Aging, Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, Dementia, aerobic exercise, physical activity, exercise, neuroimaging
Brief summary
The purpose of the aeRobic Exercise and Cognitive Health (REACH) study is to understand how an aerobic exercise intervention might help promote brain health and cognition, thereby delaying the onset of clinical symptoms of Alzheimer's disease.
Detailed description
The prevalence and costs associated with Alzheimer's disease (AD) are projected to increase exponentially owing to the unprecedented expansion in the elderly segment of the United States' population. Given this looming specter, delaying the onset of AD symptoms and curbing the progression of the underlying disease process has become a national public health imperative. Delaying symptom onset by as little as 5 years could reduce the prevalence of AD by half. Unfortunately, currently available drug treatments for AD are not curative. Similarly, clinical trials testing novel disease-modifying therapeutics have been disappointing. The urgency of alternative approaches for halting the global crisis posed by AD cannot be overstated. Animal studies have demonstrated that aerobic exercise (EXER) is a low-cost, low-risk intervention capable of altering the AD pathological process. Randomized controlled trials (RCTs) of EXER in older adults have also revealed its beneficial effects on AD-relevant measures such as brain glucose metabolism and memory/executive function. Importantly, a recent evidence review found that of 7 key modifiable risk factors for AD, physical activity had the highest impact on reducing the national prevalence of AD. However, there are presently no RCTs examining the effects of EXER in middle-aged, asymptomatic individuals at increased risk of AD. This is an important knowledge gap for several reasons. Interventions to halt the AD pathological cascade are more likely to be effective if implemented prior to pervasive neuronal damage. Secondly, persons with specific risk factors for developing AD (such as parental family history (FH)) represent a choice target population for any credible attempts at reducing the growing burden of AD. Lastly, a key limitation of prior EXER RCTs is the failure to adequately account for participants' physical activity levels outside of the intervention. Accordingly, the main objective of this study is to pilot a 26-week trial of EXER among asymptomatic, middle-aged adults with and without family history (FH) of AD enrolled in the Wisconsin Registry for Alzheimer's Prevention (WRAP) or the Wisconsin Alzheimer's Disease Research Center (WADRC). The investigators' near-term goal is to assess the feasibility and acceptability of this structured intervention and preliminarily evaluate (i) its effect on AD-relevant outcomes such as glucose metabolism and (ii) the mechanism for such effects. The investigators' longer-term goal is to use the data gathered via this pilot to further refine the intervention, estimate effect sizes for key outcomes, and seek NIH funding for a longer and more definitive assessment of whether EXER can effectively curtail AD progression in midlife. The specific aims are: AIM 1: Determine the feasibility and acceptability of a 26-week, 3-4 days per week, structured EXER regimen among middle-aged adults with FH of AD. Hypothesis: The investigators will successfully enroll the 30 participants (15 each in EXER and usual physical activity groups) targeted for this study. At least 90% of the participants within the EXER group, called the enhanced physical activity group, will complete ≥80% of scheduled training sessions. AIM 2: Preliminarily characterize the effect of the EXER intervention on AD-related brain alteration. Hypothesis: Compared to participants randomized to the usual physical activity group, those randomized to the enhanced physical activity group will demonstrate preserved brain glucose metabolism. Similar effects will be seen in secondary outcomes including cerebral blood flow, hippocampal volume, vascular health, memory/executive function, and mood. AIM 3: Preliminarily evaluate (i) the biological mechanisms by which EXER affects brain health and cognition, and (ii) the individual difference factors that potentially moderate EXER's effects. Hypotheses: (i) Persons in the enhanced physical activity group will exhibit significant increases in circulating neurotrophins and improved cardiorespiratory fitness, and (ii) the beneficial effects of EXER will be more pronounced for participants with decreased sedentary behaviors outside of the intervention (measured via accelerometry). AIM 4: Preliminarily determine whether EXER improves vascular health. Hypothesis: Individuals in the enhanced physical activity group will exhibit comparatively increased cerebral blood flow, and improved endothelial function.
