Aging and Exercise Impacts on Glymphatic Function

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.