July 02, 2014

Alzheimer's & Dementia: The Journal of the Alzheimer's Association May 2014

Full text articles are available to fee paying members of Alzheimer’s Australia NSW by emailing NSW.Library@alzheimers.org.au 

The MultiTEP platform–based Alzheimer's disease epitope vaccine activates a broad repertoire of T helper cells in nonhuman primates
As a prelude to clinical trials we have characterized B- and T-cell immune responses in macaques to AD vaccine candidates: AV-1955 and its slightly modified version, AV-1959 (with 3 additional promiscuous Th epitopes).
p. 271-283 

Epitope-based DNA vaccine for Alzheimer's disease: Translational study in macaques
Clinical trials with passive and active Alzheimer's disease (AD) vaccines suggest that early interventions are needed for improvement of cognitive and/or functional performance in patients, providing impetus for the development of safe and immunologically potent active vaccines targeting amyloid β (Aβ). The AN-1792 trial has indicated that Aβ-specific T cells may be unsafe for humans; therefore, other vaccines based on small Aβ epitopes are undergoing preclinical and clinical testing.
p. 284-295 

Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia
Vitamin D deficiency has been implicated as a risk factor for dementia in several cross-sectional studies. We tested the hypothesis that reduced plasma 25-hydroxyvitamin D (25[OH]D) is associated with increased risk of Alzheimer’s disease (AD) and vascular dementia in the general population.
p. 296-302


Validity of dementia and Alzheimer's disease diagnoses in Finnish national registers
We investigated dementia and Alzheimer disease (AD) diagnoses in three national registers in Finland: the Hospital Discharge Register (HDR), the Drug Reimbursement Register, and the Causes of Death Register (CDR).
p. 303-309 

Australian population trends and disparities in cholinesterase inhibitor use, 2003 to 2010
The Australian Pharmaceutical Benefits Scheme (PBS) first subsidized cholinesterase inhibitors (CEIs) for Alzheimer's disease in 2001, introducing a novel therapy for a previously untreatable common condition. This study aims to determine Australian rates of CEI use and to assess equality of access to treatment based on socioeconomic status and geographic remoteness.
p. 310-318 

The source of cognitive complaints predicts diagnostic conversion differentially among nondemented older adults
The objective of this study was to compare whether different sources of cognitive complaint (i.e., subjective and informant) predict diagnostic conversion in nondemented older adults.
p. 319-327 

Cognition and gait show a distinct pattern of association in the general population
With brain aging, cognition and gait deteriorate in several domains. However, the interrelationship between cognitive and gait domains remains unclear. We investigated the independent associations between cognitive and gait domains in a community-dwelling population.
p. 328- 335

APOE interacts with age to modify rate of decline in cognitive and brain changes in Alzheimer's disease
To determine (1) whether age-standardized cognitive declines and brain morphometric change differ between Young-Old patients with Alzheimer's disease (YOAD) and Very-Old patients with Alzheimer's disease (VOAD), and (2) whether the apolipoprotein E (APOE) genotype modifies these neuropsychological and morphometric changes.
p. 336-348 

Effect of APOE genotype status on targeted clinical trials outcomes and efficiency in dementia and mild cognitive impairment resulting from Alzheimer's disease
The apolipoprotein E (APOE) ε4 genotype has been recommended as a potential inclusion or exclusion criterion in targeted clinical trials for Alzheimer's disease (AD) and mild cognitive impairment (MCI) resulting from AD, and has been implemented in trials of immunotherapeutic agents.
p. 349-359 

Parkinsonism and distinct dementia patterns in a family with the MAPT R406W mutation
The Arg406Trp (R406W) missense mutation in the microtubule-associated protein-tau gene (MAPT) is a known cause of early-onset dementia. Various dementia phenotypes have been described, including frontotemporal dementia (FTD), FTD with parkinsonism, and early-onset Alzheimer disease (EOAD)-like presentations.
p. 360-365 

