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.
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.
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.
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.
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.
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.
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.
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.
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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