# Investigating age-related neural dedifferentiation longitudinally and in Alzheimer’s pathology

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $700,614

## Abstract

Project Summary/Abstract
A growing body of research has found that neural representations are less distinctive in
older relative to younger adults, a phenomenon known as age-related neural
dedifferentiation. Neural dedifferentiation has been associated with many of the behavioral
impairments typically observed in healthy aging, and evidence collected by our group
during the original funding period has found a strong relationship between neural
dedifferentiation and gamma-aminobutyric acid (GABA), the brain’s major inhibitory
neurotransmitter. Specifically, we found that GABA levels are lower in older vs. younger
adults and that older adults with less GABA exhibit greater dedifferentiation. We propose
to take this line of research in two new directions. (1) We will conduct a longitudinal study
and explore age-related trajectories of change in GABA, neural distinctiveness, and
behavior, as well as directional relationships among these measures (e.g., Do GABA
levels at age 65 predict subsequent declines in neural distinctiveness? Does neural
distinctiveness at age 65 predict behavioral declines over the next decade). (2) We will
also examine how dedifferentiation is related to Alzheimer’s pathology by collecting the
same measures in patients with Mild Cognitive Impairment in whom amyloid beta and tau
burden has already been measured. The proposed studies will provide novel insights into
how the brain changes with age and with neuropathology, whether those changes can
explain the observed behavioral deficits, and whether changes in GABA levels are a
contributing cause. Such insights could lead to novel interventions to alleviate the
behavioral impairments associated with healthy and pathological aging.

## Key facts

- **NIH application ID:** 10469464
- **Project number:** 5R01AG050523-07
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Thad A Polk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $700,614
- **Award type:** 5
- **Project period:** 2016-05-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469464

## Citation

> US National Institutes of Health, RePORTER application 10469464, Investigating age-related neural dedifferentiation longitudinally and in Alzheimer’s pathology (5R01AG050523-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10469464. Licensed CC0.

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