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Sample records for familial alzheimers disease

  1. Understanding Family Interaction Patterns in Families With Alzheimer's Disease.

    Science.gov (United States)

    Schaber, Patricia; Blair, Kate; Jost, Ellen; Schaffer, Molly; Thurner, Emily

    2016-01-01

    This qualitative study explores the dynamic changes that occur in family interaction patterns when Alzheimer's disease is present. Semi-structured interviews were conducted with 15 participants who have a family member with the disease. Using modified analytic induction, guided by the dimensions of the Family Fundamental Interpersonal Relations Orientation (FIRO) Model, participants shared how Alzheimer's disease affected family structure, control dynamics, and intimacy among family members. Findings demonstrate that (a) families reorganize and restructure based on geographic proximity and shifting roles, act out of filial responsibility, and strive to preserve shared meanings and rituals; (b) decision making increases around care of the person with Alzheimer's disease and shifts to the primary caregiver or other family members based on their abilities; and (c) expressions of intimacy intensify while personality is preserved in the person with the disease. The Family FIRO model can inform practitioners using family-centered care with families with Alzheimer's disease.

  2. Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease.

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    Quiroz, Yakeel T; Budson, Andrew E; Celone, Kim; Ruiz, Adriana; Newmark, Randall; Castrillón, Gabriel; Lopera, Francisco; Stern, Chantal E

    2010-12-01

    The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer's disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms. Twenty carriers of the Alzheimer's-associated E280A PS1 mutation and 19 PS1-negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face-name associative encoding task while in a Phillips 1.5T fMRI scanner. Analysis focused on the hippocampal system. Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face-name associations compared to matched controls. Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD.

  3. 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.

  4. Lack of familial aggregation of Parkinson disease and Alzheimer disease.

    Science.gov (United States)

    Levy, Gilberto; Louis, Elan D; Mejia-Santana, Helen; Côté, Lucien; Andrews, Howard; Harris, Juliette; Waters, Cheryl; Ford, Blair; Frucht, Steven; Fahn, Stanley; Ottman, Ruth; Marder, Karen

    2004-07-01

    To investigate the risk of Alzheimer disease (AD) in first-degree relatives of patients with Parkinson disease (PD) compared with first-degree relatives of controls. Case-control study, family history method, and reconstructed cohort approach. Probands with PD without dementia and control probands, matched by age strata, sex, and ethnicity, were examined in person and enrolled without knowledge of family history of PD and other neurological disorders. Disease status in first-degree relatives of probands with PD and control probands was ascertained through a structured family history interview administered to the proband and a second informant (self-report or another informant). Cox proportional hazards models with double-censoring techniques for missing information on age of onset of AD were used to analyze the risk of AD in first-degree relatives of patients with PD compared with first-degree relatives of controls. Four hundred eighty-seven probands with PD and 409 control probands provided family history information on 4819 first-degree relatives older than 30 years (2534 relatives of probands with PD and 2285 relatives of control probands). One hundred thirteen first-degree relatives (2.3%; 61 relatives [2.4%] of patients with PD and 52 relatives [2.3%] of controls) were diagnosed with AD. The risk of AD was not increased in relatives of patients with PD compared with relatives of controls (hazard ratio, 1.1; 95% confidence interval, 0.7-1.6; P =.65). Similarly, no significantly increased risk of AD was observed when comparing relatives of patients with early-onset (50 years) PD with relatives of controls. The lack of familial aggregation of PD and AD does not support the hypothesis of major shared genetic contributions to the etiology of the 2 most common neurodegenerative disorders.

  5. Characteristics of familial aggregation in early-onset Alzheimer`s disease: Evidence of subgroups

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    Campion, D. [INSERM, Paris (France); Martinez, M.; Babron, M.C. [and others

    1995-06-19

    Characteristics of familial aggregation of Alzheimer`s Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early-onset Alzheimer`s disease. 58 refs., 5 figs., 2 tabs.

  6. [Needs and expectations of Alzheimer's disease family caregivers].

    Science.gov (United States)

    Amieva, H; Rullier, L; Bouisson, J; Dartigues, J-F; Dubois, O; Salamon, R

    2012-06-01

    Family members of people suffering from Alzheimer's disease play a major role in providing daily life care for their relatives. Compared to non-caregivers, they present increased risks of mortality as well as psychological and physical co-morbidity. Altered relationships between caregivers and medical staff and dissatisfaction with the quality of help provided tend to increase the risk of depression and anxiety disorders among caregivers. The present study aimed at exploring the needs and expectations of family caregivers of patients with Alzheimer's disease who request medical assistance for their relatives. The present analysis is an ancillary study of a large multicentric controlled randomized study designed to assess the efficacy of three non-pharmacological treatments in Alzheimer's disease, in which 645 mild-to-moderate Alzheimer patients were enrolled. Needs and expectations of the caregivers were assessed with a French scale of patient expectations for medical consultation, the échelle d'attentes en matière de consultations (EAC), completed by caregivers during the inclusion visit. This scale consists in a self-administered 28-item questionnaire concerning four main needs: learning skills to improve daily life management of their relatives; information regarding the disease; improving caregivers' self-confidence; support to improve communication with their relatives. The ten items for which more than 40% of caregivers reported high or very high expectations referred to two main needs: information regarding the disease (treatment, prognosis…) and learning skills in order to improve daily life management of their relative. The predominance of such needs was observed whatever the relationship between the caregiver and the cared relative but seemed to be more pronounced in female spouses and children of patients with Alzheimer's disease. Needs and expectations of Alzheimer's disease family caregivers involve two major aspects: first, information regarding

  7. A family living with Alzheimer's disease: The communicative challenges.

    Science.gov (United States)

    Jones, Danielle

    2015-09-01

    Alzheimer's disease irrevocably challenges a person's capacity to communicate with others. Earlier research on these challenges focused on the language disorders associated with the condition and situated language deficit solely in the limitations of a person's cognitive and semantic impairments. This research falls short of gaining insight into the actual interactional experiences of a person with Alzheimer's and their family. Drawing on a UK data set of 70 telephone calls recorded over a two-and-a-half year period (2006-2008) between one elderly woman with Alzheimer's disease, and her daughter and son-in-law, this paper explores the role which communication (and its degeneration) plays in family relationships. Investigating these interactions, using a conversation analytic approach, reveals that there are clearly communicative difficulties, but closer inspection suggests that they arise due to the contingencies that are generated by the other's contributions in the interaction. That being so, this paper marks a departure from the traditional focus on language level analysis and the assumption that deficits are intrinsic to the individual with Alzheimer's, and instead focuses on the collaborative communicative challenges that arise in the interaction itself and which have a profound impact on people's lives and relationships.

  8. Alzheimer Disease

    Science.gov (United States)

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

  9. A Unifying Hypothesis for Familial and Sporadic Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Carole J. Proctor

    2012-01-01

    Full Text Available Alzheimer's disease (AD is characterised by the aggregation of two quite different proteins, namely, amyloid-beta (Aβ, which forms extracellular plaques, and tau, the main component of cytoplasmic neurofibrillary tangles. The amyloid hypothesis proposes that Aβ plaques precede tangle formation but there is still much controversy concerning the order of events and the linkage between Aβ and tau alterations is still unknown. Mathematical modelling has become an essential tool for generating and evaluating hypotheses involving complex systems. We have therefore used this approach to discover the most probable pathway linking Aβ and tau. The model supports a complex pathway linking Aβ and tau via GSK3β, p53, and oxidative stress. Importantly, the pathway contains a cycle with multiple points of entry. It is this property of the pathway which enables the model to be consistent with both the amyloid hypothesis for familial AD and a more complex pathway for sporadic forms.

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

    Science.gov (United States)

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

    2016-08-01

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

  11. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... with Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full ... in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 million family and friends provided 18. ...

  12. Alzheimer's Disease Facts and Figures

    Science.gov (United States)

    ... Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 million family ...

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 million family ...

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

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); 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

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

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); 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

  16. Alzheimer's Disease

    Science.gov (United States)

    ... to note that Alzheimer's disease is not a normal part of aging. What Is Alzheimer's Disease? Video length: 2 min 29 sec Click to watch this video The course of Alzheimer’s disease—which symptoms appear and how quickly changes occur—varies from person to person. The time ...

  17. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

    Science.gov (United States)

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

  18. Early behavioural changes in familial Alzheimer's disease in the Dominantly Inherited Alzheimer Network.

    Science.gov (United States)

    Ringman, John M; Liang, Li-Jung; Zhou, Yan; Vangala, Sitaram; Teng, Edmond; Kremen, Sarah; Wharton, David; Goate, Alison; Marcus, Daniel S; Farlow, Martin; Ghetti, Bernardino; McDade, Eric; Masters, Colin L; Mayeux, Richard P; Rossor, Martin; Salloway, Stephen; Schofield, Peter R; Cummings, Jeffrey L; Buckles, Virginia; Bateman, Randall; Morris, John C

    2015-04-01

    Prior studies indicate psychiatric symptoms such as depression, apathy and anxiety are risk factors for or prodromal symptoms of incipient Alzheimer's disease. The study of persons at 50% risk for inheriting autosomal dominant Alzheimer's disease mutations allows characterization of these symptoms before progressive decline in a population destined to develop illness. We sought to characterize early behavioural features in carriers of autosomal dominant Alzheimer's disease mutations. Two hundred and sixty-one persons unaware of their mutation status enrolled in the Dominantly Inherited Alzheimer Network, a study of persons with or at-risk for autosomal dominant Alzheimer's disease, were evaluated with the Neuropsychiatric Inventory-Questionnaire, the 15-item Geriatric Depression Scale and the Clinical Dementia Rating Scale (CDR). Ninety-seven asymptomatic (CDR = 0), 25 mildly symptomatic (CDR = 0.5), and 33 overtly affected (CDR > 0.5) autosomal dominant Alzheimer's disease mutation carriers were compared to 106 non-carriers with regard to frequency of behavioural symptoms on the Neuropsychiatric Inventory-Questionnaire and severity of depressive symptoms on the Geriatric Depression Scale using generalized linear regression models with appropriate distributions and link functions. Results from the adjusted analyses indicated that depressive symptoms on the Neuropsychiatric Inventory-Questionnaire were less common in cognitively asymptomatic mutation carriers than in non-carriers (5% versus 17%, P = 0.014) and the odds of experiencing at least one behavioural sign in cognitively asymptomatic mutation carriers was lower than in non-carriers (odds ratio = 0.50, 95% confidence interval: 0.26-0.98, P = 0.042). Depression (56% versus 17%, P = 0.0003), apathy (40% versus 4%, P Alzheimer's disease, we demonstrated increased rates of depression, apathy, and other behavioural symptoms in the mildly symptomatic, prodromal phase of autosomal dominant Alzheimer's disease that

  19. Experiences of Supporting People with Down Syndrome and Alzheimer's Disease in Aged Care and Family Environments

    Science.gov (United States)

    Carling-Jenkins, Rachel; Torr, Jennifer; Iacono, Teresa; Bigby, Christine

    2012-01-01

    Background: Research addressing the experiences of families of adults with Down syndrome and Alzheimer's disease in seeking diagnosis and gaining support is limited. The aim of this study was to gain a greater understanding of these processes by exploring the experiences of families and carers in supporting people with Down syndrome and…

  20. Clustering and age of onset in familial late onset Alzheimer`s disease are determined at the apoliopoprotein E locus

    Energy Technology Data Exchange (ETDEWEB)

    Houlden, H.; Rossor, M. [St. Mary`s Hospital Medical School, London (United Kingdom)

    1994-09-01

    Recent work has demonstrated that the apolipoprotein E (ApoE) genotype is of great importance in the etiology of Alzheimer`s disease (AD). Thus, inheritance of the ApoE4 allele predisposes to the occurrences of late onset disease and decreases the onset age in families with pathogenic mutations in the amyloid precursor protein gene. We analysed ApoE genotypes in 35 families multiply affected by AD and confirm that familial clustering in late onset AD is associated with the ApoE4 allele. This allele occurs in the great majority (82%) of late onset familial Alzheimer cases. Elderly unaffected sibs (80-90 years) have an allele frequency that is not significantly different to that of normal controls. Data presented from our family sets together previously published data is suggestive that the effect of a single ApoE4 allele is to increase the risk of developing AD by an amount equivalent to 5 years and that the effect of ApoE4 homozygosity is to increase the risk of developing AD by an amount equivalent to 10 years of age. Data shows significant difference between the frequency of the ApoE4 allele in the familial AD probands and controls and in both sets of unaffected sibs, p<0.01.

  1. Familial Alzheimer's disease-associated presenilin-1 alters cerebellar activity and calcium homeostasis

    NARCIS (Netherlands)

    Sepulveda-Falla, Diego; Barrera-Ocampo, Alvaro; Hagel, Christian; Korwitz, Anne; Vinueza-Veloz, Maria Fernanda; Zhou, Kuikui; Schonewille, Martijn; Zhou, Haibo; Velazquez-Perez, Luis; Rodriguez-Labrada, Roberto; Villegas, Andres; Ferrer, Isidro; Lopera, Francisco; Langer, Thomas; De Zeeuw, Chris I; Glatzel, Markus

    2014-01-01

    Familial Alzheimer's disease (FAD) is characterized by autosomal dominant heritability and early disease onset. Mutations in the gene encoding presenilin-1 (PS1) are found in approximately 80% of cases of FAD, with some of these patients presenting cerebellar damage with amyloid plaques and ataxia w

  2. Treatments for Alzheimer's Disease

    Science.gov (United States)

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

  3. Alpha-synuclein in familial Alzheimer disease: epitope mapping parallels dementia with Lewy bodies and Parkinson disease.

    Science.gov (United States)

    Lippa, C F; Schmidt, M L; Lee, V M; Trojanowski, J Q

    2001-11-01

    Alpha-synuclein is a major component of Lewy bodies (LBs) in Parkinson disease and dementia with LBs and of glial cytoplasmic inclusions in multiple system atrophy. However, epitope mapping for alpha-synuclein is distinctive in different neurodegenerative diseases. The reasons for this are poorly understood but may reflect fundamental differences in disease mechanisms. To investigate the alpha-synuclein epitope mapping properties of LBs in familial Alzheimer disease. We compared LBs in familial Alzheimer disease with those in synucleinopathies by probing 6 brains of persons with familial Alzheimer disease using a panel of antibodies to epitopes spanning the alpha-synuclein protein. Results were compared with data from brains of persons with Parkinson disease, dementia with LBs, and multiple system atrophy. The brains of persons with familial Alzheimer disease showed consistent staining of LBs with all antibodies, similar to Parkinson disease and dementia with LBs but different from alpha-synuclein aggregates that occurred in multiple system atrophy. These data suggest that the epitope profiles of alpha-synuclein in LBs are similar, regardless of whether the biological trigger is related to synuclein or a different genetic pathway. These findings support the hypothesis that the mechanism of alpha-synuclein aggregation is the same within cell types but distinctive between cell types.

  4. Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Shinohara, Mitsuru; Fujioka, Shinsuke; Murray, Melissa E; Wojtas, Aleksandra; Baker, Matthew; Rovelet-Lecrux, Anne; Rademakers, Rosa; Das, Pritam; Parisi, Joseph E; Graff-Radford, Neill R; Petersen, Ronald C; Dickson, Dennis W; Bu, Guojun

    2014-05-01

    Recent studies suggest that subcortical structures, including striatum, are vulnerable to amyloid-β accumulation and other neuropathological features in familial Alzheimer's disease due to autosomal dominant mutations. We explored differences between familial and sporadic Alzheimer's disease that might shed light on their respective pathogenic mechanisms. To this end, we analysed 12 brain regions, including neocortical, limbic and subcortical areas, from post-mortem brains of familial Alzheimer's disease (n = 10; age at death: 50.0 ± 8.6 years) with mutations in amyloid precursor protein (APP) or presenilin 1 (PSEN1), sporadic Alzheimer's disease (n = 19; age at death: 84.7 ± 7.8 years), neurologically normal elderly without amyloid-β accumulation (normal ageing; n = 13, age at death: 82.9 ± 10.8 years) and neurologically normal elderly with extensive cortical amyloid-β deposits (pathological ageing; n = 15; age at death: 92.7 ± 5.9 years). The levels of amyloid-β₄₀, amyloid-β₄₂, APP, apolipoprotein E, the synaptic marker PSD95 (now known as DLG4), the astrocyte marker GFAP, other molecules related to amyloid-β metabolism, and tau were determined by enzyme-linked immunosorbent assays. We observed that familial Alzheimer's disease had disproportionate amyloid-β₄₂ accumulation in subcortical areas compared with sporadic Alzheimer's disease, whereas sporadic Alzheimer's disease had disproportionate amyloid-β₄₂ accumulation in cortical areas compared to familial Alzheimer's disease. Compared with normal ageing, the levels of several proteins involved in amyloid-β metabolism were significantly altered in both sporadic and familial Alzheimer's disease; however, such changes were not present in pathological ageing. Among molecules related to amyloid-β metabolism, the regional distribution of PSD95 strongly correlated with the regional pattern of amyloid-β₄₂ accumulation in sporadic Alzheimer's disease and pathological ageing, whereas the

  5. Familial Alzheimer's disease: genetic analysis related to disease heterogeneity, Down syndrome and human brain evolution.

    Science.gov (United States)

    Schapiro, M B; Rapoport, S I

    1989-01-01

    Etiologically heterogeneous subgroups of patients with Alzheimer's disease (AD) exist and need to be distinguished so as to better identify genetic causes of familial cases. Furthermore, the presence of AD neuropathology in Down syndrome (trisomy 21) subjects older than 35 years suggests that AD in some cases is caused by dysregulation of expression of genes on chromosome 21. Cerebral metabolic abnormalities in life, and the distribution of AD neuropathology in the post-mortem brain, indicate that AD involves the association neocortices and subcortical regions with which they evolved during evolution of the human brain. Accordingly, understanding the molecular basis of this evolution should elucidate the genetic basis of AD, whereas knowing the genetics of AD should be informative about the genomic changes which promoted brain evolution.

  6. Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation

    DEFF Research Database (Denmark)

    Lindquist, S.G.; Holm, I.E.; Schwartz, M.

    2008-01-01

    We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic an......We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre...

  7. Familial associations of Alzheimer disease and essential tremor with Parkinson disease.

    Science.gov (United States)

    Costello, S; Bordelon, Y; Bronstein, J; Ritz, B

    2010-06-01

    We constructed a cohort of first-degree relatives of participants in a population-based case-control study of Parkinson disease (PD) and compared the occurrence of Alzheimer disease (AD) and essential tremor (ET) in relatives of PD cases and controls. We relied on proband interviews to assess family history in 372 probands with incident PD confirmed by a movement disorder specialist and 404 controls from three rural California counties. Overall, for the 2980 first-degree relatives of PD cases, the risk of AD was not increased compared with the 2981 relatives of controls. But relatives of younger onset PD cases (familial susceptibility to AD amongst first-degree relatives of younger onset PD cases.

  8. Family Stigma and Caregiver Burden in Alzheimer's Disease

    Science.gov (United States)

    Werner, Perla; Mittelman, Mary S.; Goldstein, Dovrat; Heinik, Jeremia

    2012-01-01

    Purpose: The stigma experienced by the family members of an individual with a stigmatized illness is defined by 3 dimensions: caregiver stigma, lay public stigma, and structural stigma. Research in the area of mental illness suggests that caregivers' perception of stigma is associated with increased burden. However, the effect of stigma on…

  9. Family Stigma and Caregiver Burden in Alzheimer's Disease

    Science.gov (United States)

    Werner, Perla; Mittelman, Mary S.; Goldstein, Dovrat; Heinik, Jeremia

    2012-01-01

    Purpose: The stigma experienced by the family members of an individual with a stigmatized illness is defined by 3 dimensions: caregiver stigma, lay public stigma, and structural stigma. Research in the area of mental illness suggests that caregivers' perception of stigma is associated with increased burden. However, the effect of stigma on…

  10. Neuropsychiatric symptoms of the elderly with Alzheimer's disease and the family caregivers' distress

    Directory of Open Access Journals (Sweden)

    Luana Baldin Storti

    Full Text Available ABSTRACT Objective: to analyze the relationship between the distress of the family caregiver and the presence of neuropsychiatric symptoms in elderly patients with Alzheimer's disease or mixed dementia. Method: a descriptive, cross-sectional study conducted in the Geriatric and Dementias Clinic of a general tertiary hospital, with 96 elderly people with Alzheimer's disease or mixed dementia and their family caregivers. Questionnaires to characterize the elderly and caregivers, and the Neuropsychiatric Inventory were used. Descriptive statistics and Pearson correlation test were performed. Results: 68.7% of the elderly were women, average age 80.8 years, 56.2% had Alzheimer's disease and 43.7%, mixed dementia. Among caregivers, 90.6% were women, average age 56, 70.8% took care of parents and 64.6% lived with the elderly. There was a strong (r = 0.82 and significant (p <0.01 correlation between the total score on the Neuropsychiatric Inventory and the total score on the Neuropsychiatric Inventory-Distress and strong (r = 0.80 and significant (p <0 01 correlation between the total score on the Neuropsychiatric Inventory Distress and the number of neuropsychiatric symptoms, i.e., the higher the number, frequency and severity of these symptoms in the elderly, the more intense is the caregiver distress. Conclusion: the presence of neuropsychiatric symptoms in the elderly was related to increased distress in caregivers.

  11. Neuropsychiatric symptoms of the elderly with Alzheimer's disease and the family caregivers' distress 1

    Science.gov (United States)

    Storti, Luana Baldin; Quintino, Débora Teles; Silva, Natália Michelato; Kusumota, Luciana; Marques, Sueli

    2016-01-01

    ABSTRACT Objective: to analyze the relationship between the distress of the family caregiver and the presence of neuropsychiatric symptoms in elderly patients with Alzheimer's disease or mixed dementia. Method: a descriptive, cross-sectional study conducted in the Geriatric and Dementias Clinic of a general tertiary hospital, with 96 elderly people with Alzheimer's disease or mixed dementia and their family caregivers. Questionnaires to characterize the elderly and caregivers, and the Neuropsychiatric Inventory were used. Descriptive statistics and Pearson correlation test were performed. Results: 68.7% of the elderly were women, average age 80.8 years, 56.2% had Alzheimer's disease and 43.7%, mixed dementia. Among caregivers, 90.6% were women, average age 56, 70.8% took care of parents and 64.6% lived with the elderly. There was a strong (r = 0.82) and significant (p <0.01) correlation between the total score on the Neuropsychiatric Inventory and the total score on the Neuropsychiatric Inventory-Distress and strong (r = 0.80) and significant (p <0 01) correlation between the total score on the Neuropsychiatric Inventory Distress and the number of neuropsychiatric symptoms, i.e., the higher the number, frequency and severity of these symptoms in the elderly, the more intense is the caregiver distress. Conclusion: the presence of neuropsychiatric symptoms in the elderly was related to increased distress in caregivers. PMID:27533264

  12. Complex educational and care (geron)technology for elderly individuals/families experiencing Alzheimer's disease.

    Science.gov (United States)

    Ilha, Silomar; Santos, Silvana Sidney Costa; Backes, Dirce Stein; Barros, Edaiane Joana Lima; Pelzer, Marlene Teda; Costenaro, Regina Gema Santini

    2017-01-01

    To describe the contributions of the Integrated Multidisciplinary Care Group for Caregivers of Individuals with Alzheimer's Disease as an educational and care (geron)technology in the context of Alzheimer's disease in elderly individuals from the perspective of family members/caregivers. Exploratory, descriptive study with a qualitative approach conducted with 13 family members/caregivers of elderly people participating in the support group of a university institution of the state of Rio Grande do Sul, Brazil. Data collected between January and April 2016 through a semi-structured interview were submitted to discursive textual analysis. Family members/caregivers pointed out education and care as contributions of the group; education for care and for the future; exchange, socialization, and development of knowledge through the range of knowledge existing in the Group. The Group contributes as a (geron)technology of care and education for care in which knowledge is built and applied in practice, supporting the experienced disorders and improving the quality of care provided for elderly individuals with Alzheimer's disease. Descrever as contribuições do Grupo de Assistência Multidisciplinar Integrada aos Cuidadores de Pessoas com a Doença de Alzheimer como (geronto)tecnologia cuidativo-educacional no contexto da doença de Alzheimer em pessoas idosas, na perspectiva de familiares/cuidadores. Pesquisa exploratório-descritiva, qualitativa, realizada com 13 familiares/cuidadores de pessoas idosas, participantes do grupo de apoio de uma instituição universitária do Rio Grande do Sul, Brasil. Os dados coletados entre janeiro a abril/2016, com uma entrevista semiestruturada, foram submetidos à análise textual discursiva. Os familiares/cuidadores referiram como contribuições do Grupo a educação e o cuidado; a educação para o cuidado e para o futuro; a troca, socialização e construção do conhecimento por meio dos diversos saberes existentes no Grupo. O

  13. Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.

    Science.gov (United States)

    Israel, Mason A; Yuan, Shauna H; Bardy, Cedric; Reyna, Sol M; Mu, Yangling; Herrera, Cheryl; Hefferan, Michael P; Van Gorp, Sebastiaan; Nazor, Kristopher L; Boscolo, Francesca S; Carson, Christian T; Laurent, Louise C; Marsala, Martin; Gage, Fred H; Remes, Anne M; Koo, Edward H; Goldstein, Lawrence S B

    2012-01-25

    Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt

  14. Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations.

    Science.gov (United States)

    Ringman, John M; O'Neill, Joseph; Geschwind, Daniel; Medina, Luis; Apostolova, Liana G; Rodriguez, Yaneth; Schaffer, Barbara; Varpetian, Arousiak; Tseng, Benjamin; Ortiz, Freddy; Fitten, Jaime; Cummings, Jeffrey L; Bartzokis, George

    2007-07-01

    Measures are needed that identify persons that will develop Alzheimer's disease in order to target them for preventative interventions. There is evidence from animal, pathological and imaging studies that disruption of white matter occurs in the course of Alzheimer's disease and may be an early event. Prior studies have suggested that late-myelinating regions or white matter connecting limbic structures are particularly susceptible to degradation. Persons destined to develop the disease by virtue of fully penetrant genetic alterations (familial Alzheimer's disease or FAD) provide a model in which early and even presymptomatic changes of the disease may be identified. In this study we performed diffusion tensor imaging (DTI) on 2 demented and 21 subjects at-risk for inheriting an FAD mutation. We compared global and localized fractional anisotropy (FA) measures in white matter between FAD mutation carriers and non-carriers in the preclinical (clinical dementia rating presymptomatic (clinical dementia rating = 0, n = 15) stages of the disease. There were no significant differences between mutation carriers and non-carriers with regard to absolute age, age relative to the typical age of disease diagnosis in their family, gender or Mini-Mental Status Examination Score. Among preclinical FAD mutation carriers (n = 12), mean whole brain white-matter FA (P = 0.045), FA of the columns of the fornix (P = 0.012), area of the perforant pathways bilaterally (right side: P = 0.028, left side: P = 0.027) and left orbitofrontal lobe (P = 0.024) were decreased relative to that of non-carriers (n = 8). We also found that FA in the columns of the fornix (P = 0.008) and left orbitofrontal lobe white matter (P = 0.045) were decreased in the eight presymptomatic mutation carriers compared to seven non-carriers. Logistic regression demonstrated that FA of the columns of the fornix was a better predictor of mutation status than was cross-sectional area of the fornix, global mean white

  15. Machine learning amplifies the effect of parental family history of Alzheimer's disease on list learning strategy.

    Science.gov (United States)

    Chang, Timothy S; Coen, Michael H; La Rue, Asenath; Jonaitis, Erin; Koscik, Rebecca L; Hermann, Bruce; Sager, Mark A

    2012-05-01

    Identification of preclinical Alzheimer's disease (AD) is an essential first step in developing interventions to prevent or delay disease onset. In this study, we examine the hypothesis that deeper analyses of traditional cognitive tests may be useful in identifying subtle but potentially important learning and memory differences in asymptomatic populations that differ in risk for developing Alzheimer's disease. Subjects included 879 asymptomatic higher-risk persons (middle-aged children of parents with AD) and 355 asymptotic lower-risk persons (middle-aged children of parents without AD). All were administered the Rey Auditory Verbal Learning Test at baseline. Using machine learning approaches, we constructed a new measure that exploited finer differences in memory strategy than previous work focused on serial position and subjective organization. The new measure, based on stochastic gradient descent, provides a greater degree of statistical separation (p = 1.44 × 10-5) than previously observed for asymptomatic family history and non-family history groups, while controlling for apolipoprotein epsilon 4, age, gender, and education level. The results of our machine learning approach support analyzing memory strategy in detail to probe potential disease onset. Such distinct differences may be exploited in asymptomatic middle-aged persons as a potential risk factor for AD.

  16. Familismo and its impact on the family caregiving of Latinos with Alzheimer's disease: a complex narrative.

    Science.gov (United States)

    Gelman, Caroline Rosenthal

    2014-01-01

    Despite the long-held view that Latinos' value and reliance on family leads to greater involvement of extended family in caring for sick members and reduced perception of burden, some research reports low levels of social support and high levels of distress among Latino caregivers. We explore this seeming discrepancy in a qualitative study of 41 Latino caregivers of family members with Alzheimer's disease, interviewing them regarding the role of familism in their caregiving experience. For some it facilitates caregiving in the traditional, expected manner. Other caregivers disavow its current relevance. Yet others feel a contrast between familism, which they may value in a general, abstract way and more personal, immediate negative feelings they are experiencing from caregiving. We discuss these complex, multidimensional findings, the variation among caregivers, and present implications for practice, policy, and research.

  17. Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: A possible clue to the higher incidence of Alzheimer disease in women

    Energy Technology Data Exchange (ETDEWEB)

    Payami, H.; Zareparsi, S.; Montee, K.R.; Litt, M. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1996-04-01

    Late-onset Alzheimer disease (AD) is associated with the apolipoprotein E (APOE)-{epsilon}4 allele. In late-onset familial AD, women have a significantly higher risk of developing the disease than do men. The aim of this study was to determine whether the gender difference in familial AD is a function of APOE genotype. We studied 58 late-onset familial AD kindreds. Kaplan-Meier survival analysis was used to assess genotype-specific distributions of age at onset. Odds ratios were estimated by logistic regression with adjustment for age and by conditional logistic regression with stratification on families. All methods detected a significant gender difference for the {epsilon}4 heterozygous genotype. In women, {epsilon}4 heterozygotes had higher risk than those without {epsilon}4; there was no significant difference between {epsilon}4 heterozygotes and {epsilon}4 homozygotes. In men, {epsilon}4 heterozygotes had lower risk than {epsilon}4 homozygotes; there was no significant difference between {epsilon}4 heterozygotes and those without {epsilon}4. A direct comparison of {epsilon}4 heterozygous men and women revealed a significant two-fold increased risk in women. We confirmed these results in 15 autopsy-confirmed AD kindreds from the National Cell Repository at Indiana University Alzheimer Disease Center. These observations are consistent with the increased incidence of familial AD in women and may be a critical clue to the role of gender in the pathogenesis of AD. 53 refs., 2 figs., 2 tabs.

  18. Apolipoprotein E-epsilon 4 allele and familial risk in Alzheimer's disease.

    Science.gov (United States)

    Li, G; Silverman, J M; Altstiel, L D; Haroutunian, V; Perl, D P; Purohit, D; Birstein, S; Lantz, M; Mohs, R C; Davis, K L

    1996-01-01

    Recent studies have found an association between presence of apolipoprotein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the epsilon 4 allele with the relatives of AD probands not carrying epsilon 4 and with relatives of non-demented controls. Our aim was to determine whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying epsilon 4. Seventy-seven neuropathologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were genotyped for APOE. As a comparison group, 198 non-demented probands were also included. Through family informants, demographic and diagnostic data were collected on 382 first-degree relatives (age > or = 45 years) of AD probands and 848 relatives of the controls. We found that the cumulative risk of PPD in both relatives of AD probands with and without the epsilon 4 allele was significantly higher than that in the relatives of non-demented controls. However, the increased risk in the relatives of AD probands with the epsilon 4 allele was marginally, but not significantly, lower than the risk in the relatives of probands without epsilon 4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with epsilon 4 (3.1-fold increase) was found compared to relatives of probands without epsilon 4 (1.7-fold increase), especially prior to age 70, although the difference was not statistically significant. The increased familial risk for PPD in the relatives of AD probands with the APOE-epsilon 4 allele relative to controls suggests that familial factors in addition to APOE-epsilon 4 are risk factors for AD. Differential censorship from increased mortality of heart diseases may have prevented a higher incidence of PPD among the relatives of probands with

  19. Overload of families taking care of elderly people with Alzheimer's Disease: a comparative study

    Directory of Open Access Journals (Sweden)

    Ana Carla Borghi

    2013-07-01

    Full Text Available OBJECTIVE: to compare the overload of the main and secondary family carers of patients with Alzheimer's Disease, and identify which dimension generates most impact. METHOD: a comparative study conducted in the city of Maringá, State of Paraná, with 20 primary carers of elderly patients with Alzheimer's Disease and 20 secondary caregivers. The data was collected in May and June 2012, using the Scale for Assessment of Overload of Members of Psychiatric Patients' Families (FBIS-BR, and the results were analysed using the Mann-Whitney test and analysis of variance. RESULTS: the global objective overload, and also in each subscale, was significantly greater in the group of main caregivers; the subjective overload showed no difference between the groups. Comparing the subscales, the routine assistance provided to the patient had greater influence on objective overload in both groups, and the concern with the elderly patient was the dimension that had most influence on the subjective overload of main caregivers and also of secondary caregivers. CONCLUSION: the differences in overload between the different groups reinforces the need for planning of health care actions for each type of caregiver, seeking to reduce these differences.

  20. Specific disruption of hippocampal mossy fiber synapses in a mouse model of familial Alzheimer's disease.

    Science.gov (United States)

    Wilke, Scott A; Raam, Tara; Antonios, Joseph K; Bushong, Eric A; Koo, Edward H; Ellisman, Mark H; Ghosh, Anirvan

    2014-01-01

    The earliest stages of Alzheimer's disease (AD) are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber (MF) synapse between dentate gyrus (DG) and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy (SBEM) to analyze MF microcircuitry in a mouse model of familial Alzheimer's disease (FAD). FAD mutant MF terminal complexes were severely disrupted compared to control - they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease.

  1. Specific disruption of hippocampal mossy fiber synapses in a mouse model of familial Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Scott A Wilke

    Full Text Available The earliest stages of Alzheimer's disease (AD are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber (MF synapse between dentate gyrus (DG and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy (SBEM to analyze MF microcircuitry in a mouse model of familial Alzheimer's disease (FAD. FAD mutant MF terminal complexes were severely disrupted compared to control - they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease.

  2. The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease.

    Science.gov (United States)

    Tosto, Giuseppe; Bird, Thomas D; Bennett, David A; Boeve, Bradley F; Brickman, Adam M; Cruchaga, Carlos; Faber, Kelley; Foroud, Tatiana M; Farlow, Martin; Goate, Alison M; Graff-Radford, Neill R; Lantigua, Rafael; Manly, Jennifer; Ottman, Ruth; Rosenberg, Roger; Schaid, Daniel J; Schupf, Nicole; Stern, Yaakov; Sweet, Robert A; Mayeux, Richard

    2016-10-01

    The contribution of cardiovascular disease (CV) and cerebrovascular disease to the risk for late-onset Alzheimer disease (LOAD) has been long debated. Investigations have shown that antecedent CV risk factors increase the risk for LOAD, although other investigations have failed to validate this association. To study the contribution of CV risk factors (type 2 diabetes, hypertension, and heart disease) and the history of stroke to LOAD in a data set of large families multiply affected by LOAD. The National Institute on Aging Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease family study (hereinafter referred to as NIA-LOAD study) is a longitudinal study of families with multiple members affected with LOAD. A multiethnic community-based longitudinal study (Washington Heights-Inwood Columbia Aging Project [WHICAP]) was used to replicate findings. The 6553 participants in the NIA-LOAD study were recruited from 23 US Alzheimer disease centers with ongoing data collection since 2003; the 5972 WHICAP participants were recruited at Columbia University with ongoing data collection since 1992. Data analysis was performed from 2003 to 2015. Generalized mixed logistic regression models tested the association of CV risk factors (primary association) with LOAD. History of stroke was used for the secondary association. A secondary model adjusted for the presence of an apolipoprotein E (APOE) ε4 allele. A genetic risk score, based on common variants associated with LOAD, was used to account for LOAD genetic risk beyond the APOE ε4 effect. Mediation analyses evaluated stroke as a mediating factor between the primary association and LOAD. A total of 6553 NIA-LOAD participants were included in the analyses (4044 women [61.7%]; 2509 men [38.3%]; mean [SD] age, 77.0 [9] years), with 5972 individuals from the WHICAP study included in the replication sample (4072 women [68.2%]; 1900 men [31.8%]; mean [SD] age, 76.5 [7.0] years). Hypertension was associated

  3. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... with Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: ... More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease Facts and Figures report contains data on ...

  4. Cognitive deficits in familial Alzheimer's disease associated with M239V mutation of presenilin 2.

    Science.gov (United States)

    Giovagnoli, Anna Rita; Marcon, Gabriella; Giaccone, Giorgio; Confaloni, Anna Maria; Tagliavini, Fabrizio

    2006-01-01

    The neuropsychological assessment of non-demented subjects with gene mutation of familial Alzheimer's disease (AD) provides a model for exploring the early cognitive features of the disease. We evaluated 1 patient and 6 non-demented subjects belonging to a family with AD with M239V mutation of the presenilin 2 gene, aiming to verify the contribution of specific cognitive patterns to the characterization of familial AD. One patient, 3 non-demented subjects with M239V mutation and 3 subjects without mutation from the same family underwent neuropsychological testing. The patient's cognitive profile was characterized by anosognosia, visuospatial agnosia, apraxia and fluent aphasia. Of the 3 non-demented subjects with mutation, 1 showed no deficits, another constructive apraxia and the third spatial perception and memory deficits. The 3 subjects without mutation showed normal abilities. The cognitive deficits of the non-demented subjects with mutations indicate focal dysfunction of the posterior cortical areas, resembling the more extended parieto-occipito-temporal dysfunction of the demented patient. Such grading of visuospatial, praxis, and language impairments highlights a distinctive pattern related to the M239V mutation of the presenilin 2 gene.

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

    Science.gov (United States)

    Rapp, Thomas

    2014-10-01

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

  6. Suppressor Mutations for Presenilin 1 Familial Alzheimer Disease Mutants Modulate γ-Secretase Activities.

    Science.gov (United States)

    Futai, Eugene; Osawa, Satoko; Cai, Tetsuo; Fujisawa, Tomoya; Ishiura, Shoichi; Tomita, Taisuke

    2016-01-01

    γ-Secretase is a multisubunit membrane protein complex containing presenilin (PS1) as a catalytic subunit. Familial Alzheimer disease (FAD) mutations within PS1 were analyzed in yeast cells artificially expressing membrane-bound substrate, amyloid precursor protein, or Notch fused to Gal4 transcriptional activator. The FAD mutations, L166P and G384A (Leu-166 to Pro and Gly-384 to Ala substitution, respectively), were loss-of-function in yeast. We identified five amino acid substitutions that suppress the FAD mutations. The cleavage of amyloid precursor protein or Notch was recovered by the secondary mutations. We also found that secondary mutations alone activated the γ-secretase activity. FAD mutants with suppressor mutations, L432M or S438P within TMD9 together with a missense mutation in the second or sixth loops, regained γ-secretase activity when introduced into presenilin null mouse fibroblasts. Notably, the cells with suppressor mutants produced a decreased amount of Aβ42, which is responsible for Alzheimer disease. These results indicate that the yeast system is useful to screen for mutations and chemicals that modulate γ-secretase activity.

  7. Familial Alzheimer's disease mutations differentially alter amyloid β-protein oligomerization.

    Science.gov (United States)

    Gessel, Megan Murray; Bernstein, Summer; Kemper, Martin; Teplow, David B; Bowers, Michael T

    2012-11-21

    Although most cases of Alzheimer's disease (AD) are sporadic, ∼5% of cases are genetic in origin. These cases, known as familial Alzheimer's disease (FAD), are caused by mutations that alter the rate of production or the primary structure of the amyloid β-protein (Aβ). Changes in the primary structure of Aβ alter the peptide's assembly and toxic activity. Recently, a primary working hypothesis for AD has evolved where causation has been attributed to early, soluble peptide oligomer states. Here we posit that both experimental and pathological differences between FAD-related mutants and wild-type Aβ could be reflected in the early oligomer distributions of these peptides. We use ion mobility-based mass spectrometry to probe the structure and early aggregation states of three mutant forms of Aβ40 and Aβ42: Tottori (D7N), Flemish (A21G), and Arctic (E22G). Our results indicate that the FAD-related amino acid substitutions have no noticeable effect on Aβ monomer cross section, indicating there are no major structural changes in the monomers. However, we observe significant changes to the aggregation states populated by the various Aβ mutants, indicating that structural changes present in the monomers are reflected in the oligomers. Moreover, the early oligomer distributions differ for each mutant, suggesting a possible structural basis for the varied pathogenesis of different forms of FAD.

  8. Differential damage in the frontal cortex with aging, sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Leuba, Geneviève; Vernay, André; Zimmermann, Vincent; Saini, Krishan; Kraftsik, Rudolf; Savioz, Armand

    2009-10-28

    In order to understand relationships between executive and structural deficits in the frontal cortex of patients within normal aging or Alzheimer's disease, we studied frontal pathological changes in young and old controls compared to cases with sporadic (AD) or familial Alzheimer's disease (FAD). We performed a semi-automatic computer assisted analysis of the distribution of beta-amyloid (Abeta) deposits revealed by Abeta immunostaining as well as of neurofibrillary tangles (NFT) revealed by Gallyas silver staining in Brodman areas 10 (frontal polar), 12 (ventro-infero-median) and 24 (anterior cingular), using tissue samples from 5 FAD, 6 sporadic AD and 10 control brains. We also performed densitometric measurements of glial fibrillary acidic protein, principal compound of intermediate filaments of astrocytes, and of phosphorylated neurofilament H and M epitopes in areas 10 and 24. All regions studied seem almost completely spared in normal old controls, with only the oldest ones exhibiting a weak percentage of beta-amyloid deposit and hardly any NFT. On the contrary, all AD and FAD cases were severely damaged as shown by statistically significant increased percentages of beta-amyloid deposit, as well as by a high number of NFT. FAD cases (all from the same family) had statistically more beta-amyloid and GFAP than sporadic AD cases in both areas 10 and 24 and statistically more NFT only in area 24. The correlation between the percentage of beta-amyloid and the number of NFT was significant only for area 24. Altogether, these data suggest that the frontal cortex can be spared by AD type lesions in normal aging, but is severely damaged in sporadic and still more in familial Alzheimer's disease. The frontal regions appear to be differentially vulnerable, with area 12 having the less amyloid burden, area 24 the less NFT and area 10 having both more amyloid and more NFT. This pattern of damage in frontal regions may represent a strong neuroanatomical support for the

  9. Alzheimer's Disease Facts and Figures

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    Full Text Available ... without Alzheimer's — a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, ... COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease Facts and ...

