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

Sponsor

Louis Bherer (Other)

Overall Status

Recruiting

CT.gov ID

NCT04962061

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), The Montreal Health Innovations Coordinating Center (MHICC) (Other)

318

Enrollment

Location

Arms

Anticipated Duration (Months)

8.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Aging Cardiovascular Risk Factor	Other: Cognitive Training Other: Aerobic and resistance exercises Other: Stretching and Toning	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

318 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

This clinical trial is a double-blinded study. Research personnel performing the outcome assessments will be blinded to group allocation. Participants will be aware of the type of training they receive, but they will be blinded to the "active" intervention and study hypotheses.

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Sep 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multidomain intervention 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 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. Other: Aerobic and resistance exercises 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.
Experimental: Physical exercise intervention 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 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.
Active Comparator: Active control intervention 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 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).

Arm

Intervention/Treatment

Experimental: Multidomain intervention

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

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.

Other: Aerobic and resistance exercises

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.

Experimental: Physical exercise intervention

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

Active Comparator: Active control intervention

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

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).

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Change in cerebral autoregulation - frontal cortical region [Baseline and post-intervention at 12 months.]
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.
Change in cerebral autoregulation - middle cerebral arteries [Baseline and post-intervention at 12 months.]
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.
Change in cerebral vasoreactivity - whole brain [Baseline and post-intervention at 12 months.]
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.
Change in cerebral vasoreactivity - prefrontal cortex [Baseline and post-intervention at 12 months.]
Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using NIRS in the prefrontal region.
Change in cerebral vasoreactivity - middle cerebral arteries [Baseline and post-intervention at 12 months.]
Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using TCD in the middle cerebral arteries
Change in cerebral pulsatility - cortical frontal region [Baseline and post-intervention at 12 months.]
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.
Change in cerebral pulsatility - middle cerebral arteries [Baseline and post-intervention at 12 months.]
Pulsatility will be measured as the normalized difference of relative blood flow velocities between systole and diastole, using TCD in the middle cerebral arteries.
Change in cerebral activity [Baseline and post-intervention at 12 months.]
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.
Change in brain structure [Baseline and post-intervention at 12 months.]
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.

Other Outcome Measures

Change in cardiorespiratory fitness [Baseline and post-intervention at 12 months.]
Maximum incremental cardiopulmonary exercise test (VO2 max (ml.kg.min)).
Change in peripheral endothelial function [Baseline and post-intervention at 12 months.]
Fow-mediated dilation of the brachial artery (%).
Change in central artery stiffness [Baseline and post-intervention at 12 months.]
Carotid femoral pulse-wave velocity (m/s).
Change in walking speed [Baseline and post-intervention at 12 months.]
Timed 10-meter walking test (cm/s).
Change in functional mobility [Baseline and post-intervention at 12 months.]
Timed Time up and Go test (s).
Change in Balance performance [Baseline and post-intervention at 12 months.]
Timed one-leg standing test (s).
Change in lower limb muscles strength [Baseline and post-intervention at 12 months.]
Timed Sit-to-Stand test (s)
Change in upper limb muscle strength [Baseline and post-intervention at 12 months.]
Grip strength test score (kg).
Change in total cholesterol [Baseline and post-intervention at 12 months.]
Total cholesterol levels (mmol/L)
Change in cholesterol-HDL [Baseline and post-intervention at 12 months.]
Cholesterol-HDL levels (mmol/L)
Change in cholesterol-LDL calculated [Baseline and post-intervention at 12 months.]
Cholesterol-LDL calculated levels (mmol/L)
Change in cholesterol non-HDL [Baseline and post-intervention at 12 months.]
Cholesterol non-HDL levels (mmol/L)
Change in triglycerides [Baseline and post-intervention at 12 months.]
Triglycerides levels (mmol/L)
Change in glucose [Baseline and post-intervention at 12 months.]
Glucose levels (mmol/L)
Change in glycated hemoglobin (HbA1c) [Baseline and post-intervention at 12 months.]
Glycated hemoglobin (HbA1c) (%)
Change in insulin [Baseline and post-intervention at 12 months.]
Insulin levels (pmol/L)
Change in creatinine [Baseline and post-intervention at 12 months.]
Creatinine levels (mg/dL)
Change in sodium [Baseline and post-intervention at 12 months.]
Sodium levels (mmol/L)
Change in chloride [Baseline and post-intervention at 12 months.]
Chloride levels (mmol/L)
Change in potassium [Baseline and post-intervention at 12 months.]
Potassium levels (mmol/L)
Change in high-sensitive C-reactive protein (hsCRP) [Baseline and post-intervention at 12 months.]
High-sensitive C-reactive protein (hsCRP) levels (mg/L)
Change in apolipoprotein B (ApoB) [Baseline and post-intervention at 12 months.]
Apolipoprotein B (ApoB) levels (g/L)
Change of neurotrophic biomarkers [Baseline and post-intervention at 12 months.]
Brain-derived neurotrophic factor (BDNF) plasma concentration (pg/mL).
Change in transcriptomics [Baseline and post-intervention at 12 months.]
Transcriptome analysis to assess the impact of the intervention on any changes in the activity of different cellular processes.
Change in gut microbiome [Baseline and post-intervention at 12 months]
DNA extraction from fecal samples. The fecal samples will be collected from the participants who are also performing MRI.
Change in chronic stress levels [Baseline and post-intervention at 12 months.]
Cortisol levels from saliva samples (nmol/L). The saliva samples will be collected from the participants who are also performing MRI.
Change in perceived stress [Baseline and post-intervention at 12 months.]
Perceived Stress Scale questionnaire (Score ranges from 0-4, with 0 no stress,1 mild stress, 3 moderate stress and 4 severe).
Change in anxiety [Baseline and post-intervention at 12 months.]
State-Trait Anxiety Inventory questionnaire (Score ranges from 20-80, with a higher score indicating higher anxiety).
Change in depressive symptoms [Baseline and post-intervention at 12 months.]
Geriatric Depression Scale questionnaire (Score ranges from 0-30, with a higher score indicating larger depressive symptomatology).
Change in health related quality-of-life [Baseline and post-intervention at 12 months.]
12-Item Short Form Health Survey (a completer).
Change in sleep quality [Baseline and post-intervention at 12 months.]
Pittsburg Sleep Quality Index questionnaire (Score ranges from 0-21, with a higher score indicating worse sleep quality).
Change in Dietary patterns [Baseline and post-intervention at 12 months.]
Short Diet Questionnaire (Score ranges from 15-45 points, with a score between 15-29 categorised as unhealthy, 30-37 as somewhat unