Alzheimer Disease, Healthy Aging
Conditions
Brief summary
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
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.
Interventions
BEHAVIORALAerobic 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
Sponsors
National Institute on Aging (NIA)
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
2 arm, cross-sectional
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Metabolism (Standard Uptake Value Ratio) | Resting Vs acute exercise bout: ~1 month | FDG PET measures reflecting cerebral metabolism standardized to the uptake value of the cerebellum and standardized uptake value ratios (SUVR) calculated from native-space region of interest (ROI). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lactate Area Under the Curve | Resting Vs acute exercise bout: ~1 month | Change in lactate AUC between the resting and exercise condition |
| Brain-derived Neurotrophic Factor (BDNF) Change | Resting Vs acute exercise bout: ~1 month | Pre/post change in circulating Brain Derived Neurotrophic Factor between the resting and exercise conditions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
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 | 29 |
| 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
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 | 31 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | issue with PET image (1) | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | High Intensity Aerobic Exercise | Total | Moderate Intensity Aerobic Exercise |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 27 Participants | 52 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 8 Participants | 4 Participants |
| Age, Continuous | 74.2 years STANDARD_DEVIATION 8.1 | 73.2 years STANDARD_DEVIATION 7.7 | 72.2 years STANDARD_DEVIATION 7.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 53 Participants | 24 Participants |
| Region of Enrollment United States | 31 participants | 60 participants | 29 participants |
| Sex: Female, Male Female | 16 Participants | 29 Participants | 13 Participants |
| Sex: Female, Male Male | 15 Participants | 31 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 31 |
| other Total, other adverse events | 2 / 29 | 2 / 31 |
| serious Total, serious adverse events | 0 / 29 | 0 / 31 |
Outcome results
Primary
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) calculated from native-space region of interest (ROI).
Time frame: Resting Vs acute exercise bout: ~1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Intensity Aerobic Exercise | Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Metabolism (Standard Uptake Value Ratio) | -0.0514 SUVR | Standard Deviation 0.03 |
| High Intensity Aerobic Exercise | Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Metabolism (Standard Uptake Value Ratio) | -0.0667 SUVR | Standard Deviation 0.03 |
Secondary
Brain-derived Neurotrophic Factor (BDNF) Change
Pre/post change in circulating Brain Derived Neurotrophic Factor between the resting and exercise conditions
Time frame: Resting Vs acute exercise bout: ~1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Intensity Aerobic Exercise | Brain-derived Neurotrophic Factor (BDNF) Change | 610.2 pg/mL | Standard Deviation 1071.9 |
| High Intensity Aerobic Exercise | Brain-derived Neurotrophic Factor (BDNF) Change | 353.3 pg/mL | Standard Deviation 239.8 |
Secondary
Lactate Area Under the Curve
Change in lactate AUC between the resting and exercise condition
Time frame: Resting Vs acute exercise bout: ~1 month
Population: Individuals who completed both visits with blood draws available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Intensity Aerobic Exercise | Lactate Area Under the Curve | 40.3 AUC change (mmol/L*min) | Standard Deviation 27.5 |
| High Intensity Aerobic Exercise | Lactate Area Under the Curve | 97.0 AUC change (mmol/L*min) | Standard Deviation 50.8 |