# Dopaminergic and Neuroplastic Influences on Longitudinal Change in Cognitive and Brain Aging

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2020 · $511,533

## Abstract

PROPOSAL SUMMARY (ABSTRACT) 
Distinguishing normal from pathological aging (such as Alzheimer’s Disease) is a major scientific goal. The 
projects in this application seek to utilize longitudinal design, neuroimaging techniques, and carefully selected 
candidate genes (single nucleotide polymorphisms; SNPs) to help uncover biological mechanisms in individual 
differences in brain and cognitive aging. This within-­person approach is necessary to track how an individual 
(of any age) ages across time, and to selectively investigate the role of specific risk/protective factors while 
holding other variables constant (within-­person design). Here we leverage data collected from R00 NIA award 
on 190 individuals aged 20-­94 years to begin Wave 2 follow-­up in Year 1 and Wave 3 in Year 4 of the 
proposed project. This will allow for three waves of data spanning 6.5 years in a five-­year study, providing 
crucial information about individual differences in brain and cognitive aging. Specifically, this project aims to 
capitalize on the known biological effects of SNPs in the dopaminergic system (COMTval158 and DRD2 C/T) 
and in the regulation of neuroplasticity (BDNFval66met). Aging is accompanied by stark diminution to the 
dopamine neurons and those major brain regions they originate from and innervate. However, the brain is 
surprisingly plastic to these changes, and a major factor in regulating neuroplasticity is brain-­derived growth 
factor. The first specific aim of the project is to investigate within-­person change in persons with or without 
predisposition to reduced availability of dopamine in the synapses in frontal-­parietal and fronto-­striatal brain 
regions. We will examine change in ability to modulate this circuitry in functional MRI studies of cognitive 
challenge over the course of three follow-­up points. We will further examine the brain structural changes 
(degradation of white matter connectivity, cortical thinning) that may mediate this change in neural function, as 
well as cognitive decline or preservation that results from these changes. The second specific aim will similarly 
examine within-­person changes in modulation of brain activation to difficulty in persons with or without 
predisposition to reduced availability of neuroplasticity factors, particularly in limbic circuitry and the changes to 
brain structure that may mediate these functional changes and predict cognitive outcome. Our third aim utilizes 
an innovative neuroimaging technique, NODDI (neurite orientation dispersion and density imaging), to image 
with more specificity than previously possible the neurites which form synaptic units. We will introduce this in 
Wave 2, with follow-­up in Wave 3 to measure change in dendrite/synaptic density, another marker of 
neuroplasticity. We will then further associate level and change in dendritic density in individuals based on 
genetic risk for reduced BDNF levels and at risk for Alzheimer’s Disease by examining neuri...

## Key facts

- **NIH application ID:** 9925201
- **Project number:** 5R01AG056535-04
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Kristen M. Kennedy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $511,533
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925201

## Citation

> US National Institutes of Health, RePORTER application 9925201, Dopaminergic and Neuroplastic Influences on Longitudinal Change in Cognitive and Brain Aging (5R01AG056535-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9925201. Licensed CC0.

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