pharmacological intervention with chromatin modifying compounds that modulate histone deacetylase enzymes.

Potential of chromatin modifying compounds for the treatment of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Tom C. Karagiannis

2012-02-01

Full Text Available Alzheimer's disease is a very common progressive neurodegenerative disorder affecting the learning and memory centers in the brain. The hallmarks of disease are the accumulation of β-amyloid neuritic plaques and neurofibrillary tangles formed by abnormally phosphorylated tau protein. Alzheimer's disease is currently incurable and there is an intense interest in the development of new potential therapies. Chromatin modifying compounds such as sirtuin modulators and histone deacetylase inhibitors have been evaluated in models of Alzheimer's disease with some promising results. For example, the natural antioxidant and sirtuin 1 activator resveratrol has been shown to have beneficial effects in animal models of disease. Similarly, numerous histone deacetylase inhibitors including Trichostatin A, suberoylanilide hydroxamic acid, valproic acid and phenylbutyrate reduction have shown promising results in models of Alzheimer's disease. These beneficial effects include a reduction of β-amyloid production and stabilization of tau protein. In this review we provide an overview of the histone deacetylase enzymes, with a focus on enzymes that have been identified to have an important role in the pathobiology of Alzheimer's disease. Further, we discuss the potential for pharmacological intervention with chromatin modifying compounds that modulate histone deacetylase enzymes.

Pharmacologic management of Alzheimer disease.

Science.gov (United States)

Downey, Deborah

2008-02-01

Although the diagnosis of AD can be devastating, treatment options exist that can slow the disease's progression and allow patients to continue performing ADLs, thereby improving the quality of life for both patient and caregiver. Research is ongoing, and it is estimated by the Alzheimer's Association that finding a treatment that could delay onset by only 5 years could reduce the number of individuals with AD by nearly 50% over the next 50 years (Alzheimer's Association, 2007). Although pharmacotherapy is not yet a cure, it does remain an important part of a total approach to caring for patients and families affected by AD.

Development of the Korean version of Alzheimer's Disease Assessment Scale (ADAS-K).

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Youn, J C; Lee, D Y; Kim, K W; Lee, J H; Jhoo, J H; Lee, K U; Ha, J; Woo, J I

2002-09-01

The purpose of this study was the development of the Korean Version of Alzheimer's Disease Assessment Scale (ADAS-K). ADAS-K was administrated to 84 AD patients as well as 105 non-demented control subjects. Three aspects of reliability were tested. To evaluate the validity of ADAS-K, discriminant validity and concurrent validity were tested. To evaluate the sensitivity of ADAS-K to disease severity, all subjects, AD patients and control subjects, were grouped by CDR scale and their mean scores on ADAS-K were compared. ADAS-K demonstrated high levels of reliability. Mean ADAS-K scores for AD patients were significantly different from the control group (p ADAS-K exhibited significant correlations with other tests and scales (range 0.45-0.85, p ADAS-K displayed high diagnostic efficacy and the optimal cut-off point was selected between 18/19. ADAS-K was able to discriminate the degree of AD severity according to CDR classification. Our results suggested that ADAS-K-cog was sensitive to very mild AD. We demonstrated that ADAS-K is a reliable and valid instrument not only for AD diagnosis but also for evaluation of its severity. Copyright 2002 John Wiley & Sons, Ltd.

Compensatory responses induced by oxidative stress in Alzheimer disease

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PAULA I MOREIRA

2006-01-01

Full Text Available Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques. In the first stage of development of the disease, amyloid-β deposition and hyperphosphorylated tau function as compensatory responses and downstream adaptations to ensure that neuronal cells do not succumb to oxidative damage. These findings suggest that Alzheimer disease is associated with a novel balance in oxidant homeostasis.

Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score.

Directory of Open Access Journals (Sweden)

Rahul S Desikan

2017-03-01

Full Text Available Identifying individuals at risk for developing Alzheimer disease (AD is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction.Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer's Project (IGAP Stage 1, we identified AD-associated SNPs (at p < 10-5. We then integrated these AD-associated SNPs into a Cox proportional hazard model using genotype data from a subset of 6,409 AD patients and 9,386 older controls from Phase 1 of the Alzheimer's Disease Genetics Consortium (ADGC, providing a polygenic hazard score (PHS for each participant. By combining population-based incidence rates and the genotype-derived PHS for each individual, we derived estimates of instantaneous risk for developing AD, based on genotype and age, and tested replication in multiple independent cohorts (ADGC Phase 2, National Institute on Aging Alzheimer's Disease Center [NIA ADC], and Alzheimer's Disease Neuroimaging Initiative [ADNI], total n = 20,680. Within the ADGC Phase 1 cohort, individuals in the highest PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE ε3/3 individuals, the PHS modified expected age of AD onset by more than 10 y between the lowest and highest deciles (hazard ratio 3.34, 95% CI 2.62-4.24, p = 1.0 × 10-22. In independent cohorts, the PHS strongly predicted empirical age of AD onset (ADGC Phase 2, r = 0.90, p = 1.1 × 10-26 and longitudinal progression from normal aging to AD (NIA ADC, Cochran-Armitage trend test, p = 1.5 × 10-10, and was associated with neuropathology (NIA ADC, Braak stage of neurofibrillary tangles, p = 3.9 × 10-6, and Consortium to Establish a Registry for Alzheimer's Disease score for neuritic plaques, p = 6.8 × 10-6 and in vivo markers of AD neurodegeneration (ADNI

Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers.

Science.gov (United States)

García-Blanco, Ana; Peña-Bautista, Carmen; Oger, Camille; Vigor, Claire; Galano, Jean-Marie; Durand, Thierry; Martín-Ibáñez, Nuria; Baquero, Miguel; Vento, Máximo; Cháfer-Pericás, Consuelo

2018-07-01

Lipid peroxidation plays an important role in Alzheimer Disease, so corresponding metabolites found in urine samples could be potential biomarkers. The aim of this work is to develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry analytical method to determine a new set of lipid peroxidation compounds in urine samples. Excellent sensitivity was achieved with limits of detection between 0.08 and 17 nmol L -1 , which renders this method suitable to monitor analytes concentrations in real samples. The method's precision was satisfactory with coefficients of variation around 5-17% (intra-day) and 8-19% (inter-day). The accuracy of the method was assessed by analysis of spiked urine samples obtaining recoveries between 70% and 120% for most of the analytes. The utility of the described method was tested by analyzing urine samples from patients early diagnosed with mild cognitive impairment or mild dementia Alzheimer Disease following the clinical standard criteria. As preliminary results, some analytes (17(RS)-10-epi-SC-Δ 15 -11-dihomo-IsoF, PGE 2 ) and total parameters (Neuroprostanes, Isoprostanes, Isofurans) show differences between the control and the clinical groups. So, these analytes could be potential early Alzheimer Disease biomarkers assessing the patients' pro-oxidant condition. Copyright © 2018 Elsevier B.V. All rights reserved.

Dependence and caregiver burden in Alzheimer's disease and mild cognitive impairment.

LENUS (Irish Health Repository)

Gallagher, Damien

2011-03-01

The dependence scale has been designed to be sensitive to the overall care needs of the patient and is considered distinct from standard measures of functional ability in this regard. Little is known regarding the relationship between patient dependence and caregiver burden. We recruited 100 patients with Alzheimer\\'s disease or mild cognitive impairment and their caregivers through a memory clinic. Patient function, dependence, hours of care, cognition, neuropsychiatric symptoms, and caregiver burden were assessed. Dependence was significantly correlated with caregiver burden. Functional decline and dependence were most predictive of caregiver burden in patients with mild impairment while behavioral symptoms were most predictive in patients with moderate to severe disease. The dependence scale demonstrated good utility as a predictor of caregiver burden. Interventions to reduce caregiver burden should address patient dependence, functional decline, and behavioral symptoms while successful management of the latter becomes more critical with disease progression.

Mathematical model on Alzheimer's disease.

Science.gov (United States)

Hao, Wenrui; Friedman, Avner

2016-11-18

Alzheimer disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive skills. AD is characterized by the presence of two types of neuropathological hallmarks: extracellular plaques consisting of amyloid β-peptides and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. The disease affects 5 million people in the United States and 44 million world-wide. Currently there is no drug that can cure, stop or even slow the progression of the disease. If no cure is found, by 2050 the number of alzheimer's patients in the U.S. will reach 15 million and the cost of caring for them will exceed $ 1 trillion annually. The present paper develops a mathematical model of AD that includes neurons, astrocytes, microglias and peripheral macrophages, as well as amyloid β aggregation and hyperphosphorylated tau proteins. The model is represented by a system of partial differential equations. The model is used to simulate the effect of drugs that either failed in clinical trials, or are currently in clinical trials. Based on these simulations it is suggested that combined therapy with TNF- α inhibitor and anti amyloid β could yield significant efficacy in slowing the progression of AD.

Costs of Alzheimer's disease (in Dutch); A study of the most important cost items of patients with Alzheimer's disease in the Netherlands and in France

NARCIS (Netherlands)

N. van der Roer; J.J. van Busschbach (Jan); E.S. Goes; L. van Hakkaart-van Roijen (Leona)

2001-01-01

textabstractThe most frequently occurring type of dementia is Alzheimer's disease. Alzheimer's disease is a degenerative illness affecting the brain, decreasing the patient's memory and judgement. A cure is not available but it is possible to delay the cognitive decline with medication. New drugs

Souvenaid®: a new approach to management of early Alzheimer's disease.

Science.gov (United States)

Ritchie, C W; Bajwa, J; Coleman, G; Hope, K; Jones, R W; Lawton, M; Marven, M; Passmore, P

2014-03-01

Synaptic loss correlates closely with cognitive deficits in Alzheimer's disease and represents a new target for intervention. Souvenaid® is the first medical nutrition product to be designed to support synapse formation and function in early Alzheimer's disease, and has undergone an extensive, 12-year development programme. The relatively large amount of clinical data available for Souvenaid® is unusual for a medical nutrition product. Souvenaid® contains omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid), uridine (as uridine monophosphate) and choline which are nutritional precursors required for synaptic membrane phospholipid synthesis, together with phospholipids and other cofactors. Souvenaid® has demonstrated cognitive benefits in patients with mild Alzheimer's disease but not in patients with mild-to-moderate Alzheimer's disease. Two randomised, double-blind, controlled trials (duration 12 and 24 weeks) in patients with mild Alzheimer's disease untreated with acetylcholinesterase inhibitors and/or memantine have demonstrated that Souvenaid® is well tolerated and improves episodic memory performance. The daily intake of Souvenaid® has not been associated with any harmful effects or interactions with medications and none are anticipated. The ongoing, 24-month, European Union-funded LipiDiDiet trial in subjects with prodromal Alzheimer's disease is evaluating the potential benefits of Souvenaid® on memory and in slowing progression to Alzheimer's dementia. If Souvenaid® induces synaptogenesis and improved synaptic function, it may provide benefits in other clinical conditions characterised by neurodegeneration. A number of trials are ongoing and planned to evaluate the potential wider benefits of Souvenaid®.

An Arabic Version of the Cognitive Subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog): Reliability, Validity, and Normative Data.

Science.gov (United States)

Ben Jemaa, Sonia; Attia Romdhane, Neila; Bahri-Mrabet, Amel; Jendli, Adel; Le Gall, Didier; Bellaj, Tarek

2017-01-01

The Alzheimer's Disease Assessment Scale's cognitive subscale (ADAS-Cog) is the most widely used instrument for screening cognitive dysfunction in Alzheimer's disease. The aim of the present study was to develop an Arabic version of this scale (A-ADAS-Cog), examine its psychometric properties (reliability and validity), and provide normative data. The A-ADAS-Cog), an Arabic version of the Mini-Mental State Examination (A-MMSE), and a Standardized Clinical Dementia Rating Scale (CDR) were administered to three Tunisian groups: 124 normal controls (NC), 33 patients with non-Alzheimer dementia (N-AD), and 25 patients with Alzheimer's disease (AD). The A-ADAS-Cog scores were significantly affected by age and education. A correction table was constructed to control these effects. The results showed that the A-ADAS-Cog has good internal consistency and reliability (α= 0.82 for AD). The test-retest reliability of the A-ADAS-Cog was stable over time (r = 0.97). An evaluation of the construct validity of the A-ADAS-Cog using principal component analysis led to a solution with three factors (memory, language and praxis), which explained 72% of the variance. The concurrent validity of the A-ADAS-Cog was established using the A-MMSE score (r = -0.86), CDR Sum of Boxes score (CDR-SB; r = 0.87), and global CDR score (CDR-Global; r = 0.74). Finally, the A-ADAS-Cog has an excellent discriminating power in the diagnosis of AD (ROC area = 0.92). A cut-off score of 10 (sensitivity = 84% and specificity = 91%) is indicated for the screening of the AD. Overall, the results indicated that the A-ADAS-Cog is psychometrically reliable and valid and provides promising results for screening of dementia in Arabic speaking patients.

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

Science.gov (United States)

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

2016-01-01

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

Analysis of recent failures of disease modifying therapies in Alzheimer's disease suggesting a new methodology for future studies.

Science.gov (United States)

Amanatkar, Hamid Reza; Papagiannopoulos, Bill; Grossberg, George Thomas

2017-01-01

Pharmaceutical companies and the NIH have invested heavily in a variety of potential disease-modifying therapies for Alzheimer's disease (AD) but unfortunately all double-blind placebo-controlled Phase III studies of these drugs have failed to show statistically significant results supporting their clinical efficacy on cognitive measures. These negative results are surprising as most of these medications have the capability to impact the biomarkers which are associated with progression of Alzheimer's disease. Areas covered: This contradiction prompted us to review all study phases of Intravenous Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to shed more light on these recent failures. We critically analyzed these studies, recommending seven lessons from these failures which should not be overlooked. Expert commentary: We suggest a new methodology for future treatment research in Alzheimer's disease considering early intervention with more focus on cognitive decline as a screening tool, more sophisticated exclusion criteria with more reliance on biomarkers, stratification of subjects based on the rate of cognitive decline aiming less heterogeneity, and a longer study duration with periodic assessment of cognition and activities of daily living during the study and also after a washout period.

Artificial neural networks that use single-photon emission tomography to identify patients with probable Alzheimer`s disease

Energy Technology Data Exchange (ETDEWEB)

Dawson, M R.W. [Dept. of Psychology, Univ. of Alberta, Edmonton (Canada); Dobbs, A [Dept. of Psychology, Univ. of Alberta, Edmonton (Canada); Hooper, H R [Dept. of Nuclear Medicine, Cross Cancer Inst., Edmonton, AB (Canada); McEwan, A J.B. [Dept. of Radiology and Diagnostic Imaging, Univ. of Alberta, Edmonton (Canada); Triscott, J [Dept. of Family Medicine and Div. of Geriatric Medicine, Univ. of Alberta, Edmonton (Canada); Cooney, J [Dept. of Psychiatry, Univ. of Alberta, Edmonton (Canada)

1994-12-01

Single-photon emission tomographic (SPET) images using technetium-99m labelled hexamethylpropylene amine oxime were obtained from 97 patients diagnosed as having Alzheimer`s disease, as well as from a comparison group of 64 normal subjects. Multiple linear regression was used to predict subject type (Alzheimer`s vs comparison) using scintillation counts from 14 different brain regions as predictors. These results were disappointing: the regression equation accounted for only 33.5% of the variance between subjects. However, the same data were also used to train parallel distributed processing (PDP) networks of different sizes to classify subjects. In general, the PDP networks accounted for substantially more (up to 95%) of the variance in the data, and in many instances were able to distinguish perfectly between the two subjects. These results suggest two conclusions. First, SPET images do provide sufficient information to distinguish patients with Alzheimer`s disease from a normal comparison group. Second, to access this diagnostic information, it appears that one must take advantage of the ability of PDP networks to detect higher-order nonlinear relationships among the predictor variables. (orig.)

