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The purpose of this study is to examine the effects of modifiable lifestyle factors including exercise and healthy living on brain health. The investigators will compare 2 types of interventions, moderate aerobic walking vs. healthy living education, over 6 months to evaluate changes in brain health, cognition, and physical function in older adults with cognitive concerns.
Cognitive decline in older adults is a major public health issue. The cost of caring for older adults with substantial cognitive impairment, like those with Alzheimer's Disease in the US is approximately $200 billion a year, causing major societal, economic, and caregiving burden. Despite great advances towards diagnosing these problems, the discovery of effective treatments has been minimal. Exploring non-pharmacological interventions, such as exercise and healthy living, have gained momentum. These promising, modifiable lifestyle interventions have the potential for delaying disease onset and slowing decline in cognition. However, the therapeutic effect of lifestyle interventions in patients with mild cognitive impairment, a prime intervention period for treatment, is not well understood. Therefore, in this study, the investigators will examine brain, body, and cognitive changes in older adults who engage in moderate-aerobic walking or healthy living education.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Moderate-aerobic walking | Experimental | Participants will complete a 6-month home-based moderate-aerobic walking program of 150 minutes per week with the assistance of an interventionist. |
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| Healthy Living Education | Placebo Comparator | Participants will receive monthly topics on healthy living lifestyles for self-paced reading over 6 months with the assistance of an interventionist. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Moderate-aerobic walking | Behavioral |
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| Positron Emission Tomography (PET) scan |
| Measure | Description | Time Frame |
|---|---|---|
| Functional Magnetic Resonance Imaging (fMRI) Brain Scan as a Measure of Brain Function | Functional MRI has proven to be an effective non-invasive, in-vivo tool for measuring brain function via the BOLD signal. Growing evidence supports that fMRI BOLD can detect neuronal changes that occur very early in the disease process. The hippocampus has been shown to be a selectively vulnerable region in AD, and several studies, including our own, identified a aberrant brain signal in the hippocampus in older adults. The typical range for this outcome is -10 to 10 with higher scores indicating better brain function. | Baseline and Follow-up at 6 months |
| Mnemonic Similarity Test as a Measure of Memory (Cognition) | The participants will encode a series of objects presented on a computer. Following the encoding period, they will begin their fMRI scan and be asked to indicate if they recognize the objects on the screen, which include targets (previously seen objects), lures (objects that are similar to previously seen objects) and novel (unrelated objects). The discrimination between Targets and Lures will indicate the rate at which participants "correctly reject" the Lures (via pattern separation) or "false alarm" to the Lures (via pattern completion). The theoretical range for this outcome is -1 to 1 with higher scores indicating better memory function. | Baseline and Follow-up at 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Amyloid Positron Emission Tomography (PET) Scan as a Measure of Tracer Binding (SUVr) | Each participant received PET scans with Neuraceq [florbetaben F 18 (FBB)] to measure amyloid-beta PET binding. IV injections of the tracers (FBB, -8.11 6 0.6 mCi) were done outside of the scanning room. Four 5-min frames were acquired 90 minutes after injection. | Baseline and Follow-up at 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California | Los Angeles | California | 90032 | United States |
All data requests will be reviewed by the data committee. Approved investigators will be provided de-identified participant-level data from the trial as a .CSV file.
Data will be available starting July 1, 2025 and for at least 3 years.
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Participants complete a 30-day run-in and baseline visit prior to randomization.