Variants in PPP3R1 and MAPT are associated with more rapid functional decline in Alzheimer's disease: The Cache County Dementia Progression Study
Single-nucleotide polymorphisms (SNPs) located in the gene encoding the regulatory subunit of the protein phosphatase 2B (PPP3R1, rs1868402) and the microtubule-associated protein tau (MAPT, rs3785883) gene were recently associated with higher cerebrospinal fluid (CSF) tau levels in samples from the Knight Alzheimer's Disease Research Center at Washington University (WU) and Alzheimer's Disease Neuroimaging Initiative (ADNI). In these same samples, these SNPs were also associated with faster functional decline, or progression of Alzheimer's disease (AD) as measured by the Clinical Dementia Rating sum of boxes scores (CDR-sb). We attempted to validate the latter association in an independent, population-based sample of incident AD cases from the Cache County Dementia Progression Study (DPS).
p. 365-371 

The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer's disease
The “amyloid hypothesis” has dominated Alzheimer research for more than 20 years, and proposes that amyloid is the toxic cause of neural/synaptic damage and dementia. If correct, decreasing the formation or removing amyloid should be therapeutic. Despite discrepancies in the proposed mechanism, and failed clinical trials, amyloid continues to be considered the cause of a degenerative cascade. Alternative hypotheses must explain three features: (i) why amyloid toxicity is not the etiology of Alzheimer's disease (AD), (ii) what alternative mechanisms cause the degeneration and dementia of AD, and (iii) why increased amyloid accumulates in the brain in AD. We propose that AD, which occurs in elderly, already vulnerable brains, with multiple age-related changes, is precipitated by impaired microvascular function, resulting primarily from decreased Notch-related angiogenesis. With impaired microvasculature, a lack of vascular endothelial-derived trophic factors and decreased cerebral blood flow cause the atrophy of neural structures. Therapeutic strategies should focus on supporting normal angiogenesis.
p. 372-380 

CSF Aβ1-42 combined with neuroimaging biomarkers in the early detection, diagnosis and prediction of Alzheimer's disease
The development of validated, qualified, and standardized biomarkers for Alzheimer's disease (AD) that allow for an early presymptomatic diagnosis and discrimination (classification) from other types of dementia and neurodegenerative diseases is warranted to accelerate the successful development of novel disease-modifying therapies.
p. 381-392 

Mitochondrial DNA deletions in Alzheimer's brains: A review
Mitochondrial dysfunction and increased oxidative stress have been associated with normal aging and are possibly implicated in the etiology of late-onset Alzheimer's disease (AD). DNA deletions, as well as other alterations, can result from oxidative damage to nucleic acids. Many studies during the past two decades have investigated the incidence of mitochondrial DNA deletions in postmortem brain tissues of late-onset AD patients compared with age-matched normal control subjects. Published studies are not entirely concordant, but their differences might shed light on the heterogeneity of AD itself. Our understanding of the role that mitochondrial DNA deletions play in disease progression may provide valuable information that could someday lead to a treatment.
p. 393-400 

The ε4 genotype of apolipoprotein E and white matter integrity in Alzheimer's disease
In this multicenter study, we investigated a possible association between the APOE ε4 allele and white matter (WM) integrity in Alzheimer's disease (AD) using diffusion tensor imaging (DTI).
p. 401-404 

International Alzheimer's Disease Research Portfolio (IADRP) aims to capture global Alzheimer's disease research funding
The goal of the IADRP project is to enable funding organizations to assess the changing landscape of AD research and coordinate strategies, leverage resources, and avoid duplication of effort.
p. 405-408 

Design of a comprehensive Alzheimer’s disease clinic and research center in Spain to meet critical patient and family needs
Alzheimer's disease (AD) affects people worldwide, and the prevalence is increasing as the population ages. There is an international effort to understand the biology of AD to develop primary and secondary prevention strategies, and to develop effective therapeutic interventions for individuals who are already symptomatic. One of the critically important pieces of all national plans to address AD is the call for the development of service models to deliver quality, effective care based on the best evidence available.
p. 409-415

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