# Moderate alcohol use: risk or protective factor for age-related cognitive decline, mild cognitive impairment, and brain health in aging

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $517,378

## Abstract

ABSTRACT
With the increasing prevalence of alcohol use among older adults, it is imperative to better understand the
association of alcohol use with risk of mild cognitive impairment (MCI) and brain health in aging. Although
many studies suggest that moderate drinking may protect against age-related cognitive impairment and
dementia, few studies have demonstrated a protective association of moderate drinking with rates of cognitive
decline, or with neuroimaging measures of preserved brain health. Most neuroimaging studies have shown
detrimental associations of alcohol with global or regional brain volumes. It is possible that findings of
protective associations of moderate drinking on risk of cognitive impairment and dementia stem from
inadequate control for confounders since individuals who drink moderately also tend to be of higher
socioeconomic status and to engage in other healthy behaviors (such as regular exercise), that are themselves
associated with reduced risk of dementia. Conversely, it is also possible that existing studies relating alcohol
use to rates of cognitive decline or neuroimaging measures have not used sufficiently sensitive methods to
detect subtle, positive associations. Individual differences in genetic predisposition to Alzheimer's disease, or
in alcohol metabolizing enzymes, may also obscure effects. The goal of this project, which is responsive to
PAR-17-054 “Leveraging Existing Cohort Studies to Clarify Risk and Protective Factors for Alzheimer's
Disease and Related Dementias (R01)” is to clarify the association of alcohol use with cognitive decline, risk of
MCI and neuroimaging metrics of brain health in aging by leveraging a unique existing cohort study, the
Vietnam Era Twin Study of Aging (VETSA). VETSA is a longitudinal study of ~1500 monozygotic and dizygotic
male twin pairs that examines genetic and environmental influences on aging. It contains detailed repeated
measures of alcohol use, cognitive function, and brain imaging measures (on a subset of participants), along
with a wealth of information on potential confounders. We will determine how alcohol use is associated with
rates of cognitive decline and risk of MCI (Aim 1); and with regional brain grey and white matter microstructure
and white matter lesion burden (Aim 2). We will determine if observed associations are due to differences in
confounding variables, such as socioeconomic status, health status, health behaviors, cognitive reserve or
genetic status. Examination of shared heritability between drinking and cognitive/brain outcomes will further
inform on potential causal effects of alcohol, as will analyses of discordant twin-pairs. We will also examine
whether associations of alcohol with cognitive and brain aging differ by health or genetic status (including
polygenic risk for Alzheimer's disease, or for reduced alcohol metabolism; Aim 3). Improved knowledge of
whether alcohol is associated with increased or decreased risk of MCI has potential for ...

## Key facts

- **NIH application ID:** 9904468
- **Project number:** 5R01AG062483-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Linda Kathleen McEvoy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $517,378
- **Award type:** 5
- **Project period:** 2019-04-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904468

## Citation

> US National Institutes of Health, RePORTER application 9904468, Moderate alcohol use: risk or protective factor for age-related cognitive decline, mild cognitive impairment, and brain health in aging (5R01AG062483-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9904468. Licensed CC0.

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