Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, AD, Aerobic Exercise, Exercise
Brief summary
The purpose of this study is to learn about the possible benefits of aerobic exercise in controlling or reducing the amount of amyloid present in the brain, reducing changes in brain structure that may lead to Alzheimer's Disease (AD), and increasing cognitive ability in individuals that have amyloid deposits and are at risk to develop AD.
Interventions
OTHERAerobic Exercise
Aerobic group participants will engage in 150 minutes of aerobic exercise over 4-5 days per week for 52 weeks
OTHERStandard of Care
Control group participants will be provided educational materials on starting an exercise program, but will receive no formal support for their exercise program.
Sponsors
National Institute on Aging (NIA)
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical Dementia Rating 0 (nondemented) * Age 65 or older * Florbetapir PET evidence of cerebral amyloidosis * Sedentary or underactive by the Telephone Assessment of Physical Activity * Stable doses of medications for 30 days. * Clinician judgment regarding subject's health status and likelihood to successfully complete the 1-year exercise intervention
Exclusion criteria
* Clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to standard criteria or significant psychiatric symptoms that could impair the completion of the study * Clinically-significant systemic illness that may affect safety or completion of the study * History of clinically-evident stroke * Clinically-significant infection within the last 30 days * Active cardiac condition (e.g. angina, myocardial infarction, atrial fibrillation) or pulmonary condition in the past 2 years that, in the investigator's opinion, could pose a safety risk to the participant-unless cleared for exercise by the participant's primary care physician or cardiologist. * Uncontrolled hypertension within the last 6 months * History of cancer in the last 5 years (except non-metastatic basal or squamous cell carcinoma) * History of drug or alcohol abuse as defined by DSM-IV criteria within the last 2 years * Insulin-dependent diabetes mellitus * Significant pain or musculoskeletal disorder prohibiting participation in an exercise program * Unwillingness to undergo or contraindication to brain MRI scan. * History within the last 5 years of primary or recurrent malignant disease with the exception of resected localized cutaneous squamous cell carcinoma, basal cell carcinoma, cervical carcinoma, or prostate cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amyloid Burden | Baseline to 52 weeks | Amyloid burden measure is mean Florbetapir cortical-to-cerebellar uptake ratio averaged across 6 regions of interest (frontal, temporal, parietal, anterior cingulate, posterior cingulate, and precuneus). Higher numbers mean more amyloid accumulation. There is no defined maximum value. Zero is the theoretical minimum value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whole Brain Volume | Baseline to 52 weeks | Whole brain volume in mL define by Freesurfer analysis. Higher numbers indicate greater brain volume. There is no defined maximum. Zero is the theoretical minimum. |
| Executive Function | Baseline to Week 52 | Executive Function ability to be measured using confirmatory factor analysis (CFA). CFA aggregates scores from across multiple subtests. Values are standard deviations centered on a pooled baseline (all participant scores at baseline). Higher values mean improvement over baseline testing. Lower scores (including negative) mean worse performance after baseline testing. There is no minimum or maximum score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aerobic Exercise Group Exercise 150 minutes per week (over 3 to 5 days) for 52 weeks
Aerobic Exercise: Aerobic group participants will engage in 150 minutes of aerobic exercise over 4-5 days per week for 52 weeks | 78 |
| Control Group Standard of Care exercise recommendations
Standard of Care: Control group participants will be provided educational materials on starting an exercise program, but will receive no formal support for their exercise program. | 39 |
| Total | 117 |
Baseline characteristics
| Characteristic | Aerobic Exercise Group | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 78 Participants | 39 Participants | 117 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 72.2 years STANDARD_DEVIATION 5.3 | 71.2 years STANDARD_DEVIATION 4.8 | 71.5 years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants | 39 Participants | 117 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| 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 | 1 Participants | 4 Participants | 5 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 77 Participants | 35 Participants | 112 Participants |
| Region of Enrollment United States | 78 participants | 39 participants | 117 participants |
| Sex: Female, Male Female | 55 Participants | 24 Participants | 79 Participants |
| Sex: Female, Male Male | 23 Participants | 15 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 78 | 0 / 39 |
| other Total, other adverse events | 23 / 78 | 4 / 39 |
| serious Total, serious adverse events | 8 / 78 | 4 / 39 |
Outcome results
Primary
Amyloid Burden
Amyloid burden measure is mean Florbetapir cortical-to-cerebellar uptake ratio averaged across 6 regions of interest (frontal, temporal, parietal, anterior cingulate, posterior cingulate, and precuneus). Higher numbers mean more amyloid accumulation. There is no defined maximum value. Zero is the theoretical minimum value.
Time frame: Baseline to 52 weeks
Population: Six individuals did not complete follow-up testing due to withdrawal. Two refused follow-up PET.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Group | Amyloid Burden | Baseline | 1.20 Standard Uptake Value Ratio (SUVR) | Standard Deviation 0.2 |
| Aerobic Exercise Group | Amyloid Burden | Follow-up | 1.21 Standard Uptake Value Ratio (SUVR) | Standard Deviation 0.2 |
| Control Group | Amyloid Burden | Baseline | 1.22 Standard Uptake Value Ratio (SUVR) | Standard Deviation 0.2 |
| Control Group | Amyloid Burden | Follow-up | 1.22 Standard Uptake Value Ratio (SUVR) | Standard Deviation 0.2 |
Secondary
Executive Function
Executive Function ability to be measured using confirmatory factor analysis (CFA). CFA aggregates scores from across multiple subtests. Values are standard deviations centered on a pooled baseline (all participant scores at baseline). Higher values mean improvement over baseline testing. Lower scores (including negative) mean worse performance after baseline testing. There is no minimum or maximum score.
Time frame: Baseline to Week 52
Population: Six individuals did not complete follow-up testing due to withdrawal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Group | Executive Function | Baseline | 0.029 Standard Deviations | Standard Deviation 0.46 |
| Aerobic Exercise Group | Executive Function | Week 26 | 0.017 Standard Deviations | Standard Deviation 0.63 |
| Aerobic Exercise Group | Executive Function | Follow-up | .018 Standard Deviations | Standard Deviation 0.62 |
| Control Group | Executive Function | Baseline | -0.042 Standard Deviations | Standard Deviation 0.37 |
| Control Group | Executive Function | Week 26 | -0.035 Standard Deviations | Standard Deviation 0.39 |
| Control Group | Executive Function | Follow-up | -0.037 Standard Deviations | Standard Deviation 0.45 |
Secondary
Whole Brain Volume
Whole brain volume in mL define by Freesurfer analysis. Higher numbers indicate greater brain volume. There is no defined maximum. Zero is the theoretical minimum.
Time frame: Baseline to 52 weeks
Population: Six individuals did not complete follow-up testing due to withdrawal. Seven refused follow-up MRI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Group | Whole Brain Volume | Baseline | 1068.7 mL | Standard Deviation 109.7 |
| Aerobic Exercise Group | Whole Brain Volume | Follow-up | 1063.4 mL | Standard Deviation 109.1 |
| Control Group | Whole Brain Volume | Baseline | 1061.7 mL | Standard Deviation 114.4 |
| Control Group | Whole Brain Volume | Follow-up | 1059.1 mL | Standard Deviation 115.1 |