Interventions
BEHAVIORALEnhanced Physical Activity
This is a 26-week aerobic exercise intervention. The primary mode of training is treadmill walking, with the initial speed and duration calibrated to each participant's baseline aerobic capacity. Participants will train 3-4 days per week with the goal of attaining 150+ minutes of exercise per week by the seventh week. Exercise will be set between 50-60% of maximum heart rate reserve for weeks 1-4, 60-70% for weeks 5-8, and 70-80% for weeks 9-26. Exercise duration will be approximately 15-20 minutes per session during the first week and then increase by 5 minutes each week until a duration of approximately 38-50 minutes per session is reached. Each training session will begin with a 5-minute warm-up and end with a 5-minute recovery period.
Sponsors
Alzheimer's Association
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 45 and 80 at baseline visit. * Must be currently physically inactive (i.e. not meeting national guidelines of 150+ minutes per week of moderate exercise). * Participant is not pregnant at the time of the positron emission tomography (PET) and magnetic resonance (MR) imaging exams. * Willing and able to complete all assessments and exercise intervention faithfully. * Fluent and proficient in English language and capable of completing neuropsychological testing in English. * Participant must have physician clearance to participate in this study.
Exclusion criteria
* Any significant neurologic disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma (10 min or more of loss of consciousness) followed by persistent neurologic deficits or known structural brain abnormalities. * Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, body. X-ray may be used to establish suitability for MRI. * Inability to complete exercise test due to medical restrictions such as hip surgery, knee surgery, arthritis, or other orthopedic concerns that prevent being able to walk on a treadmill, type I or II diabetes mellitus, and documented vascular disease such as coronary artery disease. * Clinically significant findings from the exercise test that prohibit participation in moderate intensity exercise (i.e. 3rd degree heart block). * Current Axis I DSM-IV disorder including but not limited to major depression within the past two years, history of bipolar I disorder, history of schizophrenia spectrum disorders (DSM IV criteria). * History of alcohol or substance abuse or dependence (DSM IV criteria). * Any significant systemic illness or unstable medical condition that could affect cognition, CBF or BOLD, or cause difficulty complying with the exam. History of chemotherapy, thyroid disease, or renal insufficiency are excluded. * Severe untreated hypertension (\>200/100mmHG). * Participants who do not have the cognitive competence and legal capacity to make informed medical decisions are excluded at entry. If a participant experiences significant cognitive decline during the study such that they no longer have medical decision making capacity the investigators will enact procedures that have been approved locally by the IRB and legal counsel at the University of Wisconsin-Madison: A) use their initial expressed and written consent as an indicator of willingness to continue to participate in the study; AND B) require that they provide assent at the time of follow-up visits witnessed and counter signed by their caregiver; AND C) signed consent from the patient's legally authorized representative. * Current use of antipsychotic medications such as non-SSRI antidepressants, neuroleptics, chronic anxiolytics, or sedative hypnotics, as well as some cardiac glycosides such as Digoxin. * Investigational agents are prohibited. * Exceptions to these criteria will be rare but may be considered on a case-by-case basis at the discretion of the investigators in consultation with study physicians.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acceptability: Percentage of Sessions Completed by Enhanced Physical Activity Group | up to 26 weeks | This intervention will be considered acceptable if participants who complete the Enhanced Physical Activity intervention, complete ≥80% of scheduled training sessions. |
| Cerebral Glucose Metabolism as Measured by FDG PET Scanning | over 26 weeks (assessed at baseline visit and at week-26 visit) | Changes in cerebral glucose metabolism will be assessed using fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning. This method measures the brain's use of blood sugar while in a resting state. Measurements were taken in the posterior cingulate cortex (PCC). An increase in this measure indicates an increase in the brain's uptake and usage of blood sugar. |