Unawareness of deficits in Alzheimer's disease: role of the cingulate cortex.

Science.gov (United States)

Amanzio, Martina; Torta, Diana M E; Sacco, Katiuscia; Cauda, Franco; D'Agata, Federico; Duca, Sergio; Leotta, Daniela; Palermo, Sara; Geminiani, Giuliano C

2011-04-01

Unawareness of deficits is a symptom of Alzheimer's disease that can be observed even in the early stages of the disease. The frontal hypoperfusion associated with reduced awareness of deficits has led to suggestions of the existence of a hypofunctioning prefrontal pathway involving the right dorsolateral prefrontal cortex, inferior parietal lobe, anterior cingulate gyri and limbic structures. Since this network plays an important role in response inhibition competence and patients with Alzheimer's disease who are unaware of their deficits exhibit impaired performance in response inhibition tasks, we predicted a relationship between unawareness of deficits and cingulate hypofunctionality. We tested this hypothesis in a sample of 29 patients with Alzheimer's disease (15 aware and 14 unaware of their disturbances), rating unawareness according to the Awareness of Deficit Questionnaire-Dementia scale. The cognitive domain was investigated by means of a wide battery including tests on executive functioning, memory and language. Neuropsychiatric aspects were investigated using batteries on behavioural mood changes, such as apathy and disinhibition. Cingulate functionality was assessed with functional magnetic resonance imaging, while patients performed a go/no-go task. In accordance with our hypotheses, unaware patients showed reduced task-sensitive activity in the right anterior cingulate area (Brodmann area 24) and in the rostral prefrontal cortex (Brodmann area 10). Unaware patients also showed reduced activity in the right post-central gyrus (Brodmann area 2), in the associative cortical areas such as the right parietotemporal-occipital junction (Brodmann area 39) and the left temporal gyrus (Brodmann areas 21 and 38), in the striatum and in the cerebellum. These findings suggest that the unawareness of deficits in early Alzheimer's disease is associated with reduced functional recruitment of the cingulofrontal and parietotemporal regions. Furthermore, in line with

The usefulness of CT scanning in clinical observation on the patients with Alzheimer's disease

International Nuclear Information System (INIS)

Golebiowski, M.; Barcikowska, M.; Pfeffer-Baczuk, A.; Luczywek, E.

1994-01-01

On the basis of brain CT studies of 150 patients of the clinic for persons with Alzheimer's disease the diagnostic utility of measurement of hippocampal fissure and craniocerebral ratios was assessed. In analyzed group hippocampal fissure measurements greater than 4 mm occurred only in patients with symptoms of Alzheimer's type dementia. The measurement showed 90% sensitivity and 70% specificity as the prognostic factor of clinical course, especially at the first part of the disease. The evaluation of the hippocampal fissure in conjunction with detailed analysis of CT picture of the atrophic brain allowed for precise final diagnosis. (author)

The Alzheimer's disease β-secretase enzyme, BACE1

Directory of Open Access Journals (Sweden)

Vassar Robert

2007-11-01

Full Text Available Abstract The pathogenesis of Alzheimer's disease is highly complex. While several pathologies characterize this disease, amyloid plaques, composed of the β-amyloid peptide are hallmark neuropathological lesions in Alzheimer's disease brain. Indeed, a wealth of evidence suggests that β-amyloid is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. The BACE1 enzyme is essential for the generation of β-amyloid. BACE1 knockout mice do not produce β-amyloid and are free from Alzheimer's associated pathologies including neuronal loss and certain memory deficits. The fact that BACE1 initiates the formation of β-amyloid, and the observation that BACE1 levels are elevated in this disease provide direct and compelling reasons to develop therapies directed at BACE1 inhibition thus reducing β-amyloid and its associated toxicities. However, new data indicates that complete abolishment of BACE1 may be associated with specific behavioral and physiological alterations. Recently a number of non-APP BACE1 substrates have been identified. It is plausible that failure to process certain BACE1 substrates may underlie some of the reported abnormalities in the BACE1-deficient mice. Here we review BACE1 biology, covering aspects ranging from the initial identification and characterization of this enzyme to recent data detailing the apparent dysregulation of BACE1 in Alzheimer's disease. We pay special attention to the putative function of BACE1 during healthy conditions and discuss in detail the relationship that exists between key risk factors for AD, such as vascular disease (and downstream cellular consequences, and the pathogenic alterations in BACE1 that are observed in the diseased state.

Alzheimer's disease: synaptic dysfunction and Abeta

LENUS (Irish Health Repository)

Shankar, Ganesh M

2009-11-23

Abstract Synapse loss is an early and invariant feature of Alzheimer\\'s disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid β-protein (Aβ) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Aβ are mediators of synaptic compromise. We also discuss the possible mechanisms of Aβ synaptotoxicity and potential targets for therapeutic intervention.

Does prevention for Alzheimer's disease exist?

Directory of Open Access Journals (Sweden)

Sonia Maria Dozzi Brucki

Full Text Available Abstract The prevention of Alzheimer's disease is a growing public health concern amidst an ageing population. Meanwhile, there is no effective or curative treatment available where prevention could greatly reduce health costs. This review was based on reports of potential preventive factors, including modifiable lifestyle factors, as well as preventive pharmacological strategies. Although the present review was not systematic, the reports selected from PubMed using "Alzheimer's disease" and "prevention" as key-words, allow us to affirm that pursuing a healthy lifestyle; physical, cognitive, leisure activities; good social engagement; a high consumption of fish, low consumption of dietary fat and moderate consumption of wine, and control of vascular risk factors appear to be potential factors for delaying dementia.

Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study.

Science.gov (United States)

Snowdon, D A; Kemper, S J; Mortimer, J A; Greiner, L H; Wekstein, D R; Markesbery, W R

1996-02-21

To determine if linguistic ability in early life is associated with cognitive function and Alzheimer's disease in late life. Two measures of linguistic ability in early life, idea density and grammatical complexity, were derived from autobiographies written at a mean age of 22 years. Approximately 58 years later, the women who wrote these autobiographies participated in an assessment of cognitive function, and those who subsequently died were evaluated neuropathologically. Convents in the United States participating in the Nun Study; primarily convents in the Milwaukee, Wis, area. Cognitive function was investigated in 93 participants who were aged 75 to 95 years at the time of their assessments, and Alzheimer's disease was investigated in the 14 participants who died at 79 to 96 years of age. Seven neuropsychological tests and neuropathologically confirmed Alzheimer's disease. Low idea density and low grammatical complexity in autobiographies written in early life were associated with low cognitive test scores in late life. Low idea density in early life had stronger and more consistent associations with poor cognitive function than did low grammatical complexity. Among the 14 sisters who died, neuropathologically confirmed Alzheimer's disease was present in all of those with low idea density in early life and in none of those with high idea density. Low linguistic ability in early life was a strong predictor of poor cognitive function and Alzheimer's disease in late life.

Deformability of Erythrocytes and Oxidative Damage in Alzheimer Disease

Directory of Open Access Journals (Sweden)

Mukerrem Betul Yerer

2012-04-01

Full Text Available Purpose: A lowered cerebral perfusion as a consequence of hemodynamic microcirculatory insufficiency is one of the factors underlying in Alzheimer's disease, which is a neurodegenerative disorder leading to progressive cognitive impairment. Erythrocyte deformability is one of the major factors affecting the microcirculatory hemodynamics which is closely related to the oxidative damage. The aim of this study is to investigate the relationship between the erythrocyte deformability, nitric oxide levels and oxidative stress in Alzheimer's disease. Methods: The blood samples of 30 elderly people in three groups consisting of healthy control and different severities of the disease (low and severe were used. Then the erythrocytes were isolated and the deformability of erythrocytes was determined by Rheodyne SSD evaluating the elongation indexes of the erythrocytes under different shear stress. The catalase, glutathione peroxidase and plasma nitric oxide levels were measured spectrophotometric ally. Results: The plasma nitric oxide levels, catalase activities were found significantly higher and glutathione peroxidase activity was significantly lower in severe Alzheimer's disease patients compared to the control group. However, the deformability of erythrocytes was not significantly affected from these alterations. Conclusion: the oxidant-antioxidant status is dramatically changed in Alzheimer's disease patients with the severity of the disease and similar alterations were seen in the nitric oxide levels without any significant change in erythrocyte deformability. [Cukurova Med J 2012; 37(2.000: 65-75

Generic and disease-specific measures of quality of life in patients with mild Alzheimer's disease

DEFF Research Database (Denmark)

Bhattacharya, Sumangala; Vogel, A.; Hansen, M.L.

2010-01-01

The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD).......The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD)....

Receiver operating characteristic analysis of regional cerebral blood flow in Alzheimer's disease

International Nuclear Information System (INIS)

Zemcov, A.; Barclay, L.L.; Sansone, J.; Metz, C.E.

1985-01-01

Receiver operating characteristic (ROC) curves were used to quantitatively assess the ability of individual detectors in a 32-detector 133 Xe inhalation system to discriminate between two populations over the range of regional cerebral blood flow (rCBF) values. These populations were clinically evaluated as normal (age 63.1 +/- 13.1, n = 23) and presumed Alzheimer's disease (age 72.7 +/- 7.0, n = 82). Summary statistics showed that for homologous detectors the average value of blood flow in the normal group was greater than the flow value in the group of subjects with Alzheimer's disease. Conclusions drawn from single values of flow or mean hemispheric flow can lead to erroneous conclusions about hemisphere asymmetries. However, the dynamic relationship between the correct identifications (true positives) compared with incorrect identifications (false positives) of Alzheimer's disease at each detector varies over the range of blood flow values, and quantitative characterization of this relationship in terms of an ROC curve provides more insight into the structure of the data. Detectors approximating the speech, auditory and association cortex were most effective in discriminating between groups. Frontal detectors were marginally useful diagnostically

Diagnosis and treatment of Alzheimer's disease

International Nuclear Information System (INIS)

Hampel, H.; Padberg, F.; Koetter, H.U.; Teipel, S.J.; Ehrhardt, T.; Hegerl, U.; Stuebner, S.; Moeller, H.J.

1997-01-01

Alzheimer's disease is often diagnosed too late. Its etiology is still largely unknown and remains one of the big challenges in neurobiological fundamental research. Optimized early and differential diagnosis can be ensured by a dynamic concept of multidisciplinary diagnosis in cooperation between practitioners specializing in brain disorders, clinical psychogeriatric deprtments, and general practitioners. This, in turn, will enable individualized planning of further living conditions and care of Alzheimer patients and their relations as well as efficient and early pharmacotherapy and psychological intervention. (orig) [de

Genome instability in Alzheimer disease

DEFF Research Database (Denmark)

Hou, Yujun; Song, Hyundong; Croteau, Deborah L

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Autosomal dominant, familial AD (fAD) is very rare and caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2) genes. The pathogenesis...

Quality of life and burden of spouses of Alzheimer disease patients.

NARCIS (Netherlands)

Dorenbos-Scholzel, C.J.M.; Draskovic, I.; Vernooij-Dassen, M.J.F.J.; Olde Rikkert, M.G.M.

2009-01-01

The objective of the study was to explore, in a sample of spouses of mild-to-moderate Alzheimer disease patients, predictors of quality of life (QoL) by rating QoL and burden. The authors assessed 97 spouses in a cross-sectional study with the Schedule for the Evaluation of Individual Quality of

ADO: a disease ontology representing the domain knowledge specific to Alzheimer's disease.

Science.gov (United States)

Malhotra, Ashutosh; Younesi, Erfan; Gündel, Michaela; Müller, Bernd; Heneka, Michael T; Hofmann-Apitius, Martin

2014-03-01

Biomedical ontologies offer the capability to structure and represent domain-specific knowledge semantically. Disease-specific ontologies can facilitate knowledge exchange across multiple disciplines, and ontology-driven mining approaches can generate great value for modeling disease mechanisms. However, in the case of neurodegenerative diseases such as Alzheimer's disease, there is a lack of formal representation of the relevant knowledge domain. Alzheimer's disease ontology (ADO) is constructed in accordance to the ontology building life cycle. The Protégé OWL editor was used as a tool for building ADO in Ontology Web Language format. ADO was developed with the purpose of containing information relevant to four main biological views-preclinical, clinical, etiological, and molecular/cellular mechanisms-and was enriched by adding synonyms and references. Validation of the lexicalized ontology by means of named entity recognition-based methods showed a satisfactory performance (F score = 72%). In addition to structural and functional evaluation, a clinical expert in the field performed a manual evaluation and curation of ADO. Through integration of ADO into an information retrieval environment, we show that the ontology supports semantic search in scientific text. The usefulness of ADO is authenticated by dedicated use case scenarios. Development of ADO as an open ADO is a first attempt to organize information related to Alzheimer's disease in a formalized, structured manner. We demonstrate that ADO is able to capture both established and scattered knowledge existing in scientific text. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

Mitochondrial Drugs for Alzheimer Disease

Directory of Open Access Journals (Sweden)

Xiongwei Zhu

2009-12-01

Full Text Available Therapeutic strategies for Alzheimer disease (AD have yet to offer a diseasemodifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus far are limited to agents that slow disease progression without halting it, and although much work towards a cure is underway, a greater understanding of disease etiology is certainly necessary for any such achievement. Mitochondria, as the centers of cellular metabolic activity and the primary generators of reactive oxidative species in the cell, received particular attention especially given that mitochondrial defects are known to contribute to cellular damage. Furthermore, as oxidative stress has come to the forefront of AD as a causal theory, and as mitochondrial damage is known to precede much of the hallmark pathologies of AD, it seems increasingly apparent that this metabolic organelle is ultimately responsible for much, if not all of disease pathogenesis. In this review, we review the role of neuronal mitochondria in the pathogenesis of AD and critically assess treatment strategies that utilize this upstream access point as a method for disease prevention. We suspect that, with a revived focus on mitochondrial repair and protection, an effective and realistic therapeutic agent can be successfully developed.

Early diagnosis of Alzheimer's disease. Clinical significance and future perspectives

International Nuclear Information System (INIS)

Buerger, K.; Teipel, S.J.; Hampel, H.

2000-01-01

Early diagnosis of Alzheimer's disease describes the recognition and diagnosis in patients with very mild dementia. Internationally accepted diagnostic criteria support the diagnosis based on clinical evaluation. Recent advances in structural and functional neuroimaging as well as studies on specific proteins in the cerebro-spinal fluid that are related to distinct pathophysiological disease processes are most promising approaches to defining biological markers of Alzheimer's disease. (orig.) [de

Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study.

