# Longitudinal MRI in Preclinical Parkinson Disease

> **NIH VA I01** · WM S. MIDDLETON MEMORIAL VETERANS HOSP · 2021 · —

## Abstract

Work Accomplished/Background: Parkinson's disease (PD) is a common disease of aging that causes motor
symptoms such as slow movement and tremor, as well as non-motor symptoms, such as cognitive difficulties
and constipation. Non-motor symptoms can precede the development of motor symptoms by years—this
observation has led to the hypothesis that PD has a long “preclinical” period during which cells in the brain and
peripheral nervous system are damaged, but the damage has not exceeded a threshold for motor symptom
expression. We do not have validated methods to detect this “preclinical” disease stage. Due to the long
timecourse of PD, such biomarkers will be critical to evaluate the effects of new therapies as they become
available.
 Using sophisticated magnetic resonance imaging (MRI) techniques that are sensitive to changes in the
brain microstructure, we have shown differences between the brains of PD subjects and age-matched healthy
controls. One such technique, diffusion tensor imaging (DTI), estimates the direction and magnitude of water
movement inside and around nerve cells in the brain. Another technique, multicomponent relaxometry, is able
to quantify the amount of water trapped inside the layers of the onion-like myelin sheaths that insulate nerve
cells. In the past four years of our VA-funded research program, we have shown both diffusion and myelin
measures to differ in PD patients in comparison to healthy controls. We hypothesize that these microstructural
differences may be detectable in preclinical disease, and may predict “conversion” from preclinical to clinical
PD.
 For this proposal we plan to study two populations at higher than background risk for PD: Veterans
who have been exposed to Agent Orange (AO) during service in Vietnam and have reduced sense of smell
(hyposmia), and persons with rapid eye movement sleep behavior disorder (RBD), a condition that causes
sleepers to act out their dreams.
Objectives: (1) To evaluate the regional distribution and degree of microstructural difference in the brains of
Veterans with high, medium, and low risk for the development of PD; (2) compare the rate of change in MRI
microstructural measures between these groups; (3) determine to what degree microstructural measures
predict the emergence of additional symptoms of PD (such as subtle motor impairment), or conversion to PD.
Methods: This 4-year project will prospectively recruit a cohort of 135 Veterans with RBD, AO exposure with
hyposmia, and AO exposure with normal olfactory function. Veterans will be recruited through the busy local
VA sleep laboratory, while Veterans with AO exposure will be contacted through the National AO Examination
Registry. AO-exposed Veterans will be mailed a standardized test of smell acuity as well as a sleep
questionnaire, which will be used to select persons to join the study. Study procedures will include a brain MRI
as well as detailed analyses of cognition and learning, movement speed, and walking abilit...

## Key facts

- **NIH application ID:** 10357728
- **Project number:** 5I01CX000555-08
- **Recipient organization:** WM S. MIDDLETON MEMORIAL VETERANS HOSP
- **Principal Investigator:** Catherine L. Gallagher
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2012-07-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357728

## Citation

> US National Institutes of Health, RePORTER application 10357728, Longitudinal MRI in Preclinical Parkinson Disease (5I01CX000555-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10357728. Licensed CC0.

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