# Contributions of Alzheimer's Pathology and Cerebrovascular Factors to Cognitive Aging

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $561,778

## Abstract

Alzheimer's disease is associated with the accumulation of pathological markers [amyloid-beta
(Aβ) and tau], brain atrophy and a progressive loss of memory functions. However, a significant
proportion of individuals with AD pathology do not develop cognitive impairment, indicating
contributions of other factors to clinical AD. Increasing evidence suggests that factors strongly
linked with brain aging, such as cerebrovascular alterations and declines in executive function,
contribute to clinical AD. This link is not straightforward though as the effects of AD pathology
and vascular alterations can be moderated by cognitive reserve and brain resilience. Our recent
results suggest that levels of Aβ and tau in cerebrospinal fluid (CSF) and cerebrovascular
declines associated with white matter hyperintensities (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 Aβ, p-tau and t-
tau, neuroimaging measures including event-related fMRI, 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 complete the same CSF and
imaging measures approximately 3 years later. We aim to (1) dissociate effects of AD pathology
and brain aging on functional compensation (2) identify the separate and synergistic effects of
AD pathology and cerebrovascular markers on cognitive declines over time and (3) identify
reserve factors that moderate relationships between vascular and AD pathology markers on
cognition. We will test hypotheses that AD 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.

## Key facts

- **NIH application ID:** 9928874
- **Project number:** 5R01AG055449-04
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** BRIAN Timothy GOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $561,778
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928874

## Citation

> US National Institutes of Health, RePORTER application 9928874, Contributions of Alzheimer's Pathology and Cerebrovascular Factors to Cognitive Aging (5R01AG055449-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9928874. Licensed CC0.

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