| Feasibility: Percentage of Participants Who Completed the Study | up to 3 years | Feasibility is in part defined as at least 90% of enrolled participants completed the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ultrasound-Measured Cerebral Blood Flow - Mean Flow Velocity | over 26 weeks (assessed at baseline visit and at week-26 visit) | Cerebral blood flow velocity changes in the middle cerebral artery will be measured using Transcranial Doppler ultrasound imaging. |
| California Verbal Learning Test-II Total Score | over 26 weeks (assessed at baseline visit and at week-26 visit) | The California Verbal Learning Test-II assesses cognitive function. Higher scores indicate more words recalled. Scores range from 0 to 100. |
| Delis-Kaplan Executive Function System Color Word Interference (D-KEFS CWI) Score | up to 26 weeks (measured at baseline and 26 weeks) | The D-KEFS CWI will be used to measure executive function. Lower times indicate improved executive function. Scores range from 0 to 90. |
| Mini Mental State Examination (MMSE) Score | up to 26 weeks (assessed at baseline and 26 weeks) | The Mini Mental State Examination (MMSE) measures global cognitive function. Scores range from 0 to 30. Higher scores indicate better cognitive function. |
| California Verbal Learning Test-II Long Delay Score | over 26 weeks (assessed at baseline visit and at week-26 visit) | The California Verbal Learning Test-II assesses cognitive function. Long delay is a test where there is a 20 minute time period between initial word list presented and recall. Higher scores indicate more words recalled. Scores range from 0 to 20. |
| Profile of Mood States (POMS) Score | up to 26 weeks (assessed at baseline and 26 weeks) | The Profile of Mood States was used to assess mood. POMS is divided into six subscales including tension-anxiety (9 items, score range: 0-36), depression (15 items, range: 0-60), anger-hostility (12 items, range: 0-48), vigor-activity (8 items, range: 0-32), fatigue (7 items, range: 0-28), and confusion-bewilderment (7 items, range: 0-28). Total mood disturbance is calculated by adding five of the six subscales (Tension, Depression, Anger, Fatigue, and Confusion) and subtracting Vigor (Scores range from -32 to 200). Lower scores typically indicate more steady mood profiles. Higher scores indicate more mood disturbance. |
| Change in Hippocampal Volume | up to 26 weeks (assessed at baseline and 26 weeks) | Hippocampal volume will be assessed using T1-weighted 3T MRI images. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Brain Derived Neurotrophic Factor | over 26 weeks (assessed at baseline visit and at week-26 visit) | The investigators will examine levels of Brain Derived Neurotrophic Factor to assess changes in blood neurotrophic levels. |
| Cardiorespiratory Fitness Measured by Peak Oxygen Consumption (VO2peak) | over 26 weeks (assessed at baseline visit and at week-26 visit) | The investigators will examine Cardiorespiratory Fitness by measuring VO2peak on a graded treadmill test - after participants fasted for 12-hours. |
| Ancillary Neuroimaging Measures | over 26 weeks (assessed at baseline visit and at week-26 visit) | Ancillary neuroimaging measures include MRI brain scans of blood flow and brain structure. |
| Vascular Endothelial Growth Factor | over 26 weeks (assessed at baseline visit and at week-26 visit | Levels of Vascular Endothelial Growth Factor will be assessed to identify changes in vascular health. |
| Subclinical Atherosclerosis Burden | over 26 weeks (assessed at baseline visit and at week-26 visit) | Changes in subclinical atherosclerosis burden will be measured using Carotid Intima-Media Thickness Ultrasound. |
| Endothelial Function | over 26 weeks (assessed at baseline visit and at week-26 visit) | Endothelial function changes will be assessed via ultrasound using Brachial Artery Reactivity Testing. |
| Sedentary Behavior Measured Via Accelerometer | up to 26 weeks (measured at baseline and 26 weeks) | Participants wore a triaxial accelerometer (GT3X+, Actigraph LLC, Pensacola, FL) for seven consecutive days to record free-living PA and sedentary behavior before and after the intervention. |
| Moderate to Vigorous Physical Activity (MVPA) | up to 26 weeks (assessed at baseline and 26 weeks) | Participants wore a triaxial accelerometer (GT3X+, Actigraph LLC, Pensacola, FL) for seven consecutive days to record free-living physical activity before and after the intervention. |
| Arterial Plaque Presence | over 26 weeks (assessed at baseline visit and at week-26 visit) | Changes in plaque presence will be measured using Comprehensive Carotid Ultrasound. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Usual Physical Activity Usual Physical Activity: Participants in this group will receive education from study staff about the importance of maintaining a healthy and active lifestyle. They will receive standardized literature such as Exercise & Physical Activity: Your Everyday Guide from the National Institute on Aging. These booklets provide vetted and reliable information for older adults on how to exercise. Participants assigned to the usual physical activity group will not be provided additional support or guidance with an exercise program. | 12 |
