# Gene by Early Life Environment Interaction on Cognitive Decline

> **NIH NIH F31** · UNIVERSITY OF CHICAGO · 2020 · $45,520

## Abstract

Project Summary/Abstract
 Cognitive decline and neurodegenerative diseases including Alzheimer’s dementia greatly impact the
health and quality of life of older adults, as well as their families and support systems. Prior research has
identified environmental and genetic risk factors for pathological cognitive decline and described
pathophysiologic processes. The Apolipoprotein (ApoE) ε4 allele is well established as the strongest genetic
risk factor for Alzheimer’s disease and has also been shown to be associated with dementia, cognitive decline
and progressive memory loss. Risk estimates vary widely, suggesting that other factors, potentially including
both other genes and environmental exposures, could modify the effect of ApoE on cognitive outcomes.
Indeed, there is evidence that genetic penetrance of ApoE variants do vary by engagement in cognitively
stimulating activities in adulthood and older ages, physical activity in adulthood and older ages, and education
achieved. Most studies that have considered whether socio-environmental conditions modify the effect of
genetic polymorphisms on late-life cognitive outcomes have examined individual educational attainment or
social and environmental measurements taken later in life as potential effect modifiers. There is less evidence
as to whether early-life circumstance might modify genetic effects. This is a striking gap, as there is a
substantial body of research exploring the relationship between early life circumstances and late-life health
outcomes, including cognition. Further, the primary mechanism by which the ApoE ε4 allele is thought to
negatively impact cognitive outcomes is via increased neuropathological burden. There is some evidence that
early life cognitive ability is associated with neuropathological burden. However, other environmental
measures, such as level of education, have not shown any associations with neuropathology, and instead
appear to influence cognitive capacity despite accumulation of AD related neuropathologies, i.e. by creating
cognitive reserve. In this study, I plan to explore whether the penetrance of genetic risk for cognitive decline
varies by early life environment, operationalized as birth cohort, childhood socioeconomic status, and
childhood adversity. Further, I plan to examine whether individual early life factors modify genetic effects on
neuropathological damage or on cognitive function given the level of neuropathological damage (i.e. via
cognitive reserve).

## Key facts

- **NIH application ID:** 9853621
- **Project number:** 5F31AG059395-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Veronica Eloesa McSorley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853621

## Citation

> US National Institutes of Health, RePORTER application 9853621, Gene by Early Life Environment Interaction on Cognitive Decline (5F31AG059395-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853621. Licensed CC0.

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