# NEURAL PHENOTYPES OF RESISTANCE AND RESILIENCY TO AD AND ADRD IN THE OLDEST OF THE OLD

> **NIH NIH U19** · WASHINGTON UNIVERSITY · 2022 · $118,828

## Abstract

ABSTRACT FOR PROJECT 4
Prior work has described several factors that confer vulnerability for or protection against risk for the development
of Alzheimer's disease (AD) and related disorders (ADRD), including demographic and social determinants of
health, (e.g., socioeconomic status and education quality/skill), systemic and organ health (including conditions
beginning at midlife, e.g. hypertension and obesity; examined in Project 1), lifestyle and wellness factors (e.g.
physical activity and sleep quality; examined in Project 2), manifestations of menopause (e.g. vasomotor
symptoms; examined in Project 3), as well as psychiatric (e.g. depression), and sociological (e.g. social network
density) domains1. Some factors begin to influence risk for ADRD early in young adulthood and mid-life and
promote cognitive impairment in relatively early old age. Thus, older adults vary greatly in function, with certain
`unsuccessful' individuals exhibiting a reduction of cognitive abilities earlier in life. These individuals are in stark
contrast to individuals in the latest decades of life who harbor cognitive risk factors but have successfully resisted
pathology or exhibit resilience against cognitive impairment when pathology is present. Findings from the large
autopsy cohort in the Rush Memory Aging Project demonstrated frequent discordance between cognition and
pathology and noted the need to examine mechanisms of cognitive resilience2. Here, we aim to elucidate factors
related to `successful aging' (minimal brain pathology and optimal cognition) in the latest stages of life.
Studies have identified neural factors that contribute to relatively preserved functioning in the very-old3,4. In
cohorts with AD pathology, high performing individuals have relatively larger hippocampal volumes than lower
performing individuals5. This preservation in brain structure may confer cognitive resilience in certain individuals.
We and others have found that vascular lesions modulate the level of AD pathology necessary for a given level
of clinical impairment6,7 and that vascular lesion burden is associated with hippocampal atrophy8. It is therefore
possible that superior vascular health (i.e., preserved vascular physiology and low vascular lesion burden)
protects against impairment from early AD pathology. In the proposed work, we will examine the impact of
advanced aging on structural and functional brain connectivity, neurochemistry, and cognitive abilities in groups
stratified by cognitive performance (high/typical performance on a cognitive composite index), and cognitive risk
(high/typical based on known risk factors; `allostatic load'). Aim 1. To determine patterns of brain connectivity
and neurochemistry that confer superior cognitive performance in very-old (80+) adults. Aim 2. To determine
associations among cerebrovascular health, connectivity, performance and lifespan risk and protective factors.
Aim 3. To further define superior performance in the very-old based...

## Key facts

- **NIH application ID:** 10492701
- **Project number:** 5U19AG073585-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** DAVID H SALAT
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $118,828
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492701

## Citation

> US National Institutes of Health, RePORTER application 10492701, NEURAL PHENOTYPES OF RESISTANCE AND RESILIENCY TO AD AND ADRD IN THE OLDEST OF THE OLD (5U19AG073585-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10492701. Licensed CC0.

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