| Enhanced Physical Activity Enhanced Physical Activity: Participants in this group will engage in a 26-week treadmill walking aerobic exercise intervention. The initial speed and duration will be calibrated to each participant's baseline aerobic capacity. Participants will train 3-4 days per week with the goal of attaining current public health recommendations of 150 minutes of moderate intensity exercise by the 7th week of training and maintaining this level of exercise for the remainder of the 26-week intervention. Exercise will be set at 50-60% of maximum heart rate reserve for weeks 1-4, 60-70% for weeks 5-8, and 70-80% for weeks 9-26. Exercise duration will be 15-20 minutes per session during the first week and then increase by 5 minutes each week until a duration of approximately 38-50 minutes per session is reached. Each training session will begin with a 5-minute warm-up and end with a 5-minute recovery period. Training will occur in individual sessions supervised by exercise specialists. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Usual Physical Activity | Total | Enhanced Physical Activity |
|---|---|---|---|
| Age, Customized Age 50-59 years | 4 Participants | 5 Participants | 1 Participants |
| Age, Customized Age 60-69 years | 7 Participants | 16 Participants | 9 Participants |
| Age, Customized Age 70-79 years | 1 Participants | 3 Participants | 2 Participants |
| BMI | 29.38 kg/m^2 STANDARD_DEVIATION 5.96 | 29.37 kg/m^2 STANDARD_DEVIATION 5.35 | 29.37 kg/m^2 STANDARD_DEVIATION 4.93 |
| Diastolic blood pressure | 79.92 mmHg STANDARD_DEVIATION 9.47 | 77.63 mmHg STANDARD_DEVIATION 9.9 | 75.33 mmHg STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 24 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| MMSE | 29.67 scores on a scale STANDARD_DEVIATION 0.49 | 29.62 scores on a scale STANDARD_DEVIATION 0.58 | 29.58 scores on a scale STANDARD_DEVIATION 0.67 |
| Number of Participants with APOE e4 positive | 5 Participants | 9 Participants | 4 Participants |
| Number of Participants with Parental History of Alzheimer's Disease | 12 Participants | 24 Participants | 12 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 | 0 Participants | 0 Participants | 0 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 | 12 Participants | 24 Participants | 12 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 13 Participants | 7 Participants |
| Systolic blood pressure | 128.50 mmHg STANDARD_DEVIATION 19.65 | 125.19 mmHg STANDARD_DEVIATION 18.92 | 121.88 mmHg STANDARD_DEVIATION 18.39 |
| Years of Education | 16.67 years STANDARD_DEVIATION 2.57 | 16.62 years STANDARD_DEVIATION 2.46 | 16.58 years STANDARD_DEVIATION 2.47 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 1 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Acceptability: Percentage of Sessions Completed by Enhanced Physical Activity Group
This intervention will be considered acceptable if participants who complete the Enhanced Physical Activity intervention, complete ≥80% of scheduled training sessions.
Time frame: up to 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enhanced Physical Activity | Acceptability: Percentage of Sessions Completed by Enhanced Physical Activity Group | 99.2 Percentage of Sessions | Standard Deviation 2.7 |
Primary
Cerebral Glucose Metabolism as Measured by FDG PET Scanning
Changes in cerebral glucose metabolism will be assessed using fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning. This method measures the brain's use of blood sugar while in a resting state. Measurements were taken in the posterior cingulate cortex (PCC). An increase in this measure indicates an increase in the brain's uptake and usage of blood sugar.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | Cerebral Glucose Metabolism as Measured by FDG PET Scanning | baseline | 1.49 arbitrary units | Standard Deviation 0.04 |
| Enhanced Physical Activity | Cerebral Glucose Metabolism as Measured by FDG PET Scanning | 26 weeks | 1.52 arbitrary units | Standard Deviation 0.04 |
| Enhanced Physical Activity | Cerebral Glucose Metabolism as Measured by FDG PET Scanning | baseline | 1.50 arbitrary units | Standard Deviation 0.03 |
| Enhanced Physical Activity | Cerebral Glucose Metabolism as Measured by FDG PET Scanning | 26 weeks | 1.54 arbitrary units | Standard Deviation 0.04 |
Primary
Feasibility: Percentage of Participants Who Completed the Study
Feasibility is in part defined as at least 90% of enrolled participants completed the study.