  10. Visual short-term memory binding deficit in familial Alzheimer's disease.

    Science.gov (United States)

    Liang, Yuying; Pertzov, Yoni; Nicholas, Jennifer M; Henley, Susie M D; Crutch, Sebastian; Woodward, Felix; Leung, Kelvin; Fox, Nick C; Husain, Masud

    2016-05-01

    Long-term episodic memory deficits in Alzheimer's disease (AD) are well characterised but, until recently, short-term memory (STM) function has attracted far less attention. We employed a recently-developed, delayed reproduction task which requires participants to reproduce precisely the remembered location of items they had seen only seconds previously. This paradigm provides not only a continuous measure of localization error in memory, but also an index of relational binding by determining the frequency with which an object is misplaced to the location of one of the other items held in memory. Such binding errors in STM have previously been found on this task to be sensitive to medial temporal lobe (MTL) damage in focal lesion cases. Twenty individuals with pathological mutations in presenilin 1 or amyloid precursor protein genes for familial Alzheimer's disease (FAD) were tested together with 62 healthy controls. Participants were assessed using the delayed reproduction memory task, a standard neuropsychological battery and structural MRI. Overall, FAD mutation carriers were worse than controls for object identity as well as in gross localization memory performance. Moreover, they showed greater misbinding of object identity and location than healthy controls. Thus they would often mislocalize a correctly-identified item to the location of one of the other items held in memory. Significantly, asymptomatic gene carriers - who performed similarly to healthy controls on standard neuropsychological tests - had a specific impairment in object-location binding, despite intact memory for object identity and location. Consistent with the hypothesis that the hippocampus is critically involved in relational binding regardless of memory duration, decreased hippocampal volume across FAD participants was significantly associated with deficits in object-location binding but not with recall precision for object identity or localization. Object-location binding may therefore

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

    Directory of Open Access Journals (Sweden)

    M. A. D. Danucalov

    2013-01-01

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

  12. Spectral Analysis of EEG in Familial Alzheimer's Disease with E280A Presenilin-1 Mutation Gene

    Science.gov (United States)

    Rodriguez, Rene; Lopera, Francisco; Alvarez, Alfredo; Fernandez, Yuriem; Galan, Lidice; Quiroz, Yakeel; Bobes, Maria Antonieta

    2014-01-01

    To evaluate the hypothesis that quantitative EEG (qEEG) analysis is susceptible to detect early functional changes in familial Alzheimer's disease (AD) preclinical stages. Three groups of subjects were selected from five extended families with hereditary AD: a Probable AD group (18 subjects), an asymptomatic carrier (ACr) group (21 subjects), with the mutation but without any clinical symptoms of dementia, and a normal group of 18 healthy subjects. In order to reveal significant differences in the spectral parameter, the Mahalanobis distance (D2) was calculated between groups. To evaluate the diagnostic efficiency of this statistic D2, the ROC models were used. The ROC curve was summarized by accuracy index and standard deviation. The D2 using the parameters of the energy in the fast frequency bands shows accurate discrimination between normal and ACr groups (area ROC = 0.89) and between AD probable and ACr groups (area ROC = 0.91). This is more significant in temporal regions. Theses parameters could be affected before the onset of the disease, even when cognitive disturbance is not clinically evident. Spectral EEG parameter could be firstly used to evaluate subjects with E280A Presenilin-1 mutation without impairment in cognitive function. PMID:24551475

  13. Spectral Analysis of EEG in Familial Alzheimer's Disease with E280A Presenilin-1 Mutation Gene.

    Science.gov (United States)

    Rodriguez, Rene; Lopera, Francisco; Alvarez, Alfredo; Fernandez, Yuriem; Galan, Lidice; Quiroz, Yakeel; Bobes, Maria Antonieta

    2014-01-01

    To evaluate the hypothesis that quantitative EEG (qEEG) analysis is susceptible to detect early functional changes in familial Alzheimer's disease (AD) preclinical stages. Three groups of subjects were selected from five extended families with hereditary AD: a Probable AD group (18 subjects), an asymptomatic carrier (ACr) group (21 subjects), with the mutation but without any clinical symptoms of dementia, and a normal group of 18 healthy subjects. In order to reveal significant differences in the spectral parameter, the Mahalanobis distance (D (2)) was calculated between groups. To evaluate the diagnostic efficiency of this statistic D (2), the ROC models were used. The ROC curve was summarized by accuracy index and standard deviation. The D (2) using the parameters of the energy in the fast frequency bands shows accurate discrimination between normal and ACr groups (area ROC = 0.89) and between AD probable and ACr groups (area ROC = 0.91). This is more significant in temporal regions. Theses parameters could be affected before the onset of the disease, even when cognitive disturbance is not clinically evident. Spectral EEG parameter could be firstly used to evaluate subjects with E280A Presenilin-1 mutation without impairment in cognitive function.

  14. Neuropsychiatric symptoms of the elderly with Alzheimer's disease and the family caregivers' distress.

    Science.gov (United States)

    Storti, Luana Baldin; Quintino, Débora Teles; Silva, Natália Michelato; Kusumota, Luciana; Marques, Sueli

    2016-08-15

    to analyze the relationship between the distress of the family caregiver and the presence of neuropsychiatric symptoms in elderly patients with Alzheimer's disease or mixed dementia. a descriptive, cross-sectional study conducted in the Geriatric and Dementias Clinic of a general tertiary hospital, with 96 elderly people with Alzheimer's disease or mixed dementia and their family caregivers. Questionnaires to characterize the elderly and caregivers, and the Neuropsychiatric Inventory were used. Descriptive statistics and Pearson correlation test were performed. 68.7% of the elderly were women, average age 80.8 years, 56.2% had Alzheimer's disease and 43.7%, mixed dementia. Among caregivers, 90.6% were women, average age 56, 70.8% took care of parents and 64.6% lived with the elderly. There was a strong (r = 0.82) and significant (p Geriatria e Demências de um Hospital Geral Terciário, com 96 idosos com doença de Alzheimer ou demência mista e seus cuidadores familiares. Foram utilizados o questionário para caracterização dos idosos e cuidadores e o Inventário Neuropsiquiátrico. Foram realizadas estatísticas descritivas e o teste de correlação de Pearson. 68,7% dos idosos eram mulheres, média de idade 80,8 anos, 56,2% possuíam doença de Alzheimer e 43,7%, demência mista. Dos cuidadores, 90,6% eram mulheres, média de idade 56 anos, 70,8% cuidavam do pai/mãe e 64,6% moravam com o idoso. Houve correlação forte (r=0,82) e significativa (p<0,01) entre o escore total do Inventário Neuropsiquiátrico e o escore total do Inventário Neuropsiquiátrico Desgaste e correlação forte (r=0,80) e significativa (p<0,01) entre o escore total do Inventário Neuropsiquiátrico Desgaste e o número de sintomas neuropsiquiátricos, ou seja, quanto maiores o número, a frequência e a gravidade destes sintomas nos idosos maior é o desgaste do cuidador. a presença dos sintomas neuropsiquiátricos nos idosos apresentou relação com maior desgaste nos cuidadores

  15. Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations.

    Science.gov (United States)

    Gómez-Tortosa, Estrella; Barquero, Sagrario; Barón, Manuel; Gil-Neciga, Eulogio; Castellanos, Fernando; Zurdo, Martín; Manzano, Sagrario; Muñoz, David G; Jiménez-Huete, Adolfo; Rábano, Alberto; Sainz, M José; Guerrero, Rosa; Gobernado, Isabel; Pérez-Pérez, Julián; Jiménez-Escrig, Adriano

    2010-01-01

    We describe the clinical phenotype of nine kindred with presenile Alzheimer's disease (AD) caused by different presenilin 1 (PS1) point mutations, and compare them with reported families with mutations in the same codons. Mutations were in exon 4 (Phe105Val), exon 5 (Pro117Arg, Glu120Gly), exon 6 (His163Arg), exon 7 (Leu226Phe), exon 8 (Val261Leu, Val272Ala, Leu282Arg), and exon 12 (Ile439Ser). Three of these amino acid changes (Phe105Val, Glu120Gly, and Ile439Ser) had not been previously reported. Distinct clinical features, including age of onset, symptoms and signs associated with the cortical-type dementia and aggressiveness of the disease, characterized the different mutations and were quite homogeneous across family members. Age of onset fell within a consistent range: some mutations caused the disease in the thirties (P117R, L226F, V272A), other in the forties (E120G, H163R, V261L, L282R), and other in the fifties (F105V, I439S). Associated features also segregated with specific mutations: early epileptic activity (E120G), spastic paraparesis (V261L), subcortical dementia and parkinsonism (V272A), early language impairment, frontal signs, and myoclonus (L226F), and late myoclonus and seizures (H163R, L282R). Neurological deterioration was particularly aggressive in PS1 mutations with earlier age of onset such as P117R, L226F, and E120G. With few exceptions, a similar clinical phenotype was found in families reported to have either the same mutation or different amino acid changes in the same codons. This series points to a strong influence of the specific genetic defect in the development of the clinical phenotype.

  16. Genetics Home Reference: Alzheimer disease

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions Alzheimer disease Alzheimer disease Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Alzheimer disease is a degenerative disease of the brain ...

  17. Rapidly progressive Alzheimer disease.

    Science.gov (United States)

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

    2011-09-01

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

  18. Role of Trisomy 21 Mosaicism in Sporadic and Familial Alzheimer's Disease.

    Science.gov (United States)

    Potter, Huntington; Granic, Antoneta; Caneus, Julbert

    2016-01-01

    Trisomy 21 and the consequent extra copy of the amyloid precursor protein (APP) gene and increased beta-amyloid (Aβ) peptide production underlie the universal development of Alzheimer's disease (AD) pathology and high risk of AD dementia in people with Down syndrome (DS). Trisomy 21 and other forms of aneuploidy also arise among neurons and peripheral cells in both sporadic and familial AD and in mouse and cell models thereof, reinforcing the conclusion that AD and DS are two sides of the same coin. The demonstration that 90% of the neurodegeneration in AD can be attributed to the selective loss of aneuploid neurons generated over the course of the disease indicates that aneuploidy is an essential feature of the pathogenic pathway leading to the depletion of neuronal cell populations. Trisomy 21 mosaicism also occurs in neurons and other cells from patients with Niemann-Pick C1 disease and from patients with familial or sporadic frontotemporal lobar degeneration (FTLD), as well as in their corresponding mouse and cell models. Biochemical studies have shown that Aβ induces mitotic spindle defects, chromosome mis-segregation, and aneuploidy in cultured cells by inhibiting specific microtubule motors required for mitosis. These data indicate that neuronal trisomy 21 and other types of aneuploidy characterize and likely contribute to multiple neurodegenerative diseases and are a valid target for therapeutic intervention. For example, reducing extracellular calcium or treating cells with lithium chloride (LiCl) blocks the induction of trisomy 21 by Aβ. The latter finding is relevant in light of recent reports of a lowered risk of dementia in bipolar patients treated with LiCl and in the stabilization of cognition in AD patients treated with LiCl.

  19. Characterization and molecular profiling of PSEN1 familial Alzheimer's disease iPSC-derived neural progenitors.

    Directory of Open Access Journals (Sweden)

    Andrew A Sproul

    Full Text Available Presenilin 1 (PSEN1 encodes the catalytic subunit of γ-secretase, and PSEN1 mutations are the most common cause of early onset familial Alzheimer's disease (FAD. In order to elucidate pathways downstream of PSEN1, we characterized neural progenitor cells (NPCs derived from FAD mutant PSEN1 subjects. Thus, we generated induced pluripotent stem cells (iPSCs from affected and unaffected individuals from two families carrying PSEN1 mutations. PSEN1 mutant fibroblasts, and NPCs produced greater ratios of Aβ42 to Aβ40 relative to their control counterparts, with the elevated ratio even more apparent in PSEN1 NPCs than in fibroblasts. Molecular profiling identified 14 genes differentially-regulated in PSEN1 NPCs relative to control NPCs. Five of these targets showed differential expression in late onset AD/Intermediate AD pathology brains. Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of Aβ42/40, and have characterized novel expression changes.

  20. Intranasal telmisartan ameliorates brain pathology in five familial Alzheimer's disease mice.

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Cohen, Hagit; Fleisher-Berkovich, Sigal

    2017-08-01

    The renin-angiotensin system (RAS) is a major circulative system engaged in homeostasis modulation. Angiotensin II (Ang II) serves as its main effector hormone upon binding to its primary receptor, Ang II receptor type 1 (AT1R). It is well established that an intrinsic independent brain RAS exists. Abnormal AT1R activation both in the periphery and in the brain probably contributes to the development of Alzheimer's disease (AD) pathology that is characterized, among others, by brain inflammation. Moreover, treatment with drugs that block AT1R (AT1R blockers, ARBs) ameliorates most of the clinical risk factors leading to AD. Previously we showed that short period of intranasal treatment with telmisartan (a brain penetrating ARB) reduced brain inflammation and ameliorated amyloid burden (a component of Alzheimer's plaques) in AD transgenic mouse model. In the present study, we aimed to examine the long-term effect of intranasally administrated telmisartan on brain inflammation features including microglial activation, astrogliosis, neuronal loss and hippocampus-dependent cognition in five-familial AD mouse model (5XFAD). Five month of intranasal treatment with telmisartan significantly reduced amyloid burden in the cortex and hippocampus of 5XFAD mice as compared with the vehicle-treated 5XFAD group. Similar effects were also observed for CD11b staining, which is a marker for microglial accumulation. Telmisartan also significantly reduced astrogliosis and neuronal loss in the cortex of 5XFAD mice compared with the vehicle-treated group. Improved spatial acquisition of the 5XFAD mice following long-term intranasal administration of telmisartan was also observed. Taken together, our data suggest a significant role for AT1R blockage in mediating neuronal loss and cognitive behavior, possibly through regulation of amyloid burden and glial inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Turning principles into practice in Alzheimer's disease

    OpenAIRE

    Lindesay, James; Bullock, Roger; Daniels, Hugo; Emre, Murat; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus

    2010-01-01

    Abstract 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 Charter, which comprises six principles that underscore the urgency for a more ambitious approach to diagnosis, treatment and care. This review highlights some of the most import...

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

    Science.gov (United States)

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

    2014-12-15

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

  3. Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants

    Directory of Open Access Journals (Sweden)

    Fraser Paul E

    2008-01-01

    Full Text Available Abstract Background Amyloid precursor protein (APP is enzymatically cleaved by γ-secretase to form two peptide products, either Aβ40 or the more neurotoxic Aβ42. The Aβ42/40 ratio is increased in many cases of familial Alzheimer's disease (FAD. The transmembrane domain (TM of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains. Results Using synthetic peptides derived from the APP-TM domain, we show that this segment is capable of forming stable transmembrane dimers. A model of a dimeric APP-TM domain reveals a putative dimerization interface, and interestingly, majority of FAD mutations in APP are localized to this interface region. We find that FAD-APP mutations destabilize the APP-TM dimer and increase the population of APP peptide monomers. Conclusion The dissociation constants are correlated to both the Aβ42/Aβ40 ratio and the mean age of disease onset in AD patients. We also show that these TM-peptides reduce Aβ production and Aβ42/Aβ40 ratios when added to HEK293 cells overexpressing the Swedish FAD mutation and γ-secretase components, potentially revealing a new class of γ-secretase inhibitors.

  4. Psychophysiological correlates of cognitive deficits in family caregivers of patients with Alzheimer Disease.

    Science.gov (United States)

    Corrêa, M S; Vedovelli, K; Giacobbo, B L; de Souza, C E B; Ferrari, P; de Lima Argimon, I I; Walz, J C; Kapczinski, F; Bromberg, E

    2015-02-12

    The progressive loss of memory and autonomy of Alzheimer's Disease (AD) patients, together with their characteristic behavioral and psychological symptoms, subjects their family caregivers to chronic stress. Several studies indicate that these caregivers are predisposed to cognitive impairments, but the physiological correlates of these alterations remain to be elucidated. Analyze the effects of chronic stress of family caregivers of AD patients on cognition, cortisol/DHEA ratios and BDNF levels and investigate the relation between these variables. Seventeen family caregivers (64.83 ± 3.64 years) of patients with AD and eighteen non-caregivers (58.29 ± 3.16 years) completed stress, depression and anxiety inventories. Exclusion criteria were current neurological disorders, major unstable medical illnesses, use of medications that could interfere with cognitive or HPA axis function and dementia. Attention, working memory and executive function were assessed with Digit Span and Trail Making tests, and declarative memory was analyzed with the Logical Memory test. Saliva was collected at 8 AM and 10 PM and its cortisol and DHEA levels determined by radioimmunoassay. Serum BDNF levels were measured by sandwich-ELISA. Results were analyzed with independent samples t test, covariance analysis and linear regressions. The statistical significance was set at pmemory and executive function tests. Caregivers also had higher cortisol/DHEA ratios and lower BDNF levels than non-caregivers. Cortisol/DHEA ratios, especially at 10 PM, were negatively related with all cognitive tasks in which caregivers showed impaired performance. On the other hand, the only cognitive task that related with the BDNF level was digit span. This study showed that caregivers' cognitive impairment is related with alterations on cortisol/DHEA ratios, and that chronic stress experienced by these subjects has the potential to alter their BDNF levels. Copyright © 2014 IBRO. Published by Elsevier Ltd. All

  5. Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases.

    Science.gov (United States)

    Wirths, Oliver; Bethge, Tobias; Marcello, Andrea; Harmeier, Anja; Jawhar, Sadim; Lucassen, Paul J; Multhaup, Gerd; Brody, David L; Esparza, Thomas; Ingelsson, Martin; Kalimo, Hannu; Lannfelt, Lars; Bayer, Thomas A

    2010-01-01

    The presence of Abeta(pE3) (N-terminal truncated Abeta starting with pyroglutamate) in Alzheimer's disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Abeta peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down's syndrome postmortem brain tissue. Importantly, Abeta(pE3) has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Abeta. We have recently shown that intraneuronal accumulation of Abeta(pE3) peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in Abeta(pE3), we have generated two novel monoclonal antibodies which were characterized as highly specific for Abeta(pE3) peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for Abeta(pE3) were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly, in APP/PS1KI mice we observed a continuous increase in Abeta(pE3) plaque load with increasing age, while the density for Abeta(1-x ) plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of Abeta are N-truncated as disease progresses, and that, Abeta(pE3) positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate.

  6. Point mutation in exon 4 of presenilin-1 gene and early-onset familial Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    Yu Liao; Fan Zhao

    2006-01-01

    BACKGROUND:A total of 50 missense mutations of presenilin-1 (PS-1) have been found thus far in early-onset familial Alzheimer disease(EOFAD),PS-1 gene might be a causative gene for Chinese EOFAD.OBJECTIVE:To investigate mutation of PS-1 gene in the blood of Chinese patients with familial Alzheimer disease(FAD).DESIGN:A design with randomized control and repeated sequencing.SETTlNG:Department of Neurology,the Second People's Hospital of Wuxi.PARTICIPANTS:The experiment was carried out in Huaihua Hospital Affiliated to Nanhua University in September 1993.Eight FAD patients were graded as FAD group.There were 6 males and 2 females with the mean age of(36±16)years.The control group was composed of 42 persons,including 8 hospitalized SAD patients diagnosed according to the criteria of Practical Neuralgia and conformed to the revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders(DCM-Ⅳ-TR),11 dementia patients caused by multipie cerebral infarction,13 normal persons in the FAD family mentioned above family,and 10 normal healthy adults provided by the health examination section of our hospital.METHODS:GeneAmp PCR System 2400 (Applied Biosystems,USA),DNA-Sequencer Model 310(Perkin Elmer,USA),Taq DNA Polymerase(Fermentas,Canada).All reagents used for DNA extraction were prepared with analytical reagents manufactured in China.The samples were stratified carefully,collected the leukocytic cream from the interface,added STMT to each sample and vortexed to suspend evenly.Then the samples were centrifugated.The nuclear pellet was resuspended in digestion solution with proteinase K and incubated under appropriate condition.Genomic DNA was extract with phenol/chloroform,precipitated with dehvdraled ethanol,and washed with 70%sterilized ethanol.Finally,genomic DNA was dissolved in ultra pure water and stored for Iater use.The sequences were 5'-ACT AAC AAT GGA TGA CCT GGT GAA ATC-3'and 3'-ACG GTC TGA CCT AAG TGA ATA GTA GAG-5' to flank the exon 2 of

  7. Cerebrospinal Fluid Biomarkers in Familial Forms of Alzheimer's Disease and Frontotemporal Dementia

    DEFF Research Database (Denmark)

    Rostgaard, Nina; Waldemar, Gunhild; Nielsen, Jørgen Erik;

    2015-01-01

    and are important when developing new therapies. Today, the core protein biomarkers amyloid-β42, total tau and phosphorylated tau in the cerebrospinal fluid (CSF) are used to diagnose Alzheimer's disease (AD), because these biomarkers have shown to reflect the underlying amyloid and tau pathology. However...

  8. Decreased DNA repair capacity in familial, but not in sporadic Alzheimer's disease

    NARCIS (Netherlands)

    M.E.T.I. Boerrigter; C.M. van Duijn (Cock); E. Mullaart; P. Eikelenboom (Piet); C.M.A. van der Togt; D.L. Knook; J. Vijg (Jan); A. Hofman (Albert)

    1991-01-01

    textabstractUsing the alkaline filter elution technique we determined the induction and disappearance of DNA single-strand breaks (SSB) in freshly isolated peripheral blood lymphocytes (PBL) from 43 Alzheimer's disease (AD) patients and 48 normal, healthy age- and sex-matched control subjects

  9. Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

    Science.gov (United States)

    Lalli, M A; Bettcher, B M; Arcila, M L; Garcia, G; Guzman, C; Madrigal, L; Ramirez, L; Acosta-Uribe, J; Baena, A; Wojta, K J; Coppola, G; Fitch, R; de Both, M D; Huentelman, M J; Reiman, E M; Brunkow, M E; Glusman, G; Roach, J C; Kao, A W; Lopera, F; Kosik, K S

    2015-11-01

    We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy.

  10. Impaired mitochondrial function due to familial Alzheimer's disease-causing presenilins mutants via Ca(2+) disruptions.

    Science.gov (United States)

    Toglia, Patrick; Cheung, King-Ho; Mak, Don-On Daniel; Ullah, Ghanim

    2016-05-01

    Mutants in presenilins (PS1 or PS2) is the major cause of familial Alzheimer's disease (FAD). FAD causing PS mutants affect intracellular Ca(2+) homeostasis by enhancing the gating of inositol trisphosphate (IP3) receptor (IP3R) Ca(2+) release channel on the endoplasmic reticulum, leading to exaggerated Ca(2+) release into the cytoplasm. Using experimental IP3R-mediated Ca(2+) release data, in conjunction with a computational model of cell bioenergetics, we explore how the differences in mitochondrial Ca(2+) uptake in control cells and cells expressing FAD-causing PS mutants affect key variables such as ATP, reactive oxygen species (ROS), NADH, and mitochondrial Ca(2+). We find that as a result of exaggerated cytosolic Ca(2+) in FAD-causing mutant PS-expressing cells, the rate of oxygen consumption increases dramatically and overcomes the Ca(2+) dependent enzymes that stimulate NADH production. This leads to decreased rates in proton pumping due to diminished membrane potential along with less ATP and enhanced ROS production. These results show that through Ca(2+) signaling disruption, mutant PS leads to mitochondrial dysfunction and potentially to cell death.

  11. Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients.

    Science.gov (United States)

    Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; Lima, Daiane Borba de; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar; Bromberg, Elke

    2016-01-01

    Older familial caregivers of Alzheimer's disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. The cognitive measures of 17 young (31-58 years) and 18 old (63-84 years) caregivers and of 17 young (37-57 years) and 18 old (62-84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: Download ... spending. Take action. Become an advocate SPECIAL REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history of medicine, ...

  13. Down Syndrome and Alzheimer's Disease

    Science.gov (United States)

    ... Find your local chapter Join our online community Down Syndrome and Alzheimer's Disease As they age, those affected ... disease. About Symptoms Diagnosis Causes & risks Treatments About Down Syndrome and Alzheimer's Higher prevalence of Alzheimer's in people ...

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease ... the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with ...

  15. Age-Specific Incidence Rates for Dementia and Alzheimer Disease in NIA-LOAD/NCRAD and EFIGA Families

    Science.gov (United States)

    Vardarajan, Badri N.; Faber, Kelley M.; Bird, Thomas D.; Bennett, David A.; Rosenberg, Roger; Boeve, Bradley F.; Graff-Radford, Neill R.; Goate, Alison M.; Farlow, Martin; Sweet, Robert A.; Lantigua, Rafael; Medrano, Martin Z.; Ottman, Ruth; Schaid, Daniel J.; Foroud, Tatiana M.; Mayeux, Richard

    2014-01-01

    IMPORTANCE Late-onset Alzheimer disease (LOAD), defined as onset of symptoms after age 65 years, is the most common form of dementia. Few reports investigate incidence rates in large family-based studies in which the participants were selected for family history of LOAD. OBJECTIVE To determine the incidence rates of dementia and LOAD in unaffected members in the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) family studies. DESIGN, SETTING, AND PARTICIPANTS Families with 2 or more affected siblings who had a clinical or pathological diagnosis of LOAD were recruited as a part of the NIA-LOAD/NCRAD Family Study. A cohort of Caribbean Hispanics with familial LOAD was recruited in a different study at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain in New York and from clinics in the Dominican Republic as part of the EFIGA study. MAIN OUTCOMES AND MEASURES Age-specific incidence rates of LOAD were estimated in the unaffected family members in the NIA-LOAD/NCRAD and EFIGA data sets. We restricted analyses to families with follow-up and complete phenotype information, including 396 NIA-LOAD/NCRAD and 242 EFIGA families. Among the 943 at-risk family members in the NIA-LOAD/NCRAD families, 126 (13.4%) developed dementia, of whom 109 (86.5%) met criteria for LOAD. Among 683 at-risk family members in the EFIGA families, 174 (25.5%) developed dementia during the study period, of whom 145 (83.3%) had LOAD. RESULTS The annual incidence rates of dementia and LOAD in the NIA-LOAD/NCRAD families per person-year were 0.03 and 0.03, respectively, in participants aged 65 to 74 years; 0.07 and 0.06, respectively, in those aged 75 to 84 years; and 0.08 and 0.07, respectively, in those 85 years or older. Incidence rates in the EFIGA families were slightly higher, at 0.03 and 0.02, 0.06 and 0.05, 0

  16. Neuroinflammation in Alzheimer's disease

    DEFF Research Database (Denmark)

    Heneka, Michael T; Carson, Monica J; Khoury, Joseph El

    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 trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded...... therapeutic or preventive strategies for Alzheimer's disease....

  17. A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

    Science.gov (United States)

    Luedecke, Daniel; Becktepe, Jos S; Lehmbeck, Jan T; Finckh, Ulrich; Yamamoto, Raina; Jahn, Holger; Boelmans, Kai

    2014-04-30

    Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with progressive deterioration of his short-term memory and a family history of early-onset dementia. Diagnostic workup included a neuropsychological examination, structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers including total tau, phosphorylated tau, and Aβ42 levels, as well as sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally, we were able to obtain archival paraffin-embedded cerebellar tissue from the patient's father for cosegregation analysis. Clinical, neuropsychological and MR imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1, leading to an amino acid change from alanine to valine at codon 275 (Ala275Val). The same mutation was found in an archival brain specimen of the patient's demented father, but not in a blood sample of the non-demented mother. This mutation alters a conserved residue in the large hydrophilic loop of PS1, suggesting pathogenic relevance. Cosegregegation analysis and the structural as well as the presumed functional role of the mutated and highly conserved residue suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val.

  18. Relation between nicotine intake and Alzheimer's disease.

    OpenAIRE

    1991-01-01

    OBJECTIVE--To study the association between Alzheimer's disease and nicotine intake through smoking. DESIGN--Population based case-control study. SETTING--City of Rotterdam and four northern provinces of The Netherlands. SUBJECTS--198 patients with early onset Alzheimer's disease, 198 controls matched for age and sex, and families of 17 patients in whom Alzheimer's disease was apparently inherited as an autosomal dominant disorder. MAIN OUTCOME MEASURES--Age of onset of dementia, relative ris...

  19. 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...

  20. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State ... news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  1. Alzheimer's Disease Facts and Figures

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    Full Text Available ... REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history of medicine, one means to progress is when ... c)(3) organization. Copyright © 2017 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's ...

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

    Science.gov (United States)

    Zhagn, Lili; Li, Zhiping

    2014-09-01

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

  3. Alzheimer's Disease Information Page

    Science.gov (United States)

    ... Translational Research Research at NINDS Focus on Research Alzheimer's & Related Dementias Bioengineering Epilepsy Health Disparities Neural Interfaces Parkinson's Disease Spinal Cord Injury Stem Cells Traumatic Brain Injury Trans-Agency Activities Interagency Research ...

  4. 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.

    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 trigg

  5. Deciphering Alzheimer disease.

    Science.gov (United States)

    Selkoe, Dennis; Mandelkow, Eckhard; Holtzman, David

    2012-01-01

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

  6. 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

  7. 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.

    2010-01-01

    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

  8. Predictors of grief in bereaved family caregivers of person's with Alzheimer's disease: a prospective study.

    Science.gov (United States)

    Romero, Melissa M; Ott, Carol H; Kelber, Sheryl T

    2014-01-01

    The purpose of this prospective study was to identify factors in 66 spouses and adult child caregivers of person's with Alzheimer's disease prior to the death that predicted higher levels of grief in bereavement. A hierarchical regression model was tested. Predeath grief, dysfunctional coping, depression, social support, and decreased positive states of mind explained 54.7% of the variance in postdeath grief. Factors that contributed significantly to postdeath grief included predeath grief and depression. Results from this study indicate that risk factors for postdeath grief can be predicted prior to the death.

  9. Evidence for major gene inheritance of Alzheimer disease in families of patients with and without Apolipoprotein E {epsilon}4

    Energy Technology Data Exchange (ETDEWEB)

    Rao, V.S.; Auerbach, S.A.; Farrer, L.A. [Boston Univ. School of Medicine, MA (United States)] [and others

    1996-09-01

    Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one {epsilon}4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking E4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband`s APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility. 76 refs., 4 tabs.

  10. Treatment of Alzheimer disease.

    Science.gov (United States)

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

    2011-06-15

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

  11. Age-specific incidence rates for dementia and Alzheimer disease in NIA-LOAD/NCRAD and EFIGA families: National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA).

    Science.gov (United States)

    Vardarajan, Badri N; Faber, Kelley M; Bird, Thomas D; Bennett, David A; Rosenberg, Roger; Boeve, Bradley F; Graff-Radford, Neill R; Goate, Alison M; Farlow, Martin; Sweet, Robert A; Lantigua, Rafael; Medrano, Martin Z; Ottman, Ruth; Schaid, Daniel J; Foroud, Tatiana M; Mayeux, Richard

    2014-03-01

    Late-onset Alzheimer disease (LOAD), defined as onset of symptoms after age 65 years, is the most common form of dementia. Few reports investigate incidence rates in large family-based studies in which the participants were selected for family history of LOAD. To determine the incidence rates of dementia and LOAD in unaffected members in the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) family studies. Families with 2 or more affected siblings who had a clinical or pathological diagnosis of LOAD were recruited as a part of the NIA-LOAD/NCRAD Family Study. A cohort of Caribbean Hispanics with familial LOAD was recruited in a different study at the Taub Institute for Research on Alzheimer's Disease and the Aging Brain in New York and from clinics in the Dominican Republic as part of the EFIGA study. Age-specific incidence rates of LOAD were estimated in the unaffected family members in the NIA-LOAD/NCRAD and EFIGA data sets. We restricted analyses to families with follow-up and complete phenotype information, including 396 NIA-LOAD/NCRAD and 242 EFIGA families. Among the 943 at-risk family members in the NIA-LOAD/NCRAD families, 126 (13.4%) developed dementia, of whom 109 (86.5%) met criteria for LOAD. Among 683 at-risk family members in the EFIGA families, 174 (25.5%) developed dementia during the study period, of whom 145 (83.3%) had LOAD. The annual incidence rates of dementia and LOAD in the NIA-LOAD/NCRAD families per person-year were 0.03 and 0.03, respectively, in participants aged 65 to 74 years; 0.07 and 0.06, respectively, in those aged 75 to 84 years; and 0.08 and 0.07, respectively, in those 85 years or older. Incidence rates in the EFIGA families were slightly higher, at 0.03 and 0.02, 0.06 and 0.05, 0.10 and 0.08, and 0.10 and 0.07, respectively, in the same age groups. Contrasting these

  12. Epidemiology of Alzheimer Disease

    Science.gov (United States)

    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

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... the number of people with this disease. As research advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we envision a future in which Alzheimer's disease is placed in the same category as ... More Alzheimer's Disease Facts in Each State ...

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... the number of people with this disease. As research advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we envision a future in which Alzheimer's disease is placed in the same category ... More Alzheimer's Disease Facts in Each State ...

  15. Cerebrolysin in Alzheimer's disease.

    Science.gov (United States)

    Antón Álvarez, X; Fuentes, Patricio

    2011-07-01

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

  16. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... and older (10 percent) has Alzheimer's dementia. Almost two-thirds of Americans with Alzheimer's are women. African- ... 15.9 million family and friends provided 18.2 billion hours of unpaid assistance to those with ...

  17. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 million family and friends provided 18. ... health care and long-term care payments in 2016 for Medicare beneficiaries with Alzheimer's or other dementias ...

  18. [The lived experience of family member caring for a person affected by Alzheimer's disease: preliminary results].

    Science.gov (United States)

    Vellone, E; Micci, F; Sansoni, J; Sinapi, N; Cattel, C

    2000-01-01

    The aim of this article is to report the preliminary results from a phenomenological study on the lived experience of Alzheimer's caregivers. Eight caregivers involved in caring for two years at list were interviewed. The analysis of interviews by Giorgi's method showed a multidimensional reality synthesizable in eight spheres of themes: Illness, Patient, Caring, Caregiver's Life and Health, Coping, Spouse/Family, Others, Feelings. Illness has a great impact on the caregivers' life and causes the loss of the affected person even before his/her death. Caring is very hard and emotionally involving. Caregivers mainly complain the lack of support from the National Health System. The continuous involvement in caring produces also health problems, depression, and negative effects within the family. Others are considered as bad. The most common feelings are fear for possible accidents to the patients and remorses. Some caregivers have good coping style putting their faith in God, valuing the closeness of the family and living daily. The utility of the eight spheres of themes are discussed in order to guide the practice toward the caregivers.

  19. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... disease is growing — and growing fast. An estimated 5.5 million Americans of all ages have Alzheimer's disease. Of the estimated 5.5 million Americans living with Alzheimer's dementia in ...

  20. Alzheimer's Disease Facts and Figures

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    Full Text Available ... ALZ | Research | Professionals | We Can Help | Join the Cause alz.org >> Living with Alzheimer's >> Home Text size: ... disease every 33 seconds. GET INVOLVED. Join the cause Mortality Alzheimer's disease is the sixth-leading cause ...

  1. 76 FR 68615 - National Alzheimer's Disease Awareness Month, 2011

    Science.gov (United States)

    2011-11-04

    ... Documents#0;#0; ] Proclamation 8745 of November 1, 2011 National Alzheimer's Disease Awareness Month, 2011... heartbreak of watching a loved one struggle with Alzheimer's disease is a pain they know all too well. Alzheimer's disease burdens an increasing number of our Nation's elders and their families, and it is...

  2. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... the National Institute on Aging – Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group ( ... More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease Facts and Figures report contains data ...

  3. Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families.

    Science.gov (United States)

    Cuenco, Karen T; Friedland, Robert; Baldwin, Clinton T; Guo, Jianping; Vardarajan, Badri; Lunetta, Kathryn L; Cupples, L Adrienne; Green, Robert C; DeCarli, Charles; Farrer, Lindsay A

    2011-02-01

    In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample. To examine the possibility that TTR SNPs affect specific components of the AD process, we tested association of these SNPs with four measures of neurodegeneration and cerebrovascular disease defined by magnetic resonance imaging (MRI) in a subset of 48 African American and 265 Caucasian sibships. Five of seven common SNPs and several haplotypes were significantly associated with hippocampal atrophy in the Caucasian sample. Two of these SNPs also showed marginal evidence for association in the African American sample. Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis.

  4. Score test for familial aggregation in probands studies: application to Alzheimer's disease

    NARCIS (Netherlands)

    D. Commenges; H. Jacqmin; L. Letenneur; C.M. van Duijn (Cock)

    1995-01-01

    textabstractWhen studying familial aggregation of a disease, the following two-stage design is often used: first select index subjects (cases and controls); then record data on their relatives. The likelihood corresponding to this design is derived and a score test of homogeneity is proposed for tes

  5. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Join the Cause alz.org >> Living with Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease ... people who receive adult day services and nursing home care. Total per-person health care and long- ...

  6. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... fast. An estimated 5.5 million Americans of all ages have Alzheimer's disease. Of the estimated 5. ... conditions to society. Total payments in 2017 for all individuals with Alzheimer's or other dementias are estimated ...

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... The number of Americans living with Alzheimer's disease is growing — and growing fast. An estimated 5.5 ... of new cases of Alzheimer's and other dementias is projected to soar. Today, someone in the United ...

  8. Alzheimer's Disease Facts and Figures

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    Full Text Available ... advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we ... on the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with ...

  9. Alzheimer's Disease Facts and Figures

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    Full Text Available ... living with Alzheimer's disease is growing — and growing fast. An estimated 5.5 million Americans of all ... effect that Alzheimer's is having in your state. FIND YOUR WALK Read past editions . Sign up for ...

  10. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: Download the ... Costs Special Report Alzheimer's in each state Quick Facts Share the facts: Prevalence The number of Americans ...

  11. Alzheimer's Disease Facts and Figures

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    Full Text Available ... for someone with Alzheimer's? Get Resources Cost to Nation The costs of health care and long-term ... of this disease in every state across the nation. Click below to see the effect that Alzheimer's ...

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we ... on the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with ...

  13. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Facts and Figures report contains data on the impact of this disease in every state across the ... c)(3) organization. Copyright © 2017 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's ...

  14. Neuroinflammation in Alzheimer's disease

    OpenAIRE

    Heneka, MT; Carson, MJ; Khoury, JE; Landreth, GE; Brosseron, F.; Feinstein, Dl; Jacobs, AH; Wyss-Coray, T; Vitorica, J; Ransohoff, RM; Herrup, K; Frautschy, SA; Finsen, B.; Brown, GC; Verkhratsky, A.

    2015-01-01

    © 2015 Elsevier Ltd. Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that severa...

  15. Validation of the Italian Version of the Caregiver Abuse Screen among Family Caregivers of Older People with Alzheimer's Disease

    Science.gov (United States)

    Di Rosa, Mirko; Barbabella, Francesco; Barbini, Norma; Chiatti, Carlos

    2017-01-01

    Introduction. Elder abuse is often a hidden phenomenon and, in many cases, screening practices are difficult to implement among older people with dementia. The Caregiver Abuse Screen (CASE) is a useful tool which is administered to family caregivers for detecting their potential abusive behavior. Objectives. To validate the Italian version of the CASE tool in the context of family caregiving of older people with Alzheimer's disease (AD) and to identify risk factors for elder abuse in Italy. Methods. The CASE test was administered to 438 caregivers, recruited in the Up-Tech study. Validity and reliability were evaluated using Spearman's correlation coefficients, principal-component analysis, and Cronbach's alphas. The association between the CASE and other variables potentially associated with elder abuse was also analyzed. Results. The factor analysis suggested the presence of a single factor, with a strong internal consistency (Cronbach's alpha = 0.86). CASE score was strongly correlated with well-known risk factors of abuse. At multivariate level, main factors associated with CASE total score were caregiver burden and AD-related behavioral disturbances. Conclusions. The Italian version of the CASE is a reliable and consistent screening tool for tackling the risk of being or becoming perpetrators of abuse by family caregivers of people with AD. PMID:28265571

  16. 2016 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2016-04-01

    This report describes the public health impact of Alzheimer's disease, including incidence and prevalence, mortality rates, costs of care, and the overall impact on caregivers and society. It also examines in detail the financial impact of Alzheimer's on families, including annual costs to families and the difficult decisions families must often make to pay those costs. An estimated 5.4 million Americans have Alzheimer's disease. By mid-century, the number of people living with Alzheimer's disease in the United States is projected to grow to 13.8 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops Alzheimer's disease every 66 seconds. By 2050, one new case of Alzheimer's is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year. In 2013, official death certificates recorded 84,767 deaths from Alzheimer's disease, making it the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age ≥ 65 years. Between 2000 and 2013, deaths resulting from stroke, heart disease, and prostate cancer decreased 23%, 14%, and 11%, respectively, whereas deaths from Alzheimer's disease increased 71%. The actual number of deaths to which Alzheimer's disease contributes is likely much larger than the number of deaths from Alzheimer's disease recorded on death certificates. In 2016, an estimated 700,000 Americans age ≥ 65 years will die with Alzheimer's disease, and many of them will die because of the complications caused by Alzheimer's disease. In 2015, more than 15 million family members and other unpaid caregivers provided an estimated 18.1 billion hours of care to people with Alzheimer's and other dementias, a contribution valued at more than $221 billion. Average per-person Medicare payments for services to beneficiaries age ≥ 65 years with Alzheimer's disease and other dementias are more than two and a half times as great as payments for all

  17. Neurological manifestations of autosomal dominant familial Alzheimer's disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS).

    Science.gov (United States)

    Tang, Mengxuan; Ryman, Davis C; McDade, Eric; Jasielec, Mateusz S; Buckles, Virginia D; Cairns, Nigel J; Fagan, Anne M; Goate, Alison; Marcus, Daniel S; Xiong, Chengjie; Allegri, Ricardo F; Chhatwal, Jasmeer P; Danek, Adrian; Farlow, Martin R; Fox, Nick C; Ghetti, Bernardino; Graff-Radford, Neill R; Laske, Christopher; Martins, Ralph N; Masters, Colin L; Mayeux, Richard P; Ringman, John M; Rossor, Martin N; Salloway, Stephen P; Schofield, Peter R; Morris, John C; Bateman, Randall J

    2016-12-01

    Autosomal dominant familial Alzheimer's disease (ADAD) is a rare disorder with non-amnestic neurological symptoms in some clinical presentations. We aimed to compile and compare data from symptomatic participants in the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS) with those reported in the literature to estimate the prevalences of non-amnestic neurological symptoms in participants with ADAD. We prospectively collected data from the DIAN-OBS database, which recruited participants from study centres in the USA, Europe, and Australia, between Feb 29, 2008, and July 1, 2014. We also did a systematic review of publications to extract individual-level clinical data for symptomatic participants with ADAD. We used data for age of onset (from first report of cognitive decline), disease course from onset to death, and the presence of 13 neurological findings that have been reported in association with ADAD. Using multivariable linear regression, we investigated the prevalences of various non-amnestic neurological symptoms and the contributions of age of onset and specific mutation type on symptoms. The DIAN-OBS dataset included 107 individuals with detailed clinical data (forming the DIAN-OBS cohort). Our systematic review yielded 188 publications reporting on 1228 symptomatic individuals, with detailed neurological examination descriptions available for 753 individuals (forming the published data cohort). The most prevalent non-amnestic cognitive manifestations in participants in the DIAN-OBS cohort were those typical of mild to moderate Alzheimer's disease, including visual agnosia (55·1%, 95% CI 45·7-64·6), aphasia (57·9%, 48·6-67·3), and behavioural changes (61·7%, 51·5-70·0). Non-amnestic cognitive manifestations were less prevalent in the published data cohort (eg, visual agnosia [5·6%, 3·9-7·2], aphasia [23·0%, 20·0-26·0], and behavioural changes [31·7%, 28·4-35·1]). Prevalence of non-cognitive neurological manifestations in

  18. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease

    OpenAIRE

    Bateman, R. J.; Aisen, P.S.; De Strooper, B.; Fox, N C.; Lemere, C. A.; Ringman, J.M.; Salloway, S.; Sperling, R. A.; Windisch, M.; Xiong, C.