Science.gov (United States)

Burnham, Samantha C; Bourgeat, Pierrick; Doré, Vincent; Savage, Greg; Brown, Belinda; Laws, Simon; Maruff, Paul; Salvado, Olivier; Ames, David; Martins, Ralph N; Masters, Colin L; Rowe, Christopher C; Villemagne, Victor L

2016-09-01

Brain amyloid β (Aβ) deposition and neurodegeneration have been documented in about 50-60% of cognitively healthy elderly individuals (aged 60 years or older). The long-term cognitive consequences of the presence of Alzheimer's disease pathology and neurodegeneration, and whether they have an independent or synergistic effect on cognition, are unclear. We aimed to characterise the long-term clinical and cognitive trajectories of healthy elderly individuals using a two-marker (Alzheimer's disease pathology and neurodegeneration) imaging construct. Between Nov 3, 2006, and Nov 25, 2014, 573 cognitively healthy individuals in Melbourne and Perth, Australia, (mean age 73·1 years [SD 6·2]; 58% women) were enrolled in the Australian Imaging, Biomarker and Lifestyle (AIBL) study. Alzheimer's disease pathology (A) was determined by measuring Aβ deposition by PET, and neurodegeneration (N) was established by measuring hippocampal volume using MRI. Individuals were categorised as A(-)N(-), A(+)N(-), A(+)N(+), or suspected non-Alzheimer's disease pathophysiology (A(-)N(+), SNAP). Clinical progression, hippocampal volume, standard neuropsychological tests, and domain-specific and global cognitive composite scores were assessed over 6 years of follow-up. Linear mixed effect models and a Cox proportional hazards model of survival were used to evaluate, compare, and contrast the clinical, cognitive, and volumetric trajectories of patients in the four AN categories. 50 (9%) healthy individuals were classified as A(+)N(+), 87 (15%) as A(+)N(-), 310 (54%) as A(-)N(-), and 126 (22%) as SNAP. APOE ε4 was more frequent in participants in the A(+)N(+) (27; 54%) and A(+)N(-) (42; 48%) groups than in the A(-)N(-) (66; 21%) and SNAP groups (23; 18%). The A(+)N(-) and A(+)N(+) groups had significantly faster cognitive decline than the A(-)N(-) group (0·08 SD per year for AIBL-Preclinical AD Cognitive Composite [PACC]; p<0·0001; and 0·25; p<0·0001; respectively). The A (+)N

Anti-Alzheimer Properties of Probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer's Disease induced Albino Rats.

Science.gov (United States)

Nimgampalle, Mallikarjuna; Kuna, Yellamma

2017-08-01

Alzheimer's disease is a type of dementia, and till now there is no suitable drug available for the complete cure of this disease. Now-a-days Probiotics, Lactobacillus strains play a therapeutic role in cognitive disorders through Gut-Brain Axis communication. The present study was aimed to evaluate the anti-Alzheimer properties of Lactobacillus plantarum MTCC1325 against D-Galactose-induced Alzheimer's disease in albino rats. Healthy rats (48) of wistar strain were divided into four groups viz., Group-I: control rats received saline, Group-II: rats received intraperitoneal injection of D-Galactose (120 mg/kg body weight) throughout experiment, Group-III: initially animals were subjected to D-Galactose injection for six weeks, then followed by simultaneously received both D-Galactose and L. plantarum MTCC1325 (12×10 8 CFU/ml; 10 ml/kg body weight) for 60 days and Group-IV: rats which were orally administered only with Lactobacillus plantarum MTCC1325 for 60 days. During the experimentation, both morphometric and behavioural aspects were studied. Later we have examined histopathological changes and estimated cholinergic levels in selected brain regions of all experimental groups of rats including control on selected days. Morphometric, behavioural changes, ACh levels were significantly decreased and pathological hallmarks such as amyloid plaques and tangles were also observed in AD model group. Treatment of AD-group with L. plantarum MTCC1325 for 60 days, not only ameliorated cognition deficits but also restored ACh and the histopathological features to control group. However, no significant effects have been observed in the group treated with L. plantarum alone. The study revealed that, L. plantarum MTCC1325 might have anti-Alzheimer properties against D-Galactose induced Alzheimer's disease.

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

Science.gov (United States)

Doulberis, Michael; Kotronis, Georgios; Thomann, Robert; Polyzos, Stergios A; Boziki, Marina; Gialamprinou, Dimitra; Deretzi, Georgia; Katsinelos, Panagiotis; Kountouras, Jannis

2018-02-01

Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the "new" discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain. We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease. Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral-nasal-olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood-brain barrier, thereby possibly triggering neurodegeneration. Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large-scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short-term and cost-effective therapeutic regimens against Helicobacter pylori-related Alzheimer's disease. © 2017 John Wiley & Sons

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): Modifications and Responsiveness in Pre-Dementia Populations. A Narrative Review.

Science.gov (United States)

Kueper, Jacqueline K; Speechley, Mark; Montero-Odasso, Manuel

2018-01-01

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was developed in the 1980s to assess the level of cognitive dysfunction in Alzheimer's disease. Advancements in the research field have shifted focus toward pre-dementia populations, and use of the ADAS-Cog has extended into these pre-dementia studies despite concerns about its ability to detect important changes at these milder stages of disease progression. If the ADAS-Cog cannot detect important changes, our understanding of pre-dementia disease progression may be compromised and trials may incorrectly conclude that a novel treatment approach is not beneficial. The purpose of this review was to assess the performance of the ADAS-Cog in pre-dementia populations, and to review all modifications that have been made to the ADAS-Cog to improve its measurement performance in dementia or pre-dementia populations. The contents of this review are based on bibliographic searches of electronic databases to locate all studies using the ADAS-Cog in pre-dementia samples or subsamples, and to locate all modified versions. Citations from relevant articles were also consulted. Overall, our results suggest the original ADAS-Cog is not an optimal outcome measure for pre-dementia studies; however, given the prominence of the ADAS-Cog, care must be taken when considering the use of alternative outcome measures. Thirty-one modified versions of the ADAS-Cog were found. Modification approaches that appear most beneficial include altering scoring methodology or adding tests of memory, executive function, and/or daily functioning. Although modifications improve the performance of the ADAS-Cog, this is at the cost of introducing heterogeneity that may limit between-study comparison.

Aluminium and Alzheimer's disease: the science that describes the link

National Research Council Canada - National Science Library

Exley, Christopher

2001-01-01

... that has been encircled is the gene for the amyloid precursor protein. (Thanks to Walter Lukiw for supplying this information.) Aluminium and Alzheimer's Disease: The Science that Describes the LinkAluminium and Alzheimer's Disease The Science that Describes the Link Edited by Christopher Exley Birchall Centre for Inorganic Chemistry and Materials Scienc...

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease : A Mendelian Randomization Study

NARCIS (Netherlands)

Ostergaard, Soren D.; Mukherjee, Shubhabrata; Sharp, Stephen J.; Proitsi, Petroula; Lotta, Luca A.; Day, Felix; Perry, John R. B.; Boehme, Kevin L.; Walter, Stefan; Kauwe, John S.; Gibbons, Laura E.; Larson, Eric B.; Powell, John F.; Langenberg, Claudia; Crane, Paul K.; Wareham, Nicholas J.; Scott, Robert A.; van der Schouw, YT

Background Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these

Oxidative Stress as an Important Factor in the Pathophysiology of alzheimer's Disease

Directory of Open Access Journals (Sweden)

Tanise Gemelli,

2013-06-01

Full Text Available Oxidative stress has been associated to play a crucial role in the pathogenesis of many diseases, including neurodegenerative diseases. Alzheimer's disease is an age-related neurodegenerative disorder, which is recognized as the most common form of dementia. In this article, the aim was to review the involvement of oxidative stress on Alzheimer's disease. Alzheimer's disease is histopathologically characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles, the presence of oligomers of amyloid-? peptide and loss of synapses. Moreover, the brain and the nervous system are more prone to oxidative stress and oxidative damage influences the neurodegenerative diseases. However, increased oxidative damage, mitochondrial dysfunction, accumulation of oxidized aggregated proteins, inflammation, and defects in proteins constitute complex intertwined pathologies that lead to neuronal cell death. Mitochondrial mutations on deoxyribonucleic acid and oxidative stress contribute to aging, affecting different cell signaling systems, as well as the connectivity and neuronal cell death may lead to the largest risk factor for neurodegenerative diseases such as Alzheimer's Disease.

Personality Change in the Preclinical Phase of Alzheimer Disease.

Science.gov (United States)

Terracciano, Antonio; An, Yang; Sutin, Angelina R; Thambisetty, Madhav; Resnick, Susan M

2017-12-01

Changes in behavior and personality are 1 criterion for the diagnosis of dementia. It is unclear, however, whether such changes begin before the clinical onset of the disease. To determine whether increases in neuroticism, declines in conscientiousness, and changes in other personality traits occur before the onset of mild cognitive impairment or dementia. A cohort of 2046 community-dwelling older adults who volunteered to participate in the Baltimore Longitudinal Study of Aging were included. The study examined personality and clinical assessments obtained between 1980 and July 13, 2016, from participants with no cognitive impairment at first assessment who were followed up for as long as 36 years (mean [SD], 12.05 [9.54] years). The self-report personality scales were not considered during consensus diagnostic conferences. Change in self-rated personality traits assessed in the preclinical phase of Alzheimer disease and other dementias with the Revised NEO Personality Inventory, a 240-item questionnaire that assesses 30 facets, 6 for each of the 5 major dimensions: neuroticism, extraversion, openness, agreeableness, and conscientiousness. Of the 2046 participants, 931 [45.5%] were women; mean (SD) age at first assessment was 62.56 (14.63) years. During 24 569 person-years, mild cognitive impairment was diagnosed in 104 (5.1%) individuals, and all-cause dementia was diagnosed in 255 (12.5%) participants, including 194 (9.5%) with Alzheimer disease. Multilevel modeling that accounted for age, sex, race, and educational level found significant differences on the intercept of several traits: individuals who developed dementia scored higher on neuroticism (β = 2.83; 95% CI, 1.44 to 4.22; P Alzheimer disease groups (eg, neuroticism: β = 0.00; 95% CI, -0.08 to 0.08; P = .91; conscientiousness: β = -0.06; 95% CI, -0.16 to 0.04; P = .24). Slopes for individuals who developed mild cognitive impairment (eg, neuroticism: β = 0.00; 95% CI, -0

Theory of mind in Alzheimer disease: Evidence of authentic impairment during social interaction.

Science.gov (United States)

Moreau, Noémie; Rauzy, Stéphane; Viallet, François; Champagne-Lavau, Maud

2016-03-01

The present study aimed to investigate theory of mind (the ability to infer others' mental states) deficit in 20 patients with mild Alzheimer's disease and 20 healthy controls, with 2 theory of mind tasks, 1 of them being a real interactive task. Previous results concerning preserved or altered theory of mind abilities in Alzheimer's disease have been inconsistent and relationships with other cognitive dysfunctions (notably episodic memory and executive functions) are still unclear. The first task we used was a false belief paradigm as frequently used in literature whereas the second task, a referential communication task, assessed theory of mind in a real situation of interaction. Participants also underwent neuropsychological evaluation to investigate potential relationships between theory of mind and memory deficits. The results showed that Alzheimer patients presented a genuine and significant theory of mind deficit compared to control participants characterized notably by difficulties to attribute knowledge to an interlocutor in a real social interaction. These results further confirm that theory of mind is altered in early stages of Alzheimer dementia which is consistent with previous works. More specifically, this study is the first to objectivize this impairment in social interaction. (c) 2016 APA, all rights reserved).

Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease

Directory of Open Access Journals (Sweden)

Benito Minjarez

2016-06-01

Full Text Available Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer׳s disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article “Identification of proteins that are differentially expressed in brains with Alzheimer’s disease using iTRAQ labeling and tandem mass spectrometry” (Minjarez et al., 2016 [1].

Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Science.gov (United States)

Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Naj, Adam C; Sims, Rebecca; Jun, Gyungah; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Denning, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Vronskaya, Maria; Johnson, Andrew D; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Hernández, Isabel; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick C; Hardy, John; Naranjo, Maria Candida Deniz; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Scarpini, Elio; Bonuccelli, Ubaldo; Mancuso, Michelangelo; Siciliano, Gabriele; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Frank-García, Ana; Panza, Francesco; Solfrizzi, Vincenzo; Caffarra, Paolo; Nacmias, Benedetta; Perry, William; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Haines, Jonathan L; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Van Broeckhoven, Christine; Farrer, Lindsay A; van Duijn, Cornelia M; Ramirez, Alfredo; Seshadri, Sudha; Schellenberg, Gerard D; Amouyel, Philippe; Williams, Julie

2014-01-01

Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Valentina Escott-Price

Full Text Available Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6 and 14 (IGHV1-67 p = 7.9×10-8 which indexed novel susceptibility loci.The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Early- and late-onset Alzheimer disease: Are they the same entity?

Science.gov (United States)

Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

2018-05-01

Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Cerebral imaging revealing Alzheimer's disease

International Nuclear Information System (INIS)

2011-01-01

Cerebral imaging is the only non-invasive means of examining the brain and is essential in studying Alzheimer's disease. As a tool for early diagnosis, evaluation and treatment monitoring, this technology is at the heart of the research being done to further improve its reliability and sensitivity. (authors)

History as a biomedical matter: recent reassessments of the first cases of Alzheimer's disease.

Science.gov (United States)

Keuck, Lara

2017-11-27

This paper examines medical scientists' accounts of their rediscoveries and reassessments of old materials. It looks at how historical patient files and brain samples of the first cases of Alzheimer's disease became reused as scientific objects of inquiry in the 1990s, when a genetic neuropathologist from Munich and a psychiatrist from Frankfurt lead searches for left-overs of Alzheimer's 'founder cases' from the 1900s. How and why did these researchers use historical methods, materials and narratives, and why did the biomedical community cherish their findings as valuable scientific facts about Alzheimer's disease? The paper approaches these questions by analysing how researchers conceptualised 'history' while backtracking and reassessing clinical and histological materials from the past. It elucidates six ways of conceptualising history as a biomedical matter: (1) scientific assessments of the past, i.e. natural scientific understandings of 'historical facts'; (2) history in biomedicine, e.g. uses of old histological collections in present day brain banks; (3) provenance research, e.g. applying historical methods to ensure the authenticity of brain samples; (4) technical biomedical history, e.g. reproducing original staining techniques to identify how old histological slides were made; (5) founding traditions, i.e. references to historical objects and persons within founding stories of scientific communities; and (6) priority debates, e.g. evaluating the role particular persons played in the discovery of a disease such as Alzheimer's. Against this background, the paper concludes with how the various ways of using and understanding 'history' were put forward to re-present historic cases as 'proto-types' for studying Alzheimer's disease in the present.

Implementation of Segmentation Methods for the Diagnosis and Prognosis of Mild Cognitive Impairment and Alzheimer Disease

International Nuclear Information System (INIS)

Matoug, S; Abdel-Dayem, A

2012-01-01

Alzheimer's disease (AD) is the most common form of dementia affecting seniors age 65 and over. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan. Advanced medical imaging is a good tool to predict conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease. Since volumetric MRI can detect changes in the size of brain regions, measuring those regions that atrophy during the progress of Alzheimer's disease can help the neurologist in his diagnostic. In the present investigation, we present an automatic tool that reads volumetric MRI and performs 2-dimensional (volume slices) and volumetric segmentation methods in order to segment gray matter, white matter and cerebrospinal fluid (CSF). We used the MRI data sets database from the Open Access Series of Imaging Studies (OASIS).