Time frame: up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enhanced Physical Activity | Feasibility: Percentage of Participants Who Completed the Study | 12 Participants |
| Enhanced Physical Activity | Feasibility: Percentage of Participants Who Completed the Study | 11 Participants |
Secondary
California Verbal Learning Test-II Long Delay Score
The California Verbal Learning Test-II assesses cognitive function. Long delay is a test where there is a 20 minute time period between initial word list presented and recall. Higher scores indicate more words recalled. Scores range from 0 to 20.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | California Verbal Learning Test-II Long Delay Score | baseline | 10.83 words | Standard Deviation 2.83 |
| Enhanced Physical Activity | California Verbal Learning Test-II Long Delay Score | 26 weeks | 11.42 words | Standard Deviation 3.26 |
| Enhanced Physical Activity | California Verbal Learning Test-II Long Delay Score | baseline | 12.00 words | Standard Deviation 2.72 |
| Enhanced Physical Activity | California Verbal Learning Test-II Long Delay Score | 26 weeks | 14.00 words | Standard Deviation 1.73 |
Secondary
California Verbal Learning Test-II Total Score
The California Verbal Learning Test-II assesses cognitive function. Higher scores indicate more words recalled. Scores range from 0 to 100.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | California Verbal Learning Test-II Total Score | baseline | 49.58 words | Standard Deviation 11.06 |
| Enhanced Physical Activity | California Verbal Learning Test-II Total Score | 26 weeks | 53.33 words | Standard Deviation 9.18 |
| Enhanced Physical Activity | California Verbal Learning Test-II Total Score | baseline | 53.18 words | Standard Deviation 7.99 |
| Enhanced Physical Activity | California Verbal Learning Test-II Total Score | 26 weeks | 60.64 words | Standard Deviation 9.04 |
Secondary
Change in Hippocampal Volume
Hippocampal volume will be assessed using T1-weighted 3T MRI images.
Time frame: up to 26 weeks (assessed at baseline and 26 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enhanced Physical Activity | Change in Hippocampal Volume | -23.67 mm cubed | Standard Deviation 222.5 |
| Enhanced Physical Activity | Change in Hippocampal Volume | -33.64 mm cubed | Standard Deviation 177 |
Secondary
Delis-Kaplan Executive Function System Color Word Interference (D-KEFS CWI) Score
The D-KEFS CWI will be used to measure executive function. Lower times indicate improved executive function. Scores range from 0 to 90.
Time frame: up to 26 weeks (measured at baseline and 26 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | Delis-Kaplan Executive Function System Color Word Interference (D-KEFS CWI) Score | baseline | 60.00 seconds | Standard Deviation 11.71 |
| Enhanced Physical Activity | Delis-Kaplan Executive Function System Color Word Interference (D-KEFS CWI) Score | 26 weeks | 60.00 seconds | Standard Deviation 11.99 |
| Enhanced Physical Activity | Delis-Kaplan Executive Function System Color Word Interference (D-KEFS CWI) Score | baseline | 64.82 seconds | Standard Deviation 15.11 |
| Enhanced Physical Activity | Delis-Kaplan Executive Function System Color Word Interference (D-KEFS CWI) Score | 26 weeks | 57.64 seconds | Standard Deviation 11.96 |
Secondary
Mini Mental State Examination (MMSE) Score
The Mini Mental State Examination (MMSE) measures global cognitive function. Scores range from 0 to 30. Higher scores indicate better cognitive function.