    2011-01-01

    Autosomal-dominant Alzheimer's disease has provided significant understanding of the pathophysiology of Alzheimer's disease. The present review summarizes clinical, pathological, imaging, biochemical, and molecular studies of autosomal-dominant Alzheimer's disease, highlighting the similarities and differences between the dominantly inherited form of Alzheimer's disease and the more common sporadic form of Alzheimer's disease. Current developments in autosomal-dominant Alzheimer's disease are...

  19. Alzheimer's Project

    Medline Plus

    Full Text Available ... disease has on those with Alzheimer's and their families. September 14, 2009 "The Alzheimer's Project" wins two ... way Americans thinks about Alzheimer's disease. Tell your family and friends. Post info on your Web site . ...

  20. Alzheimer's Project

    Medline Plus

    Full Text Available ... disease has on those with Alzheimer's and their families. September 14, 2009 "The Alzheimer's Project" wins two ... way Americans thinks about Alzheimer's disease. Tell your family and friends. Post info on your Web site . ...

  1. Alzheimer disease in 2020.

    Science.gov (United States)

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

    2012-11-01

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

  2. White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease

    Science.gov (United States)

    Adluru, Nagesh; Destiche, Daniel J.; Lu, Sharon Yuan-Fu; Doran, Samuel T.; Birdsill, Alex C.; Melah, Kelsey E.; Okonkwo, Ozioma C.; Alexander, Andrew L.; Dowling, N. Maritza; Johnson, Sterling C.; Sager, Mark A.; Bendlin, Barbara B.

    2014-01-01

    Introduction Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. Methods This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47–76 years). Results Both APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (=65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across

  3. The economic costs of Alzheimer's disease.

    Science.gov (United States)

    Hay, J W; Ernst, R L

    1987-09-01

    This paper estimates the economic costs of Alzheimer's Disease to individuals and to society, based on review of published Alzheimer's Disease-related research. The analysis is derived from epidemiological projections and cost information for the United States population in 1983. Estimated costs include both direct medical care and social support costs, as well as indirect costs, such as support services provided by family or volunteers, and the value of lost economic productivity in Alzheimer's Disease patients. Mid-range estimates of net annual expected costs for an Alzheimer's Disease patient, excluding the value of lost productivity, are $18,517 in the first year and $17,643 in subsequent years, with direct medical and social services comprising about half of these costs. Under base case assumptions, the total cost of disease per patient in 1983, was $48,544 to $493,277, depending upon patient's age at disease onset. The estimated present value of total net costs to society for all persons first diagnosed with Alzheimer's Disease in 1983 was $27.9-31.2 billion. Development of a public or private insurance market for the economic burdens of Alzheimer's Disease would fill some of the gaps in the current US system of financing long-term chronic disease care.

  4. Genetic Aspects of Alzheimer Disease

    Science.gov (United States)

    Williamson, Jennifer; Goldman, Jill; Marder, Karen S.

    2011-01-01

    Background Alzheimer disease (AD) is a genetically complex disorder. Mutations in 3 genes, presenilin 1, amyloid precursor protein, and presenilin 2, lead to early-onset familial AD in rare families with onset of disease occurring prior to age 65. Specific polymorphisms in apolipoprotein E are associated with the more common, late-onset AD occurring after age 65. In this review, we discuss current advances in AD genetics, the implications of the known AD genes, presenilin 1, presenilin 2, amyloid precursor protein, and apolipoprotein E, and other possible genes on the clinical diagnosis, treatment, and genetic counseling of patients and families with early- and late-onset AD. Review Summary In addition to the mutations in 4 known genes associated with AD, mutations in other genes may be implicated in the pathogenesis of the disease. Most recently, 2 different research groups have reported genetic association between 2 genes, sortilin-related receptor and GAB2, and AD. These associations have not changed the diagnostic and medical management of AD. Conclusions New research in the genetics of AD have implicated novel genes as having a role in the disease, but these findings have not been replicated nor have specific disease causing mutations been identified. To date, clinical genetic testing is limited to familial early-onset disease for symptomatic individuals and asymptomatic relatives and, although not recommended, amyloid precursor protein apolipoprotein E testing as an adjunct to diagnosis of symptomatic individuals. PMID:19276785

  5. Caregiving for Alzheimer's Disease or Other Dementia

    Science.gov (United States)

    ... 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 ...

  6. Family history of dementia does not influence the progression of Alzheimer's disease at two years: results from the REAL.FR Study.

    Science.gov (United States)

    Cortes, Frédéric; Gillette-Guyonnet, Sophie; Nourhashemi, Fati; Christelle, Cantet; Vellas, Bruno

    2006-01-01

    The purpose of this study was to determine whether a family history of dementia in a first-degree relative influenced the progression of Alzheimer's disease (AD) after two years of follow-up. Patients were recruited in the REAL.FR (Réseau sur la Maladie d'Alzheimer Français) study and underwent behavioral, global, nutritional, and medical evaluation with assessment of cognitive function and independence every six months. At inclusion, 113 patients reported a family history of dementia, and 358 patients had no family history of dementia. There was no statistical difference for any factors between the two groups at baseline. After two years of follow-up, a similar percentage of patients were still followed in each group, and although most parameters showed significant deterioration, there was no difference between the two groups, indicating that a family history of dementia does not appear to influence the progression of AD.

  7. Alzheimer disease update.

    Science.gov (United States)

    Matthews, Brandy R

    2010-04-01

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

  8. [Caring for a person affected by Alzheimer's disease: specific aspects of grief in family caregivers and their social support].

    Science.gov (United States)

    Malaquin-Pavan, Evelyne; Pierrot, Marylène

    2007-06-01

    Alzheimer's disease (DTA) leads to some behavioural, physical and psychic modifications in the patient that the natural helper (family-spouse-child) will have to face throughout the course of the disease. The authors have tried to identify the nature of losses experienced by helpers so as to bring out some preventive and curative support tracks. This preparatory research-action was conducted with 27 families through semi-directive conversations which enabled to reveal their difficulties (somatic-emotional-affective-organizational), their reactions of adaptation in echo with the losses of the patient along the course of the DTA as well as the elements enabling to maintain or not the ill person's family/close relation link. The analysis of obtained results is proposed according to the concepts of adaptation, affection and separation, systemic approach and coping. The comments and behaviours of helpers are put in relation with the symptoms of mourning as well as with the medical interactions, helper or not. Five chronological times were identified (before diagnosis-moment of the diagnosis-keeping at home-admission in institution-life in institution). The period of white mourning (connected to the loss of the recognition of his/her close relations by the patient) is mainly felt as a vector of suffering. As part of the dynamics of social support, the proposed tracks of nursing interventions mainly target the admission and life in institution; their aim is to offer an adapted support to natural helpers, whether they make the choice or not to support their close patients throughout the institutionalization. In appendices, all the key ideas helping to track down the elements contributing to maintain the ill person's helper/close relation link or accelerating his/her breaking down.

  9. Influence of family history of dementia in the development and progression of late-onset Alzheimer's disease.

    Science.gov (United States)

    Scarabino, Daniela; Gambina, Giuseppe; Broggio, Elisabetta; Pelliccia, Franca; Corbo, Rosa Maria

    2016-03-01

    Family history of dementia (FH) is a recognized risk factor for developing late-onset Alzheimer's disease (AD). We asked whether having FH increases AD risk and influences disease severity (age at onset and cognitive impairment) in 420 AD patients and 109 controls with (FH+) or without (FH-). The relationships of APOE and other AD risk genes with FH were analyzed as well. The proportion of APOE e4 allele carriers was higher among the FH+ than the FH- AD patients (49.6% vs. 38.9%; P = 0.04). The distribution of the risk genotypes of nine AD susceptibility genes previously examined (CHAT, CYP17, CYP19, ESR1, FSHR, P53, P73, P21, PPARG) did not differ between the FH+ and the FH- AD patients, indicating that none contributed significantly to familial clustering of disease. FH was associated with an increased AD risk (odds ratio [OR] 2.71, 95% confidence interval [CI] 1.44-5.09; P = 0.002) independent of carrying the APOE e4 allele (OR 2.61, 95%CI 1.53-4.44; P = 0.0004). Having a first-degree relative or a parent with dementia was significantly associated with AD risk (OR 2.9, 95%CI 1.3-6.4; P = 0.009 and OR 2.7, 95%CI 1.1-6.2; P = 0.02) but having a sibling with dementia was not (OR 1.7, 95%CI 0.2 to 14.7; P = 0.6). Among the FH+ AD patients, having one or both parents affected seemed to raise the risk of earlier onset age (P = 0.02) and greater cognitive impairment (P = 0.02) than having only an affected sibling, whereas having two or more affected relatives did not. © 2015 Wiley Periodicals, Inc.

  10. Ferric cycle activity and Alzheimer disease.

    Science.gov (United States)

    Dwyer, Barney E; Takeda, Atsushi; Zhu, Xiongwei; Perry, George; Smith, Mark A

    2005-07-01

    Elevated plasma homocysteine is an independent risk factor for the development of Alzheimer disease, however, the precise mechanisms underlying this are unclear. In this article, we expound on a novel hypothesis depicting the involvement of homocysteine in a vicious circle involving iron dysregulation and oxidative stress designated as the ferric cycle (Dwyer et al., 2004). Moreover, we suspect that the development of a critical heme deficiency in vulnerable neurons is an additional consequence of ferric cycle activity. Oxidative stress and heme deficiency are consistent with many pathological changes found in Alzheimer disease including mitochondrial abnormalities and impaired energy metabolism, cell cycle and cell signaling abnormalities, neuritic pathology, and other features of the disease involving alterations in iron homeostasis such as the abnormal expression of heme oxygenase-1 and iron response protein 2. Based on the ferric cycle concept, we have developed a model of Alzheimer disease development and progression, which offers an explanation for why sporadic Alzheimer disease is different than normal aging and why familial Alzheimer disease and sporadic Alzheimer disease could have different etiologies but a common end-stage.

  11. Alzheimer's disease and stigmatization

    Directory of Open Access Journals (Sweden)

    Dimitrios Kosmidis

    2012-04-01

    Full Text Available Aim: The main objective of the study was to explore social bias experienced by patients with Alzheimer's disease and to investigate the knowledge of a sample of the general population regarding this particular disease. Method: The sample consisted of 91 individuals who were first degree relatives of members of three Centers of Open Protection for the Elderly, who did not suffer from dementia as they have recently undergone screening for Alzheimer's disease. A survey design was adopted using a face-to-face questionnaire which apart from the demographical data and two open-ended questions, was based on a 5-point lickert scale, looking at knowledge, attitudes and stigma towards the disease. Data was analyzed through SPSS software using descriptive statistics while results were regarded significant at p<0,05 level of significance Results: For the quantitave questions, cronbach's a was a=0,75 and the average discrete index 0,31. Stigma was explored through a series of direct and in-direct questions and while 70 (77% persons distinguish dementia from mental illness, 9(9,9% people did not answer these questions. The majority (62,6% did not stigmatize the patient as 57 persons said that the patient is not to blame for the disease. Conclusions: from the distribution of results it becomes evident that there is a need for education, training and multifaceted enlightenment of the general population on issues concerning mental health. Answers that implied tendencies of marginalization of patients with dementia emanated mainly came from individuals in the sample with limited knowledge of the illness and relatively low educational background.

  12. NEEDS SUPPORT CAREGIVER/FAMILY CARE IN ELDERLY PATIENTS WITH ALZHEIMER'S DISEASE

    Directory of Open Access Journals (Sweden)

    Alessandra Conceição Leite Funchal Camacho

    2011-07-01

    Full Text Available Objetivo: Identificar as necessidades de suporte ao cuidador/familiar nos cuidados ao idoso com Doença de Alzheimer (DA. Método: Pesquisa de natureza quanti-qualitativa na qual o cenário deste estudo foi o consultório de enfermagem do Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro, referência no atendimento ao cliente com Doença de Alzheimer do Estado do Rio de Janeiro. Resultados: A família é a fonte de suporte a qual seus membros recorrem para resolução de problemas onde encontramos como questões relevantes no suporte o fato do cuidador ser idoso, escassa rede familiar, sobrecarga no cuidado, depressão, falta de disponibilidade para o cuidado, falta de autoridade, impacto da doença, dificuldades no desenvolvimento do cuidado e apoio emocional. Conclusão: Considerar o familiar/cuidador como atuante neste processo de cuidado através de planejamento contínuo constitui um desafio inexorável porque as relações de convivência familiar se fazem presentes e devem ser constantemente consideradas pela enfermeira.

  13. Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients

    Science.gov (United States)

    Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; de Lima, Daiane Borba; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar

    2016-01-01

    Objectives Older familial caregivers of Alzheimer’s disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. Method The cognitive measures of 17 young (31–58 years) and 18 old (63–84 years) caregivers and of 17 young (37–57 years) and 18 old (62–84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Results Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Discussion Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions. PMID:27706235

  14. Yoga and compassion meditation program improve quality of life and self-compassion in family caregivers of Alzheimer's disease patients: A randomized controlled trial.

    Science.gov (United States)

    Danucalov, Marcelo Ad; Kozasa, Elisa H; Afonso, Rui F; Galduroz, José Cf; Leite, José R

    2017-01-01

    To investigate the effects of the practice of yoga in combination with compassion meditation on the quality of life, attention, vitality and self-compassion of family caregivers of patients with Alzheimer's disease. A total of 46 volunteers were randomly allocated to two groups, the yoga and compassion meditation program group (n = 25), and the control group (CG) that received no treatment (n = 21). The program lasted 8 weeks, and comprised three yoga and meditation practices per week, with each session lasting 1 h and 15 min. Quality of life, attention, vitality, and self-compassion scores were measured pre- and postintervention. The yoga and compassion meditation program group showed statistically significant improvements (P yoga and compassion meditation program can improve the quality of life, vitality, attention, and self-compassion of family caregivers of Alzheimer's disease patients. Geriatr Gerontol Int 2017; 17: 85-91. © 2015 Japan Geriatrics Society.

  15. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Alzheimer's & Dementia | Life with ALZ | Research | Professionals | We Can Help | Join the Cause alz.org >> Living with ... diseases, such as cardiovascular disease or diabetes, which can be readily identified with biomarkers and treated before ...

  16. Modulation of Mitochondrial Complex I Activity Averts Cognitive Decline in Multiple Animal Models of Familial Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Liang Zhang

    2015-04-01

    Full Text Available Development of therapeutic strategies to prevent Alzheimer's disease (AD is of great importance. We show that mild inhibition of mitochondrial complex I with small molecule CP2 reduces levels of amyloid beta and phospho-Tau and averts cognitive decline in three animal models of familial AD. Low-mass molecular dynamics simulations and biochemical studies confirmed that CP2 competes with flavin mononucleotide for binding to the redox center of complex I leading to elevated AMP/ATP ratio and activation of AMP-activated protein kinase in neurons and mouse brain without inducing oxidative damage or inflammation. Furthermore, modulation of complex I activity augmented mitochondrial bioenergetics increasing coupling efficiency of respiratory chain and neuronal resistance to stress. Concomitant reduction of glycogen synthase kinase 3β activity and restoration of axonal trafficking resulted in elevated levels of neurotrophic factors and synaptic proteins in adult AD mice. Our results suggest that metabolic reprogramming induced by modulation of mitochondrial complex I activity represents promising therapeutic strategy for AD.

  17. Alzheimer's Disease Facts and Figures

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    Full Text Available ... meaning that they care not only for an aging parent, but also for children under age 18. ... diagnose Alzheimer's disease. Both the National Institute on Aging – Alzheimer's Association (NIA-AA) 2011 workgroup and ...

  18. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging – Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable ...

  19. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... deaths from the number one cause of death (heart disease) decreased 14 percent. Among people age 70, 61 percent of those with Alzheimer's are expected to die before the age of 80 compared with 30 percent of people without Alzheimer's — a rate twice as high. Invest in a world without ...

  20. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... or biomarkers, as part of the diagnosis. The development and validation of Alzheimer's disease biomarkers — including those ... is a not-for-profit 501(c)(3) organization. Copyright © 2017 Alzheimer's Association ® . All rights reserved. Our ...

  1. Immunotherapy for Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Weihua Wang; Liangfeng Fan; De'en Xu; Zhongmin Wen; Rong Yu; Quanhong Ma

    2012-01-01

    Alzheimer's disease (AD) is characterized by β-amyloid (Aβ) plaques consisted primarily of aggregated Aβ proteins and neurofibrillary tangles formed by hyperphosphorylated tau protein.Both Aβ and hyperphosphorylated tau are toxic both in vivo and in vitro.Immunotherapy targeting Aβ seems to provide a promising approach to reduce the toxic species in the brain.However,there is little evidence from clinical trials so far indicating the efficacy of Aβ immunotherapy in cognitive improvement.Immunization with tau peptides or anti-tau antibodies could remove the tau aggregates and improve the cognitive function in preclinical study,which provides a novel strategy of AD therapy.In this article,we will summarize the immunotherapeutic strategies targeting either Aβ or tau.

  2. Calidad de vida del cuidador familiar y dependencia del paciente con Alzheimer Family caretaker quality of life and dependence of the patient with Alzheimer disease Qualidade de vida do cuidador familiar e dependência do paciente com Alzheimer

    Directory of Open Access Journals (Sweden)

    PINTO AFANADOR NATIVIDAD

    2010-04-01

    Full Text Available El objetivo del estudio fue establecer la relación entre la calidad de vida del cuidador familiar y el grado de dependencia del paciente con Alzheimer. Es un estudio descriptivo correlacional, de corte transversal, con abordaje cuantitativo. Participaron 192 cuidadores familiares de pacientes con Alzheimer pertenecientes al programa Cuidado a Cuidadores® de la Facultad de Enfermería de la Universidad Nacional de Colombia, la Fundación Acción Familiar Alzheimer Colombia y la Asociación Colombiana de Alzheimer. Se aplicaron el instrumento “Calidad de vida versión familiar” de Betty Ferrell, quien define la calidad de vida desde las dimensiones física, psicológica, social y espiritual, y el Índice de Barthel (IB, que mide el grado de dependencia funcional del paciente. La calidad de vida general de los cuidadores obtuvo una puntuación media. El bienestar físico y espiritual presentó una tendencia positiva, mientras que el bienestar psicológico y social de este grupo poblacional mostró una tendencia negativa con riesgo de alteración a futuro. El grado de dependencia funcional del paciente con Alzheimer se encontró en dependencia total a severa, con mayor compromiso en actividades de aseo y arreglo personal. En el estudio no se encontró correlación estadística entre la calidad de vida y el grado de dependencia del paciente con Alzheimer.The purpose of the study was to establish the relation between the quality of life of the family caregiver and the level of dependence of the patient with Alzheimer. It is a co-relational descriptive, cross-sectional study, with a quantitative approach having participation of 192 family caregivers of patients with Alzheimer; they are part of the Cuidado a Cuidadores® (Care for Caregivers program of the Nursing Faculty of Universidad Nacional de Colombia, the Fundación Acción Familiar Alzheimer Colombia (Alzheimer Colombia Family Action Foundation and the Asociación Nacional de Alzheimer

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

    Science.gov (United States)

    Cohen, Gene D.

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

  4. Treatment for Alzheimer's diseases

    Directory of Open Access Journals (Sweden)

    Nina Arkadyevna Tyuvina

    2015-01-01

    Full Text Available The paper gives an update on the epidemiology, etiology, pathogenesis, prevention, and treatment of Alzheimer's disease (AD. It points out the role of acetylcholine and glutamatergic components of neurotransmission in the pathogenesis of the disease, as well as their interactions, which is important to keep in mind to have a potentiated response to therapy that includes both these components. Different approaches to AD therapy are considered on the basis of the current ideas on the pathogenetic mechanisms of a degenerative process and with regard to the clinical features of the disease (the nature of the psychopathological symptoms of the disease and its stage. Particular emphasis is placed on compensatory therapy for deficient cholinergic and glutamatergic neurotransmission. Whether psychopharmacological agents may be used and psychotherapeutic work with the relatives of patients with AD should be done are also highlighted. Data on the efficiency of replacement therapy for different dementia stages, which promotes a delay in degenerative processes and a definite stabilization of the mental status, are presented.

  5. Cannabinoids in late-onset Alzheimer's disease

    NARCIS (Netherlands)

    Ahmed, A.; Marck, M.A. van der; Elsen, G. van den; Olde Rikkert, M.G.M.

    2015-01-01

    Given the lack of effective treatments for late-onset Alzheimer's disease (LOAD) and the substantial burden on patients, families, health care systems, and economies, finding an effective therapy is one of the highest medical priorities. The past few years have seen a growing interest in the medicin

  6. Metallostasis in Alzheimer's disease.

    Science.gov (United States)

    Ayton, Scott; Lei, Peng; Bush, Ashley I

    2013-09-01

    2012 has been another year in which multiple large-scale clinical trials for Alzheimer's disease (AD) have failed to meet their clinical endpoints. With the social and financial burden of this disease increasing every year, the onus is now on the field of AD researchers to investigate alternative ideas to deliver outcomes for patients. Although several major clinical trials targeting Aβ have failed, three smaller clinical trials targeting metal interactions with Aβ have all shown benefit for patients. Here we review the genetic, pathological, biochemical, and pharmacological evidence that underlies the metal hypothesis of AD. The AD-affected brain suffers from metallostasis, or fatigue of metal trafficking, resulting in redistribution of metals into inappropriate compartments. The metal hypothesis is built upon a triad of transition elements: iron, copper, and zinc. The hypothesis has matured from early investigations showing amyloidogenic and oxidative stress consequences of these metals; recently, disease-related proteins, APP, tau, and presenilin, have been shown to have major roles in metal regulation, which provides insight into the pathway of neurodegeneration in AD and illuminates potential new therapeutic avenues.

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... have Alzheimer's or other dementias as older whites. Hispanics are about one and one-half times as ... disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. ...

  8. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... action. Become an advocate SPECIAL REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history of medicine, one ... physician I am a researcher Message boards Get the facts 10 warning signs & symptoms What is dementia ...

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

    Science.gov (United States)

    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.

  10. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... action. Become an advocate SPECIAL REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history of medicine, one ... physician I am a researcher Message boards Get the facts 10 warning signs & symptoms What is dementia ...

  11. [Biomarkers in Alzheimer's disease].

    Science.gov (United States)

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

    2014-04-01

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

  12. Neuroinhibitory molecules in Alzheimer's disease.

    Science.gov (United States)

    Larner, A J; Keynes, R J

    2006-09-01

    Aberrant neurite growth is one of the neuropathological signatures of the Alzheimer's disease brain, both around amyloid plaques and in the cortical neuropil. Disruption of neuroinhibitory or repulsive growth and guidance signals, as well as of neurotrophic or permissive signals, may contribute to this dystrophic growth. Hence, therapeutic efforts directed exclusively at restoring neurotrophic activity are unlikely to meet with success. The molecular species responsible for neuroinhibitory effects in the Alzheimer's disease brain are beginning to be elucidated.

  13. Exclusion mapping of familial Alzheimer disease (FAD) in the Volga Germans

    Energy Technology Data Exchange (ETDEWEB)

    Levy-Lehad, E.; Wijsman, E.M. [Univ. of Washington, Seattle, WA (United States); Bird, T.D. [Veterans` Affairs Medical Center, Seattle, WA (United States)] [and others

    1994-09-01

    The Volga Germans (VG) are an ethnically distinct group of 8 families in whom early-onset (mean age-of-onset <60 years) FAD segregates as an autosomal dominant trait, probably due to a founder effect. Known FAD loci are a chromosome 14q24.3 locus for which the majority of early-onset FAD families show linkage, and the ApoE4 allele of the apolipoprotein E (ApoE) gene on chromosome 19q11.3. Linkage of VG FAD to markers on chromosomes 14, 21 and 19 has been excluded, and no APP mutations were found in affected VG subjects. The VG have an increased frequency of ApoE4 but do not show an association of FAD with the ApoE4 allele. In contrast to late-onset FAD families, ApoE4 does not modify age-of-onset in the VG: mean age-of-onset is 62.2{plus_minus}10.0 years for affected individuals with no ApoE4 alleles, 62.0{plus_minus}6.0 for affecteds homozygous for ApoE4. Therefore FAD in the VG group is caused by a locus which is as yet unidentified. To map this locus we have undertaken a genome-side search using short-tandem-repeat (STRP) markers evenly spaced (about every 20 cM) on all the autosomes. We have analyzed over 30 RFLPs and over 100 STRP markers. Approximately 50% of the genome has been excluded. An exclusion map, using the EXCLUDE program, is continuously updated to indicate regions of high likelihood for linkage.

  14. Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Eugenia Trushina

    Full Text Available BACKGROUND: The identification of early mechanisms underlying Alzheimer's Disease (AD and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD mutations on mitochondrial function, dynamics, and brain energetics. METHODS AND FINDINGS: We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L and the double mutation of human amyloid precursor protein APP(Tg2576 and PS1(M146L contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. CONCLUSIONS: Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy

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

    Science.gov (United States)

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

  16. Calidad de vida del cuidador familiar y dependencia del paciente con Alzheimer Qualidade de vida do cuidador familiar e dependência do paciente com Alzheimer Family caretaker quality of life and dependence of the patient with Alzheimer disease

    Directory of Open Access Journals (Sweden)

    LINA MARÍA VARGAS ESCOBAR

    2010-06-01

    qualidade de vida desde as dimensões físicas, psicológicas, sociais e espirituais, e o Índice de Barthel (IB, que mensura o grau de dependência funcional do paciente. A qualidade de vida geral dos cuidadores conseguiu uma pontuação média. O bem-estar físico e espiritual apresentou uma tendência positiva, enquanto que o bem-estar psicológico e social deste grupo populacional demonstrou uma tendência negativa com risco de alteração futura. No tocante ao grau de dependência funcional do paciente com Alzheimer, verificou-se queera uma dependência de total a severa, com maior compromisso em atividades de asseio e cuidado pessoal. No estudo não se verificou correlação estatística entre a qualidade de vida e o grau de dependência do paciente com Alzheimer.The purpose of the study was to establish the relation between the quality of life of the family caregiver and the level of dependence of the patient with Alzheimer. It is a co-relational descriptive, cross-sectional study, with a quantitative approach having participation of 192 family caregivers of patients with Alzheimer; they are part of the Cuidado a Cuidadores® (Care for Caregivers program of the Nursing Faculty of Universidad Nacional de Colombia, the Fundación Acción Familiar Alzheimer Colombia (Alzheimer Colombia Family Action Foundation and the Asociación Nacional de Alzheimer (Colombian Alzheimer Association. Betty Ferrell´s "Quality of life, the family version" instrument (QOL was applied. She defines quality of life from the physical, psychological, social and spiritual dimensions. Barthel Index (BI, which measures the patient´s level of functional dependence, was also applied. Caregivers' general quality of life obtained an average score. Physical and spiritual welfare showed a positive trend, while the psychological and social wellbeing of this population group showed a negative trend with an alteration risk for the future. The Alzheimer patient's functional dependence level was found

  17. Derivation of induced pluripotent stem cells from a familial Alzheimer's disease patient carrying the L282F mutation in presenilin 1

    DEFF Research Database (Denmark)

    Poon, Anna Fong-Yee; Li, Tong; Pires, Carlota

    2016-01-01

    Mutations in presenilin 1 (PSEN1) lead to the most aggressive form of familial Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) derived from AD patients can be differentiated and used for disease modeling. Here, we derived hiPSC from skin fibroblasts obtained from an AD...... patient carrying a L282F mutation in PSEN1. We transfected skin fibroblasts with episomal iPSC reprogramming vectors targeting human OCT4, SOX2, L-MYC, KLF4, NANOG, LIN28, and short hairpin RNA against TP53. Our hiPSC line, L282F-hiPSC, displayed typical stem cell characteristics with consistent...

  18. [A Japanese family with familial Alzheimer's disease associated with presenilin 1 mutation: relationship between younger age of onset and ApoE gene polymorphism].

    Science.gov (United States)

    Marui, Wami; Iseki, Eizo; Sugiyama, Naoya; Matsumura, Takehiko; Suzuki, Kyoko; Odawara, Toshinari; Hino, Hiroaki; Kosaka, Kenji

    2003-04-01

    We previously reported a Japanese family with early-onset familial Alzheimer's disease associated with G 209 R presenilin 1(PS 1) mutation. There have been six patients across three generations in this family. In the present report, we described the clinical course, findings with neuroimaging and results of genetic examination of PS 1 and apolipoprotein E(ApoE) in three of six patients(II-1, III-1 and 2). The clinical course was common to all three patients. Memory disturbance, disorientation, amnestic aphasia, personality changes and perseveration appeared at early stages, whereas Gerstmann's syndrome, myoclonus and general convulsion were recognized at advanced stages. CT disclosed mild brain atrophy in the temporal lobes at early stages and diffuse brain atrophy predominantly in the fronto--temporal lobes at advanced stages. SPECT exhibited hypoperfusion in the fronto-temporal areas at early stages and hypoperfusion in the fronto-temporal and parieto-occipital areas at advanced stages. The age of onset in six patients demonstrated two clusters at age 53-55(I-1, II-1, 2 and 5) and age 46-48(III-1 and 2). PS 1 genotyping demonstrated that the heterozygous exonic missense mutation G 209 R was confirmed in all three patients. Regarding the ApoE genotyping, II-1(mother) was epsilon 3/epsilon 3, whereas III-1 and 2(children) were epsilon 3/epsilon 4. These findings suggest the possibility that there might be a gene dose effect, since the age of onset ranged from 5 to 7 years younger in patients who received epsilon 4 alleles from the father.

  19. 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 For ... you have a family member or friends with Alzheimer's disease? Are you wondering what they're going through ...

  20. [Music therapy and Alzheimer disease].

    Science.gov (United States)

    Tromeur, Emilie

    2014-01-01

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

  1. Nutritional supplementation for Alzheimer's disease?

    Science.gov (United States)

    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.

  2. Alzheimer's Disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

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

  3. Alzheimer disease: An interactome of many diseases

    Directory of Open Access Journals (Sweden)

    Balaji S Rao

    2014-01-01

    Full Text Available Alzheimer Disease (AD is an outcome as well as source of many diseases. Alzheimer is linked with many other diseases like Diabetes type 2, cholesterolemia, hypertension and many more. But how each of these diseases affecting other is still unknown to scientific community. Signaling Pathways of one disease is interlinked with other disease. But to what extent healthy brain is affected when any signaling in human body is disturbed is the question that matters. There is a need of Pathway analysis, Protein-Protein interaction (PPI and the conserved interactome study in AD and linked diseases. It will be helpful in finding the potent drug or vaccine target in conscious manner. In the present research the Protein-Protein interaction of all the proteins involved in Alzheimer Disease is analyzed using ViSANT and osprey tools and pathway analysis further reveals the significant genes/proteins linking AD with other diseases.

  4. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the ...

  5. Context memory in Alzheimer's disease

    NARCIS (Netherlands)

    El Haj, M.; Kessels, R.P.C.

    2013-01-01

    Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a gradual loss of memory. Specifically, context aspects of memory are impaired in AD. Our review sheds light on the neurocognitive mechanisms of this memory component that forms the core of episodic memory function.

  6. Context memory in Alzheimer's disease

    NARCIS (Netherlands)

    El Haj, M.; Kessels, R.P.C.

    2013-01-01

    Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a gradual loss of memory. Specifically, context aspects of memory are impaired in AD. Our review sheds light on the neurocognitive mechanisms of this memory component that forms the core of episodic memory function.

  7. Family dynamics in face of Alzheimer's in one of its members

    Directory of Open Access Journals (Sweden)

    Barbara Alana Vizzachi

    2015-12-01

    Full Text Available Abstract OBJECTIVE To understand the family dynamics when there is a member in the residence with Alzheimer's disease. METHOD A study of qualitative approach, using the creative sensitive method (CSM, and with participation of two families who had a member with Alzheimer's disease at home. RESULTS Three categories emerged: Effects of Alzheimer's disease and the family dynamics; Development process of Alzheimer's disease and Coping strategies in face of the disease. CONCLUSION It was possible to know the manifestations and consequences of Alzheimer's disease in the family, such as mutual help, the mobilization of resources to activate memories of the past, spirituality and faith. There was also understanding of the structure of family dynamics.

  8. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofi-brillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers in-volved in Alzheimer's disease therapy.

  9. A Presenilin-1 Mutation Identified in Familial Alzheimer Disease with Cotton Wool Plaques Causes a Nearly Complete Loss of γ-Secretase Activity*

    Science.gov (United States)

    Heilig, Elizabeth A.; Xia, Weiming; Shen, Jie; Kelleher, Raymond J.

    2010-01-01

    Mutations in presenilin-1 and presenilin-2 (PS1 and PS2) are the most common cause of familial Alzheimer disease. PS1 and PS2 are the presumptive catalytic components of the multisubunit γ-secretase complex, which proteolyzes a number of type I transmembrane proteins, including the amyloid precursor protein (APP) and Notch. APP processing by γ-secretase produces β-amyloid peptides (Aβ40 and Aβ42) that accumulate in the Alzheimer disease brain. Here we identify a pathogenic L435F mutation in PS1 in two affected siblings with early-onset familial Alzheimer disease characterized by deposition of cerebral cotton wool plaques. The L435F mutation resides in a conserved C-terminal PAL sequence implicated in active site conformation and catalytic activity. The impact of PS1 mutations in and around the PAL motif on γ-secretase activity was assessed by expression of mutant PS1 in mouse embryo fibroblasts lacking endogenous PS1 and PS2. Surprisingly, the L435F mutation caused a nearly complete loss of γ-secretase activity, including >90% reductions in the generation of Aβ40, Aβ42, and the APP and Notch intracellular domains. Two nonpathogenic PS1 mutations, P433L and L435R, caused essentially complete loss of γ-secretase activity, whereas two previously identified pathogenic PS1 mutations, P436Q and P436S, caused partial loss of function with substantial reductions in production of Aβ40, Aβ42, and the APP and Notch intracellular domains. These results argue against overproduction of Aβ42 as an essential property of presenilin proteins bearing pathogenic mutations. Rather, our findings provide support for the hypothesis that pathogenic mutations cause a general loss of presenilin function. PMID:20460383

  10. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases

    Science.gov (United States)

    Lanoiselée, Hélène-Marie; Nicolas, Gaël; Wallon, David; Rovelet-Lecrux, Anne; Lacour, Morgane; Rousseau, Stéphane; Richard, Anne-Claire; Pasquier, Florence; Rollin-Sillaire, Adeline; Martinaud, Olivier; Quillard-Muraine, Muriel; de la Sayette, Vincent; Boutoleau-Bretonniere, Claire; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Sarazin, Marie; le Ber, Isabelle; Epelbaum, Stéphane; Jonveaux, Thérèse; Rouaud, Olivier; Ceccaldi, Mathieu; Félician, Olivier; Godefroy, Olivier; Formaglio, Maite; Croisile, Bernard; Auriacombe, Sophie; Chamard, Ludivine; Vincent, Jean-Louis; Sauvée, Mathilde; Marelli-Tosi, Cecilia; Gabelle, Audrey; Ozsancak, Canan; Pariente, Jérémie; Paquet, Claire; Hannequin, Didier; Campion, Dominique

    2017-01-01

    Background Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. Methods and findings We report here a novel update (2012–2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers—total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42—in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. Conclusions Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only

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

    Science.gov (United States)

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

    1995-03-11

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

  12. 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

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now ... the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with ... name: Last name: *Email: *Zip: Weekly ...

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... An estimated 5.5 million Americans of all ages have Alzheimer's disease. Of the estimated 5.5 ... in 2017, an estimated 5.3 million are age 65 and older and approximately 200,000 individuals ...

  15. The burden of Alzheimer's disease.

    Science.gov (United States)

    Burns, Alistair

    2000-07-01

    Alzheimer's disease (AD) imposes a severe burden upon patients and their carers. In particular, family carers of AD patients face extreme hardship and distress that represents a major but often hidden burden on healthcare systems. Carers often experience clinically significant alterations in physical and mental health, particularly depression. A number of individual features of the dementia syndrome that are known to be particularly burdensome to carers include the degree of cognitive impairment, amount of help required with activities of daily living, personality changes and the presence of psychiatric symptoms and behavioural disturbances. The neuropsychiatric features of AD patients can adversely impact the relationship between the patient and caregiver generating feelings of strain, burden and social isolation. Individual characteristics of the caregiver including personality, gender, degree of formal and informal support and physical and mental health, as well as attributional style ('coping style') and expressed emotion (critical or hostile attitudes), also dictate carer burden. As informal caregivers play such a crucial role in the care of AD patients, appropriate management strategies that incorporate interventions which address the specific burdens of the individual caregiver are essential. Reducing the burden of care can be achieved by the combination of a number of individual and general measures, including education, respite and emotion-focused interventions. These measures, accompanied by non-pharmacological strategies, are extremely important in the total care of the AD patient, with the emphasis on maintaining people in the community as long as possible.

  16. Alzheimer's disease and euthanasia.

    Science.gov (United States)

    Alvargonzález, David

    2012-12-01

    Employing the tenets of philosophical materialism, this paper discusses the ethical debate surrounding assisted suicide for persons suffering end-stage Alzheimer's. It first presents a classification of the dissociative situations between "human individual" and "human person". It then moves on to discuss challenges to diagnosed persons and their caregivers in relation to the cardinal virtues of Spinozistic ethics--strength of character (fortitudo), firmness (animositas) and generosity (generositas). Finally, a number of ideas attached to the debate--"right of choice", "death with dignity", "quality of life" and "compassion in dying"--are discussed in order to clarify their foundations. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. 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

  18. Molecular imaging in Alzheimer's disease.

    Science.gov (United States)

    Lascola, Christopher

    2005-11-01

    Molecular imaging represents a new term for a long-standing quest to image cellular and molecular processes in vivo. The development of a successful molecular imaging approach starts with a well-defined diagnostic question best answered using in vivo imaging. A selective target for a particular disease state is then identified and a biocompatible probe selective for that target is developed. Many of the challenges of finding selective disease targets and probes that bind selectively to those targets in vivo are evident in the 25-year history of molecular imaging in Alzheimer's disease. This article provides a brief overview of molecular imaging in Alzheimer's disease and its potential for early diagnosis and treatment development.

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

    Science.gov (United States)

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

    2016-06-01

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

  20. Calidad de vida de los cuidadores familiares de los pacientes con enfermedad de Alzheimer / Quality of life of patients with family caregivers of Alzheimer's disease

    OpenAIRE

    Osorio Lambis, Martha,

    2011-01-01

    Esta investigación tiene como objetivo describir la calidad de vida del cuidador familiar de paciente con enfermedad de Alzheimer en la ciudad de Cartagena, en las dimensiones física, psicológica, social y espiritual observada y recolectada en su ambiente natural. El diseño del estudio es de tipo descriptivo con abordaje cuantitativo, la muestra fue constituida por 61 cuidadores familiares de pacientes con enfermedad de Alzheimer inscritos en la Fundación Centro Colombiano de Epileps...

  1. Nasal Application of the Galantamine Pro-drug Memogain Slows Down Plaque Deposition and Ameliorates Behavior in 5X Familial Alzheimer's Disease Mice.

    Science.gov (United States)

    Bhattacharya, Soumee; Maelicke, Alfred; Montag, Dirk

    2015-01-01

    The plant alkaloid galantamine is an established symptomatic drug treatment for Alzheimer's disease (AD), providing cognitive and global relief in human patients. However, as an acetylcholinesterase inhibitor, gastrointestinal side effects limit the dosage and duration of treatment. Memogain (Gln-1062), a pro-drug, liberates galantamine on cleavage by a carboxyesterase in the brain. The possibility to deliver Memogain intranasally may further circumvent side effects, allowing higher dosing compared to galantamine. In this study, the 5X Familial Alzheimer's Disease (5XFAD) mouse model was used to investigate the effect of chronic Memogain treatment on behavior and amyloid-β (Aβ) plaque deposition in the brain. Chronic intranasal dosage of 6 mg/kg body weight twice daily was tolerated well, whereas the double dose caused body weight loss in males and was less effective in some behavioral tests. 8 weeks of chronic treatment resulted in improved performance in behavioral tests, such as open field and light-dark avoidance, and in fear conditioning already at mildly affected stages at the age of 18 weeks compared to untreated controls. Furthermore, after treatment a significantly lower plaque density in the brain, i.e., in the entorhinal cortex (reduction 20% females, 40% males) and the hippocampus (19% females, 31% males) at the age of 18 weeks was observed. These results show that nasal application of Memogain effectively delivers the drug to the brain with the potential to retard plaque deposition and improve behavioral symptoms in AD similar to the approved galantamine.

  2. [Alzheimer's disease and human memory].

    Science.gov (United States)

    Eustache, F; Giffard, B; Rauchs, G; Chételat, G; Piolino, P; Desgranges, B

    2006-10-01

    Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way

  3. Ocular biomarkers of Alzheimer's disease.

    Science.gov (United States)

    Heaton, George R; Davis, Benjamin M; Turner, Lisa A; Cordeiro, Maria F

    2015-01-01

    Alzheimer's disease (AD) is a devastating neurodegenerative disease characterised clinically by a progressive decline in executive functions, memory and cognition. Classic neuropathological hallmarks of AD include intracellular hyper-phosphorylated tau protein which forms neurofibrillary tangles (NFT), and extracellular deposits of amyloid β (Aβ) protein, the primary constituent of senile plaques (SP). The gradual process of pathogenic amyloid accumulation is thought to occur 10-20 years prior to symptomatic manifestation. Advance detection of these deposits therefore offers a highly promising avenue for prodromal AD diagnosis. Currently, the most sophisticated method of 'probable AD' diagnosis is via neuroimaging or cerebral spinal fluid (CSF) biomarker analysis. Whilst these methods have reported a high degree of diagnostic specificity and accuracy, they fall significantly short in terms of practicality; they are often highly invasive, expensive or unsuitable for large-scale population screening. In recent years, ocular screening has received substantial attention from the scientific community due to its potential for non-invasive and inexpensive central nervous system (CNS) imaging. In this appraisal we build upon our previous reviews detailing ocular structural and functional changes in AD (Retinal manifestations of Alzheimer's disease, Alzheimer's disease and Retinal Neurodegeneration) and consider their use as biomarkers. In addition, we present an overview of current advances in the use of fluorescent reporters to detect AD pathology through non-invasive retinal imaging.

  4. Alzheimer's disease. To tell or not to tell.

    OpenAIRE

    Gordon, M.; Goldstein, D.

    2001-01-01

    OBJECTIVE: To evaluate reasons for telling or not telling patients about a diagnosis of Alzheimer's disease and to assess the effect of such a decision on patients, families, physicians, and the health care system. QUALITY OF EVIDENCE: MEDLINE was searched from January 1966 to December 1999 using the key words "Alzheimer's disease" or "dementia" and "truth disclosure" or "attitude to health." There were no randomized controlled trials (level I evidence) in the literature. Articles identified ...

  5. Alzheimer's Project

    Medline Plus

    Full Text Available ... their families. September 14, 2009 "The Alzheimer's Project" wins two Creative Arts Emmys Two installments of the ... you can help us change the way Americans thinks about Alzheimer's disease. Tell your family and friends. ...

  6. The discovery of Alzheimer's disease

    OpenAIRE

    Hippius, Hanns; Neundörfer, Gabriele

    2003-01-01

    On Novembers, 1306, a clinical psychiatrist and neuroanatomist, Alois Alzheimer, reported “A peculiar severe disease process of the cerebral cortex” to the 37th Meeting of South-West German Psychiatrists in Tubingen, He described a 50-year-old woman whom he had followed from her admission for paranoia, progressive sleep and memory disturbance, aggression, and confusion, until her death 5 years later. His report noted distinctive plaques and neurofibrillary tangles in the brain histology. It e...

