# Brain pathologies, reserve and cognition in aging and dementia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $1,377,033

## Abstract

PROJECT ABSTRACT
Alzheimer's disease and related dementias (ADRD) are known causes of cognitive and functional decline, but
some individuals are more resilient to these diseases and continue to function normally despite associated
brain changes. Cognitive reserve has been invoked to explain better cognition than expected based on the
presence and severity of disease. There is evidence modifiable lifestyle factors may build cognitive reserve;
elucidating these associations has major practical implications for public health policy and interventions to
build reserve, thus reducing the impact of ADRD and promoting healthy aging. The overarching goal of this
project is to transition from a hypothetical and often post-hoc construct of cognitive reserve to a concrete
understanding of the variables that promote resilience and the mechanisms by which they protect against
cognitive and functional decline. In this competitive renewal we will use novel imaging approaches, an
unprecedented multi-racial/ethnic sample, and prospectively collected midlife data; each of these components
constitutes a major innovation over previous studies. Aim 1 will delineate brain resources underlying cognition
and everyday function. We will employ discovery-based neuroimaging techniques to better understand the
contributions of cortical neurodegeneration, vascular brain injury, and amyloid deposition to cognitive and
functional outcomes. We will leverage four longitudinal cohorts (N = >700) with harmonized imaging,
cognitive and functional data among four major racial/ethnic groups (Latinos, non-Latino Asians, non-Latino
Blacks, and non-Latino Whites) to examine racial/ethnic group similarities and differences in brain
mechanisms underlying cognition and function. Models developed in Aim 1 will also serve to enhance the
precision by which we can operationalize cognitive reserve as residual cognition after accounting for brain
changes. We also extend our approach for cognitive reserve to operationalize functional reserve. Loss of
independence is a major concern for older adults and better understanding factors that reduce disability is
critical. Aim 2 will develop longitudinal models of cognitive and functional reserve and investigate how
dynamic reserve impacts ADRD clinical outcomes. Aim 3 will evaluate how life course risk and resilience
factors build or deplete cognitive and functional reserve and whether these relationships vary across
racial/ethnic groups. A uniquely valuable contribution of this study will be the rare ability to examine impacts
of medical, lifestyle, and psychosocial data (vascular risks, physical/cognitive activity, personality,
stress/adversity and social connection) prospectively collected in the 1960s-1990s (during midlife) in addition
to late life, thereby allowing us to answer important questions about critical periods of exposure for reserve and
its life course determinants. This project will leverage unique data, multidisciplinary expertise, and ...

## Key facts

- **NIH application ID:** 10817763
- **Project number:** 5R01AG031563-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Evan Fletcher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,377,033
- **Award type:** 5
- **Project period:** 2009-03-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817763

## Citation

> US National Institutes of Health, RePORTER application 10817763, Brain pathologies, reserve and cognition in aging and dementia (5R01AG031563-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10817763. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*