Time frame: up to 26 weeks (assessed at baseline and 26 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | Mini Mental State Examination (MMSE) Score | baseline | 29.67 scores on a scale | Standard Deviation 0.49 |
| Enhanced Physical Activity | Mini Mental State Examination (MMSE) Score | 26 weeks | 29.08 scores on a scale | Standard Deviation 1.24 |
| Enhanced Physical Activity | Mini Mental State Examination (MMSE) Score | baseline | 29.55 scores on a scale | Standard Deviation 0.69 |
| Enhanced Physical Activity | Mini Mental State Examination (MMSE) Score | 26 weeks | 29.55 scores on a scale | Standard Deviation 0.52 |
Secondary
Profile of Mood States (POMS) Score
The Profile of Mood States was used to assess mood. POMS is divided into six subscales including tension-anxiety (9 items, score range: 0-36), depression (15 items, range: 0-60), anger-hostility (12 items, range: 0-48), vigor-activity (8 items, range: 0-32), fatigue (7 items, range: 0-28), and confusion-bewilderment (7 items, range: 0-28). Total mood disturbance is calculated by adding five of the six subscales (Tension, Depression, Anger, Fatigue, and Confusion) and subtracting Vigor (Scores range from -32 to 200). Lower scores typically indicate more steady mood profiles. Higher scores indicate more mood disturbance.
Time frame: up to 26 weeks (assessed at baseline and 26 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Total Mood Disturbance | 16.09 score on a scale | Standard Deviation 15.64 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Depression | 5.36 score on a scale | Standard Deviation 5.52 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Confusion | 5.17 score on a scale | Standard Deviation 2.95 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Anger | 3.17 score on a scale | Standard Deviation 4.49 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Tension | 8.00 score on a scale | Standard Deviation 2.92 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Anger | 4.27 score on a scale | Standard Deviation 3.41 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Total Mood Disturbance | 9.58 score on a scale | Standard Deviation 19.71 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Vigor | 16.83 score on a scale | Standard Deviation 6.31 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Tension | 8.64 score on a scale | Standard Deviation 3.41 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Vigor | 16.25 score on a scale | Standard Deviation 6.86 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Confusion | 5.55 score on a scale | Standard Deviation 3.05 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Fatigue | 4.92 score on a scale | Standard Deviation 3.55 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Depression | 5.17 score on a scale | Standard Deviation 6.6 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Fatigue | 7.64 score on a scale | Standard Deviation 4.15 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Depression | 4.83 score on a scale | Standard Deviation 6.64 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Confusion | 6.83 score on a scale | Standard Deviation 2.52 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Confusion | 5.45 score on a scale | Standard Deviation 3.17 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Total Mood Disturbance | 15.17 score on a scale | Standard Deviation 19.94 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Total Mood Disturbance | 7.55 score on a scale | Standard Deviation 20.47 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Tension | 7.67 score on a scale | Standard Deviation 3.11 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Tension | 6.00 score on a scale | Standard Deviation 3.82 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Fatigue | 5.91 score on a scale | Standard Deviation 4.7 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Depression | 3.27 score on a scale | Standard Deviation 5.53 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Anger | 5.50 score on a scale | Standard Deviation 4.98 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Anger | 3.82 score on a scale | Standard Deviation 5.1 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Vigor | 16.25 score on a scale | Standard Deviation 6.86 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Post-intervention Vigor | 15.36 score on a scale | Standard Deviation 4.74 |
| Enhanced Physical Activity | Profile of Mood States (POMS) Score | Baseline Fatigue | 6.58 score on a scale | Standard Deviation 5.25 |
Secondary
Ultrasound-Measured Cerebral Blood Flow - Mean Flow Velocity
Cerebral blood flow velocity changes in the middle cerebral artery will be measured using Transcranial Doppler ultrasound imaging.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enhanced Physical Activity | Ultrasound-Measured Cerebral Blood Flow - Mean Flow Velocity | Baseline | 45.05 cm/second |