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| ID | Title | Description |
|---|---|---|
| FG000 | Moderate-aerobic Walking | Participants will complete a 6-month home-based moderate-aerobic walking program of 150 minutes per week with the assistance of an interventionist. Moderate-aerobic walking Positron Emission Tomography (PET) scan: Radioligand that binds to proteins using a PET/CT scanner. Physical activity monitor: Wrist device that will track daily physical activity |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form | Apr 26, 2024 |
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| Radiation |
Radioligand that binds to proteins using a PET/CT scanner. |
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| Healthy living education | Behavioral |
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| Physical activity monitor | Device | Wrist device that will track daily physical activity |
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| Single-stage Treadmill Test | This is a measure of cardiovascular fitness. This test has been validated against peak VO2 max with r=0.96. Heart rate response is monitored with a Polar heart rate monitor and the heart rate at the end of the 4 min test is used to estimate VO2max using an established equation for conversion. The theoretical range for this outcome is 0 to 200 with higher scores indicating better cardiovascular fitness. | Baseline and Follow-up at 6 months |
| Modified Physical Function Test | This test is a measure of multiple domains related to functional activities of daily living. Each physical activity in score is of varying difficulty level. The theoretical range for this outcome is 0 to 36 with higher scores indicating better physical function. | Baseline and Follow-up at 6 months |
| Brain-derived Neurotropic Factor (BDNF) as a Measure From Blood | We will quantitatively analyze pre- and post-measurements of brain derived neurotrophic factor (BDNF). BDNF has been shown to increase after exercise intervention in humans and peripheral increases in these hormones correlate to cell proliferation in the dentate gyrus of the hippocampus. We measure total BDNF from plasma. | Baseline and Follow-up at 6 months |
| FG001 | Healthy Living Education | Participants will receive monthly topics on healthy living lifestyles for self-paced reading over 6 months with the assistance of an interventionist. Positron Emission Tomography (PET) scan: Radioligand that binds to proteins using a PET/CT scanner. Healthy living education Physical activity monitor: Wrist device that will track daily physical activity |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Moderate-aerobic Walking | Participants will complete a 6-month home-based moderate-aerobic walking program of 150 minutes per week with the assistance of an interventionist. Moderate-aerobic walking Positron Emission Tomography (PET) scan: Radioligand that binds to proteins using a PET/CT scanner. Physical activity monitor: Wrist device that will track daily physical activity |
| BG001 | Healthy Living Education | Participants will receive monthly topics on healthy living lifestyles for self-paced reading over 6 months with the assistance of an interventionist. Positron Emission Tomography (PET) scan: Radioligand that binds to proteins using a PET/CT scanner. Healthy living education Physical activity monitor: Wrist device that will track daily physical activity |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Functional Magnetic Resonance Imaging (fMRI) Brain Scan as a Measure of Brain Function | Functional MRI has proven to be an effective non-invasive, in-vivo tool for measuring brain function via the BOLD signal. Growing evidence supports that fMRI BOLD can detect neuronal changes that occur very early in the disease process. The hippocampus has been shown to be a selectively vulnerable region in AD, and several studies, including our own, identified a aberrant brain signal in the hippocampus in older adults. The typical range for this outcome is -10 to 10 with higher scores indicating better brain function. | Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization. MRI data was not available for one participant in the Healthy Living Education group, resulting in an N of 29 for all fMRI measures. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline and Follow-up at 6 months |
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| Primary | Mnemonic Similarity Test as a Measure of Memory (Cognition) | The participants will encode a series of objects presented on a computer. Following the encoding period, they will begin their fMRI scan and be asked to indicate if they recognize the objects on the screen, which include targets (previously seen objects), lures (objects that are similar to previously seen objects) and novel (unrelated objects). The discrimination between Targets and Lures will indicate the rate at which participants "correctly reject" the Lures (via pattern separation) or "false alarm" to the Lures (via pattern completion). The theoretical range for this outcome is -1 to 1 with higher scores indicating better memory function. | Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline and Follow-up at 6 months |