  7. Cellular basis of Alzheimer's disease.

    Science.gov (United States)

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

  8. Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Sepideh Parsi

    2015-01-01

    Full Text Available Alzheimer's disease (AD is a multifactorial, fatal neurodegenerative disorder characterized by the abnormal accumulation of Aβ and Tau deposits in the brain. There is no cure for AD, and failure at different clinical trials emphasizes the need for new treatments. In recent years, significant progress has been made toward the development of miRNA-based therapeutics for human disorders. This study was designed to evaluate the efficiency and potential safety of miRNA replacement therapy in AD, using miR-15/107 paralogues as candidate drug targets. We identified miR-16 as a potent inhibitor of amyloid precursor protein (APP and BACE1 expression, Aβ peptide production, and Tau phosphorylation in cells. Brain delivery of miR-16 mimics in mice resulted in a reduction of AD-related genes APP, BACE1, and Tau in a region-dependent manner. We further identified Nicastrin, a γ-secretase component involved in Aβ generation, as a target of miR-16. Proteomics analysis identified a number of additional putative miR-16 targets in vivo, including α-Synuclein and Transferrin receptor 1. Top-ranking biological networks associated with miR-16 delivery included AD and oxidative stress. Collectively, our data suggest that miR-16 is a good candidate for future drug development by targeting simultaneously endogenous regulators of AD biomarkers (i.e., Aβ and Tau, inflammation, and oxidative stress.

  9. Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease.

    Science.gov (United States)

    Parsi, Sepideh; Smith, Pascal Y; Goupil, Claudia; Dorval, Véronique; Hébert, Sébastien S

    2015-10-06

    Alzheimer's disease (AD) is a multifactorial, fatal neurodegenerative disorder characterized by the abnormal accumulation of Aβ and Tau deposits in the brain. There is no cure for AD, and failure at different clinical trials emphasizes the need for new treatments. In recent years, significant progress has been made toward the development of miRNA-based therapeutics for human disorders. This study was designed to evaluate the efficiency and potential safety of miRNA replacement therapy in AD, using miR-15/107 paralogues as candidate drug targets. We identified miR-16 as a potent inhibitor of amyloid precursor protein (APP) and BACE1 expression, Aβ peptide production, and Tau phosphorylation in cells. Brain delivery of miR-16 mimics in mice resulted in a reduction of AD-related genes APP, BACE1, and Tau in a region-dependent manner. We further identified Nicastrin, a γ-secretase component involved in Aβ generation, as a target of miR-16. Proteomics analysis identified a number of additional putative miR-16 targets in vivo, including α-Synuclein and Transferrin receptor 1. Top-ranking biological networks associated with miR-16 delivery included AD and oxidative stress. Collectively, our data suggest that miR-16 is a good candidate for future drug development by targeting simultaneously endogenous regulators of AD biomarkers (i.e., Aβ and Tau), inflammation, and oxidative stress.

  10. Progress Report on Alzheimer Disease: Volume III.

    Science.gov (United States)

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

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

  11. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 ... Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association ...

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... is a not-for-profit 501(c)(3) organization. Copyright © 2017 Alzheimer's Association ® . All rights reserved. Our ... Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and research.

  13. Imaging the earliest stages of Alzheimer's disease.

    Science.gov (United States)

    Wu, William; Small, Scott A

    2006-12-01

    Historical progress in medicine can be charted along the lines of technical innovations that have visualized the invisible. One hundred years ago, Alois Alzheimer exploited newly developed histological stains to visualize his eponymonous disease in dead tissue under the microscope. Now, as we are entering the second century of Alzheimer's disease research, technical innovation has endowed us with a range of in vivo imaging techniques that promise to visualize Alzheimer' disease in living people. The earliest stage of Alzheimer's disease is characterized by cell-sickness, not cell-death, and can occur before the deposition of amyloid plaques or neurofibrillary tangles. In principle, 'functional' imaging techniques might be able to detect this early stage of the disease, a stage that was invisible to Alzheimer himself. Here, we will first define the neurobiological meaning of 'function' and then review the different approaches that measure brain dysfunction in Alzheimer' disease.

  14. Amyloid beta peptide immunotherapy in Alzheimer disease.

    Science.gov (United States)

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

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Alzheimer's Project

    Medline Plus

    Full Text Available ... Chicago National Alzheimer's Gala A Night at Sardi's Alzheimer's Disease Awareness Month World Alzheimer's Month HBO Alzheimer’s Project ... help us change the way Americans thinks about Alzheimer's disease. Tell your family and friends. Post info on ...

  16. Recent progress of PET in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Na NIU

    2014-03-01

    Full Text Available Alzheimer's disease is the most common cause of dementia in the current elderly population. PET can detect pathophysiological changes in Alzheimer's disease with different radiotracers. This paper will focus on evaluating the value of 18F-FDG, amyloid and tau protein PET imaging in Alzheimer's disease. PET has been demonstrated to play an important role in the research of etiology, early diagnosis, differential dignosis, prognosis and medical treatment of Alzheimer's disease. doi: 10.3969/j.issn.1672-6731.2014.03.007

  17. Alzheimer's disease and periodontitis - an elusive link

    Directory of Open Access Journals (Sweden)

    Abhijit N. Gurav

    2014-01-01

    Full Text Available Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

  18. Alzheimer's Disease: Symptoms, Diagnosis and Treatment

    Science.gov (United States)

    ... page please turn Javascript on. Feature: Alzheimer's Disease Symptoms, Diagnosis and Treatment Past Issues / Fall 2010 Table of Contents Symptoms Scientists believe that changes in the brain may ...

  19. Analyses of the similarity and difference of global gene expression profiles in cortex regions of three neurodegenerative diseases: sporadic Creutzfeldt-Jakob disease (sCJD), fatal familial insomnia (FFI), and Alzheimer's disease (AD).

    Science.gov (United States)

    Tian, Chan; Liu, Di; Xiang, Wei; Kretzschmar, Hans A; Sun, Qing-Lan; Gao, Chen; Xu, Yin; Wang, Hui; Fan, Xue-Yu; Meng, Ge; Li, Wei; Dong, Xiao-Ping

    2014-10-01

    Neurodegenerative disease is a general designation for the disorders that are progressive loss of structure or function and final death of neurons, including Alzheimer's, Parkinson's, Huntington's, prion diseases, etc. In this study, we comparatively analyzed 21 individual microarray data sets of the cortex tissues from 11 sporadic Creutzfeldt-Jakob disease (sCJD), 3 fatal familial insomnia (FFI), 3 Alzheimer's disease (AD), and 4 normal controls. After normalization, a collection of 730 differently expressed sets (DESets) were obtained by comparison of the data of three diseases with their original controls. Principal component analysis (PCA) showed a background-related distribution within the groups of FFI, AD, and normal control, but two apparently different subgroups within the group of sCJD were observed. Review of the clinical materials of 11 sCJD patients identified the difference in brain PrP(Sc) deposits between two subgroups. Hierarchical cluster analysis illustrated the relatively independent clusters of normal controls, FFIs, six sCJD cases (subgroup 1) with more PrP(Sc) deposits, respectively, while an overlapped cluster of five cases of sCJD2 (subgroup 2) with less PrP(Sc) deposits and AD patients. Despite of the presence of special gene expressions, many common features were found among those neurodegenerative diseases. The most commonly changed biological processes (BPs) were signal transduction, synaptic transmission, and neuropeptide signaling pathway. The most commonly changed pathways were MAPK signaling pathway, Parkinson's disease, and oxidative phosphorylation. Our data here provide the similarity and difference in global gene expressions among the patients with sCJD, FFI, and AD, which may help to understand the common mechanism of neurodegenerative diseases.

  20. [Stigmatization in Alzheimer's disease, a review].

    Science.gov (United States)

    Cavayas, Marilèna; Raffard, Stéphane; Gély-Nargeot, Marie-Christine

    2012-09-01

    Stigma against chronic disease or mental illness is a well-known phenomenon and results in devastating consequences for individuals who suffer from these diseases and their families. However, few studies have evaluated the stigma and its various processes associated with Alzheimer's disease (AD). The aim of the present review is to discuss the concepts that underlie stigma and its different forms, and then to explain its causes and consequences. Indeed, if the stigma primarily affects individuals with a diagnosis of AD, recent studies have shown that the caregivers of the patients as well as their relatives are also exposed to stigma by association. Moreover, past and current studies on other chronic diseases highlight the importance of using methods issued from experimental social psychology to assess the explicit representations but also the implicit stigma associated with the disease. Finally, several researches and possible interventions are proposed to reduce the stigma associated with AD and related concepts such as MCI.

  1. Alzheimer's disease and chronic periodontitis: is there an association?

    Science.gov (United States)

    Gaur, Sumit; Agnihotri, Rupali

    2015-04-01

    Alzheimer's disease, an affliction of old age, is one of the leading causes for dementia worldwide. Various risk factors including family history, genetics and infections have been implicated in its pathogenesis. The cognitive decline in this condition is mainly a result of the formation of amyloid deposits that provoke neuroinflammation, ultimately resulting in cell death. Recently, an association between peripheral inflammation and Alzheimer's disease was hypothesized. It was suggested that chronic systemic inflammation worsened the inflammatory processes in the brain. This was mainly attributed to increased levels of pro-inflammatory mediators, such as interleukin-1, interleukin -6 and tumor necrosis factor-α in the plasma. As chronic periodontitis is a widespread peripheral immunoinflammatory condition, it has been proposed to play a significant role in the aggravation of Alzheimer's disease. With this background, the current review focuses on the relationship between Alzheimer's disease and chronic periodontitis, and its therapeutic implications.

  2. White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Nagesh Adluru

    2014-01-01

    Conclusion: APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics—both expected and unexpected—may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD.

  3. Study on Alzheimer's disease model

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    It is well known that the main brain lesion in Alzheimer's disease (AD) brain is neurofibrillary tangles (NFT) and senile plaques (SP). The amount of NFT is positively correlated with clinical degree of dementia in AD. It is also well studied that the major component of NFT is abnormally hyperphosphorylated microtubule associated protein tau that is caused by an imbalance of protein kinase and protein phosphatase (PP). To reconstitute a specific AD model based on the above hypothesis, we have injected separately calcium calmodulin dependent protein kinase (CaMKKII) activator, bradykinin and PP-2B inhibitor, cyclosporin A into rat hippocampus in the present study. The results showed that the injection of bradykinin caused learning and memory deficient in rats as well as Alzheimer-like tau phosphorylation, including Ser-262/356, Thr-231/235 and Ser-396/404. On the other hand, the injection of cyclosporin A induced the same phosphorylation sites as above except Ser-262/356, however, it did not mimic rat behavior abnormality as bradykinin injection did. The data suggested that activating of CaMKII and the phosphorylation of Ser-262/356 at tau might responsible for the lesion of learning and memory in our model rats. We also incubated PP-2A and PP-1 inhibitor, okadaic acid with human neuroblastoma cell line (SH-SY5Y), and found that (1) inhibition of above PPs induced Alzheimer-like phosphorylation and accumulation of neurofilaments, and Alzheimer-like microtubule disruption, (2) melatonin showed certain protection of the cell from okadaic acid toxicity. The data obtained from this study is significant in AD specific model study.

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

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Past Issues / Winter 2015 Table of Contents ... How many Americans over age 65 may have Alzheimer's disease? as many as 5 million as many ...

  5. Memory loss in Alzheimer's disease.

    Science.gov (United States)

    Jahn, Holger

    2013-12-01

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

  6. Alzheimer's disease: synapses gone cold

    Directory of Open Access Journals (Sweden)

    Hyman Bradley T

    2011-08-01

    Full Text Available Abstract Alzheimer's disease (AD is a progressive neurodegenerative disease characterized by insidious cognitive decline and memory dysfunction. Synapse loss is the best pathological correlate of cognitive decline in AD and mounting evidence suggests that AD is primarily a disease of synaptic dysfunction. Soluble oligomeric forms of amyloid beta (Aβ, the peptide that aggregates to form senile plaques in the brain of AD patients, have been shown to be toxic to neuronal synapses both in vitro and in vivo. Aβ oligomers inhibit long-term potentiation (LTP and facilitate long-term depression (LTD, electrophysiological correlates of memory formation. Furthermore, oligomeric Aβ has also been shown to induce synapse loss and cognitive impairment in animals. The molecular underpinnings of these observations are now being elucidated, and may provide clear therapeutic targets for effectively treating the disease. Here, we review recent findings concerning AD pathogenesis with a particular focus on how Aβ impacts synapses.

  7. Triheptanoin supplementation to ketogenic diet curbs cognitive impairment in APP/PS1 mice used as a model of familial Alzheimer's disease.

    Science.gov (United States)

    Aso, Ester; Semakova, Jana; Joda, Laura; Semak, Vladislav; Halbaut, Lyda; Calpena, Ana; Escolano, Carmen; Perales, Jose C; Ferrer, Isidro

    2013-03-01

    Diets containing a high proportion of fat with respect to protein plus carbohydrates are capable of inducing ketone body production in the liver, which provides an energetic alternative to glucose. Some ketogenic diets have been tested as therapeutic strategies for treating metabolic disorders related to a deficiency in glucose-driven ATP generation. However, ketone bodies are not capable of providing extra tricarboxylic acid cycle intermediates, limiting the anabolic capacity of the cell. Therefore, it is reasonable to hypothesize that supplementing a ketogenic diet with anaplerotic compounds such as triheptanoin may improve ketogenic diet effectiveness. The present study tests this hypothesis in APP/PS1 (APPswe/PS1dE9) transgenic mice, used as a model of familial Alzheimer's disease because impaired energy supply to neurons has been linked to this neurodegenerative process. Triheptanoin supplementation to a ketogenic diet for three months and starting at the age of three months reduces the memory impairment of APP/PS1 mice at the age of 6 months. The Aβ production and deposition were not significantly altered by the ketogenic diet, supplemented or not by triheptanoin. However, mice fed with triheptanoin-rich ketogenic diet have shown decreased astroglial response in the vicinity of Aβ plaques and decreased expression of the pro-inflammatory cytokine interferon-γ in astrocytes. These findings correlate with transcriptional up-regulation of the ROS detoxifying mechanisms Sirt1 and Pparg, thus linking triheptanoin with improved mitochondrial status. Present findings support the concept that ketogenic diets supplemented with anaplerotic compounds can be considered potential therapeutic strategies at early stages of Alzheimer's disease.

  8. 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.

  9. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families.

    Directory of Open Access Journals (Sweden)

    Carlos Cruchaga

    Full Text Available Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD. Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs. We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals. Sixty sequenced individuals (13.7% carried a novel or pathogenic mutation. Eight pathogenic variants, (one each in APP and MAPT, two in PSEN1 and four in GRN three of which are novel, were found in 14 samples. Thirteen additional variants, present in 23 families, did not segregate with disease, but the frequency of these variants is higher in AD cases than controls, indicating that these variants may also modify risk for disease. The frequency of rare variants in these genes in this series is significantly higher than in the 1,000 genome project (p = 5.09 × 10⁻⁵; OR = 2.21; 95%CI = 1.49-3.28 or an unselected population of 12,481 samples (p = 6.82 × 10⁻⁵; OR = 2.19; 95%CI = 1.347-3.26. Rare coding variants in APP, PSEN1 and PSEN2, increase risk for or cause late onset AD. The presence of variants in these genes in LOAD and early-onset AD demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with AD. MAPT and GRN mutations can be found in clinical series of AD most likely due to misdiagnosis. This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS.

  10. Physiology of the Alzheimer's disease.

    Science.gov (United States)

    Hahr, Jung Y

    2015-12-01

    Alzheimer's disease is a disease that is resulted from increased plasma osmolality both the excessive consumption of animal-based proteins and reduction of sodium intake, that resulted to increase plasma osmolality. When we are exposed to high animal-based protein diets throughout life, we gradually lose extracellular sodium and the body cannot retain water, resulting in a gradual rise of plasma osmolality. When the neuronal cells of the central nervous system are exposed to high osmolality stress, they produce of phosphorylated tau, APP, and pathologic beta amyloid protein peptides. The BACE 1 protein which influences the cleavage of amyloid precursor proteins (APP) and affects the production of beta amyloid protein peptides, is also increased in a hyperosmotic stress. When pathologic beta amyloid protein peptides are produced, they are degraded by the ubiquitin proteasome proteolytic pathway, and only then are the neurotoxic effects on the central nervous system manifested, leading to Alzheimer's disease. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  11. Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia.

    Science.gov (United States)

    Tabner, Brian J; El-Agnaf, Omar M A; Turnbull, Stuart; German, Matthew J; Paleologou, Katerina E; Hayashi, Yoshihito; Cooper, Leanne J; Fullwood, Nigel J; Allsop, David

    2005-10-28

    Alzheimer disease and familial British dementia are neurodegenerative diseases that are characterized by the presence of numerous amyloid plaques in the brain. These lesions contain fibrillar deposits of the beta-amyloid peptide (Abeta) and the British dementia peptide (ABri), respectively. Both peptides are toxic to cells in culture, and there is increasing evidence that early "soluble oligomers" are the toxic entity rather than mature amyloid fibrils. The molecular mechanisms responsible for this toxicity are not clear, but in the case of Abeta, one prominent hypothesis is that the peptide can induce oxidative damage via the formation of hydrogen peroxide. We have developed a reliable method, employing electron spin resonance spectroscopy in conjunction with the spin-trapping technique, to detect any hydrogen peroxide generated during the incubation of Abeta and other amyloidogenic peptides. Here, we monitored levels of hydrogen peroxide accumulation during different stages of aggregation of Abeta-(1-40) and ABri and found that in both cases it was generated as a short "burst" early on in the aggregation process. Ultrastructural studies with both peptides revealed that structures resembling "soluble oligomers" or "protofibrils" were present during this early phase of hydrogen peroxide formation. Mature amyloid fibrils derived from Abeta-(1-40) did not generate hydrogen peroxide. We conclude that hydrogen peroxide formation during the early stages of protein aggregation may be a common mechanism of cell death in these (and possibly other) neurodegenerative diseases.

  12. Brain Imaging in Alzheimer Disease

    Science.gov (United States)

    Johnson, Keith A.; Fox, Nick C.; Sperling, Reisa A.; Klunk, William E.

    2012-01-01

    Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies. PMID:22474610

  13. Predictors of Alzheimer's Disease Caregiver Depression and Burden: What Noncaregiving Adults Can Learn from Active Caregivers

    Science.gov (United States)

    Hayslip, Bert, Jr.; Han, GiBaeg; Anderson, Cristina L.

    2008-01-01

    This study examined similarities and differences between active caregivers (adult children and spouses whose family member had Alzheimer's disease) and not-as-yet caregiving adults (adult children and spouses whose family members are older, but do not as yet suffer from Alzheimer's disease). The objective was to determine what factors predict…

  14. Predictors of Alzheimer's Disease Caregiver Depression and Burden: What Noncaregiving Adults Can Learn from Active Caregivers

    Science.gov (United States)

    Hayslip, Bert, Jr.; Han, GiBaeg; Anderson, Cristina L.

    2008-01-01

    This study examined similarities and differences between active caregivers (adult children and spouses whose family member had Alzheimer's disease) and not-as-yet caregiving adults (adult children and spouses whose family members are older, but do not as yet suffer from Alzheimer's disease). The objective was to determine what factors predict…

  15. Emerging ocular biomarkers of Alzheimer disease.

    Science.gov (United States)

    van Wijngaarden, Peter; Hadoux, Xavier; Alwan, Mostafa; Keel, Stuart; Dirani, Mohamed

    2017-01-01

    Interest in reliable biomarkers of Alzheimer disease, the leading cause of dementia, has been fuelled by challenges in diagnosing the disease and monitoring disease progression as well as the response to therapy. A range of ocular manifestations of Alzheimer disease, including retinal and lens amyloid-beta accumulation, retinal nerve fiber layer loss, and retinal vascular changes, have been proposed as potential biomarkers of the disease. Herein, we examine the evidence regarding the potential value of these ocular biomarkers of Alzheimer disease. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

  16. Novel PSEN1 mutations (H214N and R220P) associated with familial Alzheimer's disease identified by targeted exome sequencing.

    Science.gov (United States)

    Piccoli, Elena; Rossi, Giacomina; Rossi, Tommaso; Pelliccioni, Giuseppe; D'Amato, Ilaria; Tagliavini, Fabrizio; Di Fede, Giuseppe

    2016-04-01

    Autosomal dominant Alzheimer's disease (AD) is caused by mutations in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 genes and is mostly associated with early-onset form of AD (EOAD), whereas very few mutations were also found in late-onset AD (LOAD) cases. Because of the clinical overlapping between AD and other degenerative dementias such as frontotemporal dementias, a wide-spectrum genetic analysis should be envisaged in the differential diagnosis of this group of disorders. We used next-generation sequencing techniques to analyze 10 genes involved in dementia on a cohort of 20 EOAD and 20 LOAD cases. We found 5 rare coding variants (frequency <1%). PSEN1 H214N mutation, identified in a case of familial EOAD and PSEN1 R220P, found in a case of familial LOAD, are predicted to be pathogenic. These findings confirm the contribution of PSEN1 genetic variants also to LOAD, underlining the need of extending the genetic screening of presenilin mutations to LOAD patients. Two variants in microtubule-associated protein tau and 1 in progranulin appeared to be benign polymorphisms, showing no major contribution of these genes to AD.

  17. Genetic inhibition of solute-linked carrier 39 family transporter 1 ameliorates aβ pathology in a Drosophila model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Minglin Lang

    Full Text Available The aggregation or oligomerization of amyloid-β (Aβ peptide is thought to be the primary causative event in the pathogenesis of Alzheimer's disease (AD. Considerable in vitro evidence indicates that the aggregation/oligomerization of Aβ is promoted in the presence of Zn; however, the functional role of Zn in AD pathogenesis is still not well clarified in vivo. Zn is imported into the brain mainly through the solute-linked carrier (Slc 39 family transporters. Using a genetically tractable Drosophila model, we found that the expression of dZip1, the orthologue of human Slc39 family transporter hZip1 in Drosophila, was altered in the brains of Aβ42-expressing flies, and Zn homeostasis could be modulated by forcible dZip1 expression changes. An array of phenotypes associated with Aβ expression could be modified by altering dZip1 expression. Importantly, Aβ42 fibril deposits as well as its SDS-soluble form were dramatically reduced upon dZip1 inhibition, resulting in less neurodegeneration, significantly improved cognitive performance, and prolonged lifespan of the Aβ42-transgenic flies. These findings suggest that zinc contributes significantly to the Aβ pathology, and manipulation of zinc transporters in AD brains may provide a novel therapeutic strategy.

  18. The Importance of Adipokines in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seyid Ahmet Ay

    2015-06-01

    Full Text Available Dementia and Alzheimers disease are characterized by disturbances in brain function and structure. Similarly, body mass index and obesity are associated with certain brain pathologies, including Alzheimers disease and dementia. In fact, there is mounting evidence linking metabolic dysfunction with dementia and Alzheimers disease. Major endocrine axes constitute links between brain and peripheral tissues, especially adipose tissue. Adipose tissue is metabolically very active and produces a variety of adipokines known to affect both peripheral and central nervous system processes. Experimental studies suggest that changes in adipokine function may contribute to the pathogenesis of Alzheimers disease. Herein, we review the adipokines leptin and adiponectin which are associated with morbidities related to obesity as well as dementia and Alzheimers disease. [Dis Mol Med 2015; 3(2.000: 22-28

  19. Calidad de vida del cuidador familiar y dependencia del paciente con Alzheimer Family caretaker quality of life and dependence of the patient with Alzheimer disease Qualidade de vida do cuidador familiar e dependência do paciente com Alzheimer

    OpenAIRE

    PINTO AFANADOR NATIVIDAD; VARGAS ESCOBAR LINA MARÍA

    2010-01-01

    El objetivo del estudio fue establecer la relación entre la calidad de vida del cuidador familiar y el grado de dependencia del paciente con Alzheimer. Es un estudio descriptivo correlacional, de corte transversal, con abordaje cuantitativo. Participaron 192 cuidadores familiares de pacientes con Alzheimer pertenecientes al programa Cuidado a Cuidadores® de la Facultad de Enfermería de la Universidad Nacional de Colombia, la Fundación Acción Familiar Alzheimer Colombia y la Asociación Colombi...

  20. Calidad de vida del cuidador familiar y dependencia del paciente con Alzheimer Qualidade de vida do cuidador familiar e dependência do paciente com Alzheimer Family caretaker quality of life and dependence of the patient with Alzheimer disease

    OpenAIRE

    LINA MARÍA VARGAS ESCOBAR; NATIVIDAD PINTO AFANADOR

    2010-01-01

    El objetivo del estudio fue establecer la relación entre la calidad de vida del cuidador familiar y el grado de dependencia del paciente con Alzheimer. Es un estudio descriptivo correlacional, de corte transversal, con abordaje cuantitativo. Participaron 192 cuidadores familiares de pacientes con Alzheimer pertenecientes al programa Cuidado a Cuidadores® de la Facultad de Enfermería de la Universidad Nacional de Colombia, la Fundación Acción Familiar Alzheimer Colombia y la Asociación Colombi...

  1. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... and older (10 percent) has Alzheimer's dementia. Almost two-thirds of Americans with Alzheimer's are women. African- ... the nation valued at $230.1 billion. Approximately two-thirds of caregivers are women, and 34 percent ...

  2. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... cause of disability and poor health. As the population of the United States ages, Alzheimer's is becoming ... Medicare beneficiaries with Alzheimer's or other dementias were over three times as great as payments for other ...

  3. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Dementia is one of the costliest conditions to society. Total payments in 2017 for all individuals with ... c)(3) organization. Copyright © 2017 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's ...

  4. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... expected to be $56 billion. Health care costs increase with the presence of dementia. People with Alzheimer's ... with Alzheimer's or other dementias are projected to increase from $259 billion in 2017 to more than $ ...

  5. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... whites. Hispanics are about one and one-half times as likely to have Alzheimer's or other dementias ... with Alzheimer's or other dementias were over three times as great as payments for other Medicare beneficiaries. ...

  6. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Nation The costs of health care and long-term care for individuals with Alzheimer's or other dementias ... percent, of the total health care and long-term care payments for people with Alzheimer's or other ...

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... state. Read past editions . Sign up for our e-newsletter Stay up-to-date on the latest ... Alzheimer's. First name: Last name: *Email: *Zip: Weekly E-Newsletter Breaking Research Updates The Alzheimer's Association does ...

  8. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... dementias have twice as many hospital stays per year as other older people. Medicare beneficiaries with Alzheimer's ... costs for Alzheimer's and other dementias are almost five times higher than average per-person payments for ...

  9. MRI morphometry in Alzheimer's disease.

    Science.gov (United States)

    Matsuda, Hiroshi

    2016-09-01

    MRI based evaluation of brain atrophy is regarded as a valid method to stage the disease and to assess progression in Alzheimer's disease (AD). Volumetric software programs have made it possible to quantify gray matter in the human brain in an automated fashion. At present, voxel based morphometry (VBM) is easily applicable to the routine clinical procedure with a short execution time. The importance of the VBM approach is that it is not biased to one particular structure and is able to assess anatomical differences throughout the brain. Stand-alone VBM software running on Windows, Voxel-based Specific Regional analysis system for AD (VSRAD), has been widely used in the clinical diagnosis of AD in Japan. On the other hand, recent application of graph theory to MRI has made it possible to analyze changes in structural connectivity in AD.

  10. Neuropathological Alterations in Alzheimer Disease

    Science.gov (United States)

    Serrano-Pozo, Alberto; Frosch, Matthew P.; Masliah, Eliezer; Hyman, Bradley T.

    2011-01-01

    The neuropathological hallmarks of Alzheimer disease (AD) include “positive” lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and “negative” lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between “normal” aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI. PMID:22229116

  11. Biomarkers for preclinical Alzheimer's disease.

    Science.gov (United States)

    Tan, Chen-Chen; Yu, Jin-Tai; Tan, Lan

    2014-01-01

    Currently, there is a pressing need to shift the focus to accurate detection of the earliest phase of increasingly preclinical Alzheimer's disease (AD). Meanwhile, the growing recognition that the pathophysiological process of AD begins many years prior to clinically obvious symptoms and the concept of a presymptomatic or preclinical stage of AD are becoming more widely accepted. Advances in clinical identification of new measurements will be critical not only in the discovery of sensitive, specific, and reliable biomarkers of preclinical AD but also in the development of tests that will aid in the early detection and differential diagnosis of dementia and in monitoring disease progression. The goal of this review is to provide an overview of biomarkers for preclinical AD, with emphasis on neuroimaging and neurochemical biomarkers. We conclude with a discussion of emergent directions for AD biomarker research.

  12. [Alzheimer's disease: New therapeutic strategies].

    Science.gov (United States)

    Villegas, Sandra

    2015-07-20

    The rapid increase in prevalence rates of Alzheimer's disease means that treatments to prevent, stop or reverse this devastating disease are urgently needed. Despite advances in understanding its molecular pathology, there are no drugs that can halt its progression. This review takes a tour through phase 2, or higher studies, probing receptor agonist agents interfering with aggregation, inhibitors/modulators of secretases, lipid-lowering agents, and, finally and most extensively, immunotherapy. The fact that phase 3 studies with bapineuzumab and solaneuzumab have recently failed does not invalidate the potential of immunotherapy, as more information is available and new clinical trials are being initiated. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... certificates increased 89 percent, while deaths from the number one cause of death (heart disease) ... In 2016, 15.9 million family and friends provided 18.2 billion hours of ...

  14. 7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... 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 ...

  15. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well as simple ideas on how you can support the fight to end Alzheimer's. First name: Last name: *Email: *Zip: Weekly ...

  16. Candidate SNP Markers of Familial and Sporadic Alzheimer's Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

    Directory of Open Access Journals (Sweden)

    Petr Ponomarenko

    2017-07-01

    Full Text Available While year after year, conditions, quality, and duration of human lives have been improving due to the progress in science, technology, education, and medicine, only eight diseases have been increasing in prevalence and shortening human lives because of premature deaths according to the retrospective official review on the state of US health, 1990-2010. These diseases are kidney cancer, chronic kidney diseases, liver cancer, diabetes, drug addiction, poisoning cases, consequences of falls, and Alzheimer's disease (AD as one of the leading pathologies. There are familial AD of hereditary nature (~4% of cases and sporadic AD of unclear etiology (remaining ~96% of cases; i.e., non-familial AD. Therefore, sporadic AD is no longer a purely medical problem, but rather a social challenge when someone asks oneself: “What can I do in my own adulthood to reduce the risk of sporadic AD at my old age to save the years of my lifespan from the destruction caused by it?” Here, we combine two computational approaches for regulatory SNPs: Web service SNP_TATA_Comparator for sequence analysis and a PubMed-based keyword search for articles on the biochemical markers of diseases. Our purpose was to try to find answers to the question: “What can be done in adulthood to reduce the risk of sporadic AD in old age to prevent the lifespan reduction caused by it?” As a result, we found 89 candidate SNP markers of familial and sporadic AD (e.g., rs562962093 is associated with sporadic AD in the elderly as a complication of stroke in adulthood, where natural marine diets can reduce risks of both diseases in case of the minor allele of this SNP. In addition, rs768454929, and rs761695685 correlate with sporadic AD as a comorbidity of short stature, where maximizing stature in childhood and adolescence as an integral indicator of health can minimize (or even eliminate the risk of sporadic AD in the elderly. After validation by clinical protocols, these candidate SNP

  17. Candidate SNP Markers of Familial and Sporadic Alzheimer's Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters.

    Science.gov (United States)

    Ponomarenko, Petr; Chadaeva, Irina; Rasskazov, Dmitry A; Sharypova, Ekaterina; Kashina, Elena V; Drachkova, Irina; Zhechev, Dmitry; Ponomarenko, Mikhail P; Savinkova, Ludmila K; Kolchanov, Nikolay

    2017-01-01

    While year after year, conditions, quality, and duration of human lives have been improving due to the progress in science, technology, education, and medicine, only eight diseases have been increasing in prevalence and shortening human lives because of premature deaths according to the retrospective official review on the state of US health, 1990-2010. These diseases are kidney cancer, chronic kidney diseases, liver cancer, diabetes, drug addiction, poisoning cases, consequences of falls, and Alzheimer's disease (AD) as one of the leading pathologies. There are familial AD of hereditary nature (~4% of cases) and sporadic AD of unclear etiology (remaining ~96% of cases; i.e., non-familial AD). Therefore, sporadic AD is no longer a purely medical problem, but rather a social challenge when someone asks oneself: "What can I do in my own adulthood to reduce the risk of sporadic AD at my old age to save the years of my lifespan from the destruction caused by it?" Here, we combine two computational approaches for regulatory SNPs: Web service SNP_TATA_Comparator for sequence analysis and a PubMed-based keyword search for articles on the biochemical markers of diseases. Our purpose was to try to find answers to the question: "What can be done in adulthood to reduce the risk of sporadic AD in old age to prevent the lifespan reduction caused by it?" As a result, we found 89 candidate SNP markers of familial and sporadic AD (e.g., rs562962093 is associated with sporadic AD in the elderly as a complication of stroke in adulthood, where natural marine diets can reduce risks of both diseases in case of the minor allele of this SNP). In addition, rs768454929, and rs761695685 correlate with sporadic AD as a comorbidity of short stature, where maximizing stature in childhood and adolescence as an integral indicator of health can minimize (or even eliminate) the risk of sporadic AD in the elderly. After validation by clinical protocols, these candidate SNP markers may become

  18. Symptom onset in autosomal dominant Alzheimer disease

    Science.gov (United States)

    Acosta-Baena, Natalia; Aisen, Paul S.; Bird, Thomas; Danek, Adrian; Fox, Nick C.; Goate, Alison; Frommelt, Peter; Ghetti, Bernardino; Langbaum, Jessica B.S.; Lopera, Francisco; Martins, Ralph; Masters, Colin L.; Mayeux, Richard P.; McDade, Eric; Moreno, Sonia; Reiman, Eric M.; Ringman, John M.; Salloway, Steve; Schofield, Peter R.; Sperling, Reisa; Tariot, Pierre N.; Xiong, Chengjie; Morris, John C.; Bateman, Randall J.

    2014-01-01

    Objective: To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD. Methods: We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study. Results: We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex. Conclusions: Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research. PMID:24928124

  19. Diagnosis and treatment of Alzheimer`s disease; Diagnostik und Therapie der Demenz vom Alzheimer-Typ

    Energy Technology Data Exchange (ETDEWEB)

    Hampel, H.; Padberg, F.; Koetter, H.U.; Teipel, S.J.; Ehrhardt, T.; Hegerl, U.; Stuebner, S.; Moeller, H.J. [Muenchen Univ. (Germany). Psychiatrische Klinik und Poliklinik

    1997-09-05

    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) [Deutsch] Die Alzheimer-Demenz kann heute mit grosser Sicherheit auch in der hausaerztlichen Praxis festgestellt werden. Dennoch werden Hirnleistungsstoerungen meist erst spaet im Krankheitsverlauf diagnostiziert. Oft bestehen dann bereits fortgeschrittene kognitive Beeintraechtigungen, die zu schweren psychosozialen und oekonomischen Belastungen innerhalb von Familie und Gesellschaft fuehren. Es sind mehr als 50 Erkrankungen beschrieben, die eine Demenz verursachen koennen. Die Alzheimer-Demenz macht davon den groessten Anteil aus und wirft durch ihre zunehmende Haeufigkeit erhebliche medizinische, pflegerische und soziooekonomische Probleme auf. Die weiterhin ungeklaerte Aetiologie ist eine der grossen Herausforderungen der neurobiologischen Grundlagenforschung. Aktuelle klinische Therapiestudien mit Acetylcholinesterase-Hemmern konnten ihre Wirksamkeit auf die kognitive Kernsymptomatik bei leichten und mittelgradig dementiellen Syndromen nachweisen. Durch ein dynamisches Konzept der multidisziplinaeren Diagnostik im Zusammenschluss zwischen spezialisierten Gedaechtnisambulanzen, klinisch-psychogeriatrischen Abteilungen und niedergelassenen Allgemein- und Fachaerzten kann eine optimierte Frueh- und Differentialdiagnostik bei Demenz-Patienten erfolgen. Dies erlaubt eine rechtzeitige individuelle Lebens- und Pflegeplanung fuer Alzheimer-Patienten und

  20. Ten Challenges of the Amyloid Hypothesis of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2017-01-01

    The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges...... as a background model of the disease, unify our understanding of the interplay between genetic and non-genetic risk factors, and combine into one framework both the familial and sporadic forms of the disease....

  1. 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...

  2. Lipofuscin hypothesis of Alzheimer's disease.

    Science.gov (United States)

    Giaccone, Giorgio; Orsi, Laura; Cupidi, Chiara; Tagliavini, Fabrizio

    2011-01-01

    The primary culprit responsible for Alzheimer's disease (AD) remains unknown. Aβ protein has been identified as the main component of amyloid of senile plaques, the hallmark lesion of AD, but it is not definitively established whether the formation of extracellular Aβ deposits is the absolute harbinger of the series of pathological events that hit the brain in the course of sporadic AD. The aim of this paper is to draw attention to a relatively overlooked age-related product, lipofuscin, and advance the hypothesis that its release into the extracellular space following the death of neurons may substantially contribute to the formation of senile plaques. The presence of intraneuronal Aβ, similarities between AD and age-related macular degeneration, and the possible explanation of some of the unknown issues in AD suggest that this hypothesis should not be discarded out of hand.

  3. Finger agnosia in Alzheimer disease.

    Science.gov (United States)

    Shenal, Brian V; Jackson, Melissa D; Crucian, Gregory P; Heilman, Kenneth M

    2006-12-01

    The purpose of this study was to learn if a deficit of finger naming (finger agnosia or anomia) is a sensitive test for Alzheimer disease (AD) and the best means of testing for finger agnosia. The subjects were 38 patients with AD and 10 matched normal controls. All subjects were asked to name the thumb, index, and pinky fingers. No control subject had trouble naming any of these fingers, but 37% of the AD subjects did. When AD patients had difficulty with finger naming, they always had trouble naming the index finger. In the absence of stroke, the inability to name the index finger seems as an indicator of dementia. Although brief, this test is not extremely sensitive test for AD.

  4. APP processing in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Zhang Yun-wu

    2011-01-01

    Full Text Available Abstract An important pathological feature of Alzheimer's disease (AD is the presence of extracellular senile plaques in the brain. Senile plaques are composed of aggregations of small peptides called β-amyloid (Aβ. Multiple lines of evidence demonstrate that overproduction/aggregation of Aβ in the brain is a primary cause of AD and inhibition of Aβ generation has become a hot topic in AD research. Aβ is generated from β-amyloid precursor protein (APP through sequential cleavages first by β-secretase and then by γ-secretase complex. Alternatively, APP can be cleaved by α-secretase within the Aβ domain to release soluble APPα and preclude Aβ generation. Cleavage of APP by caspases may also contribute to AD pathologies. Therefore, understanding the metabolism/processing of APP is crucial for AD therapeutics. Here we review current knowledge of APP processing regulation as well as the patho/physiological functions of APP and its metabolites.

  5. Asymptomatic Alzheimer disease: Defining resilience.

    Science.gov (United States)

    Hohman, Timothy J; McLaren, Donald G; Mormino, Elizabeth C; Gifford, Katherine A; Libon, David J; Jefferson, Angela L

    2016-12-06

    To define robust resilience metrics by leveraging CSF biomarkers of Alzheimer disease (AD) pathology within a latent variable framework and to demonstrate the ability of such metrics to predict slower rates of cognitive decline and protection against diagnostic conversion. Participants with normal cognition (n = 297) and mild cognitive impairment (n = 432) were drawn from the Alzheimer's Disease Neuroimaging Initiative. Resilience metrics were defined at baseline by examining the residuals when regressing brain aging outcomes (hippocampal volume and cognition) on CSF biomarkers. A positive residual reflected better outcomes than expected for a given level of pathology (high resilience). Residuals were integrated into a latent variable model of resilience and validated by testing their ability to independently predict diagnostic conversion, cognitive decline, and the rate of ventricular dilation. Latent variables of resilience predicted a decreased risk of conversion (hazard ratio 0.02, p < 0.001), and slower rates of ventricular dilation (β < -4.7, p < 2 × 10(-15)). These results were significant even when analyses were restricted to clinically normal individuals. Furthermore, resilience metrics interacted with biomarker status such that biomarker-positive individuals with low resilience showed the greatest risk of subsequent decline. Robust phenotypes of resilience calculated by leveraging AD biomarkers and baseline brain aging outcomes provide insight into which individuals are at greatest risk of short-term decline. Such comprehensive definitions of resilience are needed to further our understanding of the mechanisms that protect individuals from the clinical manifestation of AD dementia, especially among biomarker-positive individuals. © 2016 American Academy of Neurology.

  6. A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid A beta(42)

    NARCIS (Netherlands)

    Sleegers, Kristel; Bettens, Karolien; De Roeck, Arne; Van Cauwenberghe, Caroline; Cuyvers, Elise; Verheijen, Jan; Struyfs, Hanne; Van Dongen, Jasper; Vermeulen, Steven; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; Vandenberghe, Rik; De Deyn, Peter Paul; Van Broeckhoven, Christine

    2015-01-01

    Introduction: The ability to identify individuals at increased genetic risk for Alzheimer's disease (AD) may streamline biomarker and drug trials and aid clinical and personal decision making. Methods: We evaluated the discriminative ability of a genetic risk score (GRS) covering 22 published geneti

  7. Matched and Mismatched Appraisals of the Effectiveness of Communication Strategies by Family Caregivers of Persons with Alzheimer's Disease

    Science.gov (United States)

    Savundranayagam, Marie Y.; Orange, J. B.

    2014-01-01

    Background: Communication problems stemming from Alzheimer's disease (AD) often result in misunderstandings that can be linked with problem behaviours and increased caregiver stress. Moreover, these communication breakdowns also can result either from caregivers' use of ineffective communication strategies, which paradoxically are…

  8. 阿尔茨海默病患者家属心理干预研究现状%The research progress of psychological intervention among family members of Alzheimer's disease patients

    Institute of Scientific and Technical Information of China (English)

    熊丽娜; 金燕飞; 金昌德

    2015-01-01

    With the arrival of the aging society, Alzheimer's disease is becoming increasingly prominent and taking care of these patients has become an important social responsibility. At present, most,Alzheimer's disease patients were looked after by their family members whose psychological problems has become a major healthcare issue and affects not only their own physical and mental health but also the health of Alzheimer's disease patients. Therefore, resolving the psychological problems of family members of Alzheimer's disease patients is imperative. This paper summarized the current research in China and aboard of psychological intervention among family members of Alzheimer's disease patients in order to provide theoretical basis and reference for people to resolve the psychological problems of family members of Alzheimer's disease patients.%随着老龄化社会的到来,阿尔茨海默病发病率日益增高,照顾阿尔茨海默病患者成为社会一大重任。目前阿尔茨海默病患者的护理绝大多数是由患者家属承担,而家属在照顾患者期间会产生各种心理问题,不仅影响着患者家属的身心健康,也给阿尔茨海默病患者带来负面的影响。因此,解决阿尔茨海默病患者家属的心理问题势在必行。本文通过检索近几年来国内外对阿尔茨海默病患者家属的心理问题干预的相关研究,总结阿尔茨海默病患者家属的心理问题干预的研究现状,以期为解决家属心理问题提供理论依据和参考。

  9. 77 FR 11116 - Draft National Plan To Address Alzheimer's Disease

    Science.gov (United States)

    2012-02-24

    ... HUMAN SERVICES Draft National Plan To Address Alzheimer's Disease AGENCY: Office of the Assistant.... SUMMARY: HHS is soliciting public input on the draft National Plan to Address Alzheimer's Disease, which... Alzheimer's disease. Coordinate Alzheimer's disease research and services across all federal agencies...

