Acute Exercise on Brain Insulin Sensitivity

Impact of Acute Exercise on Brain Insulin Sensitivity in Middle-aged to Older Adults

Dementia is a leading cause of death in the United States among aging adults. Brain insulin resistance has emerged as a pathologic factor affecting memory, executive function as well as systemic glucose control. Regular aerobic exercise decreases Alzheimer's Disease (AD) risk, in part, through changes in brain structure and function. However, there is limited data available on how exercise impacts brain insulin resistance in aging. This study will test the effect of acute exercise on brain insulin sensitivity in middle-aged to older adults. The study will also examine cognition and cardiometabolic health in relation to brain insulin sensitivity.

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Resistance; Aging; Cognition; Cardiovascular Disease Risk
• Intervention / Treatment: Behavioral: Exercise

Detailed Description

Obesity, hypertension, high blood glucose (e.g. prediabetes/type 2 diabetes), and physical inactivity is thought to worsen brain insulin resistance and reduce cerebral blood flow. This suggests lifestyle approaches may be necessary to counteract declines in brain health. Regular aerobic exercise decreases Alzheimer's Disease (AD) risk, in part, through changes in brain structure and function. Moreover, exercise-related structural changes in the brain, namely increased hippocampal volume, is linked to improved memory. However, there is limited data available on how exercise impacts brain insulin resistance in aging. It is also unclear if one bout of exercise may help improve brain insulin responses to insulin before fitness gains or weight loss in people at risk for dementia, type 2 diabetes and cardiovascular disease. Because single bouts of exercise are established to improve metabolic and vascular insulin sensitivity in people with obesity, the investigators anticipate exercise to raise brain insulin sensitivity in relation to cognition and cardiometabolic health.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Institute for Food, Nutrition, and Health
    • New Brunswick, New Jersey, United States, 08901
      • Robert Wood Johnson University Hospital Clinical Research Center
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers University Loree Gymnasium
    • Piscataway, New Jersey, United States, 08854
      • Center for Advanced Human Brain Imaging Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female >/=40 and </=80 years old.
• Has a body mass index >/=25 and </=45 kg/m2.
• Physical Activity (<150 min of moderate/high intensity exercise per week)

Exclusion Criteria:

• Subjects who have not been weight stable (>2 kg weight change in past 3 months)
• Subjects who are smokers or who have quit smoking <1 years ago
• Subjects with abnormal estimated glomerular filtration rate (eGFR).
• Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
• Hypertensive (>160/100 mmHg)
• Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures or impact subject safety.
• Pregnant (as evidenced by positive urine pregnancy test) or nursing women
• Subjects with contraindications to participation in an exercise
• Current Pregnancy
• Currently taking active weight suppression medication (e.g. phentermine, orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
• Subjects currently taking medications that affect heart rate and rhythm (i.e. Ca++ channel blockers, nitrates, alpha- or beta-blockers).
• Known contraindications for MRI imaging

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Rest; Individuals will rest for about 1 hour in the seated position to mimic time exercising.
Experimental: Exercise; Individuals will exercise for at medium to hard intensity for 1 hour.	Behavioral: Exercise; Exercise will be walking/jogging at a medium to hard intensity for 1 hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain insulin sensitivity	MRI arterial spin labeling, cerebral blood flow	Change from baseline to exercise; about 1 week apart

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognition	NIH Toolbox Cognitive Battery	Change from baseline to exercise; about 1 week apart
Blood Glucose	Blood draw via oxidase method	Change from baseline to exercise; about 1 week apart
Blood Free Fatty Acids	Blood draw via colorimetric assays	Change from baseline to exercise; about 1 week apart
Carbohydrate Use	Indirect Calorimetry	Change from baseline to exercise; about 1 week apart
Systolic and Diastolic Blood Pressure	Cuff around arm	Change from baseline to exercise; about 1 week apart

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Investigators: Principal Investigator: Steven K Malin, PhD, Rutgers University - New Brunswick

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2023
• Primary Completion (Actual): March 20, 2025
• Study Completion (Actual): March 25, 2025

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 11, 2023

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Exercise
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Hyperinsulinism; Overweight; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Insulin Resistance; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: Pro2022001842

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No