Acute Exercise and the Cerebral Metabolic Response in Aging and Alzheimer's Disease (AEROBIC)

Acute Exercise Response On Brain Imaging and Cognition

The overall goal is to characterize the acute exercise response as it relates to brain glucose metabolism in aging and Alzheimer's Disease (AD). The study team will also examine lactate metabolism, relationships with cognition, and the effect of exercise intensity.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Healthy Aging
• Intervention / Treatment: Behavioral: Aerobic Exercise

Detailed Description

Aim 1: Compare the effects of acute, moderate intensity and acute, higher intensity exercise on cerebral glucose metabolism in nondemented (ND) elderly and AD subjects. ND (n=30) and AD (n=30) subjects will undergo a single bout of moderate intensity (45-55% HRR) or higher intensity (65-75% HRR) exercise to assess the effect of exercise intensity on acute change in brain glucose metabolism (rest to exercise). Investigators hypothesize that both moderate and high intensity exercise will elicit a drop in global brain glucose metabolism compared to quiet rest, but that the effect will be greater with higher intensity vs. moderate intensity exercise, and greater in ND subjects than in AD subjects.

Aim 2: Characterize the effect of both exercise intensities on acute biomarker response and cognition (memory and executive function) in ND and AD subjects. The acute biomarker response to exercise and the effect on cognition has not been examined in aged or AD cohorts. Investigators hypothesize that acute higher intensity exercise will elicit a greater blood lactate response (area under the curve, AUC) compared to acute moderate intensity exercise, and that this response will be greater in ND than in AD subjects. Investigators further hypothesize that lactate AUC will track negatively with change in cerebral glucose metabolism and cognitive performance. Although investigators will focus on lactate, they will also quantify additional exercise-related biomarkers.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jill Morris; Phone Number: 913-945-7675; Email: jmorris2@kumc.edu
• Study Contact Backup: Name: Casey John; Phone Number: 913-945-7672; Email: cjohn@kumc.edu

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • Univeristy of Kansas Medical Center
      • Contact: Jill Morris; Phone Number: 913-945-7675; Email: morrisj2@kumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 60 and older
• Stable medication doses (>1month)
• Post-menopausal
• Diagnosis of either Nondemented (CDR 0) or Probable AD (CDR 0.5 or 1 only)

Exclusion Criteria:

• Inability to provide consent
• Diagnosis of insulin-dependent (Type 1) Diabetes Mellitus
• Recent ischemic heart disease (<2 years)
• Diagnosis of an clinically significant chronic disease including cardiovascular disease (CVD), other metabolic diseases (e.g., thyroid), cancer, human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome
• Excluded from or unable to complete an MRI scan
• Any Neurological disorders that have the potential to impair cognition or brain metabolism (e.g., Parkinson's disease, stroke defined as a clinical episode with neuroimaging evidence in an appropriate area to explain the symptoms).
• Clinically significant depressive symptoms that may impair cognition, abnormalities in B12, rapid plasma regain (RPR), or thyroid function that may impair cognition, use of psychoactive and investigational medications, and significant visual or auditory impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Intensity Aerobic Exercise; 45-55% of heart rat reserve (HHR) Low range = ((Max HR from Visit 1) - Resting HR ) * 0.45 + Resting HR High range = ((Max HR from Visit 1) - Resting HR) * 0.55 + Resting HR	Behavioral: Aerobic Exercise; Participants will exercise for 15 minutes based on heart rate range. The study team will employ a stationary bike to maintain control over workload
Experimental: High Intensity Aerobic Exercise; 65-75% of heart rat reserve (HHR) Low range = ((Max HR from Visit 1) - Resting HR ) * 0.65 + Resting HR High range = ((Max HR from Visit 1) - Resting HR) * 0.75 + Resting HR	Behavioral: Aerobic Exercise; Participants will exercise for 15 minutes based on heart rate range. The study team will employ a stationary bike to maintain control over workload

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluorodeoxyglucose (FDG) positron emission tomography (PET) Metabolism (Standard Uptake Value Ratio)	FDG PET measures reflecting cerebral metabolism standardized to the uptake value of the cerebellum and standardized uptake value ratios (SUVR) will be calculated from native-space region of interest (ROI).	Resting Vs acute exercise bout: ~1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate Area Under the Curve	Change in circulating lactate	Resting Vs acute exercise bout: ~1 month
Brain-derived neurotrophic factor (BDNF) Change	Change in circulating Brain Derived Neurotrophic Factor	Resting Vs acute exercise bout: ~1 month

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 6, 2020

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: STUDY00142140; 1R01AG062548-01A1 (U.S. NIH Grant/Contract)

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