  10. DNA Modifications and Alzheimer's Disease.

    Science.gov (United States)

    Smith, Rebecca G; Lunnon, Katie

    2017-01-01

    Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting millions of people worldwide. While a number of studies have focused on identifying genetic variants that contribute to the development and progression of late-onset AD, the majority of these only have a relatively small effect size. There are also a number of other risk factors, for example, age, gender, and other comorbidities; however, how these influence disease risk is not known. Therefore, in recent years, research has begun to investigate epigenetic mechanisms for a potential role in disease etiology. In this chapter, we discuss the current state of play for research into DNA modifications in AD, the most well studied being 5-methylcytosine (5-mC). We describe the earlier studies of candidate genes and global measures of DNA modifications in human AD samples, in addition to studies in mouse models of AD. We focus on recent epigenome-wide association studies (EWAS) in human AD, using microarray technology, examining a number of key study design issues pertinent to such studies. Finally, we discuss how new technological advances could further progress the research field.

  11. CD40 signaling and Alzheimer's disease pathogenesis.

    Science.gov (United States)

    Town, T; Tan, J; Mullan, M

    2001-01-01

    The interaction between CD40 and its cognate ligand, CD40 ligand, is a primary regulator of the peripheral immune response, including modulation of T lymphocyte activation, B lymphocyte differentiation and antibody secretion, and innate immune cell activation, maturation, and survival. Recently, we and others have identified CD40 expression on a variety of CNS cells, including endothelial cells, smooth muscle cells, astroglia and microglia, and have found that, on many of these cells, CD40 expression is enhanced by pro-inflammatory stimuli. Importantly, the CD40-CD40 ligand interaction on microglia triggers a series of intracellular signaling events that are discussed, beginning with Src-family kinase activation and culminating in microglial activation as evidenced by tumor necrosis factor-alpha secretion. Based on the involvement of microglial activation and brain inflammation in Alzheimer's disease pathogenesis, we have investigated co-stimulation of microglia, smooth muscle, and endothelial cells with CD40 ligand in the presence of low doses of freshly solubilized amyloid-beta peptides. Data reviewed herein show that CD40 ligand and amyloid-beta act synergistically to promote pro-inflammatory responses by these cells, including secretion of interleukin-1 beta by endothelial cells and tumor necrosis factor-alpha by microglia. As these cytokines have been implicated in neuronal injury, a comprehensive model of pro-inflammatory CD40 ligand and amyloid-beta initiated Alzheimer's disease pathogenesis (mediated by multiple CNS cells) is proposed.

  12. Advances in the study of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Angue Nkoghe Francoise; Yunman Li

    2005-01-01

    Alzheimer's disease (AD) is the most common cause of dementia, and the only treatment currently available for the disease is acetylcholinesterase inhibitors. Recent progress in understanding the molecular and cellular pathophysiology of Alzheimer's disease has suggested possible pharmacological interventions, including acetylcholineseterase inhibitors; secretase inhibitors; cholesterol lowering drugs; metal chelators and amyloid immunization. The objective of this paper is to review the main drugs possibly used for AD and their future therapeutic effects.

  13. Financial Conflicts Facing Late-Life Remarried Alzheimer's Disease Caregivers

    Science.gov (United States)

    Sherman, Carey Wexler; Bauer, Jean W.

    2008-01-01

    This qualitative study explores financial conflicts faced by late-life remarried wives providing care for their husbands with Alzheimer's disease. Interviews with 9 women identified intergenerational secrets and tensions regarding financial and inheritance decisions. Participants' remarried spouse status, underlying family boundary ambiguities,…

  14. Biological markers of Alzheimer?s disease

    Directory of Open Access Journals (Sweden)

    Leonardo Cruz de Souza

    2014-03-01

    Full Text Available The challenges for establishing an early diagnosis of Alzheimer’s disease (AD have created a need for biomarkers that reflect the core pathology of the disease. The cerebrospinal fluid (CSF levels of total Tau (T-tau, phosphorylated Tau (P-Tau and beta-amyloid peptide (Aβ42 reflect, respectively, neurofibrillary tangle and amyloid pathologies and are considered as surrogate markers of AD pathophysiology. The combination of low Aβ42 and high levels of T-tau and P-Tau can accurately identify patients with AD at early stages, even before the development of dementia. The combined analysis of the CSF biomarkers is also helpful for the differential diagnosis between AD and other degenerative dementias. The development of these CSF biomarkers has evolved to a novel diagnostic definition of the disease. The identification of a specific clinical phenotype combined with the in vivo evidence of pathophysiological markers offers the possibility to make a diagnosis of AD before the dementia stage with high specificity.

  15. Benzodiazepines may have protective effects against Alzheimer disease.

    Science.gov (United States)

    Fastbom, J; Forsell, Y; Winblad, B

    1998-03-01

    In this study, we examined the association between benzodiazepine use and the occurrence of Alzheimer disease and vascular dementia. The study was based on longitudinal data from a case-control study of 668 individuals aged 75 and older. The elderly were examined extensively by physicians, and family interviews were assessed. Dementia diagnosis was made by using DSM-III-R criteria. Individuals with a history of continuous use of benzodiazepines (BDZ+) were compared with nonusers (BDZ-), with respect to the incidence of Alzheimer disease or vascular dementia at follow-up 3 years later. It was found that there was a significantly lower incidence of Alzheimer disease in the BDZ+ group than in the BDZ- group. This negative association remained significant when controlling for age, gender, level of education, use of nonsteriodal antiinflammatory drugs, and estrogens. These results suggest that benzodiazepines may have protective effects against the disease.

  16. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  17. Insulin resistance in Alzheimer's disease.

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-12-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Polimorfismo da apolipoproteína e nos familiares em primeiro grau de pacientes com doença de Alzheimer familial ou esporádica Apolipoprotein e polymorphism in first-degree relatives of patients with familial or sporadic Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    João de Castilho Cação

    2007-06-01

    Full Text Available INTRODUÇÃO: A apolipoproteína E (apo E é reconhecida como fator de risco para doença de Alzheimer (DA. OBJETIVO: Analisar o polimorfismo da apo E nos familiares em primeiro grau de pacientes com DA familial ou esporádica do tipo tardio, comparando a famílias sem DA. MÉTODO: Foram estudados 40 pacientes com DA familial ou esporádica do tipo tardio, sendo os grupos classificados como provável, segundo critérios da NINCS-ADRDA. RESULTADO: O alelo épsilon3 foi o mais freqüente em todos os grupos. Observou-se freqüência mais elevada de épsilon4 comparando os familiares dos probandos aos do grupo controle (pINTRODUCTION: Apolipoproteín E (apo E has been recognized as a risk factor for Alzheimer disease (AD. OBJECTIVE: To analyze apo E polymorphism in first-degree relatives of patients with familial or sporadic late-onset AD comparing with families without AD. METHOD: Forty patients with familial or sporadic late-onset of AD, being both groups classified as probable, according of NINCS-ADRDA’s criteria. RESULTS: Allele epsilon3 was the most frequent in all of these groups. Higher frequency of epsilon4 when comparing the relatives of the probands with the relatives of the control group (p<0,0001 was observed. Allele epsilon2 showed significant difference only between relatives of familial AD and relatives of control group (p=0,026. CONCLUSION: Apo E polymorphism has not differentiated familial from sporadic AD. The study of families allows to amplify the alelles epsilon2 and epsilon4 representativity, revealing, their value as protecting factor and of risk for AD, respectively.

  19. Cell Therapy Products in Alzheimer Disease.

    Science.gov (United States)

    Song, Hyeon Jin; Kim, Tae-Hee; Lee, Hae-Hyeog; Kim, Jun-Mo; Park, Yoo Jin; Lee, Arum; Kim, Soo Ah; Choi, Hye Ji

    2017-04-01

    We are rapidly becoming an aging society, with the ongoing increase in challenges of the elderly. The age-related cognitive decline in accordance with aging society is of major importance in public health. Recent studies have proved the impacts of sex-steroid hormone on the brain; compliant with aging, menopause and decrease in estrogen have an effect on the occurrence and prevention of Alzheimer's disease. A new hypothesis states that Alzheimer's disease is a postmenopausal dementia, and is a negative form of estrogen deficiency. In this review article, we reckoned the cause of postmenopausal Alzheimer's disease. We further investigated new cell therapies for postmenopausal Alzheimer's disease, which are under development in some pharmaceutical companies. One remedy is cell therapy that inhibits the amyloid beta formation, and the other is the umbilical cord blood derived mesenchymal stem cell therapy.

  20. Advances in Alzheimer's disease drug development

    National Research Council Canada - National Science Library

    Rafii, Michael S; Aisen, Paul S

    2015-01-01

    Alzheimer's disease (AD) is the foremost cause of dementia worldwide. Clinically, AD manifests as progressive memory impairment followed by a gradual decline in other cognitive abilities leading to complete functional dependency...

  1. Education and the risk for Alzheimer's disease

    DEFF Research Database (Denmark)

    Letenneur, L; Launer, L J; Andersen, K

    2000-01-01

    The hypothesis that a low educational level increases the risk for Alzheimer's disease remains controversial. The authors studied the association of years of schooling with the risk for incident dementia and Alzheimer's disease by using pooled data from four European population-based follow......-up studies. Dementia cases were identified in a two-stage procedure that included a detailed diagnostic assessment of screen-positive subjects. Dementia and Alzheimer's disease were diagnosed by using international research criteria. Educational level was categorized by years of schooling as low (...), middle (8-11), or high (> or =12). Relative risks (95% confidence intervals) were estimated by using Poisson regression, adjusting for age, sex, study center, smoking status, and self-reported myocardial infarction and stroke. There were 493 (328) incident cases of dementia (Alzheimer's disease) and 28...

  2. Lithium May Fend off Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    Helen Pilcher; 夏红

    2004-01-01

    @@ Lithium, a common treatment for manic depression, might also help to stave off②Alzheimer's disease. Patients who take the drug to stabilize their mood disorder are less likely to succumb to dementia③, a study reveals.

  3. Education and the risk for Alzheimer's disease

    DEFF Research Database (Denmark)

    Letenneur, L; Launer, L J; Andersen, K

    2000-01-01

    The hypothesis that a low educational level increases the risk for Alzheimer's disease remains controversial. The authors studied the association of years of schooling with the risk for incident dementia and Alzheimer's disease by using pooled data from four European population-based follow......-up studies. Dementia cases were identified in a two-stage procedure that included a detailed diagnostic assessment of screen-positive subjects. Dementia and Alzheimer's disease were diagnosed by using international research criteria. Educational level was categorized by years of schooling as low (...), middle (8-11), or high (> or =12). Relative risks (95% confidence intervals) were estimated by using Poisson regression, adjusting for age, sex, study center, smoking status, and self-reported myocardial infarction and stroke. There were 493 (328) incident cases of dementia (Alzheimer's disease) and 28...

  4. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    Science.gov (United States)

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

  5. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Mark Ide

    Full Text Available Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

  6. [Western diet and Alzheimer's disease].

    Science.gov (United States)

    Berrino, Franco

    2002-01-01

    Alzheimer Disease, characterised by a global impairment of cognitive functions, is more and more common in Western societies, both because of longer life expectancy and, probably, because of increasing incidence. Several hints suggest that this degenerative disease is linked to western diet, characterised by excessive dietary intake of sugar, refined carbohydrates (with high glycaemic index), and animal product (with high content of saturated fats), and decreased intake of unrefined seeds--cereals, legumes, and oleaginous seeds--and other vegetables (with high content of fibres, vitamins, polyphenols and other antioxidant substances, phytoestrogens) and, in several populations, of sea food (rich in n-3 fatty acids). It has been hypothesised, in fact, that AD, may be promoted by insulin resistance, decreased endothelial production of nitric oxide, free radical excess, inflammatory metabolites, homocysteine, and oestrogen deficiency. AD, therefore, could theoretically be prevented (or delayed) by relatively simple dietary measures aimed at increasing insulin sensitivity (trough reduction of refined sugars and saturated fats from meat and dairy products), the ratio between n-3 and n-6 fatty acids (e.g. from fish and respectively seed oils), antioxidant vitamins, folic acid, vitamin B6, phytoestrogens (vegetables, whole cereals, and legumes, including soy products), vitamin B12 (bivalve molluscs, liver), and Cr, K, Mg, and Si salts. This comprehensive improvement of diet would fit with all the mechanistic hypotheses cited above. Several studies, on the contrary, are presently exploring monofactorial preventive strategies with specific vitamin supplementation or hormonal drugs, without, however, appreciable results.

  7. Does prevention for Alzheimer's disease exist?

    OpenAIRE

    Sonia Maria Dozzi Brucki

    2009-01-01

    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 ...

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

    Science.gov (United States)

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

    2017-01-14

    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.

  9. Molecular imaging of Alzheimer disease pathology.

    Science.gov (United States)

    Kantarci, K

    2014-06-01

    Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents. © 2014 by American Journal of Neuroradiology.

  10. A novel presenilin 1 mutation (L174M) in a large Cuban family with early onset Alzheimer disease.

    NARCIS (Netherlands)

    B. Marcheco Teruel; J.J. Llibre Rodriguez; N. Gomez Viera; I. Borrajero Martinez; E.A.W.F.M. Severijnen (Lies-Anne); M. Joosse (Marijke); C.M. van Duijn (Cock); L. Heredero-Baute; P. Heutink (Peter); A.M. Bertoli Avella (Aida)

    2002-01-01

    textabstractWe studied a Cuban family with presenile dementia (autosomal dominant) consisting of 281 members within six generations, the proband descended from a Spanish founder. Mean age at onset was 59 years of age. Memory impairment was the main symptom in all patients, additionally, ischemic epi

  11. Electroencephalographic rhythms in Alzheimer's disease.

    Science.gov (United States)

    Lizio, Roberta; Vecchio, Fabrizio; Frisoni, Giovanni B; Ferri, Raffaele; Rodriguez, Guido; Babiloni, Claudio

    2011-01-01

    Physiological brain aging is characterized by synapses loss and neurodegeneration that slowly lead to an age-related decline of cognition. Neural/synaptic redundancy and plastic remodelling of brain networking, also due to mental and physical training, promotes maintenance of brain activity in healthy elderly subjects for everyday life and good social behaviour and intellectual capabilities. However, age is the major risk factor for most common neurodegenerative disorders that impact on cognition, like Alzheimer's disease (AD). Brain electromagnetic activity is a feature of neuronal network function in various brain regions. Modern neurophysiological techniques, such as electroencephalography (EEG) and event-related potentials (ERPs), are useful tools in the investigation of brain cognitive function in normal and pathological aging with an excellent time resolution. These techniques can index normal and abnormal brain aging analysis of corticocortical connectivity and neuronal synchronization of rhythmic oscillations at various frequencies. The present review suggests that discrimination between physiological and pathological brain aging clearly emerges at the group level, with suggested applications also at the level of single individual. The possibility of combining the use of EEG together with biological/neuropsychological markers and structural/functional imaging is promising for a low-cost, non-invasive, and widely available assessment of groups of individuals at-risk.

  12. Inductive reasoning in Alzheimer's disease.

    Science.gov (United States)

    Smith, E E; Rhee, J; Dennis, K; Grossman, M

    2001-12-01

    We evaluated knowledge of basic level and superordinate semantic relations and the role of cognitive resources during inductive reasoning in probable Alzheimer's disease (AD). Nineteen mildly demented AD patients and 17 healthy control subjects judged the truthfulness of arguments with a premise and a conclusion that contain familiar concepts coupled with "blank" predicates, such as "Spiders contain phosphatidylcholine; therefore all insects contain phosphatidylcholine." Like healthy control subjects, AD patients were relatively insensitive to the typicality of the premise category when judging the strength of arguments with a conclusion containing a basic-level concept, but were relatively sensitive to typicality during judgments of arguments containing a superordinate in the conclusion. Moreover, AD patients resembled control subjects in judging arguments with an immediate superordinate in the conclusion compared to arguments with a distant superordinate. AD patients differed from control subjects because they could not take advantage of two premises in an argument containing basic-level concepts. We conclude that semantic knowledge is sufficiently preserved in AD to support inductive reasoning, but that limited cognitive resources may interfere with AD patients' ability to consider the entire spectrum of information available during semantic challenges.

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Almost two-thirds of Americans with Alzheimer's are women. African-Americans are about twice as likely to ... 1 billion. Approximately two-thirds of caregivers are women, and 34 percent are age 65 or older. ...

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... with third parties. Please read our security and privacy policy . Plan ahead Get help and support I ... About Us | News | Events | Press | About this Site | Privacy Policy | Copyrights & Reprints | Contact Us National Headquarters Alzheimer's ...

  15. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... individuals are under age 65 and have younger-onset Alzheimer's. One in 10 people age 65 and ... Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable ...

  16. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... quarter of dementia caregivers are "sandwich generation" caregivers — meaning that they care not only for an aging ... expected to be $56 billion. Health care costs increase with the presence of dementia. People with Alzheimer's ...

  17. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Almost two-thirds of Americans with Alzheimer's are women. African-Americans are about twice as likely to ... 1 billion. Approximately two-thirds of caregivers are women, and 34 percent are age 65 or older. ...

  18. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... third parties. Please read our security and privacy policy . Plan ahead Get help and support I have ... Us | News | Events | Press | About this Site | Privacy Policy | Copyrights & Reprints | Contact Us National Headquarters Alzheimer's Association ...

  19. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... to those with Alzheimer's and other dementias, a contribution to the nation valued at $230.1 billion. ... NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures ...

  20. [Advances in the diagnostics of Alzheimer's disease].

    Science.gov (United States)

    Fiedler, U; Wiltfang, J; Peters, N; Benninghoff, J

    2012-05-01

    Due to the demographic developments, diagnosis and treatment, dementia constitutes an increasing medical challenge and is likely to have an increasing socioeconomic impact. Dementia does not reflect a single disease but encompasses a variety of underlying conditions, heterogeneous clinical courses and therapeutic approaches, among which Alzheimer's disease represents the most common cause. Therefore, a thorough differential diagnosis of dementia is of major importance. To date the current diagnosis of dementia according to ICD-10/DMS-IV is based on clinical criteria. In addition, the concept of mild cognitive impairment comprises early cognitive dysfunction without clinically apparent dementia. Alzheimer's disease is more and more conceptualized as a disease continuum with mild cognitive impairment as an early and manifest dementia as the later stage of the disease. This review gives an overview on the current diagnostic approaches and the proposed revisions of diagnostic and research criteria for Alzheimer's disease.

  1. Familial Alzheimer's Disease Lymphocytes Respond Differently Than Sporadic Cells to Oxidative Stress: Upregulated p53-p21 Signaling Linked with Presenilin 1 Mutants.

    Science.gov (United States)

    Wojsiat, Joanna; Laskowska-Kaszub, Katarzyna; Alquézar, Carolina; Białopiotrowicz, Emilia; Esteras, Noemi; Zdioruk, Mykola; Martin-Requero, Angeles; Wojda, Urszula

    2016-09-19

    Familial (FAD) and sporadic (SAD) Alzheimer's disease do not share all pathomechanisms, but knowledge on their molecular differences is limited. We previously reported that cell cycle control distinguishes lymphocytes from SAD and FAD patients. Significant differences were found in p21 levels of SAD compared to FAD lymphocytes. Since p21 can also regulate apoptosis, the aim of this study was to compare the response of FAD and SAD lymphocytes to oxidative stress like 2-deoxy-D-ribose (2dRib) treatment and to investigate the role of p21 levels in this response. We report that FAD cells bearing seven different PS1 mutations are more resistant to 2dRib-induced cell death than control or SAD cells: FAD cells showed a lower apoptosis rate and a lower depolarization of the mitochondrial membrane. Despite that basal p21 cellular content was lower in FAD than in SAD cells, in response to 2dRib, p21 mRNA and protein levels significantly increased in FAD cells. Moreover, we found a higher cytosolic accumulation of p21 in FAD cells. The transcriptional activation of p21 was shown to be dependent on p53, as it can be blocked by PFT-α, and correlated with the increased phosphorylation of p53 at Serine 15. Our results suggest that in FAD lymphocytes, the p53-mediated increase in p21 transcription, together with a shift in the nucleocytoplasmic localization of p21, confers a survival advantage against 2dRib-induced apoptosis. This compensatory mechanism is absent in SAD cells. Thus, therapeutic and diagnostic designs should take into account possible differential apoptotic responses in SAD versus FAD cells.

  2. Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer's Disease Mice

    Institute of Scientific and Technical Information of China (English)

    Hui Shen; Xiao-Dong Pan; Jing Zhang; Yu-Qi Zeng; Meng Zhou; Lu-Meng Yang; Bing Ye

    2016-01-01

    Background:Amyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression ofAlzheimer's disease (AD).However,the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated.Methods:The five familial AD (5 ×FAD) mice and wild-type (WT) mice aged 2,7,and 12 months were used in the present study.Morris water maze test was used to evaluate their cognitive performance.Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway.Results:Compared with age-matched WT mice,5 ×FAD mice showed higher cleaved caspase-3,lower neuron-positive staining at the age of 12 months,but earlier cognitive deficit at the age of 7 months (all P < 0.05).Interestingly,for 2-month-old 5×FAD mice,the related proteins involved in the ERS-associated UPR pathway,including CHOP,cleaved caspase-12,GRP 78,and SYVN1,were significantly increased when compared with those in age-matched WT mice (all P < 0.05).Moreover,ERS occurred mainly in neurons,not in astrocytes.Conclusions:These findings suggest that compared with those of age-matched WT mice,ERS-associated pro-apoptotic and anti-apoptoticproteins are upregulated in 2-month-old 5×FAD mice,consistent with intracellular Aβ aggregation in neurons.

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

    DEFF Research Database (Denmark)

    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: Sev...

  4. Oxidative stress and Alzheimer disease.

    Science.gov (United States)

    Christen, Y

    2000-02-01

    Research in the field of molecular biology has helped to provide a better understanding of both the cascade of biochemical events that occurs with Alzheimer disease (AD) and the heterogeneous nature of the disease. One hypothesis that accounts for both the heterogeneous nature of AD and the fact that aging is the most obvious risk factor is that free radicals are involved. The probability of this involvement is supported by the fact that neurons are extremely sensitive to attacks by destructive free radicals. Furthermore, lesions are present in the brains of AD patients that are typically associated with attacks by free radicals (eg, damage to DNA, protein oxidation, lipid peroxidation, and advanced glycosylation end products), and metals (eg, iron, copper, zinc, and aluminum) are present that have catalytic activity that produce free radicals. beta-Amyloid is aggregated and produces more free radicals in the presence of free radicals; beta-amyloid toxicity is eliminated by free radical scavengers. Apolipoprotein E is subject to attacks by free radicals, and apolipoprotein E peroxidation has been correlated with AD. In contrast, apolipoprotein E can act as a free radical scavenger and this behavior is isoform dependent. AD has been linked to mitochondrial anomalies affecting cytochrome-c oxidase, and these anomalies may contribute to the abnormal production of free radicals. Finally, many free radical scavengers (eg, vitamin E, selegeline, and Ginkgo biloba extract EGb 761) have produced promising results in relation to AD, as has desferrioxamine-an iron-chelating agent-and antiinflammatory drugs and estrogens, which also have an antioxidant effect.

  5. A Survey of TCM Treatment for Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Alzheimer's disease (AD) is a disorder in the aged people, characterized by irreversible and progressive degeneration of the intelligence, memory, ability of orientation, judgment, speech and thinking. It is often accompanied with character changes. Statistical data show that 5%-15% of the old people suffer from mild to severe symptoms of dementia, which becomes a burden to their families and the society. The following is a survey of TCM treatment for the disease.

  6. The infectious etiology of Alzheimer's Disease.

    Science.gov (United States)

    Sochocka, Marta; Zwolińska, Katarzyna; Leszek, Jerzy

    2017-03-13

    Inflammation is a part of the first line of defense of the body against invasive pathogens, and plays a crucial role in tissue regeneration and repair. A proper inflammatory response ensures the suitable resolution of inflammation and elimination of harmful stimuli, but when the inflammatory reactions are inappropriate it can lead to damage of the surrounding normal cells. The relationship between infections and Alzheimer's Disease (AD) etiology, especially late-onset AD (LOAD) has been continuously debated over the past three decades. It is suggested that chronic viral, bacterial and fungal infections might be causative factors for the inflammatory pathway for AD. Emerging evidence supports the hypothesis of the role of neurotropic viruses from the Herpesviridae family, especially Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), and Human herpesvirus 2 (HHV-2), in AD neuropathology. Recent investigations also indicate the association between Hepatitis C virus (HCV) infection and dementia. Among bacteria special attention is focused on spirochetes family and on periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola that could cause chronic periodontitis and possibly contribute to the clinical onset of AD. This review discusses whether infections could be a causative factor that promotes the progression of AD and summarizes recent investigations associating infectious agents and chronic inflammation with AD. Preventive and therapeutic approaches to AD in the context of an infectious etiology of the disease are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Stem cell treatment for Alzheimer's disease.

    Science.gov (United States)

    Li, Ming; Guo, Kequan; Ikehara, Susumu

    2014-10-23

    Alzheimer's disease (AD) is a progressive and neurodegenerative disorder that induces dementia in older people. It was first reported in 1907 by Alois Alzheimer, who characterized the disease as causing memory loss and cognitive impairment. Pathologic characteristics of AD are β-amyloid plaques, neurofibrillary tangles and neurodegeneration. Current therapies only target the relief of symptoms using various drugs, and do not cure the disease. Recently, stem cell therapy has been shown to be a potential approach to various diseases, including neurodegenerative disorders, and in this review, we focus on stem cell therapies for AD.

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

    Science.gov (United States)

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

    2017-05-23

    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.

  9. 'Clinical trials in Alzheimer's disease': immunotherapy approaches.

    Science.gov (United States)

    Delrieu, Julien; Ousset, Pierre Jean; Caillaud, Céline; Vellas, Bruno

    2012-01-01

    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 (Aβ) peptide represents an important molecular target for intervention in Alzheimer's disease. Several types of Aβ peptide immunotherapy for Alzheimer's disease are under investigation, direct immunization with synthetic intact Aβ(42) , active immunization involving the administration of synthetic fragments of Aβ peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against Aβ peptide. Pre-clinical studies showed that immunization against Aβ peptide can provide protection and reversal of the pathology of Alzheimer's disease in animal models. Indeed, several adverse events have been described like meningoencephalitis with AN1792, vasogenic edema and microhemorrhages with bapineuzumab. 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 Aβ peptide immunotherapy approaches are under investigation but also against tau pathology. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  10. Biomarkers for early detection of Alzheimer disease.

    Science.gov (United States)

    Barber, Robert C

    2010-09-01

    The existence of an effective biomarker for early detection of Alzheimer disease would facilitate improved diagnosis and stimulate therapeutic trials. Multidisciplinary clinical diagnosis of Alzheimer disease is time consuming and expensive and relies on experts who are rarely available outside of specialty clinics. Thus, many patients do not receive proper diagnosis until the disease has progressed beyond stages in which treatments are maximally effective. In the clinical trial setting, rapid, cost-effective screening of patients for Alzheimer disease is of paramount importance for the development of new treatments. Neuroimaging of cortical amyloid burden and volumetric changes in the brain and assessment of protein concentrations (eg, β-amyloid 1-42, total tau, phosphorylated tau) in cerebrospinal fluid are diagnostic tools that are not widely available. Known genetic markers do not provide sufficient discriminatory power between different forms of dementia to be useful in isolation. Recent studies using panels of biomarkers for diagnosis of Alzheimer disease or mild cognitive impairment have been promising, though no such studies have been cross-validated in independent samples of subjects. The ideal biomarker enabling early detection of Alzheimer disease has not yet been identified.

  11. Imaging markers for Alzheimer disease

    Science.gov (United States)

    Bocchetta, Martina; Chételat, Gael; Rabinovici, Gil D.; de Leon, Mony J.; Kaye, Jeffrey; Reiman, Eric M.; Scheltens, Philip; Barkhof, Frederik; Black, Sandra E.; Brooks, David J.; Carrillo, Maria C.; Fox, Nick C.; Herholz, Karl; Nordberg, Agneta; Jack, Clifford R.; Jagust, William J.; Johnson, Keith A.; Rowe, Christopher C.; Sperling, Reisa A.; Thies, William; Wahlund, Lars-Olof; Weiner, Michael W.; Pasqualetti, Patrizio; DeCarli, Charles

    2013-01-01

    Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, 18F-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured (“metric”: visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR+ and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR+ and 16% and 24% of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR−. Within markers, the largest proportion of diagnostic LR+ and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials. PMID:23897875

  12. [Creative work of painters with Alzheimer's disease].

    Science.gov (United States)

    Marcus, Esther-Lee; Kaufman, Yakir; Cohen-Shalev, Amir

    2009-08-01

    Alzheimer's disease is characterized by progressive cognitive and functional decline. Recently, there have been reports in the medical literature on artists who continued to paint while suffering from Alzheimer's. This article describes the changes that occurred in the work of three artists who suffered from Alzheimer's: William Utermohlen, Carolus Horn and Willem de Kooning. In the case of William Utermohlen (1935-2007), Alzheimer's disease was diagnosed at the age of 61. A series of 15 self-portraits that he painted during the years he suffered from Alzheimer's disease provide a rare opportunity to look into the world of an Alzheimer's patient, and testifies to sustained motivation to create, despite severe cognitive impairment. Although Utermohlen's portraits show distortions in proportion and defects in spatial organization that became more evident as the disease progressed, the portraits are characterized by an extraordinary ability to express emotion, as well as by originality: each is a new piece of work, not an attempt to copy a previous painting. Carolus Horn (1921-1992) was diagnosed with Alzheimer's disease at the age of 58. In Horn's paintings, from the time he was diagnosed, there is evidence of distortion in perspective, "primitive" style, lack of individual characteristics in depicting his subjects, more schematic drawing, and a preference for using reds and yellows. In the most advanced stage of the disease Horn was only able to scribble. Despite his cognitive and functional limitations, Horn continued to draw daily, even in the advanced stages of his illness, until shortly before his death. Willem de Kooning's (1904-1997) Alzheimer's was diagnosed in his late eighties. During the following years, he painted more than 300 abstract paintings, which art critics assess as among the finest and most sensitive artistic achievements in contemporary painting. Despite cognitive limitations, de Kooning was able to muster the concentration to continue painting

  13. Geriatric Dentistry and the Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Marcelo Coelho GOIATO

    2006-08-01

    Full Text Available Introduction: The world population is getting old, mainly in countries in development like Brazil. So, the number of pathologies, which appears in the elderly, will happen in a higher frequency. Among these diseases, we can point Alzheimer, an irreversible dementia, that has been related to age, cerebral vascular disease, stroke, immunological defects and to genetic factors (Down Syndrome. It is known that with the progression of dementia, patients present difficulties of oral hygiene caused by decrease of motor and cognitive functions of Alzheimer's bearers. These patients demand specific strategies for a dental treatment without bigger difficulties. Objective: the aim of this paper was to review the articles about the relationship of geriatric dentistry and Alzheimer disease focusing and the characteristics of the patients with this kind of dementia and the cares to them. For this purpose, a peer-reviewed literature was completed using Medline database for the period from 1972 to 2006, including alzheimer disease and dentistry, and BBO for the period from 1987 to 2004, with geriatric keyword. Conclusion: The available data indicate that individuals with Alzheimer disease have more oral health problems than individuals without dementia.

  14. 家庭干预模式在早期阿尔茨海默病患者家庭中应用的效果评价%Application effect of family intervention model in early Alzheimer's disease patients' family

    Institute of Scientific and Technical Information of China (English)

    张瑞芬; 沈丽珍; 姜俊香

    2013-01-01

    Objective To investigate the impact of Friedman family intervention model on the personal life ability and psychological status of caregivers of early Alzheimer's disease patients.Methods 66 Alzheimer's disease patients,according to the random sequence,were divided into the study group and the control group with 33 patients in each group respectively.The control group received routine geriatric care,the study group was given Friedman family intervention model on the basis of routine geriatric care.Two groups were estimated with Life Scale Index and ADL before intervention and two months after intervention respectively,and the matching caregiver were evaluated with Symptom Checklist-90 (SCL-90).Results Compared with the control group,the quality of daily life after the intervention of the study group was significantly improved,and the differences of daily living skills between two groups were statistically significant.The differences of the SCL-90 total score and depression,anxiety,somatization,interpersonal factor scores of caregivers between the two groups were statistically significant after two months of intervention.Conclusions The application of Friedman family intervention model plays a significant role in the improvement of the quality of daily life and daily living skills in patients with Alzheimer's disease,and can improve the psychological status of the caregivers of AD patients.%目的 探讨Friedman家庭干预模式对早期阿尔茨海默病患者的个人生活能力及照料者心理状况的影响.方法 选择阿尔茨海默病患者66例,按随机原则分为研究组和对照组各33例.对照组采用老年科常规护理,研究组在此基础上运用Friedman家庭干预模式进行护理.2组分别在于预前和干预2个月后采用生活质量指数评定量表及日常生活能力量表评定效果,同时采用症状自评量表(SCL-90)对配对的照料者进行评定.结果 研究组在干预后生活质量明显改善,且日常生活

  15. A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Cheng Sheung-Tak

    2012-07-01

    Full Text Available Abstract Background Caregivers of relatives with Alzheimer’s disease are highly stressed and at risk for physical and psychiatric conditions. Interventions are usually focused on providing caregivers with knowledge of dementia, skills, and/or support, to help them cope with the stress. This model, though true to a certain extent, ignores how caregiver stress is construed in the first place. Besides burden, caregivers also report rewards, uplifts, and gains, such as a sense of purpose and personal growth. Finding benefits through positive reappraisal may offset the effect of caregiving on caregiver outcomes. Design Two randomized controlled trials are planned. They are essentially the same except that Trial 1 is a cluster trial (that is, randomization based on groups of participants whereas in Trial 2, randomization is based on individuals. Participants are randomized into three groups - benefit finding, psychoeducation, and simplified psychoeducation. Participants in each group receive a total of approximately 12 hours of training either in group or individually at home. Booster sessions are provided at around 14 months after the initial treatment. The primary outcomes are caregiver stress (subjective burden, role overload, and cortisol, perceived benefits, subjective health, psychological well-being, and depression. The secondary outcomes are caregiver coping, and behavioral problems and functional impairment of the care-recipient. Outcome measures are obtained at baseline, post-treatment (2 months, and 6, 12, 18 and 30 months. Discussion The emphasis on benefits, rather than losses and difficulties, provides a new dimension to the way interventions for caregivers can be conceptualized and delivered. By focusing on the positive, caregivers may be empowered to sustain caregiving efforts in the long term despite the day-to-day challenges. The two parallel trials will provide an assessment of whether the effectiveness of the intervention

  16. Ethical issues in Alzheimer's disease: an overview.

    Science.gov (United States)

    Leuzy, Antoine; Gauthier, Serge

    2012-05-01

    Alzheimer's disease (AD) accounts for the majority of dementia cases and leaves clinicians, patients, family members, caregivers, and researchers faced with numerous ethical issues that vary and evolve as a function of disease stage and severity. While the disclosure of a diagnosis of AD dementia is difficult enough, advances in the neurobiology of AD--embodied in the recent revisions to the AD diagnostic guidelines--have translated into an increasing shift toward the diagnosis being made in its pre-dementia stages, when patients have full insight into their prognosis. Genetic issues in AD are significant in the case of rare families with an early onset (before age 65) form of the disease, owing to the presence of deterministic mutations. While genetic testing for the apolipoprotein E (APOE) gene--a risk factor for sporadic AD--is widely debated, it may become necessary in the context of novel disease-modifying drugs. The current symptomatic drugs--cholinesterase inhibitors (CIs) and the NMDA receptor antagonist memantine--are relatively simple to use but their access is limited in many countries by economic considerations and therapeutic nihilism. Although their efficacy is modest, they influence the design of protocols for new drugs since placebo treatment in clinical trials involving patients with established dementia is rarely allowed beyond 3 months. Driving privileges are lost in the moderate stages of dementia, with this decision ideally reached using a standardized assessment algorithm. Physical restraints are still overused in moderate-to-severe stages, but the alternative non-pharmacological therapies and caregiver training programs are not yet fully validated using randomized studies. End-of-life care is slowly moving towards a palliative care approach similar to that for end-stage cancer. There will be new drugs in the near future, some of which will delay progression from prodromal stages to dementia, but their use will require careful stopping rules.

  17. 75 FR 67899 - National Alzheimer's Disease Awareness Month, 2010

    Science.gov (United States)

    2010-11-04

    ... terrible disease. As we continue our fight against Alzheimer's disease, we must seek new ways to prevent... and attention to those facing Alzheimer's disease. Until we find more effective treatments and a cure... Documents#0;#0; ] Proclamation 8591 of October 29, 2010 National Alzheimer's Disease Awareness Month,...

  18. Looking for Signs of Alzheimer's Disease

    Science.gov (United States)

    Hodgson, Lynne Gershenson; Cutler, Stephen J.

    2003-01-01

    This study examined the correlates of symptom-seeking behavior for Alzheimer's disease (AD) among middle-aged persons. Symptom seeking, the tendency to search for signs of disease, is one manifestation of an individual's concern about developing AD. The data were obtained from a survey of two subsamples of 40-60 year old adults: 1) 108 adult…

  19. Neuroinflammation in Alzheimer's disease wanes with age

    NARCIS (Netherlands)

    Hoozemans, J.J.M.; Rozemuller, A.J.M.; van Haastert, E.S.; Eikelenboom, P.; van Gool, W.A.

    2011-01-01

    ABSTRACT: BACKGROUND: Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between

  20. Therapeutic potential of resveratrol in Alzheimer's disease

    OpenAIRE

    Vingtdeux, Valérie; Dreses-Werringloer, Ute; Zhao, Haitian; Davies, Peter; Marambaud, Philippe

    2008-01-01

    Several epidemiological studies indicate that moderate consumption of red wine is associated with a lower incidence of dementia and Alzheimer's disease. Red wine is enriched in antioxidant polyphenols with potential neuroprotective activities. Despite scepticism concerning the bioavailability of these polyphenols, in vivo data have clearly demonstrated the neuroprotective properties of the naturally occurring polyphenol resveratrol in rodent models for stress and diseases. Furthermore, recent...

  1. Llama VHH as immunotherapeutics in Alzheimer's disease

    NARCIS (Netherlands)

    Dorresteijn, B.

    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 reversi

  2. 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.

  3. Is Alzheimer's disease a homogeneous disease entity?

    Science.gov (United States)

    Korczyn, Amos D

    2013-10-01

    The epidemic proportions of dementia in old age are a cause of great concern for the medical profession and the society at large. It is customary to consider Alzheimer's disease (AD) as the most common cause of dementia, and vascular dementia (VaD) as being the second. This dichotomous view of a primary neurodegenerative disease as opposed to a disorder where extrinsic factors cause brain damage led to separate lines of research in these two entities. New biomarkers, particularly the introduction of modern neuroimaging and cerebrospinal fluid changes, have, in recent years, helped to identify anatomical and chemical changes of VaD and of AD. Nevertheless, there is a substantial difference between the two entities. While it is clear that VaD is a heterogeneous entity, AD is supposed to be a single disorder. Nobody attempts to use CADASIL as a template to develops treatment for sporadic VaD. On the other hand, early-onset AD is used to develop therapy for sporadic AD. This paper will discuss the problems relating to this false concept and its consequences.

  4. How Can Music Help People Who Have Alzheimer's Disease?

    Science.gov (United States)

    ... help? How can music help people who have Alzheimer's disease? Answers from Jonathan Graff-Radford, M.D. Research ... provide emotional and behavioral benefits for people with Alzheimer's disease and other types of dementia. Musical memories are ...

  5. PIN1 gene variants in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Siedlecki Janusz

    2009-11-01

    Full Text Available Abstract Background Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1 plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk. Methods We performed analysis of coding and promoter regions of PIN1 in early- and late-onset AD and frontotemporal dementia (FTD patients in comparison with healthy controls. Results Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk. In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C>T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed. Conclusion Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.

  6. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qi Chen

    Full Text Available Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD, the focus is the amyloid beta peptide (Aß that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.

  7. Alzheimer's disease modeling: ups, downs, and perspectives for human induced pluripotent stem cells.

    Science.gov (United States)

    Wojda, Urszula; Kuznicki, Jacek

    2013-01-01

    Major breakthroughs are required to win the war against the increasing threat of Alzheimer's disease. Until now, however, despite enormous efforts and funds, effective therapies are lacking, and adequate models for drug validation are still unavailable. In this article, we review the available animal and cellular models of different features of human Alzheimer's disease and critically evaluate their usefulness for understanding the mechanisms of the disease. The majority of the presently used models are based on the amyloid-β and hyperphosphorylated tau hypothesis, which resembles features of familial Alzheimer's disease. Unfortunately, these models offer limited help for understanding the pathomechanisms of the early stages of sporadic Alzheimer's disease. Thus, new models are needed to discover ways to treat or delay the onset of Alzheimer's disease, and we discuss the prospects for such desperately needed models, including human induced pluripotent stem cells and in silico brain models.

  8. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study.

    Science.gov (United States)

    Acosta-Baena, Natalia; Sepulveda-Falla, Diego; Lopera-Gómez, Carlos Mario; Jaramillo-Elorza, Mario César; Moreno, Sonia; Aguirre-Acevedo, Daniel Camilo; Saldarriaga, Amanda; Lopera, Francisco

    2011-03-01

    Mild cognitive impairment (MCI) and pre-MCI have been proposed as stages preceding Alzheimer's disease (AD) dementia. We assessed descendants of individuals with a mutation in presenilin 1 (PSEN1) that causes familial AD, with the aim of identifying distinct stages of clinical progression to AD dementia. We retrospectively studied a cohort of descendants of carriers of the PSEN1 E280A mutation. Pre-dementia cognitive impairment was defined by a score 2 SD away from normal values in objective cognitive tests, and was subdivided as follows: asymptomatic pre-MCI was defined by an absence of memory complaints and no effect on activities of daily living; symptomatic pre-MCI was defined by a score on the subjective memory complaints checklist higher than the mean and no effect on activities of daily living; and MCI was defined by a score on the subjective memory complaints checklist higher than the mean, with no effect on basic activities of daily living and little or no effect on complex daily activities. Dementia was defined according to the diagnostic and statistical manual of mental disorders, fourth edition. Reference mean scores were those of participants who did not carry the PSEN1 E280A mutation. We used the Turnbull survival analysis method to identify ages at onset of each stage of the disease. We measured the time from birth until onset of the three pre-dementia stages, dementia, and death, and assessed decline in cognitive domains for each stage. Follow-up was from Jan 1, 1995, to Jan 27, 2010. 1784 patients were initially identified, 449 of whom were PSEN1 E280A carriers who had complete clinical follow-up. Median age at onset was 35 years (95% CI 30-36) for asymptomatic pre-MCI, 38 years (37-40) for symptomatic pre-MCI, 44 years (43-45) for MCI, and 49 years (49-50) for dementia. The median age at death was 59 years (95% CI 58-61). The median time of progression from asymptomatic to symptomatic pre-MCI was 4 years (95% CI 2-8), from symptomatic pre-MCI to

  9. 78 FR 66611 - National Alzheimer's Disease Awareness Month, 2013

    Science.gov (United States)

    2013-11-05

    ... Documents#0;#0; ] Proclamation 9050 of October 31, 2013 National Alzheimer's Disease Awareness Month, 2013 By the President of the United States of America A Proclamation Alzheimer's disease is an... younger Americans with early-onset Alzheimer's disease. This month, we stand with everyone confronting the...

