Lifestyle Physical Activity and Cognitive Training Interventions

Study Overview
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Brief Summary
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Older women with cardiovascular disease (CVD) are at greater risk for memory loss, an important public health issue due to the negative effects to quality of life and health care costs. This research will be the first to examine the independent and combined effects of a lifestyle physical activity intervention and cognitive training on memory performance and memory-related serum biomarkers in this vulnerable population. The investigators will incorporate a practical lifestyle approach that can be delivered in the home and community settings to prevent or delay memory loss in older women with CVD.

Detailed Description
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Women experience disproportionately high rates of cognitive dysfunction, especially with increasing age, compared to men. Some research suggests that older women have a higher incidence of cognitive dysfunction with greater severity and more rapid decline.Furthermore, cardiovascular disease (CVD) increases the risk for cognitive dysfunction by 29-66% and affects 44 million women in the US. One particularly distressing type of cognitive dysfunction due to CVD is loss of memory. Memory loss leads to reduced independence, lower quality of life, and higher healthcare costs. To prevent or delay loss of memory among older women with CVD, there is an urgent need to develop lifestyle interventions that can be scaled. The long-term goal is to create and implement multi-modal lifestyle interventions (interventions that have multiple behavioral components) that will prevent or delay memory loss in older adults. The investigators initially focus on women with CVD due to their high risk. Physical activity interventions and cognitive training each prevent memory loss in healthy older adults. Thus, the investigators will evaluate the efficacy of MindMoves, a 24-week multi-modal intervention, on memory performance and memory-related serum biomarkers. The investigators will examine the serum biomarkers of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and (c) insulin-like growth factor 1 (IGF-1). Data collection will occur at baseline, 24 weeks, 48 weeks, and 72 weeks. MindMoves is a combination of two evidence-based interventions. Mind is the cognitive training program BrainHQ modified to a lifestyle-focused electronic tablet format. Mind improves memory performance in healthy older adults and those with heart failure. Move is a modified lifestyle physical activity intervention from the Women's Lifestyle Physical Activity Program, which the investigators piloted in women with CVD. The investigators recently tested the feasibility of MindMoves. Using a 2x2 factorial design, the investigators will recruit 254 older women with CVD from cardiology clinics and randomize them to one of the following conditions: (1) Mind, (2) Move, (3) MindMoves, or (4) usual care control. This approach will allow us to evaluate main and interaction effects of Mind and/or Move on memory performance and memory-related biomarkers at 24, 48, and 72 weeks post-baseline. Specific Aim 1 (primary): Determine the independent and combined efficacies of Mind and Move on memory performance assessed by neurocognitive tests among women ≥ 65 years of age with CVD. Specific Aim 2 (secondary): Determine the independent and combined efficacies of Mind and Move on memory-related serum biomarkers (BDNF, VEGF, IGF-1) among women ≥ 65 years of age with CVD. Specific Aim 3 (exploratory): Evaluate depressive symptoms and genetic factors as potential moderators of the association between changes in target behaviors (physical activity and cognitive activity) and health outcomes (memory performance and relevant serum biomarkers). The investigators hypothesize that Mind and Move individually will each yield benefits to memory. However, it is hypothesized that the combined MindMoves will have a greater impact than the sum of the individual effects. Findings will provide key knowledge about the ability of practical multi-modal lifestyle interventions to target memory in older women with CVD.

Official Title
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Lifestyle Physical Activity and Cognitive Training Interventions: Preventing Memory Loss in Older Women With Cardiovascular Disease

Conditions
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Cognitive Decline, Cardiovascular Diseases, Cognitive Dysfunction, Cognitive Impairment, Mild Cognitive Impairment

Intervention / Treatment
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* Behavioral: Mind
* Behavioral: Move


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: self-identified as women ≥ 65 years old read/speak English patient in the Rush Heart Center for Women history of CVD (e.g., coronary artery disease, hypertension) and receiving guideline-directed medical therapy when appropriate no regular moderate-vigorous physical activity (≥ 30 minutes ≥ 3 days per week in the past month) no cognitive training program in the past month no disabilities preventing regular physical activity (Physical Activity Readiness Questionnaire, which includes cardiac and lung disease symptoms) written approval from cardiology provider (Physical Activity Readiness Medical Examination); no self-reported significant hearing loss that interferes with normal conversation access to a Bluetooth-capable phone or tablet Exclusion Criteria: symptoms of unstable cardiac or pulmonary disease in the past month (Physical Activity Readiness Questionnaire) blood pressure (systolic ≥ 160 or diastolic ≥ 100 mm Hg) cognitive status score < 19 on the blind version (for phone administration) of the Montreal Cognitive Assessment (MoCA) consistent with significant cognitive impairment diagnosis of a neurological disease found in the electronic health record (e.g., Alzheimer's disease dementia, Parkinson's disease, vascular dementia) transient ischemic attack or small-vessel stroke in the past three months taking anti-psychotic medication diabetes with an A1C ≥ 9.0 within the past six months end-stage renal disease on dialysis (Stage 5)