Follow-up of 53 Alzheimer patients with the MODA (Milan Overall Dementia Assessment).

Science.gov (United States)

Capitani, E; Manzoni, L; Spinnler, H

1997-01-01

Fifty-three patients affected by Alzheimer's disease entered a longitudinal survey aimed at studying which factors influence the rate of progression, assessed by means of the Milan Overall Dementia Assessment (MODA). The second examination was carried out, on average, after 16 months from the first assessment. Only age proved to influence the decline rate, which was faster in elders.

Attitude Towards Alzheimer's Disease Among Undergraduate Students of University of the West Indies, Trinidad and Tobago.

Science.gov (United States)

Rawlins, Joan; Mcgrowder, Donovan A; Kampradi, Lirmala; Ali, Allan; Austin, Travis; Beckles, Annalisa; Dass, Renesha; Diaram, Mahesh; Jahorie, Preenita; Mohammed, Marika; Dialsingh, Isaac

2015-09-01

Alzheimer's disease is most common among the dementias and is characterized by gradual declines in functional and cognitive abilities. Caregivers including family members play a key role in providing critically needed care for these patients. This study compared the knowledge and attitudes of pre-healthcare and non-medical undergraduate students towards patients with Alzheimer's disease. A cross-sectional study was conducted involving quota sampling of 691 undergraduate students (369 pre-healthcare and 322 non-medical). A 28-item questionnaire was utilised comprising of closed-ended questions and some based on a scale rating. The students' knowledge of Alzheimer's disease was arranged into categories such as: 0 for no knowledge about Alzheimer's disease, 1 for very little knowledge about Alzheimer's disease, 2 for fair knowledge about Alzheimer's disease and 3 for great knowledge about Alzheimer's disease. The data was analysed using the computer software SPSS and the Chi squared test of independence was also used to determine which knowledge variables were independent of student's status. Overall, 40.01% of the students have great or fair knowledge of Alzheimer's disease, with that of pre-healthcare students being satisfactory (54.47%). Pre-healthcare students have a more positive attitude towards Alzheimer's disease and 82.2% of students wished to take advantage of predictive test for Alzheimer's disease. Age and genetics were identified as risk factors of the disease. Pre-healthcare students had greater understanding of Alzheimer's disease and depicted a more empathetic and caring attitude towards patients. This can be attributed mainly to their knowledge and exposure toward the disease.

Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer's disease and Parkinson's disease

DEFF Research Database (Denmark)

Benn, Marianne; Nordestgaard, Børge G.; Frikke-Schmidt, Ruth

2017-01-01

 Risk of Alzheimer's disease, vascular dementia, all dementia, and Parkinson's disease.Results In observational analyses, the multifactorially adjusted hazard ratio for Parkinson's disease in participants with an LDL cholesterol level ....79), whereas the corresponding hazard ratios for Alzheimer's disease, vascular dementia, or any dementia did not differ from 1.0. PCSK9 and HMGCR variants combined were associated with a 9.3% lower LDL cholesterol level. In genetic, causal analyses adjusted for age, sex, and year of birth, the risk ratios...... for a lifelong 1 mmol/L lower LDL cholesterol level were 0.57 (0.27 to 1.17) for Alzheimer's disease, 0.81 (0.34 to 1.89) for vascular dementia, 0.66 (0.34 to 1.26) for any dementia, and 1.02 (0.26 to 4.00) for Parkinson's disease. Summary level data from the International Genomics of Alzheimer's Project using...

The road to restoring neural circuits for the treatment of Alzheimer's disease.

Science.gov (United States)

Canter, Rebecca G; Penney, Jay; Tsai, Li-Huei

2016-11-10

Alzheimer's disease is a progressive loss of memory and cognition, for which there is no cure. Although genetic studies initially suggested a primary role for amyloid-in Alzheimer's disease, treatment strategies targeted at reducing amyloid-have failed to reverse cognitive symptoms. These clinical findings suggest that cognitive decline is the result of a complex pathophysiology and that targeting amyloid-alone may not be sufficient to treat Alzheimer's disease. Instead, a broad outlook on neural-circuit-damaging processes may yield insights into new therapeutic strategies for curing memory loss in the disease.

Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials

OpenAIRE

Kaduszkiewicz, Hanna; Zimmermann, Thomas; Beck-Bornholdt, Hans-Peter; van den Bussche, Hendrik

2005-01-01

Objectives Pharmacological treatment of Alzheimer's disease focuses on correcting the cholinergic deficiency in the central nervous system with cholinesterase inhibitors. Three cholinesterase inhibitors are currently recommended: donepezil, rivastigmine, and galantamine. This review assessed the scientific evidence for the recommendation of these agents.

Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

DEFF Research Database (Denmark)

Lindquist, S.G.; Nielsen, J.E.; Stokholm, J.

2008-01-01

BACKGROUND: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic...... features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features. METHODS AND RESULTS: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer......'s disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense...

Computed tomography of the temporal horns at Alzheimer's disease

International Nuclear Information System (INIS)

Gerber, U.; Vogel

1989-01-01

In the literature there are different opinions referring to the involvement of the temporal lobes or horns at Alzheimer's disease. Conventionally computed tomogram of the head does not include the temporal horn in its full length. A simple method to demonstrate the temporal horns after cranial computer tomography is described. It allows the evaluation of temporal lobe and temporal horn if questionable alterations at Alzheimer's disease are to be discussed. (orig.) [de

Alzheimer Disease Signature Neurodegeneration and APOE Genotype in Mild Cognitive Impairment With Suspected Non-Alzheimer Disease Pathophysiology.

Science.gov (United States)

Schreiber, Stefanie; Schreiber, Frank; Lockhart, Samuel N; Horng, Andy; Bejanin, Alexandre; Landau, Susan M; Jagust, William J

2017-06-01

There are conflicting results claiming that Alzheimer disease signature neurodegeneration may be more, less, or similarly advanced in individuals with β-amyloid peptide (Aβ)-negative (Aβ-) suspected non-Alzheimer disease pathophysiology (SNAP) than in Aβ-positive (Aβ+) counterparts. To examine patterns of neurodegeneration in individuals with SNAP compared with their Aβ+ counterparts. A longitudinal cohort study was conducted among individuals with mild cognitive impairment (MCI) and cognitively normal individuals receiving care at Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada for a mean follow-up period of 30.5 months from August 1, 2005, to June 30, 2015. Several neurodegeneration biomarkers and longitudinal cognitive function were compared between patients with distinct SNAP (Aβ- and neurodegeneration-positive [Aβ-N+]) subtypes and their Aβ+N+ counterparts. Participants were classified according to the results of their florbetapir F-18 (Aβ) positron emission tomography and their Alzheimer disease-associated neurodegeneration status (temporoparietal glucose metabolism determined by fluorodeoxyglucose F 18 [FDG]-labeled positron emission tomography and/or hippocampal volume [HV] determined by magnetic resonance imaging: participants with subthreshold HV values were regarded as exhibiting hippocampal volume atrophy [HV+], while subthreshold mean FDG values were considered as FDG hypometabolism [FDG+]). The study comprised 265 cognitively normal individuals (135 women and 130 men; mean [SD] age, 75.5 [6.7] years) and 522 patients with MCI (225 women and 297 men; mean [SD] age, 72.6 [7.8] years). A total of 469 individuals with MCI had data on neurodegeneration biomarkers; of these patients, 107 were Aβ-N+ (22.8%; 63 FDG+, 82 HV+, and 38 FDG+HV+) and 187 were Aβ+N+ (39.9%; 135 FDG+, 147 HV+, and 95 FDG+HV+ cases). A total of 209 cognitively normal participants had data on neurodegeneration biomarkers; of these, 52 were

Estrogen use and early onset Alzheimer's disease: a population-based study

NARCIS (Netherlands)

A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); J.C.M. Witteman (Jacqueline); C.M. van Duijn (Cornelia); C. van Broeckhoven (Christine); A. Hofman (Albert)

1999-01-01

textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5

Early diagnostics and Alzheimer's disease: Beyond ‘cure’ and ‘care’

NARCIS (Netherlands)

Cuijpers, Y.M.|info:eu-repo/dai/nl/312803931; van Lente, H.|info:eu-repo/dai/nl/113255004

Research on early diagnostics for Alzheimer's disease is supported by what has been labeled as aging-and-innovation discourse, in which innovation is assumed to (partially) resolve the societal problems related to aging. This discourse draws on a specific way of understanding Alzheimer's disease and

Head trauma and Alzheimer's disease

NARCIS (Netherlands)

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

2002-01-01

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

Knowledge and perceptions of dementia and Alzheimer's disease in four ethnic groups in Copenhagen, Denmark

DEFF Research Database (Denmark)

Nielsen, T. Rune; Waldemar, Gunhild

2016-01-01

of dementia and Alzheimer's disease (AD) among four ethnic groups in Copenhagen, Denmark, and to assess the influence of education and acculturation. METHODS: Quantitative survey data from 260 participants were analyzed: 100 native Danish, and 47 Polish, 51 Turkish, and 62 Pakistani immigrants. Knowledge...... and perceptions of dementia and AD were assessed with the Dementia Knowledge Questionnaire (DKQ) supplemented with two questions from the Alzheimer's Disease Awareness Test (ADAT). Knowledge and perceptions of dementia and AD in the four groups were compared, and the influence of education and acculturation...... was assessed. RESULTS: Group differences were found on the DKQ total score as well as all sub-domains. Turkish and Pakistani people were most likely to hold normalizing and stigmatizing views of AD. Level of education and acculturation had limited influence on dementia knowledge, accounting for 22...

Google Calendar Enhances Prospective Memory in Alzheimer's Disease: A Case Report.

Science.gov (United States)

El Haj, Mohamad; Gallouj, Karim; Antoine, Pascal

2017-01-01

We investigated whether an external memory aid (i.e., Google Calendar) would alleviate prospective memory compromise in a patient with mild Alzheimer's disease. The patient was asked in the baseline phase to perform three prospective targeted events (e.g., attending her weekly bridge game at the community club) and three prospective control events (e.g., buying her weekly magazine). The same six prospective events were assessed in the intervention phase but the targeted-events were cued by Google Calendar while the control-events were not. Results showed less omission of the targeted events in the training phase than in the baseline phase, suggesting a positive effect of Google Calendar. This case report offers a unique view into how smartphone calendars may alleviate prospective memory compromise in patients with mild Alzheimer's disease.

Llama VHH as immunotherapeutics in Alzheimer's disease

NARCIS (Netherlands)

Dorresteijn, B.|info:eu-repo/dai/nl/31401635X

2013-01-01

Alzheimer's Disease (AD) is the most common form of dementia among elderly in the Western world. AD is a devastating neurodegenerative disease where patients starting with episodic memory problems end up completely bedridden and care dependent. At present there is no real therapy stopping or

Apatia na doença de Alzheimer Apathy in Alzheimer's disease

Directory of Open Access Journals (Sweden)

Antônio Lúcio Teixeira-Jr

2006-09-01

Full Text Available Apatia é a mais comum síndrome neuropsiquiátrica na doença de Alzheimer, afetando entre 30 e 60% dos pacientes. Pode ser definida como perda de motivação e se manifesta com alterações afetivas, cognitivas e comportamentais, determinando, respectivamente, redução da resposta emocional, perda de autocrítica e retração social. Nesse artigo, são apresentadas as características clínicas da síndrome apática e suas perspectivas terapêuticas. Conclui-se que há uma superposição considerável entre apatia e depressão na doença de Alzheimer, mas ambas as condições são consideradas síndromes independentes. Intervenções farmacológicas para apatia incluem psicoestimulantes, como o metilfenidato, agentes dopaminérgicos e inibidores de colinesterase; mas os resultados são controversos e não há tratamento estabelecido.Apathy is the most common neuropsychiatry syndrome in Alzheimer's disease affecting 30-60% of patients. It can be defined as a loss of motivation and manifests in affect, cognition and behavioral changes, determining blunted emotional response, lack of insight and social retraction, respectively. In this paper, the clinical features and the therapeutic perspectives of apathy are presented. There is considerable overlap between apathy and depression in Alzheimer's disease, but both are considered discrete syndromes. Pharmacological interventions for apathy include psychostimulants, such as methylphenidate, dopaminergic agents and cholinesterase inhibitors, but the results are controversial and there is no established treatment.

New NIA Booklet By and For People With Early-Stage Alzheimer's Disease

Science.gov (United States)

... Booklet By and For People With Early-Stage Alzheimer's Disease Past Issues / Fall 2007 Table of Contents ... you have a family member or friends with Alzheimer's disease? Are you wondering what they're going ...

Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

Energy Technology Data Exchange (ETDEWEB)

Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

1994-09-15

Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

Personalized medicine in Alzheimer's disease and depression.

Science.gov (United States)

Souslova, Tatiana; Marple, Teresa C; Spiekerman, A Michael; Mohammad, Amin A

2013-11-01

Latest research in the mental health field brings new hope to patients and promises to revolutionize the field of psychiatry. Personalized pharmacogenetic tests that aid in diagnosis and treatment choice are now becoming available for clinical practice. Amyloid beta peptide biomarkers in the cerebrospinal fluid of patients with Alzheimer's disease are now available. For the first time, radiologists are able to visualize amyloid plaques specific to Alzheimer's disease in live patients using Positron Emission Tomography-based tests approved by the FDA. A novel blood-based assay has been developed to aid in the diagnosis of depression based on activation of the HPA axis, metabolic, inflammatory and neurochemical pathways. Serotonin reuptake inhibitors have shown increased remission rates in specific ethnic subgroups and Cytochrome P450 gene polymorphisms can predict antidepressant tolerability. The latest research will help to eradicate "trial and error" prescription, ushering in the most personalized medicine to date. Like all major medical breakthroughs, integration of new algorithms and technologies requires sound science and time. But for many mentally ill patients, diagnosis and effective therapy cannot happen fast enough. This review will describe the newest diagnostic tests, treatments and clinical studies for the diagnosis and treatment of Alzheimer's disease and unipolar, major depressive disorder. © 2013 Elsevier Inc. All rights reserved.

99mTc-HMPAO SPECT in patients with Alzheimer's disease and multiinfraction dementia

International Nuclear Information System (INIS)

Klisarova, A.; Tranulov, G.; Deleva, N.; Kaprelian, A.; Terzieva, M.; Ivanov, B.

