Aging and Exercise Impacts on Glymphatic Function
Conditions
Keywords
Aging, Exercise, Glymphatic Function, Alzheimer's Disease
Brief summary
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.
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.
Interventions
PROCEDUREAcute 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.
Sponsors
University of Texas Southwestern Medical Center
National Institute on Aging (NIA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise-induced changes in heart rate (HR) | Baseline (pre-exercise), immediately post-exercise | During exercise, HR will be continuously monitored using photoplethysmography (ppg) by a device attached to a finger of the subjects. |
| Exercise-induced changes in cardiac output (CO) | Baseline (pre-exercise), immediately post-exercise | 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. |
| Exercise-induced changes in MRI measurements of pCSF dynamics | Baseline (pre-exercise), immediately post-exercise | pCSF will be assessed using MRI in the brain. |
| Exercise-induced changes in MRI measurements of CSF-ISF exchange | Baseline (pre-exercise), immediately post-exercise | CSF-ISF exchange will be assessed using MRI in the brain. |
Contacts
CONTACTJiaen Liu, Ph.D.
PRINCIPAL_INVESTIGATORJiaen Liu, Ph.D.
University of Texas Southwestern Medical Center
Outcome results
None listed