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mind - BrainHQ cognitive training intervention<br>The Mind intervention uses the evidence-based BrainHQ computerized cognitive training program. BrainHQ focuses on improving memory, attention, sensory function, and working memory, and has demonstrated efficacy in improving memory among healthy older adults and adults with heart failure. BrainHQ is tailored to the individual, and program difficulty automatically progresses based on performance. Training occurs during three 30-minute sessions per week, for a total of 36 hours. Participants will complete the BrainHQ program on an iPad tablet, which will be provided to them. | Behavioral: Mind<br>* See arm description.<br>|
| Experimental: Move - lifestyle physical activity intervention<br>The Move intervention is a 24-week evidence-based program based on social cognitive theory. It was originally developed for midlife women and successfully maintained increased physical activity. It has since been tailored for older women with CVD to prevent or delay cognitive decline, and includes: (1) education on the importance of lifestyle physical activity for brain health, (2) increasing lifestyle physical activity while considering CVD, and (3) including a goal for increasing Fitbit active minutes (≥ 3 METs or moderate-intensity physical activity) to ensure participants are obtaining the beneficial aerobic fitness effects during periods of lifestyle physical activity. Core elements include a personal lifestyle physical activity goal and five group meetings. | Behavioral: Move<br>* See arm description.<br>|
| Experimental: MindMoves - cognitive training and lifestyle physical activity<br>Participants who are assigned to this condition will complete both the Move lifestyle physical activity program and the Mind BrainHQ cognitive training intervention simultaneously for 24 weeks (see Move and Mind descriptions). Participants will receive both a Fitbit and iPad tablet to complete the combined MindMoves intervention. | Behavioral: Mind<br>* See arm description.<br>Behavioral: Move<br>* See arm description.<br>|
| No Intervention: Usual Care<br>Participants in the usual care group do not receive any Mind- or Move-related intervention, and will receive their usual care from their cardiology provider. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in East Boston Memory Test scores from baseline to 24 weeks, 48 weeks, and 72 weeks | The East Boston Memory Test is a performance-based neurocognitive test. Participants are read a brief story with 12 key elements. The participants are asked to recall elements immediately and again after three-minute delay. Each score (immediate and delayed recall) has a scale of 0-12, with a higher score indicating better cognitive performance. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in Category Fluency Test scores from baseline to 24 weeks, 48 weeks, and 72 weeks | The Category Fluency Test is a performance-based neurocognitive test. Participants are asked to generate examples for two semantic categories (animals, fruits/vegetables) in separate 60-second trials. There are two separate scores (number of animals generated, number of fruits/vegetables generated). A minimum possible score is 0, with an infinite possible maximum score, with a higher score indicating better cognitive performance. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in Digit Span Forwards and Backwards Test scores from baseline to 24 weeks, 48 weeks, and 72 weeks | The Digit Span Forwards and Backwards Test is a performance-based neurocognitive test. The examiner says a string of numbers (digit span). For Digit Span Forwards, participant recites digit span, gradually increasing in length. Test stops when participant fails to recite digit span of same length twice. For Digit Span Backwards, participant recites digit span backwards. There are two separate scores (Digit Span Forwards correct responses, Digit Span Backwards correct responses). Digit Span Forwards scores can range from 0-16, with higher scores indicating higher cognitive performance. Digit Span Backwards Scores range from 0-14, with higher scores indicating higher cognitive performance. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in Oral Trails A/B tests scores from baseline to 24 weeks, 48 weeks, and 72 weeks | First, participants are asked to count from 1 to 25 (Part A). For Part B, the person is asked to verbally recite alternating numbers and letters until they reach 13 and the letter M. Possible minimum score is discontinued due to failure to complete the test (a zero score). The maximum score is 300 seconds. A lower score (fewer seconds) indicates higher cognitive performance. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in Digit Ordering Tests scores from baseline to 24 weeks, 48 weeks, and 72 weeks | Participants are asked to memorize and immediately recall in ascending order a series of numbers that gradually increase in length with each trial. Possible scores range from 0-16, with a higher score indicating higher cognitive performance. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain-derived neurotrophic factor (BDNF) levels from baseline to 24 weeks, 48 weeks, and 72 weeks | We will obtain blood samples for BDNF. Pretreatment serum or plasma specimens will be prepared using standard techniques and archived at -80°C in aliquots with no specimen subjected to more than two freeze-thaw cycles. All assays performed in a blinded fashion and according to manufacturer's protocol using a 384-well modified method. Luminex FlexMAP 3D will be used with concentrations calculated based on 7-pt standard curves using a 5-parametric fit algorithm in xPONENT v4.0.3. Following recommendations, serum biomarkers will be obtained in the morning (8am-10am) following an 8-hour fast. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in vascular endothelial growth factor A (VEGF) levels from baseline to 24 weeks, 48 weeks, and 72 weeks | We will obtain blood samples for VEGF. Pretreatment serum or plasma specimens will be prepared using standard techniques and archived at -80°C in aliquots with no specimen subjected to more than two freeze-thaw cycles. All assays performed in a blinded fashion and according to manufacturer's protocol using a 384-well modified method. Luminex FlexMAP 3D will be used with concentrations calculated based on 7-pt standard curves using a 5-parametric fit algorithm in xPONENT v4.0.3. Following recommendations, serum biomarkers will be obtained in the morning (8am-10am) following an 8-hour fast. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in insulin-like growth factor 1 (IGF-1) from baseline to 24 weeks, 48 weeks, and 72 weeks | We will obtain blood samples for IGF-1. Pretreatment serum or plasma specimens will be prepared using standard techniques and archived at -80°C in aliquots with no specimen subjected to more than two freeze-thaw cycles. All assays performed in a blinded fashion and according to manufacturer's protocol using a 384-well modified method. Luminex FlexMAP 3D will be used with concentrations calculated based on 7-pt standard curves using a 5-parametric fit algorithm in xPONENT v4.0.3. Following recommendations, serum biomarkers will be obtained in the morning (8am-10am) following an 8-hour fast. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in GT3XE-Plus Triaxial Accelerometer activity minutes (light and moderate vigorous physical activity) from baseline to 24 weeks, 48 weeks, and 72 weeks | The ActiGraph accelerometer is a motion sensor device that provides a valid assessment of physical activity in adult persons during treadmill Moveing/running and daily activity. The accelerometer records vertical accelerations as counts. Participants are instructed to wear on the hip for seven consecutive days during waking hours only, except while swimming or bathing. To analyze the accelerometer data, we will use the following physical activity intensity cut points: light 100-1,565 counts/min (< 3 METS [metabolic equivalent of task]); moderate 1,566-6,139 (3.0-6.0 METS); vigorous ≥ 6,140 (≥ 6.1 METS). We will report findings in mean daily minutes of each intensity of physical activity. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in the two-minute step test of aerobic fitness score from baseline to 24 weeks, 48 weeks, and 72 weeks | This is a test of aerobic fitness that can be performed in a small space using minimal equipment. Participants step in place to a predesignated height for two minutes. This test is correlated with treadmill tests of aerobic fitness. | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in self-reported physical activity as assessed by the Community Healthy Activities Model Program for Seniors (CHAMPS) survey from baseline to 24 weeks, 48 weeks, and 72 weeks | The Community Health Activities Model Program for Seniors (CHAMPS) is a 30-item self-report questionnaire that assesses the leisure time, household, and transportation physical activity in past two weeks. Participants are asked how long they participate in 30 different activities and at what frequency. Each activity is assigned intensity. Scores include mean minutes per week of light and moderate-vigorous physical activity for both leisure time and household scales (minimum score of 0 minutes and maximum score of 24 hours, with higher scores indicating more time spent in physical activity). | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline | 
| Change in self-reported cognitive activity from baseline to 24 weeks, 48 weeks, and 72 weeks | Self-report cognitive activity is a self-report questionnaire of participation in seven activities that involve information processing with minimal physical or social demands. Participants rate on a five-point scale. The score is an average of nine items (minimum score of 9, maximum score of 54 with higher scores indicating higher self-reported levels of cognitive activity). | Baseline, and 24 weeks, 48 weeks, and 72 weeks post-baseline |