  10. 77 FR 66519 - National Alzheimer's Disease Awareness Month, 2012

    Science.gov (United States)

    2012-11-06

    ... Documents#0;#0; ] Proclamation 8897 of November 1, 2012 National Alzheimer's Disease Awareness Month, 2012... country confront the tragic realities of Alzheimer's disease--an irreversible, fatal illness that robs men... Americans grows in the coming years, Alzheimer's disease will continue to pose serious risks to our well...

  11. 阿尔茨海默病家庭负担影响因素分析%Study on factors associated with family burden of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    翟俊伟; 王晓成; 王晶莹; 宋泽婧; 余红梅

    2015-01-01

    Objective To understand the family burden of Alzheimer' s disease (AD) and associated factors.Methods The subjects were 168 caregivers of patients with AD selected from two class 3A hospitals and three communities in Taiyuan through cluster sampling.The data were collected by using the Caregiver Burden Inventory (CBI) and the Family Burden Scale (FBS) of diseases.Path analysis was applied to identify the factors associated with the total score of CBI.T-test and One-way analysis of variance were applied to identify the factors associated with the total score of FBS.Multiple linear regression analysis was applied to identify the factors associated with family burden of AD.Results The total score of the caregivers' burden was 52.41 ± 17.07.AD patients' cognitive function had direct (standardized β =-0.280,P<0.001) and indirect effect on CBI;while daily performance of AD patients had indirect effect on CBI.The total score of family burden was 16.23 ± 9.00.Univariate analysis showed that the sex,age,education level,cognitive function,daily performance,mental status,depression and dementia rating of AD patients might affect the total score of FBS (P < 0.05).Multivariate analysis showed that the factors which affected the total score of FBS included the sex (standardizedβ =0.280,P < 0.01),cognitive function (standardizedβ =-0.158,P =0.033) and daily performance of AD patients (standardizedβ=-0.155,P=0.039).Conclusion The caregiver and family burden of AD was mainly associated with the cognitive function and daily performance of AD patients.It is necessary to take targeted measures to reduce the caregiver and family burden of AD.%目的 探讨阿尔茨海默病(AD)家庭生活负担及其影响因素.方法 采用整群抽样方法,选择太原市2家三甲医院及3个社区168例已确诊AD患者的照料者为研究对象,通过照料者负担量表(CBI)和家庭负担量表(FBS)收集信息.路径分析探讨照料者负担影响因素,家庭负担总分

  12. 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...

  13. Absence of consensus in diagnostic criteria for familial neurodegenerative diseases.

    LENUS (Irish Health Repository)

    Byrne, Susan

    2012-04-01

    A small proportion of cases seen in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), Parkinson\\'s disease and Alzheimer disease are familial. These familial cases are usually clinically indistinguishable from sporadic cases. Identifying familial cases is important both in terms of clinical guidance for family members and for gene discovery.

  14. 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.

  15. Alzheimer's disease: analyzing the missing heritability.

    Directory of Open Access Journals (Sweden)

    Perry G Ridge

    Full Text Available Alzheimer's disease (AD is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer's Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease.

  16. Aripiprazole in the treatment of Alzheimer's disease

    NARCIS (Netherlands)

    De Deyn, P.P.; Drenth, Annemieke F. J.; Kremer, B.P.; Oude Voshaar, R.C.; Van Dam, D.

    2013-01-01

    Introduction: Psychosis is a common and difficult to treat symptom in Alzheimer's disease (AD). It is a cause of diminished quality of life and care-giver distress. Atypical antipsychotics are frequently used for the treatment of dementia-related psychosis, despite FDA warnings because of increased

  17. Aripiprazole in the treatment of Alzheimer's disease

    NARCIS (Netherlands)

    Deyn, P.P. de; Drenth, A.F.; Kremer, B.; Oude Voshaar, R.C.; Dam, D. Van

    2013-01-01

    INTRODUCTION: Psychosis is a common and difficult to treat symptom in Alzheimer's disease (AD). It is a cause of diminished quality of life and caregiver distress. Atypical antipsychotics are frequently used for the treatment of dementia-related psychosis, despite FDA warnings because of increased m

  18. Early psychosocial intervention in Alzheimer's disease

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Sørensen, Jan; Waldorff, Frans B

    2014-01-01

    OBJECTIVE: To assess the cost utility of early psychosocial intervention for patients with Alzheimer's disease and their primary caregivers. DESIGN: Cost utility evaluation alongside a multicentre, randomised controlled trial with 3 years of follow-up. SETTING: Primary care and memory clinics...

  19. Astroglial calcium signalling in Alzheimer's disease

    OpenAIRE

    Verkhratsky, Alexej; Rodríguez-Arellano, José J.; Parpura, Vladimir; Zorec, Robert

    2017-01-01

    Neuroglial contribution to Alzheimer's disease (AD) is pathologically relevant and highly heterogeneous. Reactive astrogliosis and activation of microglia contribute to neuroinflammation, whereas astroglial and oligodendroglial atrophy affect synaptic transmission and underlie the overall disruption of the central nervous system (CNS) connectome. Astroglial function is tightly integrated with the intracellular ionic signalling mediated by complex dynamics of cytosolic concentrations of free C...

  20. Atorvastatin attenuates oxidative stress in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Cai Zhiyou; Yan Yong; Wang Yonglong

    2008-01-01

    Objective: To investigate serum level of SOD, MDA, ox-LDL, AchE and Ach in AD, to study atorvastatin influence on serum level of SOD, MDA, ox-LDL, AchE and Acb in AD and its neuroprotection mechanisms. Methods Subjects were divided into: normal blood lipid level group with Alzheimer's disease (A), higher blood lipid level group with Alzheimer's disease (AH), normal blood lipid level Alzheimer's disease group with atorvastatin treeatment (AT),higher blood lipid level Alzheimer's disease group with atorvastatin treeatment(AHT). Ox-LDL was measured by enzyme linked immunosorbent assay; SOD, MDA, ox-LDL, AchE, Ach and blood lipid level in AD was measured by biochemistry. Results: The serum level of MDA, AchE in AH group after atorvastatin treatment is lower ;The serum level of SOD, Ach in AH group is more increased than that of in A group; The serum level of ox-LDL in AH, A groups is lower than that of in A group; The dementia degree is lower after atorvastatin treatment. Conclusion: Atorvastatin can decrease serum level of MDA, AchE and ox-LDL, and increase that of SOD, Acb, and attenuate dementia symptom in AD, especially, with hyperlipemia. The hypothesis of atorvastatin neuroprotection is concluded that atorvastatin may restrain free radical reaction and retard oxidation in AD.

  1. Structural Neuroimaging in Aging and Alzheimer's Disease

    NARCIS (Netherlands)

    Vernooij, Meike W.; Smits, Marion

    2012-01-01

    The role of structural neuroimaging in the diagnosis of Alzheimer's disease (AD) is becoming increasingly important. As a consequence, a basic understanding of what are normal brain changes in aging is key to be able to recognize what is abnormal. The first part of this article discusses normal vers

  2. Alzheimer disease pharmacologic treatment and treatment research.

    Science.gov (United States)

    Schneider, Lon S

    2013-04-01

    This article reviews marketed pharmacologic treatments for Alzheimer disease as well as their efficacy, effectiveness, adverse effects, and issues involved in their use, including duration of treatment, adverse events, and controversies. Current experimental drug development, including challenges to developing successful drugs for Alzheimer disease, are also reviewed and assessed. Cholinesterase inhibitors and memantine are the available pharmacologic treatment options. They show limited clinical effects over the shorter term for some patients, mild to moderate cholinergic adverse effects in a minority of patients, and potentially underappreciated toxicity over the longer term. No subsequent experimental drug in development has been successful thus far; there has not been a new drug marketed for Alzheimer disease since 2003. Cholinesterase inhibitors and memantine are marketed for the treatment of Alzheimer disease. Drug development programs aimed at new targets, including the amyloid-β cascade, have been unsuccessful thus far despite their designs to detect very small or minimal clinical effects from the experimental drugs. Marked advances in preclinical science nevertheless support a basis for considerable optimism that effective interventions will be found soon.

  3. Normal tension glaucoma and Alzheimer disease

    DEFF Research Database (Denmark)

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

    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...

  4. 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...

  5. 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 '

  6. 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...

  7. A light therapy for treating Alzheimer's disease

    Science.gov (United States)

    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.

  8. 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

  9. Estrogen receptor beta treats Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Zhu Tian; Jia Fan; Yang Zhao; Sheng Bi; Lihui Si; Qun Liu

    2013-01-01

    In vitro studies have shown that estrogen receptor β can attenuate the cytotoxic effect of amyloid β protein on PC12 cells through the Akt pathway without estrogen stimulation. In this study, we aimed to observe the effect of estrogen receptor β in Alzheimer's disease rat models established by intraventricular injection of amyloid β protein. Estrogen receptor β lentiviral particles delivered via intraventricular injection increased Akt content in the hippocampus, decreased interleukin-1β mRNA, tumor necrosis factor α mRNA and amyloid β protein levels in the hippocampus, and improved the learning and memory capacities in Alzheimer's disease rats. Estrogen receptor β short hairpin RNA lentiviral particles delivered via intraventricular injection had none of the above impacts on Alzheimer's disease rats. These experimental findings indicate that estrogen receptor β, independent from estrogen, can reduce inflammatory reactions and amyloid β deposition in the hippocampus of Alzheimer's disease rats, and improve learning and memory capacities. This effect may be mediated through activation of the Akt pathway.

  10. [The cost of applying the Dependency Law to Alzheimer disease].

    Science.gov (United States)

    Soto-Gordoa, Myriam; Arrospide, Arantzazu; Zapiain, Ander; Aiarza, Arantza; Abecia, Luis Carlos; Mar, Javier

    2014-01-01

    To calculate the formal cost of social care for people with Alzheimer disease according to the implementation of the dependency law in Gipuzkoa (Spain). A retrospective observational study was carried out of the database of the Dependency Care Services of Gipuzkoa from 2007 to 2012, using a prevalence-based bottom-up approach. The average annual formal cost per person was €11,730. The annual population cost was €34.7 million, representing 19% of the annual expenditure corresponding to the dependency law and 29% of the total cost of Alzheimer disease. Despite the implementation of the new law, most of the burden of the disease is bourne by the family. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  11. Targeting Functional Decline in Alzheimer Disease: A Randomized Trial.

    Science.gov (United States)

    Callahan, Christopher M; Boustani, Malaz A; Schmid, Arlene A; LaMantia, Michael A; Austrom, Mary G; Miller, Douglas K; Gao, Sujuan; Ferguson, Denisha Y; Lane, Kathleen A; Hendrie, Hugh C

    2017-02-07

    Alzheimer disease results in progressive functional decline, leading to loss of independence. To determine whether collaborative care plus 2 years of home-based occupational therapy delays functional decline. Randomized, controlled clinical trial. (ClinicalTrials.gov: NCT01314950). Urban public health system. 180 community-dwelling participants with Alzheimer disease and their informal caregivers. All participants received collaborative care for dementia. Patients in the intervention group also received in-home occupational therapy delivered in 24 sessions over 2 years. The primary outcome measure was the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale (ADCS ADL); performance-based measures included the Short Physical Performance Battery (SPPB) and Short Portable Sarcopenia Measure (SPSM). At baseline, clinical characteristics did not differ significantly between groups; the mean Mini-Mental State Examination score for both groups was 19 (SD, 7). The intervention group received a median of 18 home visits from the study occupational therapists. In both groups, ADCS ADL scores declined over 24 months. At the primary end point of 24 months, ADCS ADL scores did not differ between groups (mean difference, 2.34 [95% CI, -5.27 to 9.96]). We also could not definitively demonstrate between-group differences in mean SPPB or SPSM values. The results of this trial are indeterminate and do not rule out potential clinically important effects of the intervention. The authors could not definitively demonstrate whether the addition of 2 years of in-home occupational therapy to a collaborative care management model slowed the rate of functional decline among persons with Alzheimer disease. This trial underscores the burden undertaken by caregivers as they provide care for family members with Alzheimer disease and the difficulty in slowing functional decline. National Institute on Aging.

  12. Socio-economic Aspects of Alzheimer's Disease.

    Science.gov (United States)

    Marešová, Petra; Mohelská, Hana; Dolejš, Josef; Kuča, Kamil

    2015-01-01

    Social development, better living conditions and medical advances lead to the fact that more people have the opportunity to live longer than in the past. The aging population is a characteristic feature of demographic trends in developed countries. This trend is closely linked with the issue of increasing number of diseases in old age and increasing government expenditure on health and social care. The most frequently mentioned diseases in old age include dementia. The cause may lie in all kinds of diseases, the most common are Alzheimer's disease and cerebrovascular disease. Now the care of current 35 million patients with dementia costs over $ 600 billion per year, it is approximately one percent of global Gross Domestic Product. This review discusses the recent issues and questions in the area of social and economic aspects of Alzheimer's disease. It focuses in detail on the national strategies in the approach to Alzheimer's disease, the anticipated problems concerning the insufficient number of social workers and necessary expenses of state budgets in the future. The situation in the area of health insurance companies' expenditures is illustrated in the context of the analysis of long-term care systems, in the chosen countries within the European Union.

  13. Alzheimer disease: current concepts & future directions.

    Science.gov (United States)

    Musiek, Erik S; Schindler, Suzanne E

    2013-01-01

    Alzheimer disease (AD) is the most common cause of dementia in individuals over age 65, and is expected to cause a major public health crisis as the number of older Americans rapidly expands in the next three decades. Herein, we review current strategies for diagnosis and management of AD, and discuss ongoing clinical research and future therapeutic directions in the battle against this devastating disease.

  14. New criteria for diagnosing Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Andrei Yuryevich Emelin

    2011-01-01

    Full Text Available Department of Nervous Diseases, S.M. Kirov Military Medical Academy, Saint Petersburg The paper gives an analysis of new diagnostic criteria for different stages of Alzheimer Х s disease (AD, which is proposed by the U.S. National Institute on Aging. It considers possibilities for the early diagnosis of AD, including its preclinical diagnosis using the laboratory and neuroimaging markers beta-amyloid, neuronal damage.

  15. Early molecular changes in Alzheimer disease : can we catch the disease in its presymptomatic phase?

    NARCIS (Netherlands)

    Wirz, Kerstin T S; Keitel, Stella; Swaab, Dick F; Verhaagen, J.; Bossers, K.

    2014-01-01

    Alzheimer disease (AD) is the most common form of dementia and characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles consisting of hyperphosphorylated tau, atrophy, and progressive neurodegeneration. While the familial, early onset form of AD is known to be caused by specifi

  16. 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...

  17. Alzheimer's Disease: Mechanism and Approach to Cell Therapy.

    Science.gov (United States)

    Amemori, Takashi; Jendelova, Pavla; Ruzicka, Jiri; Urdzikova, Lucia Machova; Sykova, Eva

    2015-11-04

    Alzheimer's disease (AD) is the most common form of dementia. The risk of AD increases with age. Although two of the main pathological features of AD, amyloid plaques and neurofibrillary tangles, were already recognized by Alois Alzheimer at the beginning of the 20th century, the pathogenesis of the disease remains unsettled. Therapeutic approaches targeting plaques or tangles have not yet resulted in satisfactory improvements in AD treatment. This may, in part, be due to early-onset and late-onset AD pathogenesis being underpinned by different mechanisms. Most animal models of AD are generated from gene mutations involved in early onset familial AD, accounting for only 1% of all cases, which may consequently complicate our understanding of AD mechanisms. In this article, the authors discuss the pathogenesis of AD according to the two main neuropathologies, including senescence-related mechanisms and possible treatments using stem cells, namely mesenchymal and neural stem cells.

  18. Redesigning Systems of Care for Older Adults with Alzheimer' Disease

    Science.gov (United States)

    Callahan, Christopher M.; Sachs, Greg A.; LaMantia, Michael A.; Unroe, Kathleen T.; Arling, Greg A.; Boustani, Malaz A.

    2017-01-01

    The basic principle of care for patients with Alzheimer's disease is support for a patient-caregiver dyad. Any model of care seeking to improve the quality, efficiency, or cost of care for persons with Alzheimer's disease must attend to this principle. Models of care seeking to support this dyad began with strategies focusing mainly on the family caregiver. These models have grown in complexity to encompass team-based care that seeks to coordinate care across settings and providers of care for a defined population of patients. Most Americans in most communities, however, do not have access to these best practices models. While the effectiveness of new models of care is evidence-based, there are multiple barriers to widespread adoption including workforce limitations and the cost of practice redesign. We review the origins and content of current models and describe early efforts to improve their implementation on a broader scale. PMID:24711324

  19. 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.

  20. The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Seoyoung Yoon

    2015-09-01

    Full Text Available Alzheimer's disease is an important public concern with rising prevalence across the globe. While many therapeutic approaches for Alzheimer's disease have been developed, there are currently no validated disease-modifying treatments. Thus, in order to develop novel treatment strategies, there is a significant need to progress our understanding of the pathogenesis of Alzheimer's disease. Several large genome-wide association studies and whole genome and exome sequencing studies have identified novel genes associated with late-onset Alzheimer's disease. Interestingly, many of the genes are associated with inflammation and the immune system, including complement receptor 1, clusterin, CD33, EPH receptor A1, membrane-spanning 4-domains subfamily A, ATP-binding cassette sub-family A member 7, major histocompatibility complex class II, inositol polyphosphate-5-phosphatase, myocyte enhancer factor 2C, and triggering receptor expressed on myeloid cells 2. The pathogenetic contributions of immune reaction and neuroinflammation in Alzheimer's disease have been regarded largely as part of amyloid cascade hypothesis. The neurotoxic amyloid-β (Aβ induces activation of immune cells, such as microglia, astrocytes, perivascular macrophages and lymphocytes and decreased capability of clearing Aβ by immune system and chronic inflammation caused by activated immune cells aggravate neuronal damage and eventually Alzheimer's disease. But the precise mechanism and hereditary impact on such process is largely unknown. The current findings in genetic studies suggest that the immunological mechanisms of Alzheimer's disease may extend beyond passive reaction of Aβ, including the development of Alzheimer's disease such as time of onset and rate of progression. In this article, we aimed to review the mechanisms of immune reaction and neuroinflammation in Alzheimer's disease, with an emphasis on the function of genes known to be associated with a risk of Alzheimer

  1. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    Science.gov (United States)

    2017-04-01

    focus toward identification of Alzheimer disease (AD) risk genes over the past five years has been testing the common disease common variant (CDCV...hypothesis through the use of genome-wide association studies (GWAS) in late onset Alzheimer disease (LOAD). While common variation clearly plays a role...12-25 4 INTRODUCTION: The primary focus in the identification of Alzheimer disease (AD) risk genes has focused on the common disease

  2. Alzheimer's disease due to loss of function

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2016-01-01

    Alzheimer's Disease (AD) is a highly complex disease involving a broad range of clinical, cellular, and biochemical manifestations that are currently not understood in combination. This has led to many views of AD, e.g. the amyloid, tau, presenilin, oxidative stress, and metal hypotheses....... The amyloid hypothesis has dominated the field with its assumption that buildup of pathogenic β-amyloid (Aβ) peptide causes disease. This paradigm has been criticized, yet most data suggest that Aβ plays a key role in the disease. Here, a new loss-of-function hypothesis is synthesized that accounts...

  3. Alzheimer's disease care management plan: maximizing patient care.

    Science.gov (United States)

    Treinkman, Anna

    2005-03-01

    Nurse practitioners have the potential to significantly impact the care of patients with dementia. Healthcare providers can now offer patients medications that will control symptoms and prolong functioning. As a result of ongoing contact with patients, NPs play an important role in assessing and screening patients for AD and educating the patients, families, and caregivers about the disease. Alzheimer's disease is a chronic, progressive illness that requires long-term management. Nurse practitioners should be familiar with available medications and appreciate the need to individualize therapy to maximize efficacy and minimize potential adverse drug reactions.

  4. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... deaths from the number one cause of death (heart disease) decreased 14 percent. Among people age 70, ... DISEASE: THE NEXT FRONTIER In the history of medicine, one means to progress is when we make ...

  5. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... we make the decision that our assumptions and definitions of disease are no longer consistent with the ... this disease. As research advances a biomarker-based method for diagnosis and treatment at the earliest stages ...

  6. Alzheimer's Disease at a Glance

    Science.gov (United States)

    ... R S T U V W X Y Z Alzheimer’s Disease at a Glance Researchers have explored many ... health approaches for preventing or slowing dementia, including Alzheimer’s disease. Currently, there is no strong evidence that ...

  7. 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)

  8. 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.

  9. 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.

  10. Memory and consciousness in Alzheimer's disease.

    Science.gov (United States)

    Souchay, C; Moulin, C J A

    2009-06-01

    Human memory can be split into familiarity and recollection processes which contribute to different aspects of memory function. These separate processes result in different experiential states. In this review, we examine how this dominant theoretical framework can explain the subjective experience of people with Alzheimer's disease, the profile of their memory impairments and their inability to reflect on their performance metacognitively. We conclude with a brief overview of the brain regions supporting conscious experience of memory, and propose that the memory and awareness deficits seen in Alzheimer's disease could be conceived of as a deficit in autonoetic consciousness. A future priority for research is to take these robust constructs into research programmes examining rehabilitation and pharmacological intervention.

  11. [Progress in epigenetic research on Alzheimer disease].

    Science.gov (United States)

    Yang, Nannan; Wei, Yang; Xu, Qian; Tang, Beisha

    2016-04-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder, which features mainly with memory impairment as the initial symptom of progressive loss of cognitive function. Its main pathological changes include senile plaques and neurofibrillary tangles. The pathogenesis of AD is still unclear, though it may be connected with aging, genetic factors and environmental factors. Among these, aging and environmental factors can be modified by epigenetics. In this paper, advances in the study of epigenetic mechanisms related to the pathogenesis of AD are reviewed.

  12. Neurofibrillary pathology and aluminum in Alzheimer's disease

    OpenAIRE

    Shin, R. W.; Lee, V.M.Y.; Trojanowski, J.Q.

    1995-01-01

    Since the first reports of aluminum-induced neurofibrillary degeneration in experimental animals, extensive studies have been performed to clarify the role played by aluminum in the pathogenesis of Alzheimer's disease (AD). Additional evidence implicating aluminum in AD includes elevated levels of aluminum in the AD brain, epidemiological data linking aluminum exposure to AD, and interactions between aluminum and protein components in the pathological lesions o...

  13. Preservation of musical memory in Alzheimer's disease.

    Science.gov (United States)

    Crystal, H A; Grober, E; Masur, D

    1989-12-01

    An 82 year old musician with Alzheimer's disease (AD) showed a preserved ability to play previously learned piano compositions from memory while being unable to identify the composer or titles of each work. He also showed a preserved ability to learn the new skill of mirror reading while being unable to recall or recognise new information. Both anterograde and retrograde procedural memory may be relatively spared in AD.

  14. Preservation of musical memory in Alzheimer's disease.

    OpenAIRE

    Crystal, H.A.; Grober, E; Masur, D

    1989-01-01

    An 82 year old musician with Alzheimer's disease (AD) showed a preserved ability to play previously learned piano compositions from memory while being unable to identify the composer or titles of each work. He also showed a preserved ability to learn the new skill of mirror reading while being unable to recall or recognise new information. Both anterograde and retrograde procedural memory may be relatively spared in AD.

  15. Recent advances in imaging Alzheimer's disease.

    Science.gov (United States)

    Braskie, Meredith N; Toga, Arthur W; Thompson, Paul M

    2013-01-01

    Advances in brain imaging technology in the past five years have contributed greatly to the understanding of Alzheimer's disease (AD). Here, we review recent research related to amyloid imaging, new methods for magnetic resonance imaging analyses, and statistical methods. We also review research that evaluates AD risk factors and brain imaging, in the context of AD prediction and progression. We selected a variety of illustrative studies, describing how they advanced the field and are leading AD research in promising new directions.

  16. Advances in diagnostic testing for Alzheimer disease.

    Science.gov (United States)

    Schindler, Suzanne E; McConathy, Jonathan; Ances, Beau M; Diamond, Marc I

    2013-01-01

    The diagnosis of Alzheimer disease (AD) dementia is based primarily on the clinical history and examination, but advances in understanding the pathophysiology of AD have led to new diagnostic methods. When used appropriately, the tests can provide strong positive or negative evidence AD dementia. This article described which patients may benefit from additional testing using Cerebrospinal Fluid (CSF) biomarkers, amyloid imaging, quantitative structural magnetic resonance imaging (MRI), and fluoro-deoxyglucose positron emission tomography (FDG-PET).

  17. Risk factors for Alzheimer's disease: Overview of the EURODEM collaborative re-analysis of case-control studies

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); Th. Stijnen (Theo); A. Hofman (Albert)

    1991-01-01

    textabstractStudies of risk factors for Alzheimer's disease have been hampered by low statistical power. The data from 11 case-control studies were pooled and re-analysed to evaluate the evidence for the association of Alzheimer's disease with family history of dementia and related disorders, parent

  18. Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians

    Directory of Open Access Journals (Sweden)

    D.R.S. Souza

    2003-07-01

    Full Text Available The genetic basis for dementias is complex. A common polymorphism in the apolipoprotein E (APOE gene is considered to be the major risk factor in families with sporadic and late-onset Alzheimer's disease as well as in the general population. The distribution of alleles and genotypes of the APOE gene in late-onset Alzheimer's disease (N = 68, other late-life dementias (N = 39, and in cognitively normal controls (N = 58 was determined, as also was the risk for Alzheimer's disease associated with the epsilon4 allele. Peripheral blood samples were obtained from a total of 165 individuals living in Brazil aged 65-82 years. Genomic DNA was amplified by the polymerase chain reaction and the products were digested with HhaI restriction enzyme. APOE epsilon2 frequency was considerably lower in the Alzheimer's disease group (1%, and the epsilon3 allele and epsilon3/epsilon3 genotype frequencies were higher in the controls (84 and 72%, respectively as were the epsilon4 allele and epsilon3/epsilon4 genotype frequencies in Alzheimer's disease (25 and 41%, respectively. The higher frequency of the epsilon4 allele in Alzheimer's disease confirmed its role as a risk factor, while epsilon2 provided a weak protection against development of the disease. However, in view of the unexpectedly low frequency of the epsilon4 allele, additional analyses in a more varied Brazilian sample are needed to clarify the real contribution of apolipoprotein E to the development of Alzheimer's disease in this population.

  19. Association of Alzheimer's disease and Chlamydophila pneumoniae.

    Science.gov (United States)

    Stallings, Tiffany L

    2008-06-01

    This paper critically reviews the association of infection by Chlamydophila pneumoniae (C. pneumoniae) and Alzheimer's disease (AD). The aging population has increased interest in finding the cause of AD, but studies have yielded contradictory results that are likely due to varying diagnostic tools and different uses of diagnostic tests. Knowledge of AD's characteristics, risk factors, and hypothesized etiologies has expanded since Alois Alzheimer's initial description of AD. Epidemiologic and projection studies provide incidence estimates of AD through a two-stage method: (1) primary diagnosis of dementia by cognitive testing such as Mini-Mental State Examination (MMSE), and (2) clinical diagnosis of AD through criteria such as National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Cross-sectional studies yield prevalence estimates of infection by C. pneumoniae by detecting immunoglobulins through laboratory tests such as microimmunofluorescence (MIF). Studies examining the association of C. pneumoniae and AD are limited, but brain autopsy provides information about presence, proximity to areas associated with AD, and bacterial load. Standardization of diagnostic techniques would allow for better comparability of studies, but uncertainty about the best method of diagnosis of infection by C. pneumoniae and AD may call for revised or novel diagnostic tools.

  20. Alzheimer's disease: a report from the 7th Kuopio Alzheimer symposium.

    Science.gov (United States)

    Haapasalo, Annakaisa; Pikkarainen, Maria; Soininen, Hilkka

    2015-10-01

    The 7th Kuopio Alzheimer symposium was held on 11-13 June, 2015, in Kuopio, Finland and attracted ~250 attendees from 14 different countries around the world. The theme for the symposium in its seventh year was 'From mechanisms to prevention and intervention of Alzheimer's disease'. The 3-day international scientific symposium composed of seven oral sessions and a poster session. The program, spanning from molecular mechanisms to prevention, prediction, diagnosis and treatment of Alzheimer's disease, provided a forum for the attendees to share their research, network and to obtain a comprehensive overview of the current status and future directions of research into Alzheimer's disease.

  1. 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...

  2. 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....

  3. 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....

  4. Telephone Networks Connect Caregiving Families of Alzheimer's Victims.

    Science.gov (United States)

    Goodman, Catherine Chase; Pynoos, Jon

    1988-01-01

    Describes telephone network bringing family caregivers of Alzheimer's victims together over telephone in rotating pattern of twosomes. Explains how five caregiving spouses and five adult children were matched and connected over three months. Describes program's 25 telephone-accessed audiotapes that guided networks and provided information on…

  5. Etiology and pathophysiology of frontotemporal dementia, Parkinson disease and Alzheimer disease: lessons from genetic studies.

    Science.gov (United States)

    Wider, Christian; Wszolek, Zbigniew K

    2008-01-01

    Genetic studies have led to major discoveries in the pathogenesis of various neurodegenerative diseases. Ubiquitin-positive familial frontotemporal dementia was recently found to be caused by mutations in the progranulin gene (PGRN), and the major constituent of the inclusions, TDP-43, was subsequently identified. The tau gene (MAPT) causes frontotemporal dementia with parkinsonism linked to chromosome 17. In Parkinson disease, LRRK2 mutations have emerged as a major cause of both familial and sporadic forms, adding to the previously known genes SNCA,PRKN,DJ1 and PINK1. Several genes have been implicated in Alzheimer disease, including the APP gene and the PSEN genes. Recently, variants in the sortilin-related receptor 1 gene, SORL1, were associated with Alzheimer disease. 2008 S. Karger AG, Basel

  6. The role of novel chitin-like polysaccharides in Alzheimer disease.

    Science.gov (United States)

    Castellani, Rudy J; Perry, George; Smith, Mark A

    2007-12-01

    While controversy over the role of carbohydrates in amyloidosis has existed since the initial recognition of amyloid, current understanding of the role of polysaccharides in the pathogenesis of amyloid deposition of Alzheimer disease and other amyloidoses is limited to studies of glyco-conjugates such as heparin sulfate proteoglycan. We hypothesized that polysaccharides may play a broader role in light of 1) the impaired glucose utilization in Alzheimer disease; 2) the demonstration of amylose in the Alzheimer disease brain; 3) the role of amyloid in Alzheimer disease pathogenesis. Specifically, as with glucose polymers (amyloid), we wanted to explore whether glucosamine polymers such as chitin were being synthesized and deposited as a result of impaired glucose utilization and aberrant hexosamine pathway activation. To this end, using calcofluor histochemistry, we recently demonstrated that amyloid plaques and blood vessels affected by amyloid angiopathy in subjects with sporadic and familial Alzheimer disease elicit chitin-type characteristics. Since chitin is a highly insoluble molecule and a substrate for glycan-protein interactions, chitin-like polysaccharides within the Alzheimer disease brain could provide a scaffolding for amyloid-beta deposition. As such, glucosamine may facilitate the process of amyloidosis, and /or provide neuroprotection in the Alzheimer disease brain.

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is ...

  8. Alzheimer's Disease: Aging, Insomnia and Epigenetics

    Directory of Open Access Journals (Sweden)

    Tzong Yuan Wu

    2010-12-01

    Full Text Available Alzheimer's disease (AD is the most common form of dementia. Severe memory loss, confusion, and impaired cognitive abilities characterize AD. It was only a century after Alzheimer's discovery that scientists were able to shed light on the mystery of its cause, but AD has also become a globally important health issue and the treatment of AD is a challenge for modern medicine. At present, there are five drugs approved in the United States for the treatment of AD, namely, donepezil, galantamine, rivastigmine, and tacrine (which are all cholinesterase inhibitors; and memantine (which is a glutamate receptor antagonist. However, these drugs show only modest effects on AD patients. Thus, new investigations are necessary for pharmacological development in AD. This brief review focuses on new studies that demonstrate the link between epigenetics and AD, and explores the possibility that insomnia may be one factor that effects AD.

  9. 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...

  10. The Proteasome and Oxidative Stress in Alzheimer's Disease.

    Science.gov (United States)

    Bonet-Costa, Vicent; Pomatto, Laura Corrales-Diaz; Davies, Kelvin J A

    2016-12-01

    Alzheimer's disease is a neurodegenerative disorder that is projected to exceed more than 100 million cases worldwide by 2050. Aging is considered the primary risk factor for some 90% of Alzheimer's cases but a significant 10% of patients suffer from aggressive, early-onset forms of the disease. There is currently no effective Alzheimer's treatment and this, coupled with a growing aging population, highlights the necessity to understand the mechanism(s) of disease initiation and propagation. A major hallmark of Alzheimer's disease pathology is the accumulation of amyloid-β (Aβ) aggregates (an early marker of Alzheimer's disease), and neurofibrillary tangles, comprising the hyper-phosphorylated microtubule-associated protein Tau. Recent Advances: Protein oxidation is frequently invoked as a potential factor in the progression of Alzheimer's disease; however, whether it is a cause or a consequence of the pathology is still being debated. The Proteasome complex is a major regulator of intracellular protein quality control and an essential proteolytic enzyme for the processing of both Aβ and Tau. Recent studies have indicated that both protein oxidation and excessive phosphorylation may limit Proteasomal processing of Aβ and Tau in Alzheimer's disease. Thus, the Proteasome may be a key factor in understanding the development of Alzheimer's disease pathology; however, its significance is still very much under investigation. Discovering how the proteasome is affected, regulated, or dysregulated in Alzheimer's disease could be a valuable tool in the efforts to understand and, ultimately, eradicate the disease. Antioxid. Redox Signal. 25, 886-901.

  11. To differentiate Alzheimer's disease earlier: introduction of Alzheimer's Disease Neuroimaging Initiative (ADNI

    Directory of Open Access Journals (Sweden)

    Zhi-gang QI

    2014-04-01

    Full Text Available Alzheimer's disease (AD brought about much pressure in modern aging society both economically and psychologically, so it is meaningful to carry out AD research. Being considered as the most successful multi-center, inter-disciplinary and longitudinal research in AD field, Alzheimer's Disease Neuroimaging Initiative (ADNI has obtained outstanding achievements. In this review, we attempt to introduce the research plan of ADNI project for reference. doi: 10.3969/j.issn.1672-6731.2014.04.003

  12. Relationship Between Tau Pathology and Neuroinflammation in Alzheimer's Disease

    OpenAIRE

    Metcalfe, Maria Jose; Figueiredo-Pereira, Maria E.

    2010-01-01

    Alzheimer's disease is a chronic, age-related neurodegenerative disorder. Neurofibrillary tangles are among the pathological hallmarks of Alzheimer's disease. Neurofibrillary tangles consist of abnormal protein fibers known as paired helical filaments. The accumulation of paired helical filaments is one of the most characteristic cellular changes in Alzheimer's disease. Tau protein, a microtubule-associated protein, is the major component of paired helical filaments. Tau in paired helical fil...

  13. Expression of familial Alzheimer disease presenilin 1 gene attenuates vesicle traffic and reduces peptide secretion in cultured astrocytes devoid of pathologic tissue environment.

    Science.gov (United States)

    Stenovec, Matjaž; Trkov, Saša; Lasič, Eva; Terzieva, Slavica; Kreft, Marko; Rodríguez Arellano, José Julio; Parpura, Vladimir; Verkhratsky, Alexei; Zorec, Robert

    2016-02-01

    In the brain, astrocytes provide metabolic and trophic support to neurones. Failure in executing astroglial homeostatic functions may contribute to the initiation and propagation of diseases, including Alzheimer disease (AD), characterized by a progressive loss of neurones over years. Here, we examined whether astrocytes from a mice model of AD isolated in the presymptomatic phase of the disease exhibit alterations in vesicle traffic, vesicular peptide release and purinergic calcium signaling. In cultured astrocytes isolated from a newborn wild-type (wt) and 3xTg-AD mouse, secretory vesicles and acidic endosomes/lysosomes were labeled by transfection with plasmid encoding atrial natriuretic peptide tagged with mutant green fluorescent protein (ANP.emd) and by LysoTracker, respectively. The intracellular Ca(2+) concentration ([Ca(2+)]i) was monitored with Fluo-2 and visualized by confocal microscopy. In comparison with controls, spontaneous mobility of ANP- and LysoTracker-labeled vesicles was diminished in 3xTg-AD astrocytes; the track length (TL), maximal displacement (MD) and directionality index (DI) were all reduced in peptidergic vesicles and in endosomes/lysosomes (P vesicle mobility. Similar impairment of peptidergic vesicle trafficking was observed in wt rat astrocytes transfected to express mutated presenilin 1 (PS1M146V). The ATP-evoked ANP discharge from single vesicles was less efficient in 3xTg-AD and PS1M146V-expressing astrocytes than in respective wt controls (P vesicle dynamics and reduces evoked secretion of the signaling molecule ANP; both may contribute to the development of AD.

  14. Advances in Alzheimer's disease drug development.

    Science.gov (United States)

    Rafii, Michael S; Aisen, Paul S

    2015-03-25

    Alzheimer's disease (AD) is the foremost cause of dementia worldwide. Clinically, AD manifests as progressive memory impairment followed by a gradual decline in other cognitive abilities leading to complete functional dependency. Recent biomarker studies indicate that AD is characterized by a long asymptomatic phase, with the development of pathology occurring at least a decade prior to the onset of any symptoms. Current FDA-approved treatments target neurotransmitter abnormalities associated with the disease but do not affect what is believed to be the underlying etiology. In this review, we briefly discuss the most recent therapeutic strategies being employed in AD clinical trials, as well the scientific rationale with which they have been developed.

  15. Peripheral cholesterol, metabolic disorders and Alzheimer's disease.

    Science.gov (United States)

    Ledesma, Maria Dolores; Dotti, Carlos Gerardo

    2012-01-01

    Strong correlations have been made between high levels of blood cholesterol and the risk to suffer Alzheimer's disease (AD). The question arises on how a peripheral event contributes to a disease that so severely affects the integrity and function of the Central Nervous System. Hypercholesterolemia has been also associated to peripheral metabolic disorders like diabetes, obesity or atherosclerosis that, in turn, predispose to AD. Here we review data, which point to alterations in blood cholesterol levels as a link between these metabolic disorders and AD. We describe and discuss common, cholesterol-related, molecular mechanisms and strategies to fight these conditions that, altogether, constitute a major cause of death in our societies.

  16. GPCR, a rider of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xiaosong LIU; Jian ZHAO

    2011-01-01

    Alzheimer's disease (AD) is the most common type of dementia that affects thinking,learning,memory and behavior of older people.Based on the previous studies,three pathogenic pathways are now commonly accepted as the culprits of this disease namely,amyloid-β pathway,tauopathology and cholinergic dysfunction.This review focuses on the current findings on the regulatory roles of G protein-coupled receptors (GPCRs) in the pathological progression of AD and discusses the potential of the GPCRs as novel therapeutic targets for AD.

  17. Visual system manifestations of Alzheimer's disease.

    Science.gov (United States)

    Kusne, Yael; Wolf, Andrew B; Townley, Kate; Conway, Mandi; Peyman, Gholam A

    2016-11-19

    Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD.

  18. The PPAR-γ Agonist 15-Deoxy-Δ12,14-Prostaglandin J2 Attenuates Microglial Production of IL-12 Family Cytokines: Potential Relevance to Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Jihong Xu

    2008-01-01

    Full Text Available Accumulation of amyloid-β peptide (Aβ appears to contribute to the pathogenesis of Alzheimer's disease (AD. Therapeutic hope for the prevention or removal of Aβ deposits has been placed in strategies involving immunization against the Aβ peptide. Initial Aβ immunization studies in animal models of AD showed great promise. However, when this strategy was attempted in human subjects with AD, an unacceptable degree of meningoencephalitis occurred. It is generally believed that this adverse outcome resulted from a T-cell response to Aβ. Specifically, CD4+ Th1 and Th17 cells may contribute to severe CNS inflammation and limit the utility of Aβ immunization in the treatment of AD. Interleukin (IL-12 and IL-23 play critical roles in the development of Th1 and Th17 cells, respectively. In the present study, Aβ1−42 synergistically elevated the expression of IL-12 and IL-23 triggered by inflammatory activation of microglia, and the peroxisome proliferator-activated receptor (PPAR-γ agonist 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2 effectively blocked the elevation of these proinflammatory cytokines. Furthermore, 15d-PGJ2 suppressed the Aβ-related synergistic induction of CD14, MyD88, and Toll-like receptor 2, molecules that play critical roles in neuroinflammatory conditions. Collectively, these studies suggest that PPAR-γ agonists may be effective in modulating the development of AD.

  19. Positive feelings of caregiving among Latino Alzheimer's family caregivers: understanding the role of spirituality.

    Science.gov (United States)

    Hodge, David R; Sun, Fei

    2012-01-01

    This study used structural equation modeling to examine the effects of spirituality on positive aspects of caregiving (PAC) among a sample of American Latino family members caring for a relative with Alzheimer's disease (AD). Participants consisted of 209 Latino caregivers (CGs) drawn from baseline data from the Resources for Enhancing Alzheimer's Caregivers Health II study. The findings indicate that spirituality is positively related to PAC and may partially mediate the effect of subjective stress on PAC. AD CGs typically provide better care when they perceive the caregiving experience to be satisfying and rewarding. Toward this end, gerontological practitioners should adopt a proactive stance to ensure Latino AD CGs can operationalize their spiritual strengths.

  20. Alzheimer's disease: new diagnostic and therapeutic tools

    Directory of Open Access Journals (Sweden)

    Caruso Calogero

    2008-08-01

    Full Text Available Abstract On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lectures of M. Racchi on History and future perspectives of Alzheimer Biomarkers and of G. Scapagnini on Cellular Stress Response and Brain Ageing are summarized. Alzheimer's disease (AD is a heterogeneous and progressive neurodegenerative disease, which in Western society mainly accounts for clinica dementia. AD prevention is an important goal of ongoing research. Two objectives must be accomplished to make prevention feasible: i individuals at high risk of AD need to be identified before the earliest symptoms become evident, by which time extensive neurodegeneration has already occurred and intervention to prevent the disease is likely to be less successful and ii safe and effective interventions need to be developed that lead to a decrease in expression of this pathology. On the whole, data here reviewed strongly suggest that the measurement of conformationally altered p53 in blood cells has a high ability to discriminate AD cases from normal ageing, Parkinson's disease and other dementias. On the other hand, available data on the involvement of curcumin in restoring cellular homeostasis and rebalancing redox equilibrium, suggest that curcumin might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation, such as AD.

  1. New cardiovascular targets to prevent late onset Alzheimer disease

    NARCIS (Netherlands)

    Claassen, J.A.H.R.

    2015-01-01

    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

  2. The rat as an animal model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind...... as an animal model of Alzheimer's disease....

  3. Common Alzheimer's Disease Research Ontology: National Institute on Aging and Alzheimer's Association collaborative project.

    Science.gov (United States)

    Refolo, Lorenzo M; Snyder, Heather; Liggins, Charlene; Ryan, Laurie; Silverberg, Nina; Petanceska, Suzana; Carrillo, Maria C

    2012-07-01

    Alzheimer's disease is recognized as a public health crisis worldwide. As public and private funding agencies around the world enhance and expand their support of Alzheimer's disease research, there is an urgent need to coordinate funding strategies and leverage resources to maximize the impact on public health and avoid duplication of effort and inefficiency. Such coordination requires a comprehensive assessment of the current landscape of Alzheimer's disease research in the United States and internationally. To this end, the National Institute on Aging at the National Institutes of Health and the Alzheimer's Association developed the Common Alzheimer's Disease Research Ontology (CADRO) as a dynamic portfolio analysis tool that can be used by funding agencies worldwide for strategic planning and coordination.