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| Secondary | Amyloid Positron Emission Tomography (PET) Scan as a Measure of Tracer Binding (SUVr) | Each participant received PET scans with Neuraceq [florbetaben F 18 (FBB)] to measure amyloid-beta PET binding. IV injections of the tracers (FBB, -8.11 6 0.6 mCi) were done outside of the scanning room. Four 5-min frames were acquired 90 minutes after injection. | Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization. | Posted | Least Squares Mean | 95% Confidence Interval | standardized uptake value ratio (SUVr) | Baseline and Follow-up at 6 months |
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| Secondary | Single-stage Treadmill Test | This is a measure of cardiovascular fitness. This test has been validated against peak VO2 max with r=0.96. Heart rate response is monitored with a Polar heart rate monitor and the heart rate at the end of the 4 min test is used to estimate VO2max using an established equation for conversion. The theoretical range for this outcome is 0 to 200 with higher scores indicating better cardiovascular fitness. | Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline and Follow-up at 6 months |
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| Secondary | Modified Physical Function Test | This test is a measure of multiple domains related to functional activities of daily living. Each physical activity in score is of varying difficulty level. The theoretical range for this outcome is 0 to 36 with higher scores indicating better physical function. | Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline and Follow-up at 6 months |
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| Secondary | Brain-derived Neurotropic Factor (BDNF) as a Measure From Blood | We will quantitatively analyze pre- and post-measurements of brain derived neurotrophic factor (BDNF). BDNF has been shown to increase after exercise intervention in humans and peripheral increases in these hormones correlate to cell proliferation in the dentate gyrus of the hippocampus. We measure total BDNF from plasma. | Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization. BDNF Plasma sample for one participant in the Healthy Living Education group did not pass QC thresholds and was excluded from analyses. | Posted | Least Squares Mean | 95% Confidence Interval | pg/mL | Baseline and Follow-up at 6 months |
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Time between baseline and followup visit of 6-8 month intervention.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Moderate-aerobic Walking | Participants will complete a 6-month home-based moderate-aerobic walking program of 150 minutes per week with the assistance of an interventionist. Moderate-aerobic walking Positron Emission Tomography (PET) scan: Radioligand that binds to proteins using a PET/CT scanner. Physical activity monitor: Wrist device that will track daily physical activity | 0 | 30 | 1 | 30 | 11 | 30 |
| EG001 | Healthy Living Education | Participants will receive monthly topics on healthy living lifestyles for self-paced reading over 6 months with the assistance of an interventionist. Positron Emission Tomography (PET) scan: Radioligand that binds to proteins using a PET/CT scanner. Healthy living education Physical activity monitor: Wrist device that will track daily physical activity | 0 | 30 | 0 | 30 | 6 | 30 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac disorders | Cardiac disorders | Systematic Assessment | myocardial infarction, subsequent stent placement |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin | Skin and subcutaneous tissue disorders | Systematic Assessment | Pain at injection site for PET scan tracer [12]; skin irritation due to cleaning agent for wearable device (accelerometer) [1], ankle swelling |
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| Non-Hodgkins lymphoma | Blood and lymphatic system disorders | Systematic Assessment |
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| Falls | Musculoskeletal and connective tissue disorders | Systematic Assessment | One slipped on driveway, one slipped walking to car after a hike |
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Our study experienced delays due to the Covid-19 pandemic and impact on research. The human subjects portions of the trial were paused from March 2020 to August 2020 (a 5-month period of no human research activities on campus) due to local university Covid-19 restrictions. Once the pause was lifted, we were able to resume normal day to day activities with precautions in place, and have since completed the trial.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Judy Pa, PhD | UC San Diego | 858-246-1333 | jpa@ucsd.edu |
| Jun 24, 2024 |
| Prot_ICF_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 6, 2024 | Jun 24, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
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| ID | Term |
|---|---|
| D009682 | Magnetic Resonance Spectroscopy |
| C062942 | 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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Participants will receive monthly topics on healthy living lifestyles for self-paced reading over 6 months with the assistance of an interventionist. Positron Emission Tomography (PET) scan: Radioligand that binds to proteins using a PET/CT scanner. Healthy living education Physical activity monitor: Wrist device that will track daily physical activity |
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