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.

Study Overview

• Status: Not yet recruiting
• Conditions: Aging and Exercise Impacts on Glymphatic Function
• Intervention / Treatment: Procedure: Acute Aerobic exercise

Detailed Description

The purpose of this research study is to understand how the human brain removes amyloid beta (Aβ) protein which can lead to Alzheimer's disease (AD), using non-invasive magnetic resonance imaging (MRI) techniques. Participants will first go through screening including health survey and blood draw. Depending on their age, enrolled participants will take neuropsychological assessment, sleep and quality-of-life survey, exercise testing, MRI and positron emission tomography (PET) scans. Depending on individual age, the study may include up to three separate visits, a blood draw, an MRI visits and a PET scan visit. The greatest risks of this study include the possibility of injury during the exercise testing, MRI and PET scans, and loss of confidentiality.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiaen Liu, Ph.D.; Phone Number: 612/423-8380; Email: Jiaen.Liu@UTSouthwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute aerobic exercise- Interventional Group; This group will include all enrolled participants from all age groups, will receive MRI scans for glymphatic function and participate in acute aerobic exercise (intervention) between MRI sessions. They may / may not undergo PET scans.	Procedure: Acute Aerobic exercise; During the MRI session, subject will perform aerobic exercise on a MR-compatible ergometer and will be guided to reach certain heart rate level depending on subject's age. Their vital signs will be closely monitored by the research team to ensure safety.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise-induced changes in heart rate (HR)	During exercise, HR will be continuously monitored using photoplethysmography (ppg) by a device attached to a finger of the subjects.	Baseline (pre-exercise), immediately post-exercise
Exercise-induced changes in cardiac output (CO)	During exercise, CO will be calculated based on HR and real time blood pressure (BP) acquired on the index finger using an MRI-compatible device.	Baseline (pre-exercise), immediately post-exercise
Exercise-induced changes in MRI measurements of pCSF dynamics	pCSF will be assessed using MRI in the brain.	Baseline (pre-exercise), immediately post-exercise
Exercise-induced changes in MRI measurements of CSF-ISF exchange	CSF-ISF exchange will be assessed using MRI in the brain.	Baseline (pre-exercise), immediately post-exercise

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Jiaen Liu, Ph.D., University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: August 12, 2026
• First Submitted That Met QC Criteria: August 17, 2026
• First Posted (Actual): August 20, 2026

Study Record Updates

• Last Update Posted (Actual): August 20, 2026
• Last Update Submitted That Met QC Criteria: August 17, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Alzheimer's Disease; Aging; Glymphatic Function
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Behavior; Alzheimer Disease; Motor Activity
• Other Study ID Numbers: STU20260916

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in publication, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Between the time range beginning 3 months and ending 5 years following publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be directed to Jiaen.Liu@UTSouthwestern.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at NIH's data repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No