  4. Depressive symptoms associated with hereditary Alzheimer's disease: a case description.

    Science.gov (United States)

    Contreras, Mónica Yicette Sánchez; Vargas, Paula Alejandra Osorio; Ramos, Lucero Rengifo; Velandia, Rafael Alarcón

    The authors describe a family group studied by the Centro de Biología Molecular y Biotecnología, and the Clínica de la Memoria, las Demencias y el Envejecimiento (Universidad Tecnológica de Pereira, Colombia), and evaluate the association of depressive symptoms with Alzheimer's disease (AD). This family presented a hereditary pattern for AD characterized by an early onset of dementia symptoms, a long preclinical depressive course, and, once the first symptoms of dementia appeared, a rapid progression to severe cognitive function impairment. The authors found a high prevalence of depressive symptoms in this family and propose that the symptoms could be an important risk factor for developing AD in the presence of other risk factors such as the APOE E4 allele.

  5. Expression of Alzheimer's disease risk genes in ischemic brain degeneration.

    Science.gov (United States)

    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Januszewski, Sławomir; Kocki, Janusz; Bogucka-Kocka, Anna; Czuczwar, Stanisław J

    2016-12-01

    We review the Alzheimer-related expression of genes following brain ischemia as risk factors for late-onset of sporadic Alzheimer's disease and their role in Alzheimer's disease ischemia-reperfusion pathogenesis. More recent advances in understanding ischemic etiology of Alzheimer's disease have revealed dysregulation of Alzheimer-associated genes including amyloid protein precursor, β-secretase, presenilin 1 and 2, autophagy, mitophagy and apoptosis. We review the relationship between these genes dysregulated by brain ischemia and the cellular and neuropathological characteristics of Alzheimer's disease. Here we summarize the latest studies supporting the theory that Alzheimer-related genes play an important role in ischemic brain injury and that ischemia is a needful and leading supplier to the onset and progression of sporadic Alzheimer's disease. Although the exact molecular mechanisms of ischemic dependent neurodegenerative disease and neuronal susceptibility finally are unknown, a downregulated expression of neuronal defense genes like alfa-secretase in the ischemic brain makes the neurons less able to resist injury. The recent challenge is to find ways to raise the adaptive reserve of the brain to overcome such ischemic-associated deficits and support and/or promote neuronal survival. Understanding the mechanisms underlying the association of these genes with risk for Alzheimer's disease will provide the most meaningful targets for therapeutic development to date. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Neuroimaging Measures as Endophenotypes in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Meredith N. Braskie

    2011-01-01

    Full Text Available Late onset Alzheimer's disease (AD is moderately to highly heritable. Apolipoprotein E allele ε4 (APOE4 has been replicated consistently as an AD risk factor over many studies, and recently confirmed variants in other genes such as CLU, CR1, and PICALM each increase the lifetime risk of AD. However, much of the heritability of AD remains unexplained. AD is a complex disease that is diagnosed largely through neuropsychological testing, though neuroimaging measures may be more sensitive for detecting the incipient disease stages. Difficulties in early diagnosis and variable environmental contributions to the disease can obscure genetic relationships in traditional case-control genetic studies. Neuroimaging measures may be used as endophenotypes for AD, offering a reliable, objective tool to search for possible genetic risk factors. Imaging measures might also clarify the specific mechanisms by which proposed risk factors influence the brain.

  7. Immunotherapy against amyloid pathology in Alzheimer's disease.

    Science.gov (United States)

    Galimberti, Daniela; Ghezzi, Laura; Scarpini, Elio

    2013-10-15

    The first drugs developed for Alzheimer's disease (AD), anticholinesterase inhibitors (AchEI), increase acetylcholine levels, previously demonstrated to be reduced in AD. To date, four AchEI are approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine. These treatments are symptomatic, whereas drugs under development are supposed to modify pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are currently termed "disease modifying" drugs. To block the progression of the disease, they have to interfere with pathogenic steps at the basis of clinical symptoms, including the deposition of extracellular amyloid beta (Aβ) plaques and of intracellular neurofibrillary tangles. The most innovative approach is represented by the vaccination and passive immunization against Aβ peptide. In this article, current knowledge about concluded and ongoing clinical trials with both vaccination with different antigens and passive immunization will be reviewed and discussed.

  8. Frontal variant of Alzheimer's disease and typical Alzheimer's disease: a comparative study

    Directory of Open Access Journals (Sweden)

    Bernardino Fernández-Calvo

    2013-01-01

    Full Text Available Clinical heterogeneity is one of the characteristics of Alzheimer's disease (AD. Hence, the atypical frontal or dysexecutive presentation is becoming increasingly well-known, although the underlying factors are still unknown. In this study, the neuropsychological performance of two groups of patients with AD (frontal variant--ADfv--and typical--TAD were compared. The ADfv group (n = 13 was selected due to the existence of frontal hypoperfusion on a simple photon emission computer tomography (SPECT. The results revealed that the ADfv group displayed a severe dysexecutive disorder, more severe neuropsychiatric symptomatology (disinhibition and apathy, more functional impairment, and it generated a higher caregiver overload than the TAD group without frontal impairment (n = 47. Despite the facts that the ADfv group's performance was poorer in all the neuropsychological tests, significant group differences were only found in the processing speed and visuoconstruction tasks. Logistic regression analysis revealed that the processing speed and mental flexibility scores significantly predicted a diagnosis of ADfv. The existence of the grasp reflex, anosognosia, and the absence of apolipoprotein E epsilon 4 allele (APOE e4 were also more prevalent in the ADfv group. This group had a predominance of males and it was more likely to have a positive family history of AD. To conclude, the study suggests that ADfv represents a subtype of AD that seems to have different clinical, neuropsychological, and genetic characteristics from TAD.

  9. Alzheimer's disease - the ways of prevention.

    Science.gov (United States)

    Kivipelto, M; Solomon, A

    2008-01-01

    Several vascular and lifestyle related factors have been suggested to influence the development of dementia and Alzheimer's disease (AD), creating new prevention opportunities. This paper discusses current epidemiological evidence and new findings from the Finnish population based CAIDE study linking some of these factors to dementia/AD. Such findings provide an optimistic outlook especially for persons with genetic susceptibility; it may be possible to reduce the risk or postpone the onset of dementia by adopting healthy lifestyle options. The interplay of genes and environment in the aetiology of AD needs to be further investigated as well as the role of lifestyle and pharmacological interventions for the prevention of dementia.

  10. Serotonin: A New Hope in Alzheimer's Disease?

    Science.gov (United States)

    Claeysen, Sylvie; Bockaert, Joël; Giannoni, Patrizia

    2015-07-15

    Alzheimer's disease (AD) is the most common form of dementia affecting 35 million individuals worldwide. Current AD treatments provide only brief symptomatic relief. It is therefore urgent to replace this symptomatic approach with a curative one. Increasing serotonin signaling as well as developing molecules that enhance serotonin concentration in the synaptic cleft have been debated as possible therapeutic strategies to slow the progression of AD. In this Viewpoint, we discuss exciting new insights regarding the modulation of serotonin signaling for AD prevention and therapy.

  11. Alzheimer's disease camouflaged by histrionic personality disorder.

    Science.gov (United States)

    Hellwig, Sabine; Dykierek, Petra; Hellwig, Bernhard; Zwernemann, Stefan; Meyer, Philipp T

    2012-02-01

    A common condition in Alzheimer's disease (AD) is unawareness of deficits. Different concepts try to elucidate the nature of this symptom. An essential question relates to the interaction of organic and psychogenic factors. Here we present a patient who displayed her cognitive deficits as attention-seeking behaviour. There was a history of histrionic personality disorder according to ICD-10 criteria. Unexpectedly, the final diagnosis after extensive diagnostic work-up was AD. The unusual coincidence of AD and a histrionic personality disorder hampered the clinical process of diagnosing dementia. We discuss unawareness as a complex concept incorporating neuroanatomical, psychiatric, and psychosocial aspects.

  12. Microglia, Alzheimer's Disease, and Complement

    Directory of Open Access Journals (Sweden)

    Helen Crehan

    2012-01-01

    Full Text Available Microglia, the immune cell of the brain, are implicated in cascades leading to neuronal loss and cognitive decline in Alzheimer’s disease (AD. Recent genome-wide association studies have indicated a number of risk factors for the development of late-onset AD. Two of these risk factors are an altered immune response and polymorphisms in complement receptor 1. In view of these findings, we discuss how complement signalling in the AD brain and microglial responses in AD intersect. Dysregulation of the complement cascade, either by changes in receptor expression, enhanced activation of different complement pathways or imbalances between complement factor production and complement cascade inhibitors may all contribute to the involvement of complement in AD. Altered complement signalling may reduce the ability of microglia to phagocytose apoptotic cells and clear amyloid beta peptides, modulate the expression by microglia of complement components and receptors, promote complement factor production by plaque-associated cytokines derived from activated microglia and astrocytes, and disrupt complement inhibitor production. The evidence presented here indicates that microglia in AD are influenced by complement factors to adopt protective or harmful phenotypes and the challenge ahead lies in understanding how this can be manipulated to therapeutic advantage to treat late onset AD.

  13. Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project

    Science.gov (United States)

    Brugulat-Serrat, Anna; Rojas, Santiago; Bargalló, Nuria; Conesa, Gerardo; Minguillón, Carolina; Fauria, Karine; Gramunt, Nina; Molinuevo, José Luis; Gispert, Juan Domingo

    2017-01-01

    Objectives To describe the prevalence of brain MRI incidental findings (IF) in a cohort of cognitively normal first-degree descendants of patients with Alzheimer's disease (AD). Design Cross-sectional observational study. Setting All scans were obtained with a 3.0 T scanner. Scans were evaluated by a single neuroradiologist and IF recorded and categorised. The presence of white matter hyperintensities (WMH) was determined with the Fazekas scale and reported as relevant if ≥2. Participants 575 participants (45–75 years) underwent high-resolution structural brain MRI. Participants were cognitively normal and scored over the respective cut-off values in all the following neuropsychological tests: Mini-Mental State Examination (≥26), Memory Impairment Screen (≥6), Time Orientation Subtest of the Barcelona Test II (≥68), verbal semantic fluency (naming animals ≥12). Clinical Dementia Rating (CDR) had to be 0. Results 155 participants (27.0%) presented with at least one IF. Relevant WMH were present in 7.8% of the participants, and vascular abnormalities, cyst and brain volume loss in 10.7%, 3.1% and 6.9% of the study volunteers, respectively. Neoplastic brain findings were found in 2.4% of participants and within these, meningiomas were the most common (1.7%) and more frequently found in women. A positive correlation between increasing age and the presence of IF was found. Additionally, brain atrophy greater than that expected by age was significantly more prevalent in participants without a parental history of AD. Conclusions Brain MRIs of healthy middle-aged participants show a relatively high prevalence of IF even when study participants have been screened for subtle cognitive alterations. Most of our participants are first-degree descendants of patients with AD, and therefore these results are of special relevance for novel imaging studies in the context of AD prevention in cognitively healthy middle-aged participants. Trial registration number NCT

  14. Impaired default network functional connectivity in autosomal dominant Alzheimer disease

    Science.gov (United States)

    Chhatwal, Jasmeer P.; Schultz, Aaron P.; Johnson, Keith; Benzinger, Tammie L.S.; Jack, Clifford; Ances, Beau M.; Sullivan, Caroline A.; Salloway, Stephen P.; Ringman, John M.; Koeppe, Robert A.; Marcus, Daniel S.; Thompson, Paul; Saykin, Andrew J.; Correia, Stephen; Schofield, Peter R.; Rowe, Christopher C.; Fox, Nick C.; Brickman, Adam M.; Mayeux, Richard; McDade, Eric; Bateman, Randall; Fagan, Anne M.; Goate, Allison M.; Xiong, Chengjie; Buckles, Virginia D.; Morris, John C.

    2013-01-01

    Objective: To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network. Methods: Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, United Kingdom, and Australia. Using group-independent component analysis, fcMRI was compared using mutation status and Clinical Dementia Rating to stratify groups, and related to each participant's estimated years from expected symptom onset (eYO). Results: We observed significantly decreased DMN fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident in the precuneus/posterior cingulate and parietal cortices (p < 0.001). Comparison of asymptomatic mutation carriers with noncarriers demonstrated decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right parietal cortex (p = 0.0016). We observed a significant interaction between mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation carriers approached and surpassed their eYO. Conclusion: Functional disruption of the DMN occurs early in the course of autosomal dominant Alzheimer disease, beginning before clinically evident symptoms, and worsening with increased impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease. PMID:23884042

  15. [A new definition for Alzheimer's disease].

    Science.gov (United States)

    Dubois, Bruno

    2013-01-01

    In 2007 and 2010, the International Working Group on Research Criteria for Alzheimer's Disease introduced a new conceptual framework that included a diagnostic algorithm covering early prodromal stages. There is a growing consensus that Alzheimer's disease (AD) should be considered as a clinical-biological entity characterized by: i) a well-defined clinical phenotype (an amnestic syndrome of the hippocampal type in typical AD), and ii) biomarkers, especially pathophysiological biomarkers, of the underlying disease process. The IWG criteria created the possibility for AD to be diagnosed prior to the onset of dementia, and also integrated biomarkers into the diagnostic framework. Although these criteria were intended for research purposes, they are increasingly used in expert centers for early diagnosis, for example of young-onset AD and complex cases (posterior cortical atrophy, primary progressive aphasia, etc.), where biomarkers can improve the diagnostic accuracy. In this article we present this new approach, together with the results of ongoing validation studies and data obtained by a French research team.

  16. 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.

  17. Alzheimer's Disease and Exercise: A Literature Review.

    Science.gov (United States)

    Cass, Shane P

    Alzheimer's disease (AD) is a progressive neurodegenerative disease that impairs memory and cognitive judgment. It is the leading cause of dementia in late adult life and is associated with a significant social burden and increased morbidity and mortality in the elderly. Because of mixed effectiveness of medications, exercise has been considered as a treatment for pre-clinical AD, late stage AD, and as a prevention strategy. Exercise appears to improve brain blood flow, increase hippocampal volume, and improve neurogenesis. Prospective studies indicate that physical inactivity is one of the most common preventable risk factors for developing AD and that higher physical activity levels are associated with a reduced risk of development of disease. Exercise as a treatment for AD shows improvement in cognitive function, decreased neuropsychiatric symptoms, and a slower decline in activities of daily living (ADL). Exercise has been shown to have fewer side effects and better adherence compared to medications.

  18. Imaging Alzheimer's disease pathophysiology with PET

    Directory of Open Access Journals (Sweden)

    Lucas Porcello Schilling

    Full Text Available ABSTRACT Alzheimer's disease (AD has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI, and dementia stages. Positron emission tomography (PET associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD.

  19. Imbalanced cholesterol metabolism in Alzheimer's disease.

    Science.gov (United States)

    Xue-shan, Zhao; Juan, Peng; Qi, Wu; Zhong, Ren; Li-hong, Pan; Zhi-han, Tang; Zhi-sheng, Jiang; Gui-xue, Wang; Lu-shan, Liu

    2016-05-01

    Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease that is mainly caused by β-amyloid accumulation. A large number of studies have shown that elevated cholesterol levels may perform a function in AD pathology, and several cholesterol-related gene polymorphisms are associated with this disease. Although numerous studies have shown the important function of cholesterol in AD pathogenesis and development, the underlying mechanism remains unclear. To further elucidate cholesterol metabolism disorder and AD, we first, review metabolism and regulation of the cholesterol in the brain. Second, we summarize the literature stating that hypercholesterolemia is one of the risk factors of AD. Third, we discuss the main mechanisms of abnormal cholesterol metabolism that increase the risk of AD. Finally, the relationships between AD and apolipoprotein E, PCSK9, and LRP1 are discussed in this article.

  20. Alzheimer's disease prevention: A way forward.

    Science.gov (United States)

    Bermejo-Pareja, F; Llamas-Velasco, S; Villarejo-Galende, A

    2016-12-01

    This review proposes a more optimistic view of Alzheimer's disease (AD), in contrast to that contributed by the ageing of the population and the failure of potentially curative therapies (vaccines and others). Treatment failure is likely due to the fact that AD gestates in the brain for decades but manifests in old age. This review updates the concept of AD and presents the results of recent studies that show that primary prevention can reduce the incidence and delay the onset of the disease. Half of all cases of AD are potentially preventable through education, the control of cardiovascular risk factors, the promotion of healthy lifestyles and specific drug treatments. These approaches could substantially reduce the future incidence rate of this disease. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  1. CSF Biomarkers for Alzheimer's Disease Diagnosis

    Directory of Open Access Journals (Sweden)

    A. Anoop

    2010-01-01

    Full Text Available Alzheimer's disease (AD is the most common form of dementia that affects several million people worldwide. The major neuropathological hallmarks of AD are the presence of extracellular amyloid plaques that are composed of Aβ40 and Aβ42 and intracellular neurofibrillary tangles (NFT, which is composed of hyperphosphorylated protein Tau. While the amyloid plaques and NFT could define the disease progression involving neuronal loss and dysfunction, significant cognitive decline occurs before their appearance. Although significant advances in neuroimaging techniques provide the structure and physiology of brain of AD cases, the biomarker studies based on cerebrospinal fluid (CSF and plasma represent the most direct and convenient means to study the disease progression. Biomarkers are useful in detecting the preclinical as well as symptomatic stages of AD. In this paper, we discuss the recent advancements of various biomarkers with particular emphasis on CSF biomarkers for monitoring the early development of AD before significant cognitive dysfunction.

  2. Metal ions, Alzheimer's disease and chelation therapy.

    Science.gov (United States)

    Budimir, Ana

    2011-03-01

    In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases.

  3. Vascular contribution to Alzheimer disease: predictors of rapid progression.

    Science.gov (United States)

    Diomedi, Marina; Misaggi, Giulia

    2013-06-01

    Different courses of Alzheimer disease are observed in clinical practice. The rapidly progressive form could be associated with the presence of a major microcirculatory involvement and hemodynamic insufficiency. This short review aims to provide an overview of the current knowledge of cerebrovascular contribution to Alzheimer disease presentation and progression, hypothesizing the possible vascular markers of rapidly progressive form.

  4. 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....

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

    Science.gov (United States)

    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…

  6. Distinct Mechanisms of Impairment in Cognitive Ageing and Alzheimer's Disease

    Science.gov (United States)

    Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.

    2008-01-01

    Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…

  7. Efficacy of psychosocial intervention in patients with mild Alzheimer's disease

    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....

  8. HEAD TRAUMA AND THE RISK OF ALZHEIMERS-DISEASE

    NARCIS (Netherlands)

    VANDUIJN, CM; TANJA, TA; HAAXMA, R; SCHULTE, W; SAAN, RJ; LAMERIS, AJ; ANTONIDESHENDRIKS, G; HOFMAN, A

    1992-01-01

    A population-based case-control study of the association between head trauma and Alzheimer's disease was conducted in the Netherlands from 1980 to 1987. The study comprised 198 patients with clinically diagnosed early onset Alzheimer's disease and 198 age- and sex-matched population controls. Adjust

  9. 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.

  10. Distinct Mechanisms of Impairment in Cognitive Ageing and Alzheimer's Disease

    Science.gov (United States)

    Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.

    2008-01-01

    Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…

  11. 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…

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

    NARCIS (Netherlands)

    C.M. van Duijn (Cock)

    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? Are

  13. 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…

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

    Science.gov (United States)

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

    2009-01-01

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

  15. Providing Counseling for Individuals with Alzheimer's Disease and Their Caregivers

    Science.gov (United States)

    Granello, Paul F.; Fleming, Matthew S.

    2008-01-01

    Alzheimer's disease is a progressive condition that results in brain wasting and eventual death. With its increasing diagnosis rate, counselors will likely acquire clients with Alzheimer's disease or their caregivers. Important background information and several practical counseling methods are provided that may assist counselors working with this…

  16. 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

    2011-01-01

    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. Studie

  17. Alzheimer's disease under the mask of stroke

    Directory of Open Access Journals (Sweden)

    A. A. Naumenko

    2016-01-01

    Full Text Available Cognitive impairments (CIs are common in poststroke patients. The basis for this condition is frequently a neurodegenerative process and most often Alzheimer's disease (AD. Stroke may promote the manifestation of clinically asymptomatic AD, worsen prestroke cognitive deficit or merely manifest prestroke CIs.The paper discusses the epidemiology, risk factors, and pathogenesis of poststroke CIs, current methods for its diagnosis, as well as symptomatic and pathogenetic treatment. The most informative method for the diagnosis of poststroke CIs is neuropsychological examination that should be made in the early poststroke period (if the patient's consciousness is clear. The most common screening tests include mini-mental state examination (the most sensitive to evaluate cognitive dysfunction in Alzheimer type dementias and the Montreal cognitive assessment. Magnetic resonance imaging of the brain, positron emission tomography, cerebrospinal fluid examination, and genetic testing are used to reveal AD at its preclinical stages. Preventive measures include regular physical activity, a balanced diet, and sufficient mental workload. The prevention of stroke and other cardiovascular diseases are also important.The major groups of drugs used to treat AD and vascular CIs are acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. It is expedient to use glutamatergic and acetylcholinergic therapy earlier in patients with obvious CIs that are unassociated with emotional problems and disturbance of consciousness. Akatinol memantine is a drug that can be regarded not only as a symptomatic but also pathogenetic agent. 

  18. [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.

  19. 阿尔茨海默病患者亲属照顾体验质性研究的Meta-整合%Experiences of taking care of patients with Alzheimer Disease by family members:A Meta-synthesis

    Institute of Scientific and Technical Information of China (English)

    周璇; 王琦

    2015-01-01

    目的:分析阿尔茨海默病患者亲属的照顾体验。方法:检索PubMed、EBSCO、EMBase、CINAHL、Cochrane、CNKI、万方和维普等数据库,纳入所有相关的质性研究,在进行质量评价之后进行整合与分析。结果:共纳入8篇相关文献,将研究结果重新归纳分类,得出7个主题:面临疾病照护困难,身体劳累,心理压力,经济负担,自我付出与牺牲,自我调整与寻求帮助,精神动力与收获。结论:照顾者的压力是较为显著的体验,但经过付出与牺牲,调整与改变,照顾者可以感受到精神动力与收获。%Objective:To analyse experiences of taking care of patients with Alzheimer Disease by family members. Methods:The authors searched Pubmed, EBSCO, EMBase, CINAHL, Cochrane, CNKI and other databases. Qualitative researches which reported the caregivers' experiences of taking care of patients with Alzheimer Disease were enrolled, appraised and synthesized. Results:Eight qualitative studies were recruited. Seven themes were identified:confronting nursing care problems, physically exhausted, mental stress, ifnancial burden, sacriifce, adjustment and seeking help, mental motivation and gains. Conclusion:Stress is the most notable experience for caregivers. However, through sacriifce and adjustment, they may have mental motivation and gains.

  20. Do statins prevent Alzheimer's disease? A narrative review.

    Science.gov (United States)

    Daneschvar, Homayoun L; Aronson, Mark D; Smetana, Gerald W

    2015-11-01

    Alzheimer's disease is the most common cause of dementia and occurs commonly in patients 65 and older. There is an urgent need to find an effective management that could help prevent or at least slow down the progress of this major public health problem. Cholesterol related pathways might play a role in the pathogenesis of Alzheimer's disease. Treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) has been suggested to promote the prevention of Alzheimer's disease. In this review, we discuss potential pathogenetic pathways for the development of Alzheimer's disease and review the evidence regarding the value of statins as a strategy to prevent or delay progression of Alzheimer's disease. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  1. 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......, diagnostic, or monitoring therapeutic efficacy); (3) a critical evaluation of the ongoing biomarker approaches; and (4) highlighting the need for standardization of preanalytical variables and analytical methodologies used by the field. © 2014 The Alzheimer's Association. All rights reserved....

  2. When is category specific in Alzheimer's disease?

    Science.gov (United States)

    Laws, Keith R; Gale, Tim M; Leeson, Verity C; Crawford, John R

    2005-08-01

    Mixed findings have emerged concerning whether category-specific disorders occur in Alzheimer's disease. Factors that may contribute to these inconsistencies include: ceiling effects/skewed distributions for control data in some studies; differences in the severity of cognitive deficit in patients; and differences in the type of analysis (in particular, if and how controls are used to analyse single case data). We examined picture naming in Alzheimer's patients and matched elderly healthy normal controls in three experiments. These experiments used stimuli that did and did not produce ceiling effects/skewed data in controls. In Experiment 1, we examined for category effects in individual DAT patients using commonly used analyses for single cases (chi2 and z-scores). The different techniques produced quite different outcomes. In Experiment 2a, we used the same techniques on a different group of patients with similar outcomes. Finally, in Experiment 2b, we examined the same patients but (a) used stimuli that did not produce ceiling effects/skewed distributions in healthy controls, and (b) used statistical methods that did not treat the control sample as a population. We found that ceiling effects in controls may markedly inflate the incidence of dissociations in which living things are differentially impaired and seriously underestimate dissociations in the opposite direction. In addition, methods that treat the control sample as a population led to inflation in the overall number of dissociations detected. These findings have implications for the reliability of category effects previously reported both in Alzheimer patients and in other pathologies. In particular, they suggest that the greater proportion of living than nonliving deficits reported in the literature may be an artifact of the methods used.

  3. [Prevention of dementia (including Alzheimer's disease)].

    Science.gov (United States)

    Kornhuber, H H

    2004-05-01

    Prevention of dementia: Life expectancy still increases linearly, and the elderly part of the European population grows rapidly in relation to the young. Dementia, however, grows even more rapidly, because it increases exponentially after age 65; it will become a great burden if nothing is done. The discussion so far is concentrated on treatment, whereas prevention is neglected. The therapy of dementia, however, has limited effect. Contrary to a widespread opinion prevention is possible. Genetic factors alone dominate the fate of cognition only in about 3 % of the cases. Besides age, lifestyle and the vascular risk factors exercise a great influence. High blood pressure carries a fourfold risk, diabetes more than doubles the risk both of the vascular and of the Alzheimer type; combined even more. Especially cerebral microangiopathy is strongly associated with Alzheimer's dementia, it triggers the vicious circle which leads to amyloid deposition. The importance of the circulation is underestimated, because most of the microvascular cerebral lesions are not perceived by the patient. All the risk factors for Alzheimer's disease after age 65 are also vascular risk factors especially for microangiopathy: Apo-E4, oestrogen deficiency, insulin resistance, diabetes, arterial hypertension, high cholesterol, old age and increased plasma homocystin which is often caused by alcohol consumption even in moderate doses. A healthy life style with daily outdoor activity and a Mediterranean diet not only reduces the risk of dementia, but also of coronary death and cancer. Cognitively stimulating activity protects even more than physical activity against dementia; the basis for this is acquired in youth by education. Therapy with statins is advisable if atherosclerosis cannot be reasonably counteracted by physical activity and diet.

  4. Chemokines in CSF of Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa

    2011-06-01

    Full Text Available Some studies have linked the presence of chemokines to the early stages of Alzheimer's disease (AD. Then, the identification of these mediators may contribute to diagnosis. Our objective was to evaluate the levels of beta-amyloid (BA, tau, phospho-tau (p-tau and chemokines (CCL2, CXCL8 and CXCL10 in the cerebrospinal fluid (CSF of patients with AD and healthy controls. The correlation of these markers with clinical parameters was also evaluated. The levels of p-tau were higher in AD compared to controls, while the tau/p-tau ratio was decreased. The expression of CCL2 was increased in AD. A positive correlation was observed between BA levels and all chemokines studied, and between CCL2 and p-tau levels. Our results suggest that levels of CCL2 in CSF are involved in the pathogenesis of AD and it may be an additional useful biomarker for monitoring disease progression.

  5. The role of inflammasome in Alzheimer's disease.

    Science.gov (United States)

    Liu, Li; Chan, Christina

    2014-05-01

    Alzheimer's disease (AD) is a chronic, progressive and irreversible neurodegenerative disease with clinical characteristics of memory loss, dementia and cognitive impairment. Although the pathophysiologic mechanism is not fully understood, inflammation has been shown to play a critical role in the pathogenesis of AD. Inflammation in the central nervous system (CNS) is characterized by the activation of glial cells and release of proinflammatory cytokines and chemokines. Accumulating evidence demonstrates that inflammasomes, which cleave precursors of interleukin-1β (IL-1β) and IL-18 to generate their active forms, play an important role in the inflammatory response in the CNS and in AD pathogenesis. Therefore, modulating inflammasome complex assembly and activation could be a potential strategy for suppressing inflammation in the CNS. This review aims to provide insight into the role of inflammasomes in the CNS, with respect to the pathogenesis of AD, and may provide possible clues for devising novel therapeutic strategies.

  6. Iron: a pathological mediator of Alzheimer disease?

    Science.gov (United States)

    Bishop, Glenda M; Robinson, Stephen R; Liu, Quan; Perry, George; Atwood, Craig S; Smith, Mark A

    2002-01-01

    Brains from patients with Alzheimer disease (AD) show a disruption in the metabolism of iron, such that there is an accumulation of iron in senile plaques, and an altered distribution of iron transport and storage proteins. One of the earliest events in AD is the generation of oxidative stress, which may be related to the generation of free radicals by the excess iron that is observed in the disease. Iron has also been shown to mediate the in vitro toxicity of amyloid-beta peptide, and the presence of iron in most in vitro systems could underlie the toxicity that is normally attributed to amyloid-beta in these studies. In contrast, several recent studies have suggested that amyloid-beta may decrease oxidative stress and decrease the toxicity of iron. Continued examination of the complex interactions that occur between iron and amyloid-beta may assist in the elucidation of the mechanisms that underlie the neurodegeneration that leads to dementia in AD.

  7. ABC Transporters and the Alzheimer's Disease Enigma.

    Science.gov (United States)

    Wolf, Andrea; Bauer, Björn; Hartz, Anika M S

    2012-01-01

    Alzheimer's disease (AD) is considered the "disease of the twenty-first century." With a 10-fold increase in global incidence over the past 100 years, AD is now reaching epidemic proportions and by all projections, AD patient numbers will continue to rise. Despite intense research efforts, AD remains a mystery and effective therapies are still unavailable. This represents an unmet need resulting in clinical, social, and economic problems. Over the last decade, a new AD research focus has emerged: ATP-binding cassette (ABC) transporters. In this article, we provide an overview of the ABC transporters ABCA1, ABCA2, P-glycoprotein (ABCB1), MRP1 (ABCC1), and BCRP (ABCG2), all of which are expressed in the brain and have been implicated in AD. We summarize recent findings on the role of these five transporters in AD, and discuss their potential to serve as therapeutic targets.

  8. FDA Facilitates Research on Earlier Stages of Alzheimer's Disease

    Science.gov (United States)

    ... Updates FDA Facilitates Research on Earlier Stages of Alzheimer's Disease Share Tweet Linkedin Pin it More sharing ... disease.” back to top New Paths for New Alzheimer’s Drugs FDA’s draft guidance aims to encourage research ...

  9. Cerebral microvascular pathology in aging and Alzheimer's disease

    NARCIS (Netherlands)

    Farkas, E; Luiten, PGM

    The aging of the central nervous system and the development of incapacitating neurological diseases like Alzheimer's disease (AD) are generally associated with a wide range of histological and pathophysiological changes eventually leading to compromised cognitive status. Although the diverse

  10. Cerebral microvascular pathology in aging and Alzheimer's disease

    NARCIS (Netherlands)

    Farkas, E; Luiten, PGM

    2001-01-01

    The aging of the central nervous system and the development of incapacitating neurological diseases like Alzheimer's disease (AD) are generally associated with a wide range of histological and pathophysiological changes eventually leading to compromised cognitive status. Although the diverse trigger

  11. Secretases as targets for drug design in Alzheimer's disease

    NARCIS (Netherlands)

    Hendriksen, JVRB; Nottet, HSLM; Smits, HA; Smits, H.J.

    Alzheimer's disease accounts for the majority of dementia in the elderly. Worldwide, approximately 20 million people are suffering from this devastating disease, with no effective treatment currently available. For efficient drug design, it is important to identify the molecular mechanisms

  12. Biological and genetic markers of sporadic Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Engelborghs S

    2001-04-01

    Full Text Available With the development of new treatments, there is an increasing need for early diagnosis of sporadic Alzheimer's disease. Therefore, biological markers allowing positive diagnosis early in the course of the disease are highly desirable. Cerebrospinal fluid levels of protein tau were shown to be significantly increased in patients with Alzheimer's disease. Although sensitivity is high, poor specificity limits the diagnostic value of this marker. The same is true for the 42 amino acid isoform of beta-amyloid protein that is significantly decreased in cerebrospinal fluid of Alzheimer's disease patients. However, combining both markers could improve specificity at least allowing differentiation between Alzheimer's disease, normal ageing and depressive pseudodementia. Other biological markers such as cerebrospinal fluid levels of neurotransmitters, cytokines or superoxide dismutase were shown to have even less diagnostic value. The apolipoprotein epsilon 4 allele is a risk factor for Alzheimer's disease but not a diagnostic marker as many individuals who inherit epsilon 4 do not develop the disease. Till now, a single diagnostic marker allowing discrimination between Alzheimer's disease and other dementias does not exist. Combined cerebrospinal fluid levels of beta-amyloid protein and tau protein might be used as a marker that helps discriminating Alzheimer's disease from normal ageing and depression.

  13. Alzheimer's disease: The next frontier-Special Report 2017.

    Science.gov (United States)

    Karlawish, Jason; Jack, Clifford R; Rocca, Walter A; Snyder, Heather M; Carrillo, Maria C

    2017-04-01

    In the history of medicine, one means to progress is when we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging-Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis. This Special Report examines how the development and validation of Alzheimer's disease biomarkers-including those detectable in the blood or cerebral spinal fluid, or through neuroimaging-is a top research priority. This has the potential to markedly change how we diagnose Alzheimer's disease and, as a result, how we count the number of people with this disease. As research advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we envision a future in which Alzheimer's disease is placed in the same category as other chronic diseases, such as cardiovascular disease or diabetes, which can be readily identified with biomarkers and treated before irrevocable disability occurs. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  14. 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.

  15. Hippocampal atrophy rates in Alzheimer disease

    Science.gov (United States)

    Henneman, W J.P.; Sluimer, J D.; Barnes, J; van der Flier, W M.; Sluimer, I C.; Fox, N C.; Scheltens, P; Vrenken, H; Barkhof, F

    2009-01-01

    Objective: To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls. Methods: We included 64 patients with AD (67 ± 9 years; F/M 38/26), 44 patients with MCI (71 ± 6 years; 21/23), and 34 controls (67 ± 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 ± 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools. Results: All MRI measures differed between groups (p < 0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio [HR]: 5.7 [95% confidence interval: 1.5–22.2]), hippocampal atrophy rate (5.2 [1.9–14.3]), and whole brain atrophy rate (2.8 [1.1–7.2]) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1–606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression. Conclusion: Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD. GLOSSARY AD = Alzheimer disease; BET = brain

  16. Domain adaptation for Alzheimer's disease diagnostics.

    Science.gov (United States)

    Wachinger, Christian; Reuter, Martin

    2016-10-01

    With the increasing prevalence of Alzheimer's disease, research focuses on the early computer-aided diagnosis of dementia with the goal to understand the disease process, determine risk and preserving factors, and explore preventive therapies. By now, large amounts of data from multi-site studies have been made available for developing, training, and evaluating automated classifiers. Yet, their translation to the clinic remains challenging, in part due to their limited generalizability across different datasets. In this work, we describe a compact classification approach that mitigates overfitting by regularizing the multinomial regression with the mixed ℓ1/ℓ2 norm. We combine volume, thickness, and anatomical shape features from MRI scans to characterize neuroanatomy for the three-class classification of Alzheimer's disease, mild cognitive impairment and healthy controls. We demonstrate high classification accuracy via independent evaluation within the scope of the CADDementia challenge. We, furthermore, demonstrate that variations between source and target datasets can substantially influence classification accuracy. The main contribution of this work addresses this problem by proposing an approach for supervised domain adaptation based on instance weighting. Integration of this method into our classifier allows us to assess different strategies for domain adaptation. Our results demonstrate (i) that training on only the target training set yields better results than the naïve combination (union) of source and target training sets, and (ii) that domain adaptation with instance weighting yields the best classification results, especially if only a small training component of the target dataset is available. These insights imply that successful deployment of systems for computer-aided diagnostics to the clinic depends not only on accurate classifiers that avoid overfitting, but also on a dedicated domain adaptation strategy.

  17. Alzheimer disease and pre-emptive suicide.

    Science.gov (United States)

    Davis, Dena S

    2014-08-01

    There is a flood of papers being published on new ways to diagnose Alzheimer disease (AD) before it is symptomatic, involving a combination of invasive tests (eg, spinal tap), and pen and paper tests. This changes the landscape with respect to genetic tests for risk of AD, making rational suicide a much more feasible option. Before the availability of these presymptomatic tests, even someone with a high risk of developing AD could not know if and when the disease was approaching. One could lose years of good life by committing suicide too soon, or risk waiting until it was too late and dementia had already sapped one of the ability to form and carry out a plan. One can now put together what one knows about one's risk, with continuing surveillance via these clinical tests, and have a good strategy for planning one's suicide before one becomes demented. This has implications for how these genetic and clinical tests are marketed and deployed, and the language one uses to speak about them. The phrase 'there is nothing one can do' is insulting and disrespectful of the planned suicide option, as is the language of the Risk Evaluation and Education for Alzheimer's Disease (REVEAL) studies and others that conclude that it is 'safe' to tell subjects their risk status for AD. Further, the argument put forward by some researchers that presymptomatic testing should remain within research protocols, and the results not shared with subjects until such time as treatments become available, disrespects the autonomy of people at high risk who consider suicide an option.

  18. 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.

  19. Interneurons in the human olfactory system in Alzheimer's disease.

    Science.gov (United States)

    Saiz-Sanchez, Daniel; Flores-Cuadrado, Alicia; Ubeda-Bañon, Isabel; de la Rosa-Prieto, Carlos; Martinez-Marcos, Alino

    2016-02-01

    The principal olfactory structures display Alzheimer's disease (AD) related pathology at early stages of the disease. Consequently, olfactory deficits are among the earliest symptoms. Reliable olfactory tests for accurate clinical diagnosis are rarely made. In addition, neuropathological analysis postmortem of olfactory structures is often not made. Therefore, the relationship between the clinical features and the underlying pathology is poorly defined. Traditionally, research into Alzheimer's disease has focused on the degeneration of cortical temporal projection neurons and cholinergic neurons. Recent evidence has demonstrated the neurodegeneration of interneuron populations in AD. This review provides an updated overview of the pathological involvement of interneuron populations in the human olfactory system in Alzheimer's disease.

  20. Toward precision medicine in Alzheimer's disease.

    Science.gov (United States)

    Reitz, Christiane

    2016-03-01

    In Western societies, Alzheimer's disease (AD) is the most common form of dementia and the sixth leading cause of death. In recent years, the concept of precision medicine, an approach for disease prevention and treatment that is personalized to an individual's specific pattern of genetic variability, environment and lifestyle factors, has emerged. While for some diseases, in particular select cancers and a few monogenetic disorders such as cystic fibrosis, significant advances in precision medicine have been made over the past years, for most other diseases precision medicine is only in its beginning. To advance the application of precision medicine to a wider spectrum of disorders, governments around the world are starting to launch Precision Medicine Initiatives, major efforts to generate the extensive scientific knowledge needed to integrate the model of precision medicine into every day clinical practice. In this article we summarize the state of precision medicine in AD, review major obstacles in its development, and discuss its benefits in this highly prevalent, clinically and pathologically complex disease.

  1. The news advances on Alzheimer's disease's therapeutics.

    Science.gov (United States)

    Sun, H-Q; Zhang, X; Huang, W-J; Chen, W-W

    2016-05-01

    Alzheimer's disease (AD) is a multifaceted disorder, characterized by the failure of memory and dementia. AD affects mostly elder above 65 years of age and is confirmed by post-mortem detection in the brain, of extracellular senile plaques of amyloid-beta (Aβ) and intracellular neurofibrillary tangles. These pathological hallmarks appear in the brain when the disease is already installed. The difficulty of earlier diagnosis and possibly, the poor understanding of the disease etiology, limit the benefits afforded by available treatments. Indeed, several putative drugs resulting from thorough investigations in preclinical studies have failed to produce clinical results, suggesting the development of further therapeutic alternatives. Recently, the regular practice of physical activity has been shown as one of the effective preventive or curative mean against AD. This finding rekindles the debate on the place of the intrinsic vascular component in the AD pathogenesis which is an aspect of the disease often considered as a distinct pathology. A new integrative conception of the disease may offer an advantage to current therapies which may gain in potency if combined in a multi-target manner to yield true improvements. This review will revisit the pathophysiology of AD and discuss the advanced therapeutics currently in use.

  2. The value of incomplete mouse models of Alzheimer's disease.

    Science.gov (United States)

    Radde, Rebecca; Duma, Cecilia; Goedert, Michel; Jucker, Mathias

    2008-03-01

    To study Alzheimer's disease (AD), a variety of mouse models has been generated through the overexpression of the amyloid precursor protein and/or the presenilins harboring one or several mutations found in familial AD. With aging, these mice develop several lesions similar to those of AD, including diffuse and neuritic amyloid deposits, cerebral amyloid angiopathy, dystrophic neurites and synapses, and amyloid-associated neuroinflammation. Other characteristics of AD, such as neurofibrillary tangles and nerve cell loss, are not satisfactorily reproduced in these models. Mouse models that recapitulate only specific aspects of AD pathogenesis are of great advantage when deciphering the complexity of the disease and can contribute substantially to diagnostic and therapeutic innovations. Incomplete mouse models have been key to the development of Abeta42-targeted therapies, as well as to the current understanding of the interrelationship between cerebral beta-amyloidosis and tau neurofibrillary lesions, and are currently being used to develop novel diagnostic agents for in vivo imaging.

  3. Familial Pompe Disease

    National Research Council Canada - National Science Library

    Tecellioglu, Mehmet; Kamisli, Ozden

    2015-01-01

    .... We present a family with Pompe disease consisting of the asymptomatic mother and two siblings who presented with muscle weakness and respiratory failure and who had been followed-up with a diagnosis...

  4. Metal dyshomeostasis and oxidative stress in Alzheimer's disease.

    Science.gov (United States)

    Greenough, Mark A; Camakaris, James; Bush, Ashley I

    2013-04-01

    Alzheimer's disease is the leading cause of dementia in the elderly and is defined by two pathological hallmarks; the accumulation of aggregated amyloid beta and excessively phosphorylated Tau proteins. The etiology of Alzheimer's disease progression is still debated, however, increased oxidative stress is an early and sustained event that underlies much of the neurotoxicity and consequent neuronal loss. Amyloid beta is a metal binding protein and copper, zinc and iron promote amyloid beta oligomer formation. Additionally, copper and iron are redox active and can generate reactive oxygen species via Fenton (and Fenton-like chemistry) and the Haber-Weiss reaction. Copper, zinc and iron are naturally abundant in the brain but Alzheimer's disease brain contains elevated concentrations of these metals in areas of amyloid plaque pathology. Amyloid beta can become pro-oxidant and when complexed to copper or iron it can generate hydrogen peroxide. Accumulating evidence suggests that copper, zinc, and iron homeostasis may become perturbed in Alzheimer's disease and could underlie an increased oxidative stress burden. In this review we discuss oxidative/nitrosative stress in Alzheimer's disease with a focus on the role that metals play in this process. Recent studies have started to elucidate molecular links with oxidative/nitrosative stress and Alzheimer's disease. Finally, we discuss metal binding compounds that are designed to cross the blood brain barrier and restore metal homeostasis as potential Alzheimer's disease therapeutics.

