A Combined Multidomain Intervention to Prevent Cognitive Decline Associated With Cardiovascular Risk Factors.

Study Overview
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Brief Summary
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The ACTIONcardioRisk trial is designed to investigate the effect of aerobic and progressive resistance training exercises combined with cognitive training, on neurocognitive functioning of sedentary older adults with and without cardiovascular risk factors.

Detailed Description
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The proportion of older adults is on the rise in Canada, with the fastest growth recorded among those seventy years of age or older. The prevalence of cardiovascular risk factors (CVRF) such as diabetes, hypertension, and high cholesterol increases drastically with age. Individuals with CVRF often show impaired cognition, such as attention and memory deficits. In healthy older adults, exercise training and cognitive stimulation can help enhance cognitive performances. More precisely, combined intervention, including physical and cognitive training, has shown beneficial effects on cognition in older adults without cognitive impairment and with mild cognitive impairment. However, the effect of such programs on cognition in individuals with CVRF is not well documented. This project compares the effect of a physical exercise program, including aerobic and resistance training, alone or combined with cognitive training on cognitive performances and brain imaging outcomes in individuals with CVRF and healthy controls.

Official Title
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Impacts of Aerobic, Resistance and Cognitive Training Interventions on Neurocognitive Functions in Older Adults With Cardiovascular Risk Factors.

Conditions
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Aging, Cardiovascular Risk Factor

Intervention / Treatment
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* Other: Cognitive Training
* Other: Aerobic and resistance exercises
* Other: Stretching and Toning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult aged 60 and older, Normal or corrected vision and normal hearing for their age range, No cognitive impairment (Mini-Mental State Examination - MMSE ≥ 25), Inactive (< 150 min of physical activity per week). Exclusion Criteria: MMSE ≤ 24 or diagnosis of dementia, Uncontrolled psychological / psychiatric condition within the past 6 months, Neurological disease, Severe exercise intolerance, Respiratory disease (e.g., asthma, COPD), Excessive alcohol consumption (> 15 drinks/week), Documented cerebral, peripheral or coronary atherosclerotic disease, Chronic systolic or diastolic heart failure, Symptomatic aortic stenosis, Atrial fibrillation, Automatic implantable defibrillator or permanent pacemaker, Malignant exertional arrhythmias, Non-cardiopulmonary limitation to exercise (e.g., arthritis).