2002-01-01

Alzheimer's disease (AD) and multiinfarktion dementia (MD) are the commonest causes giving rise to progressive cognitive function deficit in adult individuals. It is the purpose of the study to evaluate 99m Tc-HMPAO SPECT in making the diagnosis and differential diagnosis of Alzheimer's disease and multiinfarction dementia in patients presenting progressive cognitive disorders. Twenty patients with symptoms of dementia divided up in two groups (10 suspected for AD, and 10 with evidence of MD) are subjected to 99m Tc-HMPAO SPECT. To assay the scintigraphic images semi-quantitative perfusion indices are introduced. Bilateral hypoperfusion zones in the temporoparietal and temporal regions are detected in nine AD patients. In 4 of them in advanced stage of the disease hypoperfusion zones are found in the frontal lobe. In 8/10 MD patients vascular dependent hypoperfusion areas are located along the course of vessels. The perfusion indices implemented in practice contribute to the semi-quantitative evaluation of hypoperfusion areas and precise assessment of the scintigraphic findings. 99m Tc-HMPAO SPECT is an atraumatic, noninvasive technique, taken to be the method of choice in making the diagnosis and differential diagnosis of Alzheimer's disease and multiinfarction dementia in routine clinical practice. (authors)

Differing astrocytic cytoskeleton alterations in alzheimer's disease

Czech Academy of Sciences Publication Activity Database

Olabarria, M.; Noristani, H.; Chvátal, Alexandr; Verkhratsky, Alexei; Rodríguez Arellano, Jose Julio

2009-01-01

Roč. 57, č. 13 (2009), S103-S104 ISSN 0894-1491. [European Meeting on Glial Cells in Health and Disease /9./. 09.09.2009-12.09.2009, Paris] Institutional research plan: CEZ:AV0Z50390703 Keywords : Alzheimer ´s disease Subject RIV: FH - Neurology

Alzheimer's disease: A review of recent developments

African Journals Online (AJOL)

2011-06-15

Jun 15, 2011 ... Keywords:Advancing age, Alzheimer's disease, cognitive dysfunction, dementia, neuropsychological testing, primary ..... of associated behavioral and neurologic problems. ... whether to continue therapy with a particular drug.

Dual task and postural control in Alzheimer's and Parkinson's disease

Directory of Open Access Journals (Sweden)

Larissa Pires de Andrade

2014-03-01

Full Text Available Patients with neurodegenerative diseases are required to use cognitive resources while maintaining postural control. The aim of this study was to investigate the effects of a frontal cognitive task on postural control in patients with Alzheimer, Parkinson and controls. Thirty-eight participants were instructed to stand upright on a force platform in two experimental conditions: single and dual task. Participants with Parkinson's disease presented an increase in the coefficient of variation greater than 100% in the dual task as compared to the single task for center of pressure (COP area and COP path. In addition, patients with Parkinson's and Alzheimer's disease had a higher number of errors during the execution of the cognitive task when compared to the group of elderly without neurodegenerative diseases. The motor cortex, which is engaged in postural control, does not seem to compete with frontal brain regions in the performance of the cognitive task. However, patients with Parkinson's and Alzheimer's disease presented worsened performance in cognitive task.

Alzheimer's disease therapies: Selected advances and future ...

African Journals Online (AJOL)

Among the neurodegenerative diseases, Alzheimer's disease (AD) represents one of the biggest challenges that the modern health care system has to deal with. The lack of data about the etiology and the complexity of the underlying pathogenesis constitute the biggest struggle facing the development of new therapeutical ...

A conceptual framework and ethics analysis for prevention trials of Alzheimer Disease.

Science.gov (United States)

Peters, Kevin R; Lynn Beattie, B; Feldman, Howard H; Illes, Judy

2013-11-01

As our understanding of the neurobiology of Alzheimer Disease deepens, it has become evident that early intervention is critical to achieving successful therapeutic impact. The availability of diagnostic criteria for preclinical Alzheimer Disease adds momentum to research directed at this goal and even to prevention. The landscape of therapeutic research is thus poised to undergo a dramatic shift in the next 5-10 years, with clinical trials involving subjects at risk for Alzheimer Disease who have few or no symptoms. These trials will also likely rely heavily on genetics, biomarkers, and or risk factor stratification to identify individuals at risk for Alzheimer Disease. Here, we propose a conceptual framework to guide this next generation of pharmacological and non-pharmacological clinical pursuit, and discuss some of the foreseeable ethical considerations that may accompany them. Copyright © 2013 Elsevier Ltd. All rights reserved.

Whole Exome Analysis of Early Onset Alzheimer’s Disease

Science.gov (United States)

2017-04-01

Alzheimer’s Disease 5a. CONTRACT NUMBER W81XWH-12-1-0013 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Margaret A. Pericak-Vance, Ph.D...Gerald D. Schellenberg, Goldie S . Byrd, Jonathan L. Haines, Margaret A. Pericak-Vance, and the Alzheimer Disease Genetics Consortium. ABCA7 Frameshift...Alzheimer’s & Parkinson’s Diseases (AD/PD), Vienna, Austria, Mar 29-Apr 2, 2017: Cukier HN, Gross SP, Kunkle BW, Rolati S , Hamilton-Nelson KL, Whitehead PL

Alzheimer's Disease and Stem Cell Therapy

OpenAIRE

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

2014-01-01

The loss of neuronal cells in the central nervous system may occur in many neurodegenerative diseases. Alzheimer's disease is a common senile disease in people over 65 years, and it causes impairment characterized by the decline of mental function, including memory loss and cognitive impairment, and affects the quality of life of patients. However, the current therapeutic strategies against AD are only to relieve symptoms, but not to cure it. Because there are only a few therapeutic strategie...

Pittsburgh Compound B and AV-1451 positron emission tomography assessment of molecular pathologies of Alzheimer's disease in progressive supranuclear palsy.

Science.gov (United States)

Whitwell, Jennifer L; Ahlskog, J Eric; Tosakulwong, Nirubol; Senjem, Matthew L; Spychalla, Anthony J; Petersen, Ronald C; Jack, Clifford R; Lowe, Val J; Josephs, Keith A

2018-03-01

Little is known about Alzheimer's disease molecular proteins, beta-amyloid and paired helical filament (PHF) tau, in progressive supranuclear palsy (PSP). Recent techniques have been developed to allow for investigations of these proteins in PSP. We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features. Thirty probable PSP participants underwent MRI, [ 18 F]AV-1451 PET and Pittsburgh compound B (PiB) PET. Apolipoprotein (APOE) genotyping was also performed. A global PiB standard-uptake value ratio (SUVR) was calculated. AV-1451 SUVRs were calculated for a set of Alzheimer's disease (AD)-related regions and a set of PSP-related regions. Voxel-level analyses were conducted to assess for differences in AV-1451 uptake patterns and MRI atrophy between PiB(+) and PiB(-) cases compared to 60 normal PiB(-) controls. Statistical testing for correlations and associations between variables of interest were also performed. Twelve subjects (40%) showed beta-amyloid deposition. Higher PiB SUVR correlated with older age but not with AV-1451 SUVR in the AD- or PSP-related regions. Higher AV-1451 SUVR in AD-related regions was associated with higher AV-1451 SUVR in PSP-related regions. We found little evidence for beta-amyloid related differences in clinical metrics, proportion of APOE e4 carriers, pattern of AV-1451 uptake, or pattern of atrophy. Beta-amyloid deposition occurs in a relatively high proportion of PSP subjects. Unlike in Alzheimer's disease, however, there is little evidence that beta-amyloid, and PHF-tau, play a significant role in neurodegeneration in PSP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Data-driven models of dominantly-inherited Alzheimer's disease progression.

Science.gov (United States)

Oxtoby, Neil P; Young, Alexandra L; Cash, David M; Benzinger, Tammie L S; Fagan, Anne M; Morris, John C; Bateman, Randall J; Fox, Nick C; Schott, Jonathan M; Alexander, Daniel C

2018-03-22

Dominantly-inherited Alzheimer's disease is widely hoped to hold the key to developing interventions for sporadic late onset Alzheimer's disease. We use emerging techniques in generative data-driven disease progression modelling to characterize dominantly-inherited Alzheimer's disease progression with unprecedented resolution, and without relying upon familial estimates of years until symptom onset. We retrospectively analysed biomarker data from the sixth data freeze of the Dominantly Inherited Alzheimer Network observational study, including measures of amyloid proteins and neurofibrillary tangles in the brain, regional brain volumes and cortical thicknesses, brain glucose hypometabolism, and cognitive performance from the Mini-Mental State Examination (all adjusted for age, years of education, sex, and head size, as appropriate). Data included 338 participants with known mutation status (211 mutation carriers in three subtypes: 163 PSEN1, 17 PSEN2, and 31 APP) and a baseline visit (age 19-66; up to four visits each, 1.1 ± 1.9 years in duration; spanning 30 years before, to 21 years after, parental age of symptom onset). We used an event-based model to estimate sequences of biomarker changes from baseline data across disease subtypes (mutation groups), and a differential equation model to estimate biomarker trajectories from longitudinal data (up to 66 mutation carriers, all subtypes combined). The two models concur that biomarker abnormality proceeds as follows: amyloid deposition in cortical then subcortical regions (∼24 ± 11 years before onset); phosphorylated tau (17 ± 8 years), tau and amyloid-β changes in cerebrospinal fluid; neurodegeneration first in the putamen and nucleus accumbens (up to 6 ± 2 years); then cognitive decline (7 ± 6 years), cerebral hypometabolism (4 ± 4 years), and further regional neurodegeneration. Our models predicted symptom onset more accurately than predictions that used familial estimates: root mean squared error of 1

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

Science.gov (United States)

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.

Therapeutic role of rifampicin in Alzheimer's disease.

Science.gov (United States)

Yulug, Burak; Hanoglu, Lütfü; Ozansoy, Mehmet; Isık, Dogan; Kilic, Ulkan; Kilic, Ertugrul; Schabitz, Wolf Rüdiger

2018-03-01

Rifampicin exerts significant brain protective functions in multiple experimental models. Here we summarize the underlying mechanisms of the neuroprotective and pro-cognitive effects of rifampicin that are mediated by its anti-inflammatory, anti-tau, anti-amyloid, and cholinergic effects. Beyond suggesting that rifampicin shows strong brain protective effects in preclinical models of Alzheimer's disease, we also provide substantial clinical evidence for the neuroprotective and pro-cognitive effects of rifampicin. Future neuroimaging studies combined with clinical assessment scores are the following steps to be taken in this field of research. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

The future of blood-based biomarkers for Alzheimer's disease

DEFF Research Database (Denmark)

Henriksen, Kim; O'Bryant, Sid E; Hampel, Harald

2014-01-01

Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease...

Hypocretin (orexin) loss in Alzheimer's disease.

NARCIS (Netherlands)

Fronczek, R.; Geest, S. de; Frolich, M.; Overeem, S.; Roelandse, F.W.; Lammers, G.J.; Swaab, D.F.

2012-01-01

Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter

Hypocretin (orexin) loss in Alzheimer's disease

NARCIS (Netherlands)

Fronczek, Rolf; van Geest, Sarita; Frölich, Marijke; Overeem, Sebastiaan; Roelandse, Freek W. C.; Lammers, Gert Jan; Swaab, Dick F.

2012-01-01

Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter

Normal tension glaucoma and Alzheimer disease

DEFF Research Database (Denmark)

Bach-Holm, Daniella; Kessing, Svend Vedel; Mogensen, Ulla Brasch

2012-01-01

Purpose: To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD). Methods: A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet...

Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

Directory of Open Access Journals (Sweden)

Adalberto Studart Neto

Full Text Available ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD, when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

Application of PET in Alzheimer's disease

International Nuclear Information System (INIS)

Zhang Chun

2003-01-01

Alzheimer's disease (AD) is a neurodegenerative disease of central nervous system that causes progressive cognitive and memory deterioration in the elderly people. Affected brains of AD patients are characterized by the presence of senile plaques (SP) and neurofilbrillary tangles (NFT). The review will focus on the application of positron emission tomography (PET) in the diagnosis, progression prediction, treatment and evaluation of neurotransmission activity of AD

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

DEFF Research Database (Denmark)

Sobol, N A; Hoffmann, K; Frederiksen, K S

2016-01-01

INTRODUCTION: 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. METHODS: The single blinded...

Failure of Neuronal Maturation in Alzheimer Disease Dentate Gyrus

Science.gov (United States)

Li, Bin; Yamamori, Hidenaga; Tatebayashi, Yoshitaka; Shafit-Zagardo, Bridget; Tanimukai, Hitoshi; Chen, She; Iqbal, Khalid; Grundke-Iqbal, Inge

2011-01-01

The dentate gyrus, an important anatomic structure of the hippocampal formation, is one of the major areas in which neurogenesis takes place in the adult mammalian brain. Neurogenesis in the dentate gyrus is thought to play an important role in hippocampus-dependent learning and memory. Neurogenesis has been reported to be increased in the dentate gyrus of patients with Alzheimer disease, but it is not known whether the newly generated neurons differentiate into mature neurons. In this study, the expression of the mature neuronal marker high molecular weight microtubule-associated protein (MAP) isoforms MAP2a and b was found to be dramatically decreased in Alzheimer disease dentate gyrus, as determined by immunohistochemistry and in situ hybridization. The total MAP2, including expression of the immature neuronal marker, the MAP2c isoform, was less affected. These findings suggest that newly generated neurons in Alzheimer disease dentate gyrus do not become mature neurons, although neuroproliferation is increased. PMID:18091557

Regulation of gamma-Secretase in Alzheimer's Disease

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Zhou, Shuxia; Zhou, Hua; Walian, Peter; Jap, Bing

2007-02-07

The {gamma}-secretase complex is an intramembrane aspartyl protease that cleaves its substrates along their transmembrane regions. Sequential proteolytic processing of amyloid precursor protein by {beta}- and {gamma}-secretase produces amyloid {beta}-peptides, which are the major components of amyloid plaques in the brains of Alzheimer's disease patients. The {gamma}-secretase complex is therefore believed to be critical in the pathogenesis of Alzheimer's disease. Here we review the range of factors found to affect the nature and degree of {gamma}-secretase complex activity; these include {gamma}-secretase complex assembly and activation, the integral regulatory subunit CD147, transient or weak binding partners, the levels of cholesterol and sphingolipids in cell membranes, and inflammatory cytokines. Integrated knowledge of the molecular mechanisms supporting the actions of these factors is expected to lead to a comprehensive understanding of the functional regulation of the {gamma}-secretase complex, and this, in turn, should facilitate the development of novel therapeutic strategies for the treatment of Alzheimer's disease.

Why Do We Get Alzheimer's Disease?

International Nuclear Information System (INIS)

Wyss-Coray, Tony

2006-01-01

Neurodegenerative diseases and Alzheimer's disease (AD) in particular, are among the major health concerns of the elderly in industrialized societies. The cause of AD is unknown and no disease-modifying treatments are available. The disease is characterized clinically by a progressive dementia and pathologically by the accumulation of protein aggregates in the brain and a profound loss of nerve cells. It has also become clear recently that local immune responses are activated in the AD brain and may have a role in the disease. Our laboratory uses genetic mouse models to understand the disease process and to identify potential therapeutic targets.

Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease?

