Grants and Contracts Details
Description
This proposal is a response to RFA PAR-15-357: Understanding Alzheimer's Disease in the
Context of the Aging Brain. Alzheimer’s disease involves accumulation of pathological levels of
amyloid-beta (Aâ) and phospho-tau proteins, brain atrophy and a progressive loss of memory
functions. However, a significant proportion of individuals with AD pathology and brain atrophy
do not have clinical AD, indicating contributions of other factors. Increasing evidence suggests
that neurocognitive patterns common in aging such—such as cerebrovascular alterations and
related declines in executive function—contribute to clinical AD. This link is not straightforward
though as the effects of AD pathology and white matter alterations can be moderated by
cognitive reserve and brain resilience. Our recent results suggest that levels of Aâ and tau in
cerebrospinal fluid (CSF) and cerebrovascular declines associated with white matter
hyperintensity (WMHs) are differentially related to patterns of executive function in cognitively
normal older adults. In addition, our results suggest that some of the patterns appear modifiable
based on positive lifestyle variables. This proposal seeks to define the interplay between AD
pathology, cerebrovascular-related alterations and cognitive reserve that distinguish normal
brain aging from AD-like cognitive declines. We propose to study of 120 cognitively normal
older adults using measures of CSF Aâ, p-tau and t-tau, inflammatory markers, neuroimaging
measures including event-related fMRI, and multiple structural imaging measures. Structural
neuroimaging measures will include volumetric measures, FLAIR imaging for quantification of
WMH volumes and diffusion tensor imaging for quantification of regionally distributed white
matter abnormalities. A subset of participants will be complete the same CSF and imaging
measures approximately 3 years later. We aim to (1) understand the separate and synergistic
effects of clinically silent pathology and cerebrovascular factors on neurocognitive functions, (2)
determine the contributions of AD pathology and vascular measures to change in cognition over
time and (3) identify reserve factors that moderate relationships between pathology, brain
structure on functional imaging and cognitive patterns. We will test hypotheses that clinically
silent pathology and cerebrovascular factors synergistically interact to predict AD-like cognitive
declines. We will also test the hypothesis that reserve factors will offset the effects of some of
these pathological and vascular changes on cognitive functions via mechanisms of brain
maintenance or plastic functional brain reorganization of large-scale brain functional networks in
some older adults.
PUBLIC HEALTH RELEVANCE: Overall, this project will begin to dissociate the relative
contributions of ‘normal’ aging and AD pathology to cognition in older adults and identify factors
that may promote optimal cognitive aging.
Status | Finished |
---|---|
Effective start/end date | 9/15/17 → 4/30/23 |
Funding
- National Institute on Aging: $2,301,528.00
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