# Conjoint Effects of Dopamine and Tau on Cognition in Aging

> **NIH NIH F32** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $78,784

## Abstract

Project Summary/Abstract
Aging is associated with dopamine system dysfunction and the aggregation of hyperphosphorylated tau.
Previous studies of cognitive aging have demonstrated the independent effects of dopamine dysregulation (e.g.
deficits in reward processing) and tau aggregation (e.g. memory deficits). We propose to study the joint effects
of dopamine and tau on cognition in aging using multimodal MR/PET neuroimaging. The central hypothesis is
that increased levels of dopamine protect against cognitive decline, and can stabilize memory performance in
the face of tau burden.
The proposed work will leverage a unique training opportunity and collaboration between interdisciplinary
researchers at the MGH Martinos Center for Biomedical Imaging and Brandeis University. I will gain expertise in
cognitive aging as well as integrating fMRI and PET methodologies. Older adult participants from the ongoing
longitudinal Brandeis Aging Brain Study will be invited to undergo simultaneous MR/PET neuroimaging to
measure dopamine levels and neural activity during a reward memory task. Additionally, participants will return
for a tau-PET scanning session. Our specific aims will test the hypotheses 1) that increased endogenous
dopamine release is associated with better reward memory, especially in individuals with lower levels of tau, 2)
that increased dopamine release is associated with increased variability in hippocampal neural activity (leading
to improved reward memory), and 3) that individual baseline levels of dopamine and tau will be predictive of
memory improvements upon receiving a dopamine-enhancing pharmaceutical (methylphenidate).
Based on preliminary data, we expect to find that increased levels of dopamine will lead to more variable brain
activity in the hippocampus and better reward memory in older adults, but that these effects will be attenuated
by tau aggregation. We also predict that older adults with lower levels dopamine will show the greatest potential
for memory improvements following pharmaceutically-induced dopamine enhancement, despite baseline levels
of tau. Previously, the influences of dopamine and tau on cognitive aging have mostly been studied
independently. This work will begin to bridge these subfields by studying the joint influences tau and dopamine
on memory together in the same individuals. These experiments will contribute to an improved understanding of
how neurochemistry and protein pathology interact to affect memory in older adults, and may suggest a
mechanism by which cognitive function is preserved in the pre-clinical stages of age-related disease.

## Key facts

- **NIH application ID:** 10896737
- **Project number:** 1F32AG084259-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Thomas Morin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $78,784
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896737

## Citation

> US National Institutes of Health, RePORTER application 10896737, Conjoint Effects of Dopamine and Tau on Cognition in Aging (1F32AG084259-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896737. Licensed CC0.

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