Comparing the Effects of Cognitive Training and Physical Exercise on Cognition, Cerebral Autoregulation and Cerebral Vasoreactivity in Men and Women With Heart Failure

Study Overview
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Brief Summary
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The objective of this project is to assess the effects of combined physical exercise and cognitive training interventions on cognitive and brain health in patients with heart failure (HF). Also, the role of sex on the effects of the interventions will be assessed.

Detailed Description
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Cognitive impairment (CI) affects up to 50% of patients with heart failure (HF), and is associated with high mortality rates, poor quality of life, reduced functional capacities, and an overwhelming economic burden in Western countries. Non-pharmacological strategies could help enhance cognition in HF patients with CI. Combined physical exercise and cognitive training interventions have recently shown promising enhancement effects on cognition in patients with cardiovascular risk factors and mild cognitive impairment. The effects of combined interventions have never been tested in HF. The main objective is to assess the effects of combined physical exercise and cognitive training interventions on cognition in patients with HF. Secondary objectives include: to characterize baseline and intervention-related changes in cerebral autoregulation and vasoreactivity and to assess the role of sex on the effects of the interventions. Two-hundred and sixteen participants (36 men and 36 women/group) with stable HF regardless of aetiology and LVEF will take part in this study. All participants will have signed a written consent form before taking part in the study. Patients will be stratified according to sex and LVEF (FEVG < 40% et FEVG > 40%), and will be randomly assigned to one of the 3 following study arms: 1) Combined physical exercise and cognitive training; 2) Physical exercise alone; and 3) Usual medical care.

Official Title
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Comparing the Effects of Cognitive Training and Physical Exercise on Cognition, Cerebral Autoregulation and Cerebral Vasoreactivity in Men and Women With Heart Failure

Conditions
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Aging, Chronic Heart Failure

Intervention / Treatment
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* Other: Cognitive training
* Other: Exercise training
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 60 years old Stable chronic HF on maximally tolerated background treatment for at least 2 months (stable therapy with ACE-I, ARBs and MRA for at least 2 months), regardless of LVEF with no limitation of physical activity in ordinary physical activity (i.e. NYHA class I), moderate symptoms (i.e. NYHA class II) or marked limitation in activity (i.e. NYHA class III) Able to perform cognitive and physical training. Exclusion Criteria: Acute cardiovascular event 1 month prior to randomization, including emergency visit or hospitalization for decompensated HF, acute myocardial infarction, stroke, and transient ischemic attack Planned cardiovascular intervention within 6 months (implantation of any cardiac device, cardiac revascularization, heart transplantation) Severe exercise intolerance Contraindications for exercise testing (e.g., uncorrected severe aortic or carotid stenosis, severe pulmonary hypertension, severe non-revascularizable coronary disease including left main coronary stenosis, significant myocardial ischemia or arrhythmia during low-intensity exercise, acute HF) Severe respiratory disease Non-cardiopulmonary limitation to exercise (e.g., arthritis, claudication or any peripheral neurological disease including other neurodegenerative diseases such as disabling Parkinson) Uncontrolled diabetes or untreated thyroid dysfunction Current or recent malignancy with life expectancy < 1 year Chronic hemodialysis or peritoneal dialysis Unable to read the informed consent form or unable to understand the oral explanations provided by the assessor.

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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No

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
Interventional Model Description: parallel assignment (1:1:1)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined<br>Combined physical exercise and cognitive training. The combined intervention will include a cognitive training with aerobic and resistance exercises training, three sessions per week for 6 months. Participants will be allowed to perform cognitive and exercise training sessions either home-based or centre-based. | Other: Cognitive training<br>* The cognitive training will involve attention control training and memory training, with thrice-weekly 30-min sessions. 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: Exercise training<br>* Participants will follow a 20-week physical training program, with 60-min thrice-weekly trainings. The training sessions will start with a 5-min warm-up, followed by an aerobic training (20 min) after which 20-min of resistance/muscular training will take place. The program will end with a 10-min cool-down. Training will be adapted to individuals' baseline capacity as measured by the baseline cardiorespiratory test. For home-training sessions, participants will have access to a complete exercise training program. A certified kinesiologist will supervise trainings. With the Heart rate sensor Polar H10, all the characteristics of the activities will be recorded (type of the activity, intensity, heart rate, duration). A kinesiologist will call participants every week to ensure the smooth running of the exercises training sessions and individualize the care according to the patient's level.<br>Other: Usual care<br>* All patients will receive usual care and be treated according to evidence-based treatments. This will include optimal medical therapy, systematic information regarding dietary and fluid management, and a recommendation for regular physical activity consistent with the latest update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure. Moreover, patients who benefit from a prescription for a cardiovascular rehabilitation program will be able to follow it, but they will not receive other forms of intervention for the duration of the study.<br>|
| Experimental: Exercise<br>The physical exercises intervention will include aerobic and resistance exercises training, three sessions per week for 6 months. Participants will be allowed to perform exercise training sessions either home-based or centre-based. | Other: Exercise training<br>* Participants will follow a 20-week physical training program, with 60-min thrice-weekly trainings. The training sessions will start with a 5-min warm-up, followed by an aerobic training (20 min) after which 20-min of resistance/muscular training will take place. The program will end with a 10-min cool-down. Training will be adapted to individuals' baseline capacity as measured by the baseline cardiorespiratory test. For home-training sessions, participants will have access to a complete exercise training program. A certified kinesiologist will supervise trainings. With the Heart rate sensor Polar H10, all the characteristics of the activities will be recorded (type of the activity, intensity, heart rate, duration). A kinesiologist will call participants every week to ensure the smooth running of the exercises training sessions and individualize the care according to the patient's level.<br>Other: Usual care<br>* All patients will receive usual care and be treated according to evidence-based treatments. This will include optimal medical therapy, systematic information regarding dietary and fluid management, and a recommendation for regular physical activity consistent with the latest update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure. Moreover, patients who benefit from a prescription for a cardiovascular rehabilitation program will be able to follow it, but they will not receive other forms of intervention for the duration of the study.<br>|
| Active Comparator: Usual care<br>Usual medical care with no interventions | Other: Usual care<br>* All patients will receive usual care and be treated according to evidence-based treatments. This will include optimal medical therapy, systematic information regarding dietary and fluid management, and a recommendation for regular physical activity consistent with the latest update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure. Moreover, patients who benefit from a prescription for a cardiovascular rehabilitation program will be able to follow it, but they will not receive other forms of intervention for the duration of the study.<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 6 months | 
| Change in processing speed | Validated remote version of neuropsychological tests and iPad tests (Composite Z-score). | Baseline and post-intervention at 6 months | 
| Change in executive functions | Validated remote version of neuropsychological tests and iPad tests (Composite Z-score). | Baseline and post-intervention at 6 months | 
| Change in episodic memory | Validated remote version of neuropsychological tests (Composite Z-score). | Baseline and post-intervention at 6 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 6 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 6 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 6 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 6 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 6 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 6 months | 
| Change in cerebral activity | Significant changes in brain activity evoked by a N-back 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 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognition, physical exercise, cognitive training, brain functions, combined intervention, heart failure, biomarkers, cerebral vasoreactivity, fitness