# The Role of Executive Functions in Cognitive Aging and Risk for Mild Cognitive Impairment

> **NIH NIH R03** · UNIVERSITY OF COLORADO · 2021 · $46,928

## Abstract

PROJECT SUMMARY
Efforts to improve treatment of Alzheimer’s disease (AD) are beginning to focus on early identification
because diagnosing individuals in the mild cognitive impairment (MCI) stage could improve patient quality of
life and substantially reduce the financial impact of the disease. Cognitive assessments in middle age provide
ideal early predictors or screeners because they are low cost and non- invasive tools. Although predictive
studies of MCI and AD generally focus on episodic memory, executive functions (EFs) are of substantial
importance because they control and integrate multiple cognitive processes, and because their performance
and associated brain regions are some of the first to decline in middle age. Indeed, there are prominent
deficits in EFs in MCI and AD, but few studies have examined these associations longitudinally. We propose
that EF deficits can appear as early (or earlier) than memory deficits in the progression to MCI and AD. We
will evaluate EFs and memory as predictors of MCI in middle age in combination with another promising early
indicator – AD polygenic scores (Aim 1). Genetic risk scores may become highly useful in prospective studies
because genotyping procedures are also non-invasive and can be done anytime in life. Specifically, we will
examine whether cognitive measures predict MCI more strongly in individuals with high AD genetic risk
scores. We will also examine how other early life factors (cognitive reserve) elucidate the associations
between EFs, white matter, and AD genetic risk in midlife (Aim 2).
We will examine data from the Vietnam Era Twin Study of Aging, which follows a large sample of male twins
across 3 time-points in late middle age (mean age 56, 62, and 67; N~1200 at each wave). Twins completed
extensive assessment of EFs at all waves (including multiple measures of response inhibition, task-set
shifting, working memory, and verbal fluency) as well as multiple measures of other cognitive abilities
(including memory), health, and cardiovascular factors. Early adult general cognitive ability (N=1552; our
proxy for cognitive reserve) and genotyping (N=1162) are available for most individuals. White matter data are
also available for many subjects (N~ 350 to 400 at each wave). The comprehensive cognitive assessment in
VETSA allows for the examination of EFs and memory at the level of latent variables, increasing power and
generalizability of findings. Moreover, the genetically-informative nature of the sample (i.e., twins and direct
genotyping), allows for the decomposition of associations between EFs and white matter into genetic and
environmental influences, and examination of the role of AD genetic risk scores in these associations.
This award will provide an ideal opportunity to advance our understanding of EFs and cognitive changes
across middle age in a rich dataset. Because all research involves secondary analyses of existing data, there
will be ample time to achieve the research aims...

## Key facts

- **NIH application ID:** 10728182
- **Project number:** 7R03AG065643-03
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Daniel Gustavson
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,928
- **Award type:** 7
- **Project period:** 2023-03-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10728182

## Citation

> US National Institutes of Health, RePORTER application 10728182, The Role of Executive Functions in Cognitive Aging and Risk for Mild Cognitive Impairment (7R03AG065643-03). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10728182. Licensed CC0.

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