# Neural Correlates and Modifiers of Cognitive Aging

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $698,016

## Abstract

Project Summary
Aging is associated with multiple differential changes in the brain, and understanding the neural mechanisms
that drive age-related cognitive declines is a matter of great importance. Charting the natural course of aging in
healthy adults and elucidating the neural mechanism of change and their modifiers has been an overarching
goal of our research work in the past two decades. The results of our studies in the past two decades confirm
earlier findings of particular vulnerability in the brain regions (hippocampus, orbital–frontal cortex,
entorhinal/parahippocampal cortex and cerebellum) and association white matte fibers that connect these
areas. In investigating the possible mechanism underlying these changes, we found that increase in iron
content (a proxy for oxidative stress) of the striatum influences shrinkage of that region and mediate changes
in cognitive skill such as working memory. We also found that whereas shrinkage of age-sensitive brain
regions predicts changes in important cognitive abilities, possession of better cognitive endowment at baseline
predicted lesser shrinkage of one of the most important brain regions – the prefrontal cortex, thus suggesting
that in aging, the relationship between brain and cognition is reciprocal and that better cognitive abilities may
act as a neuroprotective modifier of aging. In addition, we found that physiological and genetic indicators of
vascular and metabolic risk as well as proneness to systemic inflammation play a role in promoting age-related
brain declines. In the proposed continuation study, we will carry on collecting longitudinal data initiated at the
inception of this project as it will provide us with an opportunity to examine the shape of age-related change
trajectory and test the possibility of non-linear course. At the same time, we will expand the focus of our search
for mechanisms of cognitive aging by turning attention to two domains whose importance in cognitive aging
has been bolstered in the past decade: maintenance of subcortical and cortical myelin and preservation of the
brain energy metabolism. We will conduct (for the first time) longitudinal assessment in these two domains in
conjunction with continuing previously introduced measurement of brain volume, white matter microstructure
and iron accumulation. We will test hypotheses pertaining to the temporal dynamics of brain and cognitive
aging and will examine the lag-lead relationships between brain energy metabolisms (hypothesized as the
primary instigator of neurocognitive aging), structural shrinkage, and myelin loss and iron accumulation (the
main mediators of structural change). We will examine the reciprocal role of changes in the brain and age-
sensitive cognitive functions as well as moderating role of vascular, metabolic and inflammatory risk factors in
these relationships. It is our hope that understanding of the brain mechanisms that underpin normal cognitive
aging will arm us with necessary kn...

## Key facts

- **NIH application ID:** 9949569
- **Project number:** 5R01AG011230-25
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Ana Marie Daugherty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $698,016
- **Award type:** 5
- **Project period:** 1993-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949569

## Citation

> US National Institutes of Health, RePORTER application 9949569, Neural Correlates and Modifiers of Cognitive Aging (5R01AG011230-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9949569. Licensed CC0.

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