| Enhanced Physical Activity | Ultrasound-Measured Cerebral Blood Flow - Mean Flow Velocity | 26 Weeks | 49.47 cm/second |
| Enhanced Physical Activity | Ultrasound-Measured Cerebral Blood Flow - Mean Flow Velocity | Baseline | 41.13 cm/second |
| Enhanced Physical Activity | Ultrasound-Measured Cerebral Blood Flow - Mean Flow Velocity | 26 Weeks | 45.85 cm/second |
Other Pre-specified
Ancillary Neuroimaging Measures
Ancillary neuroimaging measures include MRI brain scans of blood flow and brain structure.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
Other Pre-specified
Arterial Plaque Presence
Changes in plaque presence will be measured using Comprehensive Carotid Ultrasound.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
Other Pre-specified
Brain Derived Neurotrophic Factor
The investigators will examine levels of Brain Derived Neurotrophic Factor to assess changes in blood neurotrophic levels.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
Other Pre-specified
Cardiorespiratory Fitness Measured by Peak Oxygen Consumption (VO2peak)
The investigators will examine Cardiorespiratory Fitness by measuring VO2peak on a graded treadmill test - after participants fasted for 12-hours.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | Cardiorespiratory Fitness Measured by Peak Oxygen Consumption (VO2peak) | baseline | 25.74 mL/kg/min | Standard Error 6.58 |
| Enhanced Physical Activity | Cardiorespiratory Fitness Measured by Peak Oxygen Consumption (VO2peak) | 26 weeks | 27.18 mL/kg/min | Standard Error 6.05 |
| Enhanced Physical Activity | Cardiorespiratory Fitness Measured by Peak Oxygen Consumption (VO2peak) | baseline | 23.57 mL/kg/min | Standard Error 4.97 |
| Enhanced Physical Activity | Cardiorespiratory Fitness Measured by Peak Oxygen Consumption (VO2peak) | 26 weeks | 27.46 mL/kg/min | Standard Error 4.71 |
Other Pre-specified
Endothelial Function
Endothelial function changes will be assessed via ultrasound using Brachial Artery Reactivity Testing.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | Endothelial Function | Baseline | 2.22 Percentage of dilation | Standard Deviation 1.78 |
| Enhanced Physical Activity | Endothelial Function | 26 Weeks | 2.71 Percentage of dilation | Standard Deviation 1.69 |
| Enhanced Physical Activity | Endothelial Function | Baseline | 1.86 Percentage of dilation | Standard Deviation 0.93 |
| Enhanced Physical Activity | Endothelial Function | 26 Weeks | 2.33 Percentage of dilation | Standard Deviation 1.71 |
Other Pre-specified
Moderate to Vigorous Physical Activity (MVPA)
Participants wore a triaxial accelerometer (GT3X+, Actigraph LLC, Pensacola, FL) for seven consecutive days to record free-living physical activity before and after the intervention.
Time frame: up to 26 weeks (assessed at baseline and 26 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | Moderate to Vigorous Physical Activity (MVPA) | baseline | 78.97 minute/day | Standard Deviation 10.19 |
| Enhanced Physical Activity | Moderate to Vigorous Physical Activity (MVPA) | 26 weeks | 69.3 minute/day | Standard Deviation 8.37 |
| Enhanced Physical Activity | Moderate to Vigorous Physical Activity (MVPA) | baseline | 60.58 minute/day | Standard Deviation 7.08 |
| Enhanced Physical Activity | Moderate to Vigorous Physical Activity (MVPA) | 26 weeks | 89.05 minute/day | Standard Deviation 15.48 |
Other Pre-specified
Sedentary Behavior Measured Via Accelerometer
Participants wore a triaxial accelerometer (GT3X+, Actigraph LLC, Pensacola, FL) for seven consecutive days to record free-living PA and sedentary behavior before and after the intervention.
Time frame: up to 26 weeks (measured at baseline and 26 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enhanced Physical Activity | Sedentary Behavior Measured Via Accelerometer | 26 weeks | 690.1 minute/day | Standard Deviation 26.7 |
| Enhanced Physical Activity | Sedentary Behavior Measured Via Accelerometer | Baseline | 670.73 minute/day | Standard Deviation 27.2 |
| Enhanced Physical Activity | Sedentary Behavior Measured Via Accelerometer | Baseline | 726.0 minute/day | Standard Deviation 22.9 |
| Enhanced Physical Activity | Sedentary Behavior Measured Via Accelerometer | 26 weeks | 698.6 minute/day | Standard Deviation 27.1 |
Other Pre-specified
Subclinical Atherosclerosis Burden
Changes in subclinical atherosclerosis burden will be measured using Carotid Intima-Media Thickness Ultrasound.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit)
Other Pre-specified
Vascular Endothelial Growth Factor
Levels of Vascular Endothelial Growth Factor will be assessed to identify changes in vascular health.
Time frame: over 26 weeks (assessed at baseline visit and at week-26 visit