Comparing the Effects of Combining Cognitive and Physical Exercise Training on Cognition, and Cerebral Blood Flow Regulation in Men and Women With Chronic Heart Failure (ReCARDIO)

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.

Study Overview

• Status: Recruiting
• Conditions: Aging; Chronic Heart Failure
• Intervention / Treatment: Other: Cognitive training; Other: Exercise training; Other: Usual care

Detailed Description

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, pulsatility and neurovascular coupling and to assess the role of sex on intervention effects.

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.

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Louis Bherer, PhD; Phone Number: 4355 +1 514-374-1480; Email: louis.bherer@umontreal.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T1N6
      • Recruiting
      • Preventive medicine and physical activity centre (centre EPIC), Montreal Heart Institute
      • Sub-Investigator: Jean Rouleau, MD
      • Contact: Louis Bherer, PhD; Phone Number: 4355 514-374-1480; Email: louis.bherer@umontreal.ca
      • Principal Investigator: Louis Bherer, PhD
      • Sub-Investigator: Anil Nigam, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 50 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined; 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; 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.; Other: Exercise training; 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.; Other: Usual care; 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.
Experimental: Exercise; 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; 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.; Other: Usual care; 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.
Active Comparator: Usual care; Usual medical care with no interventions	Other: Usual care; 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.

What is the study measuring?

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 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 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 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cardiorespiratory fitness	Maximum incremental cardiopulmonary exercise test (VO2 max (ml.kg.min)	Baseline and post-intervention at 6 months
Change in 6-min walking test performance	maximum distance performed in 6 minutes (distance, m)	Baseline and post-intervention at 6 months
Change in upper limb muscle strength	Grip strength test score (kg).	Baseline and post-intervention at 6 months
Change in quality of life	score on the 23 items of the Kansas City Cardiomyopathy Questionnaire (KCCQ)	Baseline and post-intervention at 6 months
Change in perceived self care behaviour	European Heart Failure Self-care Behaviour Scale (EHFScB-9) will be completed. This self-reported questionnaire assesses the adherence to different self-care behaviours (e.g., eating low-salt diet, etc.).	Baseline and post-intervention at 6 months
Change in anxiety	State-Trait Anxiety Inventory questionnaire (Score ranges from 20-80, with a higher score indicating higher anxiety).	Baseline and post-intervention at 6 months
Change in depressive symptoms	Geriatric Depression Scale questionnaire (Score ranges from 0-30, with a higher score indicating larger depressive symptomatology).	Baseline and post-intervention at 6 months
Change in sleep quality	Pittsburgh Sleep Quality Index questionnaire (Score ranges from 0-21, with a higher score indicating worse sleep quality). symptomatology).	Baseline and post-intervention at 6 months
Cognitive reserve	Rami and colleagues' cognitive reserve questionnaire (Scale ranges from 0-26, with a higher score indicating a greater cognitive reserve).	Baseline
Genotyping data	genotyping data that include the APOE gene	baseline
Change in NT-pro-BNP	NT-pro-BNP (ng/L)	Baseline and post-intervention at 6 months
Change in high-sensitive Troponin T	hsTnT (ng/mL)	Baseline and post-intervention at 6 months

Collaborators and Investigators

• Sponsor: Montreal Heart Institute
• Collaborators: Canadian Institutes of Health Research (CIHR); The Montreal Health Innovations Coordinating Center (MHICC)
• Investigators: Principal Investigator: Louis Bherer, PhD, Montreal Heart Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Estimated): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: biomarkers; cognition; heart failure; cognitive training; physical exercise; fitness; cerebral vasoreactivity; brain functions; combined intervention
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Behavior; Heart Failure; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Patient Care; Health Services; Health Care Facilities Workforce and Services; Rehabilitation; Aftercare; Continuity of Patient Care; Neurological Rehabilitation; Exercise; Cognitive Training
• Other Study ID Numbers: MP-33-2018-2406

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No