  5. Immunotherapeutic Strategies for Alzheimer's Disease Treatment

    Directory of Open Access Journals (Sweden)

    Beka Solomon

    2009-01-01

    Full Text Available Naturally occurring antibodies against amyloid-β peptides have been found in human cerebrospinal fluid and in the plasma of healthy individuals, but were significantly lower in Alzheimer's disease (AD patients, suggesting that AD may be an immunodeficient disorder. The performance of anti-amyloid-β antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system, preventing and dissolving amyloid-β plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Active and/or passive immunization against the amyloid-β peptide has been proposed as a method for preventing and/or treating AD. Immunotherapy represents fascinating ways to test the amyloid hypothesis and offers genuine opportunities for AD treatment, but requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.

  6. Memory for music in Alzheimer's disease: unforgettable?

    Science.gov (United States)

    Baird, Amee; Samson, Séverine

    2009-03-01

    The notion that memory for music can be preserved in patients with Alzheimer's Disease (AD) has been raised by a number of case studies. In this paper, we review the current research examining musical memory in patients with AD. In keeping with models of memory described in the non-musical domain, we propose that various forms of musical memory exist, and may be differentially impaired in AD, reflecting the pattern of neuropathological changes associated with the condition. Our synthesis of this literature reveals a dissociation between explicit and implicit musical memory functions. Implicit, specifically procedural musical memory, or the ability to play a musical instrument, can be spared in musicians with AD. In contrast, explicit musical memory, or the recognition of familiar or unfamiliar melodies, is typically impaired. Thus, the notion that music is unforgettable in AD is not wholly supported. Rather, it appears that the ability to play a musical instrument may be unforgettable in some musicians with AD.

  7. Metaphor comprehension in Alzheimer's disease: novelty matters.

    Science.gov (United States)

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

    2008-10-01

    The comprehension of non-literal language was investigated in 20 probable Alzheimer's disease (pAD) patients by comparing their performance to that of 20 matched control subjects. pAD patients were unimpaired in the comprehension of conventional metaphors and idioms. However, their performance was significantly lower in the case of non-conventional (novel) metaphor comprehension. This ability was not related to global cognitive deterioration or to deficits in the cognitive domains of attention, memory and language comprehension. On the other hand, the impairment in verbal reasoning appeared to be relevant for both novel and conventional metaphor comprehension. The relationship between novel metaphor comprehension and performance in the visual-spatial planning task of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) suggests that executive impairment, possibly related to prefrontal dysfunction, may be responsible for the pAD patients' poor performance in novel metaphor comprehension. The present findings suggest a role of the prefrontal cortex in novel metaphor comprehension.

  8. Nutrition and the Risk of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Nan Hu

    2013-01-01

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD.

  9. New Acetylcholinesterase Inhibitors for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Mona Mehta

    2012-01-01

    Full Text Available Acetylcholinesterase (AChE remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEI continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This pharmacological approach continues to be active with many promising compounds.

  10. Alzheimer's disease: recent advances and future perspectives.

    Science.gov (United States)

    Ubhi, Kiren; Masliah, Eliezer

    2013-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory deficits and other cognitive disturbances. Neuropathologically, AD is characterized by the progressive loss of basal forebrain cholinergic neurons that innervate the hippocampus and cortex and the abnormal extracellular accumulation of amyloid-β and intracellular tau protein. Current research on AD is focused on the mechanisms underlying the abnormal oligomerization, fibrillation, and accumulation of the amyloid-β and tau proteins, mechanisms that may alter the dynamics of this accumulation and on experimental therapeutics approaches aimed at the clearance of the abnormally folded proteins and other potentially neuroprotective interventions. This review will summarize the main areas of investigation in AD and present ways forward for future work.

  11. Preclinical Alzheimer disease-the challenges ahead.

    Science.gov (United States)

    Sperling, Reisa A; Karlawish, Jason; Johnson, Keith A

    2013-01-01

    There is growing recognition that the pathophysiological process of Alzheimer disease (AD) begins many years prior to clinically obvious symptoms, and the concept of a presymptomatic or preclinical stage of AD is becoming more widely accepted. Advances in biomarker studies have enabled detection of AD pathology in vivo in clinically normal older individuals. The predictive value of these biomarkers at the individual patient level, however, remains to be elucidated. The ultimate goal of identifying individuals in the preclinical stages of AD is to facilitate early intervention to delay and perhaps even prevent emergence of the clinical syndrome. A number of challenges remain to be overcome before this concept can be validated and translated into clinical practice.

  12. Implicit memory for music in Alzheimer's disease.

    Science.gov (United States)

    Halpern, A R; O'Connor, M G

    2000-07-01

    Short, unfamiliar melodies were presented to young and older adults and to Alzheimer's disease (AD) patients in an implicit and an explicit memory task. The explicit task was yes-no recognition, and the implicit task was pleasantness ratings, in which memory was shown by higher ratings for old versus new melodies (the mere exposure effect). Young adults showed retention of the melodies in both tasks. Older adults showed little explicit memory but did show the mere exposure effect. The AD patients showed neither. The authors considered and rejected several artifactual reasons for this null effect in the context of the many studies that have shown implicit memory among AD patients. As the previous studies have almost always used the visual modality for presentation, they speculate that auditory presentation, especially of nonverbal material, may be compromised in AD because of neural degeneration in auditory areas in the temporal lobes.

  13. Retromer in Alzheimer disease, Parkinson disease and other neurological disorders.

    Science.gov (United States)

    Small, Scott A; Petsko, Gregory A

    2015-03-01

    Retromer is a protein assembly that has a central role in endosomal trafficking, and retromer dysfunction has been linked to a growing number of neurological disorders. First linked to Alzheimer disease, retromer dysfunction causes a range of pathophysiological consequences that have been shown to contribute to the core pathological features of the disease. Genetic studies have established that retromer dysfunction is also pathogenically linked to Parkinson disease, although the biological mechanisms that mediate this link are only now being elucidated. Most recently, studies have shown that retromer is a tractable target in drug discovery for these and other disorders of the nervous system.

  14. Delaying the onset of Alzheimer disease

    Science.gov (United States)

    Craik, Fergus I.M.; Bialystok, Ellen; Freedman, Morris

    2010-01-01

    Objectives: There is strong epidemiologic evidence to suggest that older adults who maintain an active lifestyle in terms of social, mental, and physical engagement are protected to some degree against the onset of dementia. Such factors are said to contribute to cognitive reserve, which acts to compensate for the accumulation of amyloid and other brain pathologies. We present evidence that lifelong bilingualism is a further factor contributing to cognitive reserve. Methods: Data were collected from 211 consecutive patients diagnosed with probable Alzheimer disease (AD). Patients' age at onset of cognitive impairment was recorded, as was information on occupational history, education, and language history, including fluency in English and any other languages. Following this procedure, 102 patients were classified as bilingual and 109 as monolingual. Results: We found that the bilingual patients had been diagnosed 4.3 years later and had reported the onset of symptoms 5.1 years later than the monolingual patients. The groups were equivalent on measures of cognitive and occupational level, there was no apparent effect of immigration status, and the monolingual patients had received more formal education. There were no gender differences. Conclusions: The present data confirm results from an earlier study, and thus we conclude that lifelong bilingualism confers protection against the onset of AD. The effect does not appear to be attributable to such possible confounding factors as education, occupational status, or immigration. Bilingualism thus appears to contribute to cognitive reserve, which acts to compensate for the effects of accumulated neuropathology. GLOSSARY AD = Alzheimer disease; MMSE = Mini-Mental State Examination. PMID:21060095

  15. Copernicus revisited: amyloid beta in Alzheimer's disease.

    Science.gov (United States)

    Joseph, J; Shukitt-Hale, B; Denisova, N A; Martin, A; Perry, G; Smith, M A

    2001-01-01

    The beta-amyloid hypothesis of Alzheimer's Disease (AD) has dominated the thinking and research in this area for over a decade and a half. While there has been a great deal of effort in attempting to prove its centrality in this devastating disease, and while an enormous amount has been learned about its properties (e.g., putative toxicity, processing and signaling), Abeta has not proven to be both necessary and sufficient for the development, neurotoxicity, and cognitive deficits associated with this disease. Instead, the few treatments that are available have emerged from aging research and are primarily directed toward modification of acetylcholine levels. Clearly, it is time to rethink this position and to propose instead that future approaches should focus upon altering the age-related sensitivity of the neuronal environment to insults involving such factors as inflammation and oxidative stress. In other words "solve the problems of aging and by extension those of AD will also be reduced." This review is being submitted as a rather Lutherian attempt to "nail an alternative thesis" to the gate of the Church of the Holy Amyloid to open its doors to the idea that aging is the most pervasive element in this disease and Abeta is merely one of the planets.

  16. Targeting synaptic dysfunction in Alzheimer's disease therapy.

    Science.gov (United States)

    Nisticò, Robert; Pignatelli, Marco; Piccinin, Sonia; Mercuri, Nicola B; Collingridge, Graham

    2012-12-01

    In the past years, major efforts have been made to understand the genetics and molecular pathogenesis of Alzheimer's disease (AD), which has been translated into extensive experimental approaches aimed at slowing down or halting disease progression. Advances in transgenic (Tg) technologies allowed the engineering of different mouse models of AD recapitulating a range of AD-like features. These Tg models provided excellent opportunities to analyze the bases for the temporal evolution of the disease. Several lines of evidence point to synaptic dysfunction as a cause of AD and that synapse loss is a pathological correlate associated with cognitive decline. Therefore, the phenotypic characterization of these animals has included electrophysiological studies to analyze hippocampal synaptic transmission and long-term potentiation, a widely recognized cellular model for learning and memory. Transgenic mice, along with non-Tg models derived mainly from exogenous application of Aβ, have also been useful experimental tools to test the various therapeutic approaches. As a result, numerous pharmacological interventions have been reported to attenuate synaptic dysfunction and improve behavior in the different AD models. To date, however, very few of these findings have resulted in target validation or successful translation into disease-modifying compounds in humans. Here, we will briefly review the synaptic alterations across the different animal models and we will recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. Finally, we will highlight intrinsic limitations in the use of experimental systems and related challenges in translating preclinical studies into human clinical trials.

  17. Explorative and targeted neuroproteomics in Alzheimer's disease.

    Science.gov (United States)

    Brinkmalm, Ann; Portelius, Erik; Öhrfelt, Annika; Brinkmalm, Gunnar; Andreasson, Ulf; Gobom, Johan; Blennow, Kaj; Zetterberg, Henrik

    2015-07-01

    Alzheimer's disease (AD) is a progressive brain amyloidosis that injures brain regions involved in memory consolidation and other higher brain functions. Neuropathologically, the disease is characterized by accumulation of a 42 amino acid peptide called amyloid β (Aβ42) in extracellular senile plaques, intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles, and neuronal and axonal degeneration and loss. Biomarker assays capturing these pathologies have been developed for use on cerebrospinal fluid samples but there are additional molecular pathways that most likely contribute to the neurodegeneration and full clinical expression of AD. One way of learning more about AD pathogenesis is to identify novel biomarkers for these pathways and examine them in longitudinal studies of patients in different stages of the disease. Here, we discuss targeted proteomic approaches to study AD and AD-related pathologies in closer detail and explorative approaches to discover novel pathways that may contribute to the disease. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology.

  18. Assessing impulsivity changes in Alzheimer disease.

    Science.gov (United States)

    Rochat, Lucien; Delbeuck, Xavier; Billieux, Joël; d'Acremont, Mathieu; Van der Linden, Anne-Claude Juillerat; Van der Linden, Martial

    2008-01-01

    Impulsive behaviors are common in brain-damaged patients including those with neurodegenerative diseases such as Alzheimer disease (AD). The objective of this study was to develop and validate a short version of the UPPS Impulsive Behavior Scale assessing changes on 4 different dimensions of impulsivity, namely urgency, (lack of) premeditation, (lack of) perseverance, and sensation seeking, arising in the course of a neurodegenerative disease. To this end, caregivers of 83 probable AD patients completed a short questionnaire adapted from the UPPS Impulsive Behavior Scale. Exploratory and confirmatory factor analyses of the data were performed and revealed that a model with 4 distinct but related latent variables corresponding to 4 different dimensions of impulsivity fit the data best. Furthermore, the results showed that lack of perseverance, followed by lack of premeditation and urgency, increased after the onset of the disease, whereas sensation seeking decreased. Overall, the multifaceted nature of impulsivity was confirmed in a sample of AD patients, whose caregivers reported significant changes regarding each facet of impulsivity. Consequently, the short version of the UPPS Impulsive Behavior Scale opens up interesting prospects for a better comprehension of behavioral symptoms of dementia.

  19. The role of high-fat diet in an APP/PS1 model of familial Alzheimer disease = Efecto de una dieta rica en grasas en ratones APP/PS1, modelo familiar de la enfermedad de Alzheimer

    OpenAIRE

    Petrov, Dmitry

    2015-01-01

    La obesidad es una pandemia mundial, la cual según estudios recientes afecta a más de 2.000 millones de personas en todo el mundo y conlleva una fuerte presión de los sistemas sanitarios globales. El problema se ve aumentado no sólo por los costes directos asociados al sobrepeso, sino también por las comorbilidades relacionadas, entre ellas el incremento del riesgo de desarrollo de enfermedades neurodegenerativas, como por ejemplo la enfermedad de Alzheimer (EA), principal causa de demencia s...

  20. Neural stem cells and Alzheimer's disease: challenges and hope.

    Science.gov (United States)

    Zhongling Feng; Gang Zhao; Lei Yu

    2009-01-01

    Alzheimer's disease is characterized by degeneration and dysfunction of synapses and neurons in brain regions critical for learning and memory functions. The endogenous generation of new neurons in certain regions of the mature brain, derived from primitive cells termed neural stem cells, has raised hope that neural stem cells may be recruited for structural brain repair. Stem cell therapy has been suggested as a possible strategy for replacing damaged circuitry and restoring learning and memory abilities in patients with Alzheimer's disease. In this review, we outline the promising investigations that are raising hope, and understanding the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in Alzheimer's disease.

  1. Beclin 1 complex in autophagy and Alzheimer disease.

    Science.gov (United States)

    Jaeger, Philipp A; Wyss-Coray, Tony

    2010-10-01

    Beclin 1 is a protein involved in the regulation of autophagy and has been shown to be reduced in patients with Alzheimer disease. This review summarizes the current research data that link disturbances in autophagy, a cellular degradation and maintenance pathway, to the development of Alzheimer disease and related neurodegenerative diseases. It also provides a brief overview of the existing pharmacological interventions available to modulate autophagy activity in mammalian cells.

  2. 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.

  3. The Alzheimer's disease β-secretase enzyme, BACE1

    OpenAIRE

    Vassar Robert; Cole Sarah L

    2007-01-01

    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 m...

  4. 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.

  5. The storm before the quiet : neuronal hyperactivity and Aβ in the presymptomatic stages of Alzheimer's disease

    NARCIS (Netherlands)

    Stargardt, Anita; Swaab, Dick F; Bossers, K.

    2015-01-01

    Neuronal activity directly promotes the production and secretion of amyloid β (Aβ). Interestingly, neuronal hyperactivity can be observed in presymptomatic stages of both sporadic and familial Alzheimer's disease (AD) and in several AD mouse models. In this review, we will highlight the recent evide

  6. Alzheimer's Disease Phenotypes and Genotypes Associated with Mutations in Presenilin 2

    Science.gov (United States)

    Jayadev, Suman; Leverenz, James B.; Steinbart, Ellen; Stahl, Justin; Klunk, William; Yu, Cheng-En; Bird, Thomas D.

    2010-01-01

    Mutations in presenilin 2 are rare causes of early onset familial Alzheimer's disease. Eighteen presenilin 2 mutations have been reported, although not all have been confirmed pathogenic. Much remains to be learned about the range of phenotypes associated with these mutations. We have analysed our unique collection of 146 affected cases in 11…

  7. Alzheimer's Disease Phenotypes and Genotypes Associated with Mutations in Presenilin 2

    Science.gov (United States)

    Jayadev, Suman; Leverenz, James B.; Steinbart, Ellen; Stahl, Justin; Klunk, William; Yu, Cheng-En; Bird, Thomas D.

    2010-01-01

    Mutations in presenilin 2 are rare causes of early onset familial Alzheimer's disease. Eighteen presenilin 2 mutations have been reported, although not all have been confirmed pathogenic. Much remains to be learned about the range of phenotypes associated with these mutations. We have analysed our unique collection of 146 affected cases in 11…

  8. A sobrecarga do cuidador familiar de idoso com Alzheimer = Family caregiver burden caring for the elderly with Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Seima, Márcia Daniele

    2011-01-01

    Full Text Available Trata-se de estudo de corte transversal cujo objetivo foi identificar o nível de sobrecarga do cuidador familiar do idoso com Alzheimer de uma comunidade. A amostra de conveniência foi composta de 208 cuidadores familiares. Os dados foram coletados por meio da aplicação de questionário socioeconômico/demográfico e clínico e escala do Inventário de Sobrecarga de Zarit. Os dados foram compilados e analisados no programa Microsoft Excel 2007. Dos 208 cuidadores, 47 (22,6% apresentaram sobrecarga pequena, 96 (46,2% sobrecarga moderada, 54 (26% sobrecarga moderada a severa e 11 (5,2% sobrecarga severa. O processo de cuidado dos profissionais da saúde junto aos cuidadores não pode ser apenas prescritivo, esse deve ser desenvolvido sob demanda, com intuito de minimizar as sobrecargas, que enfrentam nas situações de cuidado com o idoso portador de Alzheimer

  9. Neuropathological and clinical phenotype of an Italian Alzheimer family with M239V mutation of presenilin 2 gene.

    Science.gov (United States)

    Marcon, Gabriella; Giaccone, Giorgio; Cupidi, Chiara; Balestrieri, Matteo; Beltrami, Carlo Alberto; Finato, Nicoletta; Bergonzi, Paolo; Sorbi, Sandro; Bugiani, Orso; Tagliavini, Fabrizio

    2004-03-01

    Presenilin 1 and 2 are 2 highly homologous genes involved in familial Alzheimer disease. While more than 100 mutations in presenilin 1 are known to segregate with the disease in familial Alzheimer disease, only 9 mutations of presenilin 2 have been identified to date. We report the clinical and neuropathological phenotype of FLO10, the large Italian Alzheimer kindred associated with methionine to valine substitution at residue 239 of presenilin 2. The patients showed a remarkable variability in age of onset of symptoms, disease duration, and clinical presentation. The neuropathological study of 2 patients revealed peculiar features in addition to neurofibrillary changes and A beta amyloid deposits in the neuropil and vessel wall. Ectopic neurons in the subcortical white matter, often containing neurofibrillary tangles, were found in both patients, one of whom presented with epilepsy. Furthermore, 1 patient showed an unusually high number of ghost tangles in the cerebral cortex. These observations indicate that the Alzheimer kindred FLO10 associated with M239V mutation of presenilin 2 is characterized by some peculiarities of the clinical and neuropathologic phenotype compared to sporadic Alzheimer disease.

  10. Estrogen Intake and Copper Depositions: Implications for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Florian Amtage

    2014-06-01

    Full Text Available We present a patient with chronic postmenopausal estrogen intake with presence of Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the pathophysiological mechanisms of estrogen intake and copper accumulation in various tissues, including the central nervous system. Sonography was compatible with copper accumulation in the basal ganglia, but the patient showed no clinical signs of Wilson's disease. Magnetic resonance imaging and positron emission tomography revealed a typical pattern for Alzheimer's disease. We propose increased copper levels as a direct effect of estrogen intake due to an augmented ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free serum copper on accompanying Alzheimer's disease, knowing that copper plays a crucial role in the formation of amyloid plaques and tau aggregation. This might offer a partial explanation for the observation that postmenopausal estrogen therapy is associated with a higher risk of mild cognitive impairment and Alzheimer's disease.

  11. Neuroinflammation in Alzheimer's disease wanes with age

    Directory of Open Access Journals (Sweden)

    Hoozemans Jeroen JM

    2011-12-01

    Full Text Available Abstract Background Inflammation is a prominent feature in Alzheimer's disease (AD. It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated. Methods In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years. The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodies directed against CD68 (KP1, HLA class II (CR3/43 and glial fibrillary acidic protein (GFAP. Results By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD. Conclusion Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease.

  12. Bimanual Gesture Imitation in Alzheimer's Disease.

    Science.gov (United States)

    Sanin, G Nter; Benke, Thomas

    2017-01-01

    Unimanual gesture production or imitation has often been studied in Alzheimer's disease (AD) during apraxia testing. In the present study, it was hypothesized that bimanual motor tasks may be a sensitive method to detect impairments of motor cognition in AD due to increased demands on the cognitive system. We investigated bimanual, meaningless gesture imitation in 45 AD outpatients, 38 subjects with mild cognitive impairment (MCI), and 50 normal controls (NC) attending a memory clinic. Participants performed neuropsychological background testing and three tasks: the Interlocking Finger Test (ILF), Imitation of Alternating Hand Movements (AHM), and Bimanual Rhythm Tapping (BRT). The tasks were short and easy to administer. Inter-rater reliability was high across all three tests. AD patients performed significantly poorer than NC and MCI participants; a deficit to imitate bimanual gestures was rarely found in MCI and NC participants. Sensitivity to detect AD ranged from 0.5 and 0.7, specificity beyond 0.9. ROC analyses revealed good diagnostic accuracy (0.77 to 0.92). Impairment to imitate bimanual gestures was mainly predicted by diagnosis and disease severity. Our findings suggest that an impairment to imitate bimanual, meaningless gestures is a valid disease marker of mild to moderate AD and can easily be assessed in memory clinic settings. Based on our preliminary findings, it appears to be a separate impairment which can be distinguished from other cognitive deficits.

  13. Alzheimer's disease drug development: translational neuroscience strategies.

    Science.gov (United States)

    Cummings, Jeffrey L; Banks, Sarah J; Gary, Ronald K; Kinney, Jefferson W; Lombardo, Joseph M; Walsh, Ryan R; Zhong, Kate

    2013-06-01

    Alzheimer's disease (AD) is an urgent public health challenge that is rapidly approaching epidemic proportions. New therapies that defer or prevent the onset, delay the decline, or improve the symptoms are urgently needed. All phase 3 drug development programs for disease-modifying agents have failed thus far. New approaches to drug development are needed. Translational neuroscience focuses on the linkages between basic neuroscience and the development of new diagnostic and therapeutic products that will improve the lives of patients or prevent the occurrence of brain disorders. Translational neuroscience includes new preclinical models that may better predict human efficacy and safety, improved clinical trial designs and outcomes that will accelerate drug development, and the use of biomarkers to more rapidly provide information regarding the effects of drugs on the underlying disease biology. Early translational research is complemented by later stage translational approaches regarding how best to use evidence to impact clinical practice and to assess the influence of new treatments on the public health. Funding of translational research is evolving with an increased emphasis on academic and NIH involvement in drug development. Translational neuroscience provides a framework for advancing development of new therapies for AD patients.

  14. Mitochondrial dysfunctions in neurodegenerative diseases: relevance to Alzheimer's disease.

    Science.gov (United States)

    Hroudová, Jana; Singh, Namrata; Fišar, Zdeněk

    2014-01-01

    Mitochondrial dysfunctions are supposed to be responsible for many neurodegenerative diseases dominating in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). A growing body of evidence suggests that defects in mitochondrial metabolism and particularly of electron transport chain may play a role in pathogenesis of AD. Structurally and functionally damaged mitochondria do not produce sufficient ATP and are more prominent in producing proapoptotic factors and reactive oxygen species (ROS), and this can be an early stage of several mitochondrial disorders, including neurodegenerative diseases. Mitochondrial dysfunctions may be caused by both mutations in mitochondrial or nuclear DNA that code mitochondrial components and by environmental causes. In the following review, common aspects of mitochondrial impairment concerned about neurodegenerative diseases are summarized including ROS production, impaired mitochondrial dynamics, and apoptosis. Also, damaged function of electron transport chain complexes and interactions between pathological proteins and mitochondria are described for AD particularly and marginally for PD and HD.

  15. Randomized controlled trials for Alzheimer disease and Parkinson disease.

    Science.gov (United States)

    Lauretani, Fulvio; Ticinesi, Andrea; Meschi, Tiziana; Teresi, Giulio; Ceda, Gian Paolo; Maggio, Marcello

    2016-06-01

    The continuous increase in elderly and oldest-old population, and subsequent rise in prevalence of chronic neurological diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), are a major challenge for healthcare systems. These two conditions are the most prevalent neurodegenerative diseases in older persons and physicians should engage treatment for these patients. In this field, Randomized Clinical Trials (RCTs) specifically focused on elderly populations are still lacking. The aim of this study was to identify RCTs conducted among AD and PD and to examine the difference between mean age of enrollment and incidence of these two neurodegenerative diseases. We found that the scenario is different between PD and AD. In particular, the enrollment for PD trials seems to include younger persons than AD, although the incidence of both diseases is similar and highest after 80 years old. The consequence of these results could influence conclusive guidelines of treatment in older parkinsonian patients.

  16. Evidence for a membrane defect in Alzheimer disease brain

    Science.gov (United States)

    Nitsch, R. M.; Blusztajn, J. K.; Pittas, A. G.; Slack, B. E.; Growdon, J. H.; Wurtman, R. J.

    1992-01-01

    To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.

  17. Cognitive disability in alzheimer's disease and its management.

    Science.gov (United States)

    Corsi, M; Di Raimo, T; Di Lorenzo, C; Rapp-Ricciardi, M; Archer, T; Ricci, S; Businaro, R

    2016-01-01

    Cognitive disability linked to neurodegenerative diseases and in particular to Alzheimer's disease, remains an increasing cause for concern through a dramatic prevalence increment and associated socio-economic burdens. Initially Alzheimer's disease develops asymptomatically with primary clinical signs, such as memory impairment, decline of spatial and perceptual abilities, occurring at a later stage. This delay implies the possibility of promoting early interventions during the pre-symptomatic stage of the disease. Different strategies have been applied in order to prevent/delay onset of Alzheimer's disease or at least to improve quality of life and health conditions of Alzheimer's disease patients and their caregivers, especially in the absence of current viable therapies. Multidomain interventions, aimed at affecting several risk factors simultaneously, offer a versatility that may attain improved outcomes in comparison with single-domain prevention trials. These multidomain interventions involve diet, physical exercise, cognitive training and social activities, while music therapy, improving self-consciousness and reducing neurofibrils, may contribute to deceleration/delay onset of Alzheimer's disease progression. Information and Communication Technology (ICT) provides broad applications to improve quality of life and well-being of Alzheimer's disease patients and caregivers, suffering from psychological distress, as well as reducing additional public health costs.

  18. Assessment of Alzheimer's disease symptom recognition in Korean Americans and psychometric analysis of Alzheimer's Disease Symptom Recognition Scale (ADSRS).

    Science.gov (United States)

    Lee, Sang E; Casado, Banghwa Lee

    2015-01-01

    This study examined recognition of Alzheimer's disease symptoms among Korean Americans (KAs) and assessed psychometric properties of the Alzheimer's Disease Symptom Recognition Scale (ADSRS). A cross-sectional survey collected data from 209 KAs, using a self-administered questionnaire. Results show that KAs recognized symptoms related to memory and cognitive functioning well, but had very limited recognition of neuropsychiatric symptoms. Psychometric analysis of ADSRS identified 4 factors in their symptom recognition. Findings suggest a need to raise awareness of Alzheimer's symptoms over the course of the disease. Assessment using ADSRS can be incorporated in communication in the practice context and public outreach.

  19. Are Alzheimer's disease, hypertension, and cerebrocapillary damage related?

    NARCIS (Netherlands)

    Farkas, E; De Vos, RAI; Steur, ENHJ; Luiten, PGM

    2000-01-01

    Alzheimer's disease (AD) patients are often subject to vascular dysfunction besides their specific CNS pathology, which warrants further examination of the interaction between vascular factors and the development of dementia. The association of decreased cerebral blood flow (CBF) or hypertension

  20. The rationale for deep brain stimulation in Alzheimer's disease.

    Science.gov (United States)

    Mirzadeh, Zaman; Bari, Ausaf; Lozano, Andres M

    2016-07-01

    Alzheimer's disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer's disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials.

  1. Lentivirus-expressed siRNA vectors against Alzheimer disease.

    Science.gov (United States)

    Peng, Kevin A; Masliah, Eliezer

    2010-01-01

    Amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer disease, and the accumulation of APP products ultimately leads to the familiar histopathological and clinical manifestations associated with this most common form of dementia. A protein that has been shown to promote APP accumulation is beta-secretase (beta-site APP cleaving enzyme 1, or BACE1), which is increased in the cerebrospinal fluid in those affected with Alzheimer disease. Through in vivo studies using APP transgenic mice, we demonstrated that decreasing the expression of BACE1 via lentiviral vector delivery of BACE1 siRNA has the potential for significantly reducing the cleavage of APP, accumulation of these products, and consequent neurodegeneration. As such, lentiviral-expressed siRNA against BACE1 is a therapeutic possibility in the treatment of Alzheimer disease. We detail the use of lentivirus-expressed siRNA as a method to ameliorate Alzheimer disease neuropathology in APP transgenic mice.

  2. Why musical memory can be preserved in advanced Alzheimer's disease

    National Research Council Canada - National Science Library

    Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

    2015-01-01

    Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory...

  3. Alzheimer's Disease - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... d'Alzheimer - français (French) Bilingual PDF Health Information Translations Inside the Brain: An Interactive Tour English Exploration Interactive de l'Intérieur du Cerveau - français (French) Alzheimer's Association German (Deutsch) Inside the Brain: An Interactive Tour English Im ...

  4. Research Sheds Light on Mechanism of Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Scientists from the Shanghai Institute of Materia Medica (SIMM) under the CAS Shanghai Institutes for Biological Sciences have made significant progress in suggesting a possible mechanism for the accumulation of amyloid β-peptides (Aβs), which are believed to cause Alzheimer's disease. Aβs are fragments of a protein that is snipped from another protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments would be broken down and eliminated. In Alzheimer's disease, unfortunately, the fragments accumulate to form hard, insoluble plaques, which are the characteristic lesions found in Alzheimer's patients and could dramatically inhibit several genes critical to memory and learning.

  5. 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....

  6. 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.

  7. Emotion-discrimination deficits in mild Alzheimer disease.

    Science.gov (United States)

    Kohler, Christian G; Anselmo-Gallagher, Gerri; Bilker, Warren; Karlawish, Jason; Gur, Raquel E; Clark, Christopher M

    2005-11-01

    Mild Alzheimer disease (AD) preferentially affects temporal lobe regions, which represent important structures in memory and emotional processes. This study investigated emotion discrimination in people with mild AD, versus Caretakers. Twenty AD subjects and 22 caretakers underwent computerized testing of emotion recognition and differentiation. Performances between groups were compared, controlling for possible effects of age and cognitive abilities. AD subjects showed diminished recognition of happy, sad, fearful, and neutral expressions. They also exhibited decreased differentiation between happy and sad expressions. Controlling for effects of cognitive dysfunction, AD subjects differed on recognition of happy and sad, and differentiation of sad facial expressions, and in error patterns for fearful and neutral faces. Diminished abilities for emotion discrimination are present in persons with mild AD. In persons with mild AD, who frequently reside in their own home or with close family, this diminished ability may adversely affect social functioning and quality of life.

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

    Directory of Open Access Journals (Sweden)

    Dawit A. Weldemichael

    2010-01-01

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

  9. Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Valérie Leduc

    2011-01-01

    Full Text Available Alzheimer's disease (AD—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE, the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD.

  10. The role of adenosine in Alzheimer's disease.

    Science.gov (United States)

    Rahman, Anisur

    2009-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system manifested by cognitive and memory deterioration, a variety of neuropsychiatric symptoms, behavioral disturbances, and progressive impairment of daily life activities. Current pharmacotherapies are restricted to symptomatic interventions but do not prevent progressive neuronal degeneration. Therefore, new therapeutic strategies are needed to intervene with these progressive pathological processes. In the past several years adenosine, a ubiquitously released purine ribonucleoside, has become important for its neuromodulating capability and its emerging positive experimental effects in neurodegenerative diseases. Recent research suggests that adenosine receptors play important roles in the modulation of cognitive function. The present paper attempts to review published reports and data from different studies showing the evidence of a relationship between adenosinergic function and AD-related cognitive deficits. Epidemiological studies have found an association between coffee (a nonselective adenosine receptor antagonist) consumption and improved cognitive function in AD patients and in the elderly. Long-term administration of caffeine in transgenic animal models showed a reduced amyloid burden in brain with better cognitive performance. Antagonists of adenosine A2A receptors mimic these beneficial effects of caffeine on cognitive function. Neuronal cell cultures with amyloid beta in the presence of an A2A receptor antagonist completely prevented amyloid beta-induced neurotoxicity. These findings suggest that the adenosinergic system constitutes a new therapeutic target for AD, and caffeine and A2A receptor antagonists may have promise to manage cognitive dysfunction in AD.

  11. New Perspectives on Alzheimer's Disease and Nutrition.

    Science.gov (United States)

    Gustafson, Deborah R; Clare Morris, Martha; Scarmeas, Nikolaos; Shah, Raj C; Sijben, John; Yaffe, Kristine; Zhu, Xiongwei

    2015-01-01

    Accumulating evidence shows nutritional factors influence the risk of developing Alzheimer's disease (AD) and its rate of clinical progression. Dietary and lifestyle guidelines to help adults reduce their risk have been developed. However, the clinical dementia picture remains complex, and further evidence is required to demonstrate that modifying nutritional status can protect the brain and prevent, delay, or reduce pathophysiological consequences of AD. Moreover, there is a pressing need for further research because of the global epidemic of overweight and obesity combined with longer life expectancy of the general population and generally observed decreases in body weight with aging and AD. A new research approach is needed, incorporating more sophisticated models to account for complex scenarios influencing the relationship between nutritional status and AD. Systematic research should identify and address evidence gaps. Integrating longitudinal epidemiological data with biomarkers of disease, including brain imaging technology, and randomized controlled interventions may provide greater insights into progressive and subtle neurological changes associated with dietary factors in individuals at risk for or living with AD. In addition, greater understanding of mechanisms involved in nutritional influences on AD risk and progression, such as oxidative stress and loss of neuronal membrane integrity, will better inform possible interventional strategies. There is consensus among the authors that nutritional deficits, and even states of excess, are associated with AD, but more work is needed to determine cause and effect. Appropriately designed diets or nutritional interventions may play a role, but additional research is needed on their clinical-cognitive effectiveness.

  12. Aluminum and Alzheimer's disease: a new look.

    Science.gov (United States)

    Miu, Andrei C; Benga, Oana

    2006-11-01

    Despite the circumstantial and sometimes equivocal support, the hypothetic involvement of aluminum (Al) in the etiology and pathogenesis of Alzheimer's disease (AD) has subsisted in neuroscience. There are very few other examples of scientific hypotheses on the pathogenesis of a disease that have been revisited so many times, once a new method that would allow a test of Al's accumulations in the brain of AD patients or a comparison between Al-induced and AD neuropathological signs has become available. Although objects of methodological controversies for scientists and oversimplification for lay spectators, several lines of evidence have strongly supported the involvement of Al as a secondary aggravating factor or risk factor in the pathogenesis of AD. We review evidence on the similarities and dissimilarities between Al-induced neurofibrillary degeneration and paired helical filaments from AD, the accumulation of Al in neurofibrillary tangles and senile plaques from AD, the neuropathological dissociation between AD and dialysis associated encephalopathy, and the epidemiological relations between Al in drinking water and the prevalence of AD. We also critically analyze the prospects of Al-amyloid cascade studies and other evolving lines of evidence that might shed insights into the link between Al and AD. The message between the lines of the following article is that the involvement of Al in the pathogenesis of AD should not be discarded, especially in these times when the amyloid dogma of AD etiology shows its myopia.

  13. Involvement of oxidative stress in Alzheimer disease.

    Science.gov (United States)

    Nunomura, Akihiko; Castellani, Rudy J; Zhu, Xiongwei; Moreira, Paula I; Perry, George; Smith, Mark A

    2006-07-01

    Genetic and lifestyle-related risk factors for Alzheimer disease (AD) are associated with an increase in oxidative stress, suggesting that oxidative stress is involved at an early stage of the pathologic cascade. Moreover, oxidative stress is mechanistically and chronologically associated with other key features of AD, namely, metabolic, mitochondrial, metal, and cell-cycle abnormalities. Contrary to the commonly held notion that pathologic hallmarks of AD signify etiology, several lines of evidence now indicate that aggregation of amyloid-beta and tau is a compensatory response to underlying oxidative stress. Therefore, removal of proteinaceous accumulations may treat the epiphenomenon rather than the disease and may actually enhance oxidative damage. Although some antioxidants have been shown to reduce the incidence of AD, the magnitude of the effect may be modified by individual factors such as genetic predisposition (e.g. apolipoprotein E genotype) and habitual behaviors. Because caloric restriction, exercise, and intellectual activity have been experimentally shown to promote neuronal survival through enhancement of endogenous antioxidant defenses, a combination of dietary regimen of low total calorie and rich antioxidant nutrients and maintaining physical and intellectual activities may ultimately prove to be one of the most efficacious strategies for AD prevention.

  14. RNA干扰对阿尔茨海默病家族性瑞典型APP突变的沉默作用%Induction of silencing effect of Alzheimer disease familial Swedish mutant APP by RNA interference

    Institute of Scientific and Technical Information of China (English)

    邱昕; 潘纪安; 陈宇; 张玮莹; 杨华静; 张苏明

    2005-01-01

    Objectives To observe the silencing effect of amyloid precursor protein (APP) carrying Swedish mutation of familial Alzheimer disease triggered by small interference RNA (siRNA). Methods We designed one oligonucleotide against Swedish mutant APP(APPswe) which was endogenously expressed by small interference RNA(siRNA) expressing plasmid . In order to observe the silence effect of siRNA on APP, COS-7 cells were transiently co-transfected with APPEGFP recombinant plasmid and siRNA expressing plasmid. The silencing effect of siRNA was determined by the assay of reporter gene-GFP expression levels. Results APPswe expression in COS-7 cells was knocked down by the application of siRNA. APPswesiRNA was more effective in silencing APPswe gene than wild type APP (APPwt) gene. Conclusion APPswe siRNA can effectively silence APPswe gene expression and such effect is allele-specific. Therefore, siRNA directed against APPswe may have therapeutic potential for the treatment of Alzheimer disease.%目的诱导小干涉RNA(small interference RNA,siRNA)对阿尔茨海默病淀粉样前体蛋白家族性瑞典型突变(APPswe)的沉默作用.方法设计一对针对APPswe的寡核苷酸,构建成内源性表达相应siRNA的质粒,与构建的APP-EGFP重组质粒瞬时共转染COS-7细胞,利用GFP报告基因来间接观察siRNA对APPswe的沉默作用.结果siRNA可有效地下调突变型APP,相比APPwt而言,针对突变型APP的siRNA对APPswe的沉默作用更强.结论针对APPswe的siRNA可有效地沉默APPswe基因,并有一定的等位基因特异性.因此,针对APPswe的siRNA将在阿尔茨海默病治疗研究领域扮演重要角色.

  15. Proxy-rated quality of life in Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Bhattacharya, Suvosree; Waldemar, Gunhild

    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....

  16. Ethnic differences in acetylcholinesterase inhibitor use for Alzheimer disease

    OpenAIRE

    Mehta, Kala M; Yin, Maggie; Resendez, Cynthia; Yaffe, Kristine

    2005-01-01

    Acetylcholinesterase inhibitors (AChIs) have been demonstrated to improve Alzheimer disease symptoms. Whether the use of AChIs varies by ethnicity is unknown. More than 2500 ethnically diverse patients (6% African American, 14% Latino, and 7% Asian patients) from the Alzheimer's Disease Research Centers in California were studied. Compared with white patients with AD, minority patients had 40% lower odds of AChI use (odds ratio 0.6, 95% confidence interval: 0.5 to 0.7).

  17. Ethnic differences in acetylcholinesterase inhibitor use for Alzheimer disease.

    Science.gov (United States)

    Mehta, Kala M; Yin, Maggie; Resendez, Cynthia; Yaffe, Kristine

    2005-07-12

    Acetylcholinesterase inhibitors (AChIs) have been demonstrated to improve Alzheimer disease symptoms. Whether the use of AChIs varies by ethnicity is unknown. More than 2500 ethnically diverse patients (6% African American, 14% Latino, and 7% Asian patients) from the Alzheimer's Disease Research Centers in California were studied. Compared with white patients with AD, minority patients had 40% lower odds of AChI use (odds ratio 0.6, 95% confidence interval: 0.5 to 0.7).

  18. 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...

  19. Genetic heterogeneity in Alzheimer disease and implications for treatment strategies.

    Science.gov (United States)

    Ringman, John M; Goate, Alison; Masters, Colin L; Cairns, Nigel J; Danek, Adrian; Graff-Radford, Neill; Ghetti, Bernardino; Morris, John C

    2014-11-01

    Since the original publication describing the illness in 1907, the genetic understanding of Alzheimer's disease (AD) has advanced such that it is now clear that it is a genetically heterogeneous condition, the subtypes of which may not uniformly respond to a given intervention. It is therefore critical to characterize the clinical and preclinical stages of AD subtypes, including the rare autosomal dominant forms caused by known mutations in the PSEN1, APP, and PSEN2 genes that are being studied in the Dominantly Inherited Alzheimer Network study and its associated secondary prevention trial. Similar efforts are occurring in an extended Colombian family with a PSEN1 mutation, in APOE ε4 homozygotes, and in Down syndrome. Despite commonalities in the mechanisms producing the AD phenotype, there are also differences that reflect specific genetic origins. Treatment modalities should be chosen and trials designed with these differences in mind. Ideally, the varying pathological cascades involved in the different subtypes of AD should be defined so that both areas of overlap and of distinct differences can be taken into account. At the very least, clinical trials should determine the influence of known genetic factors in post hoc analyses.

  20. Biomarkers in translational research of Alzheimer's disease.

    Science.gov (United States)

    Tarawneh, Rawan; Holtzman, David M

    2010-01-01

    The identification and characterization of amyloid-beta (Abeta) and tau as the main pathological substrates of Alzheimer's disease (AD) have driven many efforts in search for suitable biomarkers for AD. In the last decade, research in this area has focused on developing a better understanding of the principles that govern protein deposition, mechanisms that link aggregation to toxicity and neuronal death, and a better understanding of protein dynamics in brain tissue, interstitial fluid and CSF. While Abeta and tau represent the two key pathological mediators of disease, other aspects of this multifaceted disease (e.g. oxidative stress, calcium-mediated toxicity, and neuroinflammation) are being unraveled, with the hope to develop a more comprehensive approach in exploring disease mechanisms. This has not only expanded possible areas for disease-modifying therapies, but has also allowed the introduction of novel, and potentially useful, fluid and radiological markers for the presence and progression of AD pathology. There is no doubt that the identification of several fluid and imaging biomarkers that can reliably detect the early stages of AD will have great implications in the design of clinical trials, in the selection of homogenous research populations, and in the assessment of disease outcomes. Markers with good diagnostic specificity will aid researchers in differentiating individuals with preclinical and probable AD from individuals who do not have AD pathology or have other dementing disorders. Markers that change with disease progression may offer utility in assessing the rates of disease progression and the efficacy of potential therapeutic agents on AD pathology. For both of these purposes, CSF Abeta42, amyloid imaging, and CSF tau appear to be very good markers of the presence of AD pathology as well as predictive of who will progress from MCI to AD. Volumetric MRI is also good at separating individuals with MCI and AD from controls and is predictive of