# Culture-Gene Relationship:  A Novel Model of Aging Cognitive Health

> **NIH NIH U01** · YALE UNIVERSITY · 2020 · $418,750

## Abstract

Abstract
 To reduce the prevalence of Alzheimer's disease (AD), scientists and policy makers have called for new
models of the disease. The proposed project tests a novel model of how culture and genes may interact to
influence AD and cognitive health. This project will provide the first investigation of whether a modifiable,
culture-based environmental factor, negative age beliefs, exacerbates the effect of the genetic-risk-factor
apolipoprotein E4 (APOE ε4) on adverse cognitive outcomes, including risk for AD, and whether positive age
beliefs increase the likelihood that APOE ε2 leads to beneficial cognitive outcomes, including reduced AD risk.
The proposed project builds on our findings with older individuals that (a) negative age beliefs can lead to
greater stress, worse cognitive outcomes, and a greater accumulation of AD biomarkers; and (b) positive age
beliefs can protect against these outcomes. This project also builds on the finding that APOE ε4 and ε2
account for less than half of aging-cognition variance; age beliefs may help to explain the remaining variance.
Our proposed project with older persons will examine four specific aims for the first time:
Aim 1. To examine whether the APOE genotype moderates age beliefs' impact on cognitive outcomes. We
predict: (a) APOE ε4 carriers will show a greater detrimental impact of negative age beliefs on cognitive
outcomes, compared to non-APOE ε4 carriers; and (b) APOE ε2 carriers will show a greater beneficial impact
of positive age beliefs on cognitive outcomes, compared to non-APOE ε2 carriers.
Aim 2. To examine whether our age belief-APOE genotype model helps to explain disparities by race and sex
on cognitive outcomes. Considering that members of marginalized groups may be more sensitive to age
stereotypes, we predict: (a) African Americans will show a stronger additive influence of APOE ε4 and negative
age beliefs on detrimental cognitive outcomes, as well as a stronger additive influence of APOE ε2 and positive
age beliefs on beneficial cognitive outcome, compared to Whites; and (b) women, compared to men, will show
the same pattern as older African Americans described in Aim 2a.
Aim 3. To examine whether psychosocial factors, related to age beliefs, influence Aim 1 patterns. We predict:
(a) those higher in vulnerability factors (e.g., perceived discrimination) will show a stronger additive influence of
APOE ε4 and negative age beliefs on detrimental cognitive outcomes, as well as a weaker additive influence of
APOE ε2 and positive age beliefs on beneficial cognitive outcomes; and (b) those higher in resiliency factors
(e.g., feeling useful to others) will show the reverse pattern.
Aim 4. To examine whether psychological and behavioral mechanisms link the age belief-genotype predictor
to cognitive outcomes. We predict: stress and physical activity will act as mediators of this association.
 This proposed project will draw on three longitudinal datasets with common key variables. This study...

## Key facts

- **NIH application ID:** 9970376
- **Project number:** 5U01AG032284-08
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** BECCA R LEVY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2009-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970376

## Citation

> US National Institutes of Health, RePORTER application 9970376, Culture-Gene Relationship:  A Novel Model of Aging Cognitive Health (5U01AG032284-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9970376. Licensed CC0.

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