January 22, 2015

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

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

Editorial
Why a woodpecker?
…Perhaps, a fundamental (or at least a popular) question surrounding “woodpecker research” is not so tangentially related to Alzheimer's disease and dementia research: how does a woodpecker remain conscious while pecking? 

African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles
These data have therapeutic implications for the age of onset risk algorithm estimates and the design of a prevention trial for African-Americans or other mixed ethnic populations. 

R47H TREM2 variant increases risk of typical early-onset Alzheimer's disease but not of prion or frontotemporal dementia
We find p.R47H is a risk factor for AD, but not frontotemporal dementia or prion disease. 

Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans
Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism.

APOE ε4 and risk for Alzheimer's disease: Do regionally distributed white matter hyperintensities play a role?
APOE ε4 is associated with increased parietal lobe WMH. 

APOE ε4 influences β-amyloid deposition in primary progressive aphasia and speech apraxia
APOE ε4 increases the risk of β-amyloid deposition in PPA and progressive speech apraxia but does not influence regional β-amyloid distribution or severity. 

Genetic modification of the relationship between phosphorylated tau and neurodegeneration
Our results suggest that rs4728029 modifies the relationship between PTau and both ventricular dilation and cognition, perhaps through an altered neuroinflammatory response. 

A point-based tool to predict conversion from mild cognitive impairment to probable Alzheimer's disease
A point-based risk score combining functional dependence, cerebral MRI measures, and neuropsychological test scores provided good accuracy for prediction of conversion from amnestic MCI to AD. 

Development and validation of a brief dementia screening indicator for primary care
The Dementia Screening Indicator is a simple tool that may be useful in primary care settings to identify high-risk patients to target for cognitive screening. 

An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease
We have identified a composite cognitive test score representing multiple cognitive domains that has improved power compared with the most sensitive single test item to track preclinical AD decline and evaluate preclinical AD treatments. We are confirming the power of the composite in independent cohorts and with other analytical approaches, which may result in refinements, have designated it as the primary endpoint in the Alzheimer's Prevention Initiative's preclinical treatment trials for individuals at high imminent risk for developing symptoms due to late-onset AD. 

Diagnostic accuracy and practice effects in the National Alzheimer's Coordinating Center Uniform Data Set neuropsychological battery
The total score’s classification accuracy discriminates between cognitively normal versus participants who have dementia. The total score appears subject to practice effects. 

Diagnostic accuracy and practice effects in the National Alzheimer's Coordinating Center Uniform Data Set neuropsychological battery
The total score’s classification accuracy discriminates between cognitively normal versus participants who have dementia. The total score appears subject to practice effects. 

Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer's disease
Prospective diagnostic criteria for AD should address the relative importance of markers of neuronal injury and elaborate a way of dealing with conflicting biomarker findings.

Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease
For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers. 

Extension and refinement of the predictive value of different classes of markers in ADNI: Four-year follow-up data
This model of prediction is consistent with the previous model at 2 years, thus highlighting the importance of cognitive measures in progression from MCI to AD. Cognitive markers were more robust predictors than biomarkers. 

The cerebrospinal fluid “Alzheimer profile”: Easily said, but what does it mean?
A tau/Aβ42 ratio of >0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers. 

Alzheimer's disease biomarker discovery using SOMAscan multiplexed protein technology
The newly identified proteins could be potential biomarkers and are worthy of further investigation.
 
Trajectories of Alzheimer disease-related cognitive measures in a longitudinal sample
Our findings reconcile reports of early changes in immediate recall with greater reliance on delayed recall performance in clinical settings. Moreover, the utility of cognitive markers in evaluating AD progression depends on the stage of cognitive decline, suggesting that optimal endpoints in therapeutic trials may vary across different stages of the disease process.

Aβ and cognitive change: Examining the preclinical and prodromal stages of Alzheimer's disease
In healthy individuals, high Aβ likely indicates that Alzheimer's disease (AD)-related neurodegeneration has begun. Once commenced, the rate of decline in cognitive function remains constant across the preclinical and prodromal stages of AD. 

Subjective cognitive concerns, episodic memory, and the APOE ε4 allele
APOE ε4 carriers with self-assessed cognitive concerns appear to have worse memory, and possibly accelerated memory decline. 

A comparison of neuropsychological performance between US and Russia: Preparing for a global clinical trial
Sources of variation include cultural differences, health conditions, and exposure to test stimuli. Findings highlight the importance of local norms to interpret test performance. 

The Israel Diabetes and Cognitive Decline (IDCD) study: Design and baseline characteristics
Tracking cognition, with face-to-face evaluations, exploiting 15 years of historical detailed computerized, easily accessible, and validated T2D-related characteristics may provide novel insights into T2D-related dementia. 

Independent comparison of CogState computerized testing and a standard cognitive battery with neuroimaging
CogState subtests were cross-sectionally comparable to standard neuropsychological tests in their relatively weak associations with neurodegeneration imaging markers. 

Can a novel computerized cognitive screening test provide additional information for early detection of Alzheimer's disease?
Compared with ERP, MRI, or neuropsychological tests alone, the VR-DOT could provide additional predictive information in a low-cost, computerized, and noninvasive way. 

Plasma proteins predict conversion to dementia from prodromal disease
We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints. 

The clinical use of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: A consensus paper from the Alzheimer's Biomarkers Standardization Initiative
Changes in Aβ1-42, T-tau, and P-tau181P allow diagnosis of AD in its prodromal stage. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. 

Social cognition in Alzheimer's disease: A separate construct contributing to dependence
Results underscore the relevance of considering social cognition when modeling disease and estimating clinical outcomes related to patient disability. 

Neural correlates of empathic impairment in the behavioral variant of frontotemporal dementia
We proved an empathic impairment, with the ability to infer emotional states showing the most severe deficit. These results provide further evidence of selective disease-specific vulnerability of the limbic and frontoinsular network in bvFTD and highlight the usefulness of empathy assessment in early patients. 

The effects of cognitive impairment on nursing home residents' emergency department visits and hospitalizations
Higher rates of ED visits among those with mild CI may represent a unique marker in the presentation of acute illness and warrant further investigation. 

A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease
There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD).  

Assessing cognition and function in Alzheimer's disease clinical trials: Do we have the right tools?
The focus of the discussion included the need for improved cognitive and functional outcome measures for clinical of participants with preclinical AD and those diagnosed with Mild Cognitive Impairment due to AD.
 
APOE ε4: The most prevalent yet understudied risk factor for Alzheimer's disease
The allele ε4 of apolipoprotein E4 (APOE ε4), is the most prevalent genetic risk factor for sporadic AD, and is expressed in more than half of the AD patients. However, in spite of its genetic prominence, the allele APOE ε4 and its corresponding protein product apoE4 have been understudied. We presently briefly discuss the reasons underlying this situation and review newly developed AD therapeutic approaches that target apoE4 and which pave the way for future studies.

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