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multidomain intervention<br>The multidomain intervention will combine a cognitive training with aerobic and resistance exercises training, three sessions per week for 46 weeks. Participants will be allowed to perform cognitive and exercise training sessions either home-based or centre-based. | Other: Cognitive Training<br>* Participants will be encouraged to perform sessions of cognitive training 3 times per week (30 minutes/session). Two of these sessions will involve computer- or tablet-based attentional control training targeting dual-tasking, updating and working memory, as well as inhibition and switching. Difficulty of cognitive training will be tailored to participants' performances. The remaining session will consist of memory training. Participants will be instructed mnemotechnic, as well as be taught about memory in aging in general.<br>Other: Aerobic and resistance exercises<br>* Participants will follow a periodized exercise training program with thrice-weekly 60 minutes trainings. The sessions will start with a 5-10mins warm-up, followed by aerobic and resistance trainings, and ends with a 5-10mins cool-down and stretching period. Intensity of aerobic sessions will be monitored with heart rate chest strap and should match with the moderate to vigorous intensity zone as defined by the ACSM (65% of Heart Rate maximum or more and a Perceived Exertion higher than 12 on the 6 to 20 Borg scale). Exercise intensity and duration will be gradually increased during the program. After aerobic training, a 15-20mins resistance training will be performed with a gradual progression of higher intensities and/or numbers of sets. The one maximal repetition (1RM) will be assessed for each RT movements at baseline, during (each 3 months) and at the end of the program. RT intensities will go from 40 to 70% of 1RM, with 8 to 10 forms of exercise involving majors muscle groups.<br>|
| Experimental: Physical exercise intervention<br>The physical exercises intervention will include aerobic and resistance exercises training, three sessions per week for 46 weeks. Participants will be allowed to perform cognitive and exercise training sessions either home-based or centre-based. | Other: Aerobic and resistance exercises<br>* Participants will follow a periodized exercise training program with thrice-weekly 60 minutes trainings. The sessions will start with a 5-10mins warm-up, followed by aerobic and resistance trainings, and ends with a 5-10mins cool-down and stretching period. Intensity of aerobic sessions will be monitored with heart rate chest strap and should match with the moderate to vigorous intensity zone as defined by the ACSM (65% of Heart Rate maximum or more and a Perceived Exertion higher than 12 on the 6 to 20 Borg scale). Exercise intensity and duration will be gradually increased during the program. After aerobic training, a 15-20mins resistance training will be performed with a gradual progression of higher intensities and/or numbers of sets. The one maximal repetition (1RM) will be assessed for each RT movements at baseline, during (each 3 months) and at the end of the program. RT intensities will go from 40 to 70% of 1RM, with 8 to 10 forms of exercise involving majors muscle groups.<br>|
| Active Comparator: Active control intervention<br>The active control intervention will include stretching and toning exercises, three sessions per week for 46 weeks. Participants will be allowed to perform cognitive and exercise training sessions either home-based or centre-based. | Other: Stretching and Toning<br>* Participants in the active control condition will take part in three 60 minutes stretching and toning sessions per week. Each session will start with a five-minutes warm-up, followed by fifteen min of body stretching exercises mainly in a seated position and finish with a five-minutes cool down. Participants will engage in four muscle-toning exercises (light intensity) using dumbbells or resistance bands, two exercises designed to improve balance, one yoga sequence, and one exercise of their choice. Intensity of stretching and toning sessions will be monitored with heart rate chest strap and should not exceed the light intensity zone as defined by the ACSM (64% of Heart Rate maximum or less and a Perceived Exertion lower than 11 on the 6 to 20 Borg scale).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in general cognitive functioning | Montreal Cognitive Assessment (0-30 score, with a higher score indicating a better cognitive functioning). | Baseline and post-intervention at 12 months. | 
| Change in processing speed | Validated remote version of neuropsychological tests and iPad tests (Composite Z-score). | Baseline and post-intervention at 12 months. | 
| Change in executive functions | Validated remote version of neuropsychological tests and iPad tests (Composite Z-score). | Baseline and post-intervention at 12 months. | 
| Change in episodic memory | Validated remote version of neuropsychological tests and iPad tests (Composite Z-score). | Baseline and post-intervention at 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cerebral autoregulation - frontal cortical region | Variations of prefrontal cortical oxygen saturation (rSO2, [HbO]/([HbO]+[HbR])) will be measured by Near Infrared Spectroscopy (NIRS), as a surrogate of cortical blood flow. Variations of continuous peripheral blood pressure (mm Hg) will be simultaneously measured by plethysmography at the finger. Autoregulation indices (unitless) will be derived from the correlation between variations of oxygen saturation measures and variations of peripheral blood pressure. | Baseline and post-intervention at 12 months. | 
| Change in cerebral autoregulation - middle cerebral arteries | Variations of cerebral blood flow velocity (cm/s) at the level of the middle cerebral artery will be measured by Transcranial Doppler (TCD). Variations of continuous peripheral blood pressure (mm Hg) will be simultaneously measured by plethysmography at the finger. Autoregulation indices (unitless) will be derived from the correlation between variations of cerebral blood flow measures and variations of peripheral blood pressure. | Baseline and post-intervention at 12 months. | 
| Change in cerebral vasoreactivity - whole brain | Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured by Arterial Spin Labeling MRI in two third of the study participants who do not present contra-indication for imaging studies. | Baseline and post-intervention at 12 months. | 
| Change in cerebral vasoreactivity - prefrontal cortex | Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using NIRS in the prefrontal region. | Baseline and post-intervention at 12 months. | 
| Change in cerebral vasoreactivity - middle cerebral arteries | Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using TCD in the middle cerebral arteries | Baseline and post-intervention at 12 months. | 
| Change in cerebral pulsatility - cortical frontal region | Pulsatility will be measured as the normalized difference of relative near-infrared light intensity changes between systole and diastole, using NIRS in the prefrontal cortical region. | Baseline and post-intervention at 12 months. | 
| Change in cerebral pulsatility - middle cerebral arteries | Pulsatility will be measured as the normalized difference of relative blood flow velocities between systole and diastole, using TCD in the middle cerebral arteries. | Baseline and post-intervention at 12 months. | 
| Change in cerebral activity | Significant changes in brain activity evoked by a Stroop task relative to baseline will be assessed by t-statistics maps, computed from variations of [HbO] and [HbR] measured by NIRS at the prefrontal cortex. | Baseline and post-intervention at 12 months. | 
| Change in brain structure | Multimodal structural MRI will be performed in two third of the study participants who do not present contra-indication for imaging studies, to measure regional cerebral volumes, as well as volume of angiopathic markers (eg lacunes, microbleeds, white matter hyperintensities), in cm3. | Baseline and post-intervention at 12 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Functions, Aging, Cardiovascular Risk factor, Cognition, Combined Intervention, Cognitive Training, Physical Exercise, Biomarkers