May 01, 2014

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

Full text articles are available to fee paying members of Alzheimer’s Australia NSW by emailing

The prevalence of dementia in urban and rural areas of China
The Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas.A notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban–rural differences. 

Unobtrusive measurement of daily computer use to detect mild cognitive impairment

Mild disturbances of higher order activities of daily living are present in people diagnosed with mild cognitive impairment (MCI). These deficits may be difficult to detect among those still living independently. Unobtrusive continuous assessment of a complex activity such as home computer use may detect mild functional changes and identify MCI. We sought to determine whether long-term changes in remotely monitored computer use differ in persons with MCI in comparison with cognitively intact volunteers.
Conclusions Computer use change can be monitored unobtrusively and indicates individuals with MCI. With 79% of those 55 to 64 years old now online, this may be an ecologically valid and efficient approach to track subtle, clinically meaningful change with aging. 
p. 10-17

Association of diabetes with amnestic and nonamnestic mild cognitive impairment

Background Type 2 diabetes may increase the risk of amnestic mild cognitive impairment (aMCI) through Alzheimer's disease (AD)-related and vascular pathology and may also increase the risk of nonamnestic MCI (naMCI) through vascular disease mechanisms. We examined the association of type 2 diabetes with mild cognitive impairment (MCI) and MCI subtype (aMCI and naMCI) overall and by sex.
Conclusions Diabetes was associated with an increased risk of MCI in elderly persons. The association of diabetes with MCI may vary with subtype, number of domains, and sex. Prevention and control of diabetes may reduce the risk of MCI and Alzheimer's disease.
p. 18-26

Estrogen receptor polymorphisms and incident dementia: The prospective 3C study
Background Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors.
Conclusions Although there was only weak support for a gender-specific association between the common ESR1 rs2234693 polymorphism and AD, this polymorphism may act as an effect modifier, modifying the association between an ESR2 polymorphism and dementia, as well as the risk of AD associated with the APOE ε4 allele.
p. 27-35

Vitamin E and memantine in Alzheimer's disease: Clinical trial methods and baseline data

Background Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD.
Conclusion This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013.
p. 36-44 

Genome-wide association study of the rate of cognitive decline in Alzheimer's disease

Background  Substantial interindividual variability exists in the disease trajectories of Alzheimer's disease (AD) patients. Some decline rapidly whereas others decline slowly, and there are no known explanations for this variability. We describe the first genome-wide association study to examine rate of cognitive decline in a sample of AD patients with longitudinal measures of cognition.
Conclusion SPON1 has not been previously associated with AD risk, but is plausibly related because the gene product binds to the amyloid precursor protein and inhibits its cleavage by β-secretase. These data suggest that SPON1 may be associated with the differential rate of cognitive decline in AD. 
p. 45-52

Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer's disease

Background A practical biomarker is required to facilitate the preclinical diagnosis of Alzheimer's disease (AD).
Conclusion Our findings are consistent with a number of published plasma Aβ studies and, although the prognostic value of individual measures in any given subject is limited, the diagnostic contribution of plasma Aβ may demonstrate utility when combined with a panel of peripheral biomarkers. 
p. 53-61

Microbleeds in the logopenic variant of primary progressive aphasia

Background Microbleeds have been associated with Alzheimer's disease (AD), although it is unclear whether they occur in atypical presentations of AD, such as the logopenic variant of primary progressive aphasia (lvPPA). We aimed to assess the presence and clinical correlates of microbleeds in lvPPA.
Conclusions Microbleeds occur in approximately one third of subjects with lvPPA, with older women at the highest risk. 
p. 62-66

Glutathione relates to neuropsychological functioning in mild cognitive impairment

Background Mild cognitive impairment (MCI) represents an at-risk state for Alzheimer's disease in which underlying pathophysiological mechanisms could be delineated. Oxidative stress has been implicated in Alzheimer's disease and can be measured by levels of the antioxidant glutathione. This study aims to assess in vivo levels of glutathione via proton magnetic resonance spectroscopy in patients with MCI and to determine how glutathione relates to cognitive decline.
Conclusion This study has shown for the first time that MCI is associated with increased glutathione in the cingulate, which in turn relates to neuropsychological performance. This finding may be indicative of an early compensatory or neuroprotective response, and the role of glial cells and glutathione enzymes requires delineation. Longitudinal studies examining the utility of glutathione as a marker for cognitive decline are now required. 
p. 67-75

AD dementia risk in late MCI, in early MCI, and in subjective memory impairment

Objective To compare the risk of developing Alzheimer’s disease (AD) dementia in late mild cognitive impairment (LMCI), early MCI (EMCI), and subjective memory impairment (SMI) with normal test performance.
Conclusions SMI and EMCI with self-reported concerns were associated with the same risk of AD dementia, suggesting that pre-LMCI risk conditions should be extended to SMI with concerns.
p. 76-83

The neuropsychology of normal aging and preclinical Alzheimer's disease

Objective A National Institute on Aging–sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD.
Conclusions Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design. 
p. 84-92

Subjective cognitive decline: Self and informant comparisons

Background It is unclear whether self- or informant-based subjective cognition better distinguishes emotional factors from early-stage Alzheimer's disease (AD).
Conclusions Self- and informant-based subjective decline correlated with greater psychological distress and slightly lower cognitive performance. Those with incident MCI generally self-endorsed decline earlier than informants. 
p. 93-98

Gray matter atrophy pattern in elderly with subjective memory impairment

Background Individuals with subjective memory impairment (SMI) report worsening of memory without impairment in cognitive tests. Despite normal cognitive performance, they may be at higher risk of cognitive decline compared with individuals without SMI.
Conclusions Our results indicate a link between the gray matter atrophy pattern of patients with AD and the presence of SMI. Furthermore, multivariate pattern recognition approaches seem to be a sensitive method for identifying subtle brain changes that correspond to future memory decline in SMI.
p. 99-108
Developing novel blood-based biomarkers for Alzheimer's disease
Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant discussion, including potential next steps to move this area of research forward. 
p. 109-114

The future of blood-based biomarkers for Alzheimer's disease
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 progression or treatment response, and most are measured in cerebrospinal fluid, which limits their applicability. With these aspects in mind, the aim of this article is to underscore the concerted efforts of the Blood-Based Biomarker Interest Group, an international working group of experts in the field. The points addressed include: (1) the major challenges in the development of blood-based biomarkers of AD, including patient heterogeneity, inclusion of the “right” control population, and the blood–brain barrier; (2) the need for a clear definition of the purpose of the individual markers (e.g., prognostic, 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.
p. 115-131


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