Science.gov (United States)

Visser, P; Scheltens, P; Verhey, F

2005-01-01

Background: Drugs effective in Alzheimer-type dementia have been tested in subjects with mild cognitive impairment (MCI) because these are supposed to have Alzheimer's disease in the predementia stage. Objectives: To investigate whether MCI criteria used in these drug trials can accurately diagnose subjects with predementia Alzheimer's disease. Methods: MCI criteria of the Gal-Int 11 study, InDDEx study, ADCS memory impairment study, ampakine CX 516 study, piracetam study, and Merck rofecoxib study were applied retrospectively in a cohort of 150 non-demented subjects from a memory clinic. Forty two had progressed to Alzheimer type dementia during a five year follow up period and were considered to have predementia Alzheimer's disease at baseline. Outcome measures were the odds ratio, sensitivity, specificity, and positive and negative predictive value. Results: The odds ratio of the MCI criteria for predementia Alzheimer's disease varied between 0.84 and 11. Sensitivity varied between 0.46 and 0.83 and positive predictive value between 0.43 and 0.76. None of the criteria combined a high sensitivity with a high positive predictive value. Exclusion criteria for depression led to an increase in positive predictive value and specificity at the cost of sensitivity. In subjects older than 65 years the positive predictive value was higher than in younger subjects. Conclusions: The diagnostic accuracy of MCI criteria used in trials for predementia Alzheimer's disease is low to moderate. Their use may lead to inclusion of many patients who do not have predementia Alzheimer's disease or to exclusion of many who do. Subjects with moderately severe depression should not be excluded from trials in order not to reduce the sensitivity. PMID:16170074

Cognitive decline in patients with Alzheimer's disease, vascular dementia and senile dementia of Lewy body type.

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Ballard, C; Patel, A; Oyebode, F; Wilcock, G

1996-05-01

One hundred and twenty-four patients with DSM-III-R dementia were assessed with a standardized battery which included the Geriatric Mental State Schedule, the History and Aetiology Schedule, the Secondary Dementia Schedule and the CAMCOG. Patients with Alzheimer's disease, vascular dementia and senile dementia of Lewy body type (SDLT) all had a similar degree of cognitive impairment at the time of the baseline interview. Patients with Alzheimer's disease and vascular dementia each experienced a mean decline of 27 points in patients with SDLT. Patients with SDLT had a significantly greater decline of verbal fluency than both the other groups. Women were significantly more impaired than men at the time of the baseline assessment but experienced a similar decline during the year of follow-up.

Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer's disease.

Science.gov (United States)

Boggio, Paulo Sérgio; Valasek, Claudia Aparecida; Campanhã, Camila; Giglio, Ana Carolina Alem; Baptista, Nathalia Ishikawa; Lapenta, Olivia Morgan; Fregni, Felipe

2011-10-01

Alzheimer's disease (AD) is a neurodegenerative and progressive disease related to a gradual decline in cognitive functions such as memory, attention, perceptual-spatial abilities, language, and executive functions. Recent evidence has suggested that interventions promoting neural plasticity can induce significant cognitive gains especially in subjects at risk of or with mild AD. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques that can induce significant and long-lasting changes in focal and non-focal neuroplasticity. In this review, we present initial preliminary evidence that TMS and tDCS can enhance performance in cognitive functions typically impaired in AD. Also, we reviewed the initial six studies on AD that presented early findings showing cognitive gains such as in recognition memory and language associated with TMS and tDCS treatment. In addition, we showed that TMS has also been used to assess neuroplasticity changes in AD supporting the notion that cortical excitability is changed in AD due to the neurodegenerative process. Due to the safe profile, cost of these tools, and initial clinical trials results, further studies are warranted in order to replicate and extend the initial findings of rTMS and tDCS as cognitive enhancers in AD. Further trials should explore different targets of stimulation along with different paradigms of stimulation including combination with behavioural interventions.

Medications Used for Cognitive Enhancement in Patients With Schizophrenia, Bipolar Disorder, Alzheimer's Disease, and Parkinson's Disease.

Science.gov (United States)

Hsu, Wen-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Cognitive impairment, which frequently occurs in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease, has a significant impact on the daily lives of both patients and their family. Furthermore, since the medications used for cognitive enhancement have limited efficacy, the issue of cognitive enhancement still remains a clinically unsolved challenge. We reviewed the clinical studies (published between 2007 and 2017) that focused on the efficacy of medications used for enhancing cognition in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease. Acetylcholinesterase inhibitors and memantine are the standard treatments for Alzheimer's disease and Parkinson's disease. Some studies have reported selective cognitive improvement in patients with schizophrenia following galantamine treatment. Newer antipsychotics, including paliperidone, lurasidone, aripiprazole, ziprasidone, and BL-1020, have also been reported to exert cognitive benefits in patients with schizophrenia. Dopaminergic medications were found to improve language function in patients with Parkinson's disease. However, no beneficial effects on cognitive function were observed with dopamine agonists in patients with schizophrenia. The efficacies of nicotine and its receptor modulators in cognitive improvement remain controversial, with the majority of studies showing that varenicline significantly improved the cognitive function in schizophrenic patients. Several studies have reported that N -methyl-d-aspartate glutamate receptor (NMDAR) enhancers improved the cognitive function in patients with chronic schizophrenia. NMDAR enhancers might also have cognitive benefits in patients with Alzheimer's disease or Parkinson's disease. Raloxifene, a selective estrogen receptor modulator, has also been demonstrated to have beneficial effects on attention, processing speed, and memory in female patients with schizophrenia. Clinical trials with

Assessment of cerebral perfusion with single-photon emission tomography in normal subjects and in patients with Alzheimer's disease: effects of region of interest selection

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Claus, J J [Dept. of Neurology, Univ. Hospital, Rotterdam (Netherlands) Dept. of Epidemiology and Biostatistics, Erasmus Univ. Medical School, Rotterdam (Netherlands); Harskamp, F van [Dept. of Neurology, Univ. Hospital, Rotterdam (Netherlands); Breteler, M M.B. [Dept. of Epidemiology and Biostatistics, Erasmus Univ. Medical School, Rotterdam (Netherlands); Krenning, E P [Dept. of Nuclear Medicine, Univ. Hospital, Rotterdam (Netherlands); Cammen, T.J.M. van der (Dept. of Geriatric Medicine, Univ. Hospital, Rotterdam (Netherlands)); Hofman, A [Dept. of Epidemiology and Biostatistics, Erasmus Univ. Medical School, Rotterdam (Netherlands); Hasan, D [Dept. of Neurology, Univ. Hospital, Rotterdam (Netherlands)

1994-10-01

We compared three different ROIs in a SPET study with 60 controls and in 48 patients with probable Alzheimer's disease diagnosed according to the NINCDS-ADRDA criteria. Regional cerebral blood flow (rCBF) was assessed with SPET using technetium-99m d,l-hexamethylpropylene amine oxime ([sup 99m]Tc-HMPAO), normalized to the mean activity in a cerebellar reference slice. The three different ROIs were: a multi-slice and a single-slice ROI with reference to the normal brain anatomy (using an anatomical atlas), and a rectangular (2x4 pixels) ROI in the frontal, temporal, temporoparietal and occipital cortices. No differences were observed for the means of rCBF values between the single-slice and multi-slice ROI's with reference to the normal anatomy, but some variability was present for individual comparisons. In contrast, significantly higher mean rCBF values were obtained with the single-slice rectangular ROIs in all four regions for both patients and controls and considerable variability was shown for individual subjects. After analysis with multivariate logistic regression and receiver operator characteristic curves, the ability of SPET to discriminate between controls and Alzheimer patients was similar in the three methods for mild and moderate Alzheimer patients (Global Deterioration Scale = GDS of 3 and 4). However, with increasing dementia severity (GDS>4) the rectangular ROIs showed lower ability to discriminate between groups compared to the single-slice and multi-slice anatomically defined ROIs. This study suggests that results of rCBF assessment with SPET using [sup 99m]Tc-HMPAO in patients with severe Alzheimer's disease are influenced by the shape and size of the ROI. (orig.)

Assessment of cerebral perfusion with single-photon emission tomography in normal subjects and in patients with Alzheimer's disease: effects of region of interest selection

International Nuclear Information System (INIS)

Claus, J.J.; Harskamp, F. van; Breteler, M.M.B.; Krenning, E.P.; Cammen, T.J.M. van der; Hofman, A.; Hasan, D.

1994-01-01

We compared three different ROIs in a SPET study with 60 controls and in 48 patients with probable Alzheimer's disease diagnosed according to the NINCDS-ADRDA criteria. Regional cerebral blood flow (rCBF) was assessed with SPET using technetium-99m d,l-hexamethylpropylene amine oxime ( 99m Tc-HMPAO), normalized to the mean activity in a cerebellar reference slice. The three different ROIs were: a multi-slice and a single-slice ROI with reference to the normal brain anatomy (using an anatomical atlas), and a rectangular (2x4 pixels) ROI in the frontal, temporal, temporoparietal and occipital cortices. No differences were observed for the means of rCBF values between the single-slice and multi-slice ROI's with reference to the normal anatomy, but some variability was present for individual comparisons. In contrast, significantly higher mean rCBF values were obtained with the single-slice rectangular ROIs in all four regions for both patients and controls and considerable variability was shown for individual subjects. After analysis with multivariate logistic regression and receiver operator characteristic curves, the ability of SPET to discriminate between controls and Alzheimer patients was similar in the three methods for mild and moderate Alzheimer patients (Global Deterioration Scale = GDS of 3 and 4). However, with increasing dementia severity (GDS>4) the rectangular ROIs showed lower ability to discriminate between groups compared to the single-slice and multi-slice anatomically defined ROIs. This study suggests that results of rCBF assessment with SPET using 99m Tc-HMPAO in patients with severe Alzheimer's disease are influenced by the shape and size of the ROI. (orig.)

Evaluation of medication treatment for Alzheimer's disease on clinical evidence

Directory of Open Access Journals (Sweden)

Meng-qiu LI

2014-03-01

Full Text Available Objective To formulate the best treatment plan for Alzheimer's disease patients by evaluating the therapeutic efficacy and side effect of various evidence-based programs. Methods Alzheimer's disease, donepezil, rivastigmine, galantamine, memantine, rosiglitazone, etc. were defined as retrieval words. PubMed, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases were used with applying of manual searching. Systematic reviews, randomized controlled trials (RCT, controlled clinical trials and case-observation studies were collected and evaluated by Jadad Scale. Results After screening, 33 selected resources included 14 systematic reviews, 14 randomized controlled trials, 4 controlled clinical trials and 1 case-observation study. According to Jadad Scale, total 28 articles were evaluated to be high quality (12 with score 4, 10 score 5, 6 score 7, and 5 were low quality with score 3. It was summarized as follows: 1 Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. To date, only symptomatic treatments with cholinesterase inhibitors (donepezil, rivastigmine, galantamine and an N-methyl-D-aspartate (NMDA receptor noncompetitive antagonist (memantine, are effective and well tolerated to counterbalance the neurotransmitter disturbance, but cannot limit or impact on disease progression. 2 Disease modifying drug is an potential agent, with persistent effect on slowing the progression of structural damage, and can be detected even after withdrawing the treatment. Many types of disease modifying drugs are undergoing clinical trials. Conclusions Using evidence-based medicine methods can provide best clinical evidence on Alzheimer's disease treatment. doi: 10.3969/j.issn.1672-6731.2014.03.009

Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

Science.gov (United States)

de la Monte, Suzanne M

Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

Exposure to mobile phone radiation opens new horizons in Alzheimer's disease treatment.

Science.gov (United States)

Mortazavi, Sar; Shojaei-Fard, Mb; Haghani, M; Shokrpour, N; Mortazavi, Smj

2013-09-01

Alzheimer's disease, the most common type of dementia and a progressive neurodegenerative disease, occurs when the nerve cells in the brain die. Although there are medications that can help delay the development of Alzheimer's disease, there is currently no cure for this disease. Exposure to ionizing and non-ionizing radiation may cause adverse health effects such as cancer.  Looking at the other side of the coin, there are reports indicating stimulatory or beneficial effects after exposure to cell phone radiofrequency radiation. Mortazavi et al. have previously reported some beneficial cognitive effects such as decreased reaction time after human short-term exposure to cell phone radiation or occupational exposure to radar microwave radiation. On the other hand, some recent reports have indicated that RF radiation may have a role in protecting against cognitive impairment in Alzheimer's disease. Although the majority of these data come from animal studies that cannot be easily extrapolated to humans, it can be concluded that this memory enhancing approach may open new horizons in treatment of cognitive impairment in Alzheimer disease.

Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer's disease

International Nuclear Information System (INIS)

Lannfelt, L.; Lilius, L.; Viitanen, M.; Winblad, B.; Basun, H.; Houlden, H.; Rossor, M.; Hardy, J.

1995-01-01

Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer's disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid presursor protein gene involvement in Alzheimer's disease families, as it is closely linked to the gene. Most cases of Alzheimer's disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer's disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. (au) (26 refs.)

Familial aggregation of Alzheimer's disease and related disorders: A collaborative re-analysis of case-control studies

NARCIS (Netherlands)

C.M. van Duijn (Cornelia); D.G. Clayton (David); V. Chandra; L. Fratiglioni (Laura); A.B. Graves; A. Heyman; A.F. Jorm; E. Kokmen (Emre); K. Kondo; J.A. Mortimer; W.A. Rocca; S.L. Shalat; H. Soininen; A. Hofman (Albert)

1991-01-01

textabstractCase-control studies of Alzheimer's disease were re-analysed to examine the association of Alzheimer's disease with family history in first degree relatives of dementia, Down's syndrome and Parkinson's disease. Overall, the relative risk of Alzheimer's disease for those with at least one

Alzheimer disease : presenilin springs a leak

NARCIS (Netherlands)

Gandy, S.; Doeven, M.K.; Poolman, B.

2006-01-01

Presenilins are thought to contribute to Alzheimer disease through a protein cleavage reaction that produces neurotoxic amyloid-beta peptides. A new function for presenilins now comes to light - controlling the leakage of calcium out of the endoplasmic reticulum. Is this a serious challenge to the

International Work Group Criteria for the Diagnosis of Alzheimer Disease

NARCIS (Netherlands)

Cummings, J.L.; Dubois, B; Molinuevo, J.L.; Scheltens, P.

2013-01-01

Alzheimer-type biomarker changes are identifiable in asymptomatic and mildly symptomatic predementia phases of Alzheimer disease (AD) and AD dementia. The International Work Group (IWG) guidelines for diagnosis identify a unified spectrum of 3 phases. The classic clinical feature that indicates AD

Alcohol consumption and mortality in patients with mild Alzheimer's disease

DEFF Research Database (Denmark)

Berntsen, Sine; Kragstrup, Jakob; Siersma, Volkert

2015-01-01

OBJECTIVE: To investigate the association between alcohol consumption and mortality in patients recently diagnosed with mild Alzheimer's disease (AD). DESIGN: A post hoc analysis study based on a clinical trial population. SETTING: The data reported were collected as part of the Danish Alzheimer...

Effect of aromatherapy on patients with Alzheimer's disease.

Science.gov (United States)

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.

Polygenic Risk Score for Alzheimer's Disease: Implications for Memory Performance and Hippocampal Volumes in Early Life.

