The goal of this clinical trial is to learn whether Nicotinamide Riboside, a form of Vitamin B3 also known as NR, can improve blood vessel health in the brain, memory, and physical function in eligible study participants. NR is considered investigational for this study because it is not yet established for this specific use.

The main questions it aims to answer are:

Can NR improve non-invasive measures of blood vessel health in the brain? Can NR improve memory testing results and physical function?

Researchers will compare participants who receive NR with participants who receive a placebo, an inactive substance that looks like the study drug, to see if NR has beneficial effects. Participants will be randomly assigned to receive either NR or placebo.

They will complete 3 study visits over 13 weeks at the Translational Geroscience Laboratory at the University of Oklahoma Health Campus. During the visits, participants will complete questionnaires, memory testing, non-invasive blood vessel measurements, physical function tests, and a blood draw.

This is a single-site, randomized, placebo-controlled clinical trial evaluating oral nicotinamide riboside (NR), a form of vitamin B3, in adults over 55 years of age with Parkinson's disease. NR is commercially available as a dietary supplement, however, its use in this study for Parkinson's disease is considered investigational because it is not approved by the U.S. Food and Drug Administration as a treatment for Parkinson's disease.

The purpose of this study is to explore whether daily NR supplementation over 12 weeks may improve measures related to brain health, memory, motor function, physical performance, and vascular function in participants with Parkinson's disease. Participants will be randomly assigned to receive either NR or placebo. Neither the participants nor the investigators will choose the assigned group.

Study participation includes 3 in-person visits: screening, baseline, and follow-up. Study procedures include collection of medical and health information, questionnaires, blood draw, memory and cognitive testing, non-invasive measurements of brain activity and blood vessel function, walking and balance assessments, grip strength testing, and use of a study watch to assess activity and sleep patterns.

The study procedures will be conducted at the Translational Geroscience Laboratory at the University of Oklahoma Health Sciences Center.

Inclusion Criteria:

• Clinical diagnosis of Parkinson's disease according to Movement Disorder Society clinical diagnostic criteria (59), Hoehn and Yahr stages I-III at enrollment (ON medication state when applicable) (60).
• Age ≥55 years at enrollment.
• Adequate hearing and visual acuity to participate in the examinations
• Ability to provide written informed consent in English.
• Ability to complete study procedures, including seated tasks and walking tasks (with or without an assistive device, if needed for safety).
• Stable antiparkinsonian medication regimen for ≥4 weeks prior to baseline (or drug-naive).

Exclusion Criteria:

• Not able to communicate or follow instructions due to aphasia or severe cognitive impairment.
• Active CNS disease including multiple sclerosis, uncontrolled seizures, active cancer.
• Cerebrovascular accident other than TIA within 60 days prior to Visit 0.
• Major psychiatric disease, including major depression not currently controlled on medications, alcohol or drug abuse.
• Abnormal kidney function (creatinine >2mg/dL or EGFR <30mL/min) by most recent labs within 6 months prior to Visit 0.
• Elevated liver enzymes (AST and/or ALT above x2 upper limit of normal) by most recent labs within 6 months prior to Visit 0.
• Treatment with other NAD enhancers (Nicotinamide riboside or nicotinamide mononucleotide) within 4 weeks prior to randomization.
• Any other medical condition and/or unstable or severe medical illness which, in the opinion of investigator, would render the patient inappropriate or too unstable to complete the study protocol.