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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Acute Exercise Response On Brain Imaging and Cognition

Conditions
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Healthy Aging, Alzheimer Disease

Intervention / Treatment
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* Behavioral: Aerobic Exercise


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 arm, cross-sectional
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moderate Intensity Aerobic Exercise<br>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<br>* Participants will exercise for 15 minutes based on heart rate range. The study team will employ a stationary bike to maintain control over workload<br>|
| Experimental: High Intensity Aerobic Exercise<br>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<br>* Participants will exercise for 15 minutes based on heart rate range. The study team will employ a stationary bike to maintain control over workload<br>|

What is the study measuring?
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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 |