Science.gov (United States)

Axelrud, Luiza K; Santoro, Marcos L; Pine, Daniel S; Talarico, Fernanda; Gadelha, Ary; Manfro, Gisele G; Pan, Pedro M; Jackowski, Andrea; Picon, Felipe; Brietzke, Elisa; Grassi-Oliveira, Rodrigo; Bressan, Rodrigo A; Miguel, Eurípedes C; Rohde, Luis A; Hakonarson, Hakon; Pausova, Zdenka; Belangero, Sintia; Paus, Tomas; Salum, Giovanni A

2018-06-01

Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume. Participants were children 6-14 years of age in two Brazilian cities, constituting the discovery (N=364) and replication samples (N=352). As an additional replication, data from a Canadian sample (N=1,029), with distinct tasks, MRI protocol, and genetic risk, were included. Cognitive tests quantified memory and executive function. Reading and writing abilities were assessed by standardized tests. Hippocampal volumes were derived from the Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation brain algorithm. Genetic risk for Alzheimer's disease was quantified using summary statistics from the International Genomics of Alzheimer's Project. Analyses showed that for the Brazilian discovery sample, each one-unit increase in z-score for Alzheimer's polygenic risk score significantly predicted a 0.185 decrement in z-score for immediate recall and a 0.282 decrement for delayed recall. Findings were similar for the Brazilian replication sample (immediate and delayed recall, β=-0.259 and β=-0.232, both significant). Quantile regressions showed lower hippocampal volumes bilaterally for individuals with high polygenic risk scores. Associations fell short of significance for the Canadian sample. Genetic risk for Alzheimer's disease may affect early-life cognition and hippocampal volumes, as shown in two independent samples. These data support previous evidence that some forms of late-life dementia may represent developmental conditions with roots in childhood. This result may vary depending on a sample's genetic risk and may be specific to some types of memory tasks.

The potential use of Raman spectroscopy for the diagnosis of Alzheimer's disease

Science.gov (United States)

Sudworth, Caroline D.; Archer, John K. J.; Mann, David

2005-09-01

Alzheimer's disease currently affects over 800,000 people in the UK, and this figure is set to exceed 1.5 million by 2050. The disease causes a severe breakdown of the brain, resulting in the progressive decline in the mental health of the patient. It also remains without a long-term cure. A definitive diagnosis of the disease can only be gained at post-mortem, whilst other technologies are limited to monitoring the physical breakdown of the brain. The early identification of the chemicals responsible for the disease, and their structure, is therefore essential for improved diagnosis, treatment and care. This research demonstrates the use of Raman spectroscopy, and principle components analysis, as a method for the diagnosis, and examination of, the specific proteins responsible for Alzheimer's disease. Analyses of ethically approved ex vivo brain tissues from normal elderly (n=3), Alzheimer's disease (n=12) and Huntingdon's disease (n=3) brain sections (from the frontal and occipital lobes) are presented. Subsequently, a further 12 blinded individual samples were examined and the preliminary results are presented. Spectra originating from these tissues are highly reproducible, and results indicate a vital difference in protein content and protein conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Principle components analysis has been shown to differentiate normal elderly tissues from diseased tissues. These results show great promise for the early identification of Alzheimer's disease, and secondary information regarding other brain diseases and dementias. These results demonstrate the potential use of Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

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

Directory of Open Access Journals (Sweden)

Luciane F. Viola

2011-01-01

Full Text Available OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatry 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

For better or worse: Immune system involvement in Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Emma L. Walton

2018-02-01

Full Text Available In this issue of the Biomedical Journal, we explore the key role of the immune system in the development of Alzheimer's disease. We also learn more about the link between two disorders related to metabolic imbalances, with findings that could help to inform future screening programs. Finally, we would like to highlight some big news for our journal: the Biomedical Journal will be indexed in the Science Citation Index and receive its first official impact factor from this year. Keywords: Alzheimer's disease, Tau, Immune responses, Subclinical hypothyroidism, Metabolic disease

Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

International Nuclear Information System (INIS)

Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

1989-01-01

No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect

[Non-verbal communication in Alzheimer's disease].

Science.gov (United States)

Schiaratura, Loris Tamara

2008-09-01

This review underlines the importance of non-verbal communication in Alzheimer's disease. A social psychological perspective of communication is privileged. Non-verbal behaviors such as looks, head nods, hand gestures, body posture or facial expression provide a lot of information about interpersonal attitudes, behavioral intentions, and emotional experiences. Therefore they play an important role in the regulation of interaction between individuals. Non-verbal communication is effective in Alzheimer's disease even in the late stages. Patients still produce non-verbal signals and are responsive to others. Nevertheless, few studies have been devoted to the social factors influencing the non-verbal exchange. Misidentification and misinterpretation of behaviors may have negative consequences for the patients. Thus, improving the comprehension of and the response to non-verbal behavior would increase first the quality of the interaction, then the physical and psychological well-being of patients and that of caregivers. The role of non-verbal behavior in social interactions should be approached from an integrative and functional point of view.

The olfactory deficit and fMRI in the Alzheimer's disease

International Nuclear Information System (INIS)

Yin Jianzhong; Wang Jianli; Yang Qingxian; Qi Ji

2008-01-01

Olfactory deficit is a common symptom occurring at the early stage of Alzheimer's disease, the purpose of this review is to summarize MRI research on olfactory deficit in the Alzheimer's disease and potential clinical relevance of fMRI in this area. (authors)

Clinical meaningfulness of Alzheimer's Disease Assessment Scale-Cognitive subscale change in relation to goal attainment in patients on cholinesterase inhibitors.

Science.gov (United States)

Rockwood, Kenneth; Howlett, Susan E; Hoffman, Deborah; Schindler, Rachel; Mitnitski, Arnold

2017-10-01

The clinical meaningfulness of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) subscale change is disputed. We compared 2- to 4-point ADAS-Cog changes with changes in Goal Attainment Scaling (GAS) and everyday function across initial ADAS-Cog scores and treatment responses. This exploratory analysis evaluated mild-moderate Alzheimer's disease patients treated with donepezil (12 months) or galantamine (8 months). Clinical meaningfulness was defined as concomitant ADAS-Cog and GAS changes of ±3 points and/or functional improvement. Patients with ≥3-point ADAS-Cog improvement significantly improved on GAS but not on standard tests of everyday function. ADAS-Cog "no change" (≤±3 points) was seen with mean GAS improvement. Initial ADAS-Cog improvement made endpoint improvement (ADAS-Cog 3 points and GAS 1 point) more likely (odds ratio = 6.9; 95% confidence interval = 2.5-19.5). In contrast, initial deterioration made endpoint improvement unlikely (0.33; 0.14-0.64). ADAS-Cog improvement and no change were each associated with GAS improvement. Initial ADAS-Cog worsening was unlikely to result in later improvement. ISRCTN26167328. Copyright © 2017. Published by Elsevier Inc.

High-frequency electroacupuncture evidently reinforces hippocampal synaptic transmission in Alzheimer's disease rats

Science.gov (United States)

Li, Wei; Kong, Li-hong; Wang, Hui; Shen, Feng; Wang, Ya-wen; Zhou, Hua; Sun, Guo-jie

2016-01-01

The frequency range of electroacupuncture in treatment of Alzheimer's disease in rats is commonly 2–5 Hz (low frequency) and 50–100 Hz (high frequency). We established a rat model of Alzheimer's disease by injecting β-amyloid 1–42 (Aβ1–42) into the bilateral hippocampal dentate gyrus to verify which frequency may be better suited in treatment. Electroacupuncture at 2 Hz or 50 Hz was used to stimulate Baihui (DU20) and Shenshu (BL23) acupoints. The water maze test and electrophysiological studies demonstrated that spatial memory ability was apparently improved, and the ranges of long-term potentiation and long-term depression were increased in Alzheimer's disease rats after electroacupuncture treatment. Moreover, the effects of electroacupuncture at 50 Hz were better than that at 2 Hz. These findings suggest that high-frequency electroacupuncture may enhance hippocampal synaptic transmission and potentially improve memory disorders in Alzheimer's disease rats. PMID:27335565

Manifestações da apraxia de fala na doença de Alzheimer Manifestations of apraxia of speech in Alzheimer's disease

Directory of Open Access Journals (Sweden)

Maysa Luchesi Cera

2011-09-01

Full Text Available OBJETIVO: Identificar as manifestações práxicas de pacientes com doença de Alzheimer em diferentes estágios da doença e verificar as similaridades entre as suas ocorrências. MÉTODOS: Foram avaliados noventa pacientes com doença de Alzheimer, 30 em cada fase da doença (leve, moderada e grave, por meio dos instrumentos: Escala de Avaliação Clínica da Demência (CDR, Mini-Exame do Estado Mental (MEEM, Avaliação das Atividades Instrumentais de Vida Diária (Índice Lawton e Protocolo de Avaliação da Apraxia Verbal e Não-verbal. Foram avaliados 66 pacientes do gênero feminino e 24 do masculino, a média da idade foi 80,2±7,2 e da escolaridade foi 4,2±3,5 anos. RESULTADOS: Na fase leve, as proporções de ensaio, repetição e adição foram semelhantes, assim como omissão, substituição e autocorreção. Na fase moderada foram semelhantes: ensaio e repetição, substituição, omissão e adição, e autocorreção. Na fase grave, todas as manifestações se assemelharam, exceto a adição. O erro do tipo adição diferenciou os pacientes em relação às fases da doença. CONCLUSÃO: Os pacientes dos três estágios da doença apresentam diferentes padrões de manifestações práxicas verbais.PURPOSE: To identify praxic speech manifestations in patients diagnosed with different stages of Alzheimer's disease, and to verify similarities among their occurrences. METHODS: Participants were 90 patients with Alzheimer's, 30 in each stage of the disease (mild, moderate and severe, who were assessed using the following instruments: Clinical Dementia Rating (CDR, Mini-Mental State Examination (MMSE, Lawton Instrumental Activities of Daily Living, and the Assessment Protocol of Verbal and Orofacial Apraxia. Sixty six female subjects and 24 male subjects were assessed; mean age was 80.2±7.2 years, and mean level of education was 4.2±3.5 years. RESULTS: In the mild stage, the proportions of trial-and-error, repetition and addition were

Searching for new pharmacological targets for the treatment of Alzheimer's disease in Down syndrome.

Science.gov (United States)

Caraci, Filippo; Iulita, M Florencia; Pentz, Rowan; Flores Aguilar, Lisi; Orciani, Chiara; Barone, Concetta; Romano, Corrado; Drago, Filippo; Cuello, A Claudio

2017-12-15

Individuals with Down syndrome are at increased risk of developing Alzheimer's disease due to increase gene dosage resulting from chromosome 21 triplication. Although virtually all adults with Down syndrome will exhibit the major neuropathological hallmarks that define Alzheimer's disease, not all of them will develop the clinical symptoms associated with this disorder (i.e. dementia). Therefore, a good understanding of the pathophysiology of Alzheimer's disease in Down syndrome will be crucial for the identification of novel pharmacological targets to develop disease-modifying therapies for the benefit of Down syndrome individuals and for Alzheimer's sufferers alike. The study of biomarkers will also be essential for the development of better screening tools to identify dementia at its incipient stages. This review discusses the best-validated pharmacological targets for the treatment of cognitive impairment and Alzheimer's disease in Down syndrome. We further examine the relevance of newly discovered biological markers for earlier dementia diagnosis in this population. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Usefulness of Diffusion Tensor Imaging of White Matter in Alzheimer Disease and Vascular Dementia

International Nuclear Information System (INIS)

Sugihara, S.; Kinoshita, T.; Matsusue, E.; Fujii, S.; Ogawa, T.

2004-01-01

Purpose: To evaluate the usefulness of diffusion tensor imaging in detecting the water diffusivity caused by neuro pathological change in Alzheimer disease and vascular dementia. Material and Methods: Twenty patients with Alzheimer disease, 20 with vascular dementia, and 10 control subjects were examined. Diffusion tensor imaging applied diffusion gradient encoding in six non-collinear directions. Fractional anisotropy values were compared in the genu and splenium of the corpus callosum, and anterior and posterior white matter among the three groups. Results: In the patients with Alzheimer disease, fractional anisotropy values of the posterior white matter were significantly lower than those of controls. In patients with vascular dementia, fractional anisotropy values of the anterior white matter tended to be lower than those of the posterior white matter (P=0.07). Conclusion: Diffusion tensor imaging reflects the neuro pathological changes in the white matter, and may be useful in the diagnosis of Alzheimer disease and vascular dementia. Keywords: Alzheimer disease, .; diffusion tensor imaging, .; vascular dementia

Microprobe PIXE analysis and EDX analysis on the brain of patients with Alzheimer's disease

International Nuclear Information System (INIS)

Yumoto, S.; Horino, Y.; Mokuno, Y.; Fujii, K.; Kakimi, S.; Mizutani, T.; Matsushima, H.; Ishikawa, A.

1996-01-01

To investigate the cause of Alzheimer's disease (senile dementia of Alzheimer's disease type), we examined aluminium (Al) in the brain (hippocampus) of patients with Alzheimer's disease using heavy ion (5 MeV Si 3+ ) microprobe particle-induced X-ray emission (PIXE) analysis. Heavy ion microprobes (3 MeV Si 2+ ) have several times higher sensitivity for Al detection than 2 MeV proton microprobes. We also examined Al in the brain of these patients by energy dispersive X-ray spectroscopy (EDX). (1) Al was detected in the cell nuclei isolated from the brain of patients with Alzheimer's disease using 5 MeV Si 3+ microprobe PIXE analysis, and EDX analysis. (2) EDX analysis demonstrated high levels of Al in the nucleolus of nerve cells in frozen sections prepared from the brain of these patients. Our results support the theory that Alzheimer's disease is caused by accumulation of Al in the nuclei of brain cells. (author)

Progression of Alzheimer Disease in Europe

DEFF Research Database (Denmark)

Vellas, B; Hausner, L; Frolich, L

2012-01-01

The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North...

[Musical long-term memory throughout the progression of Alzheimer disease].

Science.gov (United States)

Groussard, Mathilde; Mauger, Caroline; Platel, Hervé

2013-03-01

In Alzheimer patients with a solid musical background, isolated case-reports have reported the maintenance of remarkable musical abilities despite clear difficulties in their verbal memory and linguistic functions. These reports have encouraged a number of scientists to undertake more systematic studies which would allow a rigorous approach to the analysis of musical memory in Alzheimer patients with no formal musical background. Although restricted in number, the latest data are controversial regarding preserved musical capacities in Alzheimer patients. Our current review of the literature addresses this topic and advances the hypothesis that the processes of musical memory are function of illness progression. In the earlier stages, the majority of evaluations concerned musical episodic memory and suggested a dysfunction of this memory whereas in the moderate and severe stages, musical semantic memory and implicit learning are the majority of investigations and seemed more resistant to Alzheimer disease. In summary, our current review bring to understand the memory circuits involved and highlight the necessity to adapted the investigational tools employed to conform with the severity of the signs and symptoms of progressive Alzheimer disease in order to demonstrate the preserved musical capacities.

Schooling mediates brain reserve in Alzheimer's disease: findings of fluoro-deoxy-glucose-positron emission tomography.

