Aging and Exercise Impacts on Glymphatic Function

Impact of Aging and Exercise on Glymphatic Function Using Multi-modal MRI

This is a prospective, interventional, non-blinded, single center research project that will recruit cognitively unimpaired subjects in the 25-55 year old and 55-75 year old range. This study will use acute aerobic exercise as a natural intervention model to increase cardiac activity which may further drive the glymphatic function. There will be no randomization, and all enrolled subjects will participate in the exercise session.

Hypotheses: revealed by the multi-modal magnetic resonance imaging (MRI) approach, glymphatic dysfunction increases with age and is associated with preclinical Alzheimer's Disease (AD) pathology in cognitively unimpaired individuals. Using acute aerobic exercise as a human model, the enhancement of cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange caused by elevated cardiac activity and paravascular cerebrospinal fluid (pCSF) dynamics can be validated.

Inclusion Criteria:

• age 25-75 years old
• cognitively unimpaired (CU)
• Mini-Mental State Examination (MMSE) score ≥27 at enrollment screening
• matched gender
• all racial/ethnic groups

Exclusion Criteria:

• pregnant women
• history of stroke or other major cerebrovascular disease;
• diagnosis of Alzheimer's disease (AD) or other types of dementia;
• diagnosis of major neurologic and psychiatric disorders (e.g., Parkingson's disease, major depression);
• history of prior head trauma, significant autoimmune disorders,
• sleep apnea;
• major systemic illness likely to affect the central nervous system, e.g., uncontrolled diabetes, severe cardiovascular disease, cancer, etc.;
• prior or current alcoholism or drug abuse;
• resistant hypertension (SBP ≥140 or DBP ≥ 90 mmHg despite 3 antihypertensive drugs at maximal doses);
• orthostatic hypotension defined as the third standing systolic blood pressure (SBP) < 100mmHg; any contraindications to having a MRI, e.g., claustrophobia, pacemaker or other medical device of metal;
• any conditions judged by the investigators to be medically inappropriate, risky or likely to cause poor study compliance.