# Genetic influences on response to gait rehabilitation in Parkinson’s disease

> **NIH VA I21** · VA PUGET SOUND HEALTHCARE SYSTEM · 2020 · —

## Abstract

The completion of the Human Genome Project in 2003 marked the beginning of the genomic era and
the birth of “personalized” (precision) medicine. In the last decade, genetics have provided a new
understanding of predicting, diagnosing, and treating individual health conditions. Indeed, such
precision medicine has begun to impact virtually all areas of medicine, with significant potential to
influence the timing, dosage, and intensity of physical rehabilitation.
The long-term goals of this research are: (1) to determine if certain genetic variants associated to
learning impairments impact the motor and cognitive benefit experienced in response to physical
rehabilitation in Veterans with Parkinson's disease (PD), and (2) to use that knowledge to identify
subpopulations of patients that may require rehabilitative strategies tailored to their genotype to
optimize physical rehabilitation. To achieve these goals we will enroll 30 Veterans with PD in a 10-week
moderate intensity gait training program consisting of 2 times per week treadmill training with verbal
cues for gait quality. Aim 1 will examine the association between variants in 2 genes known to affect
cognition and motor learning (APOE-ɛ4 and BDNF-Met66), and motor improvements after gait training.
Specifically, changes in walking from during and after training will be sensitively and objectively
assessed using state-of-the-art quantitative gait analysis, and compared between three genotype
groups (carriers of BDNF-Met66 (N=10), carriers of APOE-ɛ4 (N=10) and those not carrying either of
those variants (N=10)). Aim 2 will examine the effect of APOE-ɛ4 and BDNF-Met66 genetic variants on
cognitive changes in response to this training program. In order to do this we will measure cognitive
performance pre- and post-training using a brief, targeted battery aimed at assessing attention,
processing speed, executive function, and learning/memory, the domains more affected, and more
likely to improve with physical exercise in PD. We will test the hypothesis that Veterans with PD who
carry an APOE-ɛ4 or BDNF-Met66 allele will demonstrate smaller improvements in gait (Aim 1) and
cognition (Aim 2) in response to a 10-week gait training program. Overall the results of this project will
enhance our knowledge regarding the influence of different genetic profiles in the response to physical
rehabilitation in Veterans with PD, and will generate supporting data that will translate to more
personalized and effective rehabilitation programs for people with PD.

## Key facts

- **NIH application ID:** 10174833
- **Project number:** 5I21RX002553-04
- **Recipient organization:** VA PUGET SOUND HEALTHCARE SYSTEM
- **Principal Investigator:** CYRUS P ZABETIAN
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174833

## Citation

> US National Institutes of Health, RePORTER application 10174833, Genetic influences on response to gait rehabilitation in Parkinson’s disease (5I21RX002553-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10174833. Licensed CC0.

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