Science.gov (United States)

Perneczky, R; Drzezga, A; Diehl-Schmid, J; Schmid, G; Wohlschläger, A; Kars, S; Grimmer, T; Wagenpfeil, S; Monsch, A; Kurz, A

2006-09-01

Functional imaging studies report that higher education is associated with more severe pathology in patients with Alzheimer's disease, controlling for disease severity. Therefore, schooling seems to provide brain reserve against neurodegeneration. To provide further evidence for brain reserve in a large sample, using a sensitive technique for the indirect assessment of brain abnormality (18F-fluoro-deoxy-glucose-positron emission tomography (FDG-PET)), a comprehensive measure of global cognitive impairment to control for disease severity (total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery) and an approach unbiased by predefined regions of interest for the statistical analysis (statistical parametric mapping (SPM)). 93 patients with mild Alzheimer's disease and 16 healthy controls underwent 18F-FDG-PET imaging of the brain. A linear regression analysis with education as independent and glucose utilisation as dependent variables, adjusted for global cognitive status and demographic variables, was conducted in SPM2. The regression analysis showed a marked inverse association between years of schooling and glucose metabolism in the posterior temporo-occipital association cortex and the precuneus in the left hemisphere. In line with previous reports, the findings suggest that education is associated with brain reserve and that people with higher education can cope with brain damage for a longer time.

Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET

DEFF Research Database (Denmark)

De Leon, Mony J.; Li, Yi; Okamura, Nobuyuki

2017-01-01

Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribrif......Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing...

Homeostasis of metals in the progression of Alzheimer's disease.

Science.gov (United States)

González-Domínguez, Raúl; García-Barrera, Tamara; Gómez-Ariza, José Luis

2014-06-01

In order to study the involvement of metals in the progression of Alzheimer's disease, serum samples from patients with Alzheimer and mild cognitive impairment were investigated. For this purpose, metal content was analyzed after size-fractionation of species and then, inter-element and inter-fraction ratios were computed. In this way, the analysis allowed discovering changes that could be used as markers of disease, but also provided a new insight into the interactions in the homeostasis of elements in neurodegeneration and its progression. Aluminum and labile forms of iron and copper were increased in demented patients, while manganese, zinc and selenium were reduced. Interestingly, levels of different elements, principally iron, aluminum and manganese, were closely inter-related, which could evidence a complex interdependency between the homeostasis of the different metals in this disorder. On the other hand, imbalances in metabolism of copper, zinc and selenium could be associated to abnormal redox status. Therefore, this study may contribute to our understanding of the pathological mechanisms related to metals in Alzheimer's disease.

Measurement of temporal regional cerebral perfusion with single-photon emission tomography predicts rate of decline in language function and survival in early Alzheimer`s disease

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Claus, J.J.; Walstra, G.J.M.; Hijdra, A.; Gool, W.A. van [Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Royen, E.A. van [Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam (Netherlands); Verbeeten, B. Jr. [Department of Radiology, Academic Medical Center, University of Amsterdam (Netherlands)

1999-03-01

We determined the relationship between regional cerebral blood flow (rCBF) measured with single-photon emission tomography (SPET) and decline in cognitive function and survival in Alzheimer`s disease. In a prospective follow-up study, 69 consecutively referred patients with early probable Alzheimer`s disease (NINCDS/ADRDA criteria) underwent SPET performed at the time of initial diagnosis using technetium-99m-labelled hexamethylpropylene amine oxime. Neuropsychological function was assessed at baseline and after 6 months and survival data were available on all patients, extending to 5.5 years of follow-up. Lower left temporal (P<0.01) and lower left parietal (P<0.01) rCBF were statistically significantly related to decline in language function after 6 months. The association between left temporal rCBF and survival was also statistically significant (P<0.05) using Cox proportional hazards regression analysis. Performing analysis with quartiles of the distribution, we found a threshold effect for low left temporal rCBF (rCBF<73.7%, P<0.01) and high risk of mortality. In this lowest quartile, median survival time was 2.7 years (follow-up to 5.2 years), compared with 4.4 years in the other quartiles (follow-up to 5.5 years). Kaplan-Meier survival curves showed statistically significant (P<0.05, log rank test) survival curves for the lowest versus other quartiles of left temporal rCBF. All results were unaffected by adjustment for age, sex, dementia severity, duration of symptoms, education and ratings of local cortical atrophy. We conclude that left temporal rCBF predicts decline in language function and survival in patients with early probable Alzheimer`s disease, with a threshold effect of low rCBF and high risk of mortality. (orig.) With 3 figs., 3 tabs., 44 refs.

Memory Correlates of Alzheimer's Disease Cerebrospinal Fluid Markers

DEFF Research Database (Denmark)

Reijs, Babette L R; Ramakers, Inez H G B; Köhler, Sebastian

2017-01-01

BACKGROUND: Performance on episodic, semantic, and working memory tests is impaired in Alzheimer's disease (AD)-type dementia, but it is unclear which type of memory test is most strongly associated with early AD biomarkers in cerebrospinal fluid (CSF), and most useful for monitoring disease...

Alzheimer's disease and intelligence.

Science.gov (United States)

Yeo, R A; Arden, R; Jung, R E

2011-06-01

A significant body of evidence has accumulated suggesting that individual variation in intellectual ability, whether assessed directly by intelligence tests or indirectly through proxy measures, is related to risk of developing Alzheimer's disease (AD) in later life. Important questions remain unanswered, however, such as the specificity of risk for AD vs. other forms of dementia, and the specific links between premorbid intelligence and development of the neuropathology characteristic of AD. Lower premorbid intelligence has also emerged as a risk factor for greater mortality across myriad health and mental health diagnoses. Genetic covariance contributes importantly to these associations, and pleiotropic genetic effects may impact diverse organ systems through similar processes, including inefficient design and oxidative stress. Through such processes, the genetic underpinnings of intelligence, specifically, mutation load, may also increase the risk of developing AD. We discuss how specific neurobiologic features of relatively lower premorbid intelligence, including reduced metabolic efficiency, may facilitate the development of AD neuropathology. The cognitive reserve hypothesis, the most widely accepted account of the intelligence-AD association, is reviewed in the context of this larger literature.

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

OpenAIRE

Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

2017-01-01

Background Synaptic dysfunction contributes to cognitive impairment in Alzheimer?s disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer?s disease. Methods Thirty-four drug-naive patients with mild Alzheimer?s disease (Mini Mental State Examination score ?20) were enrolled in this exploratory, double-blind, randomized...

Errors in self-reports of health services use: impact on alzheimer disease clinical trial designs.

Science.gov (United States)

Callahan, Christopher M; Tu, Wanzhu; Stump, Timothy E; Clark, Daniel O; Unroe, Kathleen T; Hendrie, Hugh C

2015-01-01

Most Alzheimer disease clinical trials that compare the use of health services rely on reports of caregivers. The goal of this study was to assess the accuracy of self-reports among older adults with Alzheimer disease and their caregiver proxy respondents. This issue is particularly relevant to Alzheimer disease clinical trials because inaccuracy can lead both to loss of power and increased bias in study outcomes. We compared respondent accuracy in reporting any use and in reporting the frequency of use with actual utilization data as documented in a comprehensive database. We next simulated the impact of underreporting and overreporting on sample size estimates and treatment effect bias for clinical trials comparing utilization between experimental groups. Respondents self-reports have a poor level of accuracy with κ-values often below 0.5. Respondents tend to underreport use even for rare events such as hospitalizations and nursing home stays. In analyses simulating underreporting and overreporting of varying magnitude, we found that errors in self-reports can increase the required sample size by 15% to 30%. In addition, bias in the reported treatment effect ranged from 3% to 18% due to both underreporting and overreporting errors. Use of self-report data in clinical trials of Alzheimer disease treatments may inflate sample size needs. Even when adequate power is achieved by increasing sample size, reporting errors can result in a biased estimate of the true effect size of the intervention.

Longitudinal Study of the Transition From Healthy Aging to Alzheimer Disease

Science.gov (United States)

Johnson, David K.; Storandt, Martha; Morris, John C.; Galvin, James E.

2009-01-01

Background Detection of the earliest cognitive changes signifying Alzheimer disease is difficult. Objective To model the cognitive decline in preclinical Alzheimer disease. Design Longitudinal archival study comparing individuals who became demented during follow-up and people who remained nondemented on each of 4 cognitive factors: global, verbal memory, visuospatial, and working memory. Setting Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri. Participants One hundred thirty-four individuals who became demented during follow-up and 310 who remained nondemented. Main Outcome Measures Inflection point in longitudinal cognitive performance. Results The best-fitting model for each of the 4 factors in the stable group was linear, with a very slight downward trend on all but the Visuospatial factor. In contrast, a piecewise model with accelerated slope after a sharp inflection point provided the best fit for the group that progressed. The optimal inflection point for all 4 factors was prior to diagnosis of dementia: Global, 2 years; Verbal and Working Memory, 1 year; and Visuospatial, 3 years. These results were also obtained when data were limited to the subset (n=44) with autopsy-confirmed Alzheimer disease. Conclusions There is a sharp inflection point followed by accelerating decline in multiple domains of cognition, not just memory, in the preclinical period in Alzheimer disease when there is insufficient cognitive decline to warrant clinical diagnosis using conventional criteria. Early change was seen in tests of visuospatial ability, most of which were speeded. Research into early detection of cognitive disorders using only episodic memory tasks may not be sensitive to all of the early manifestations of disease. PMID:19822781

Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer's disease.

Science.gov (United States)

Janel, N; Alexopoulos, P; Badel, A; Lamari, F; Camproux, A C; Lagarde, J; Simon, S; Feraudet-Tarisse, C; Lamourette, P; Arbones, M; Paul, J L; Dubois, B; Potier, M C; Sarazin, M; Delabar, J M

2017-06-20

Early identification of Alzheimer's disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.

Assessing cardiorespiratory capacity in older adults with major depression and Alzheimer disease

Directory of Open Access Journals (Sweden)

Marcos Felipe Zanco

2016-03-01

Full Text Available ABSTRACT Objective To assess cardiorespiratory capacity through subjective and objective tests in older adults diagnosed with major depression (MDD, Alzheimer disease (AD and healthy older adults. Methods Fifty seven subjects (72 ± 7.9 years were divided into three groups: MDD (n = 20, AD (n = 17 and Healthy (n = 20. The subjects answered Hamilton Scale (HAM-D, Mini-Mental State Examination (MMSE, Veterans Specific Activity Questionnaire (VSAQ and 2-minute Step test. Results MDD and AD showed lower scores than healthy group for Nomogram VSAQ (p < 0.001 and 2-minute Step (p = 0.009; p = 0.008, respectively. Adjusted for age and educational level, no differences among groups were observed for Step (MDD, p = 0.097; AD, p = 0.102. AD group did not present differences to healthy group for Step, when adjusting for MMSE (p = 0.261. Conclusions Despite the lower cardiorespiratory fitness of elderly patients with DM and DA have been found in both evaluations, the results should be viewed with caution, since the tests showed low correlation and different risk classifications of functional loss. In addition, age, level educational and cognitive performance are variables that can influence the performance objective evaluation.

Verb Agreements during On-Line Sentence Processing in Alzheimer's Disease and Frontotemporal Dementia

Science.gov (United States)

Price, C.C.; Grossman, M.

2005-01-01

An on-line ''word detection'' paradigm was used to assess the comprehension of thematic and transitive verb agreements during sentence processing in individuals diagnosed with probable Alzheimer's Disease (AD, n=15) and Frontotemporal Dementia (FTD, n=14). AD, FTD, and control participants (n=17) were asked to listen for a word in a sentence.…

Alzheimer's Disease Facts and Figures

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Full Text Available ... people without Alzheimer's — a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty- ... IL 60601 Alzheimer's Association is a not-for-profit 501(c)(3) organization. Copyright © 2018 Alzheimer's Association ® . ...

Ecological assessment of mild cognitive impairment and Alzheimer disease using the Rivermead Behavioural Memory Test.

Science.gov (United States)

Bolló-Gasol, S; Piñol-Ripoll, G; Cejudo-Bolivar, J C; Llorente-Vizcaino, A; Peraita-Adrados, H

2014-01-01

The Rivermead Behavioural Memory Test (RBMT) is a short, ecologically-valid memory test battery that can provide data about a subject's memory function in daily life. We used RBMT to examine daily memory function in patients with mild cognitive impairment (MCI), Alzheimer disease (AD), and in healthy controls. We also evaluated differences between the memory profiles of subjects whose MCI remained stable after 1 year and those with conversion to AD. Sample of 91 subjects older than 60 years: 30 controls, 27 MCI subjects and 34 AD patients. Subjects were assessed using MMSE and RBMT. The 40 men and 51 women in the sample had a mean age of 74.29±6.71 and 5.87±2.93 years of education. For the total profile and screening RBMT scores (Pde Neurología. Published by Elsevier Espana. All rights reserved.

Rates of cognitive change in Alzheimer disease: Observations across a decade of placebo-controlled clinical trials with donepezil

DEFF Research Database (Denmark)

Jones, Roy W; Schwam, Elias; Wilkinson, David

2009-01-01

Treatment success in Alzheimer disease (AD) trials is generally based on benefits over placebo-treated controls. Consequently, variation in rates of decline among placebo-treated patients could impact outcomes from AD trials. In the present analyses, individual patient data [baseline Mini......-Mental State Examination (MMSE): 10 to 26] were pooled from randomized, placebo-controlled studies of donepezil for AD conducted during the 1990s, and grouped by initiation year-group 1: 1990 to 1994; group 2: 1996 to 1999. Changes in MMSE and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS...

Music therapy and Alzheimer's disease: Cognitive, psychological, and behavioural effects.

Science.gov (United States)

Gómez Gallego, M; Gómez García, J

2017-06-01

Music therapy is one of the types of active ageing programmes which are offered to elderly people. The usefulness of this programme in the field of dementia is beginning to be recognised by the scientific community, since studies have reported physical, cognitive, and psychological benefits. Further studies detailing the changes resulting from the use of music therapy with Alzheimer patients are needed. Determine the clinical improvement profile of Alzheimer patients who have undergone music therapy. Forty-two patients with mild to moderate Alzheimer disease underwent music therapy for 6 weeks. The changes in results on the Mini-mental State Examination, Neuropsychiatric Inventory, Hospital Anxiety and Depression Scale and Barthel Index scores were studied. We also analysed whether or not these changes were influenced by the degree of dementia severity. Significant improvement was observed in memory, orientation, depression and anxiety (HAD scale) in both mild and moderate cases; in anxiety (NPI scale) in mild cases; and in delirium, hallucinations, agitation, irritability, and language disorders in the group with moderate Alzheimer disease. The effect on cognitive measures was appreciable after only 4 music therapy sessions. In the sample studied, music therapy improved some cognitive, psychological, and behavioural alterations in patients with Alzheimer disease. Combining music therapy with dance therapy to improve motor and functional impairment would be an interesting line of research. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Quantifying cognition and behavior in normal aging, mild cognitive impairment, and Alzheimer's disease

Science.gov (United States)

Giraldo, Diana L.; Sijbers, Jan; Romero, Eduardo

2017-11-01

The diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) is based on neuropsychological evaluation of the patient. Different cognitive and memory functions are assessed by a battery of tests that are composed of items devised to specifically evaluate such upper functions. This work aims to identify and quantify the factors that determine the performance in neuropsychological evaluation by conducting an Exploratory Factor Analysis (EFA). For this purpose, using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), EFA was applied to 67 item scores taken from the baseline neuropsychological battery of the three phases of ADNI study. The found factors are directly related to specific brain functions such as memory, behavior, orientation, or verbal fluency. The identification of factors is followed by the calculation of factor scores given by weighted linear combinations of the items scores.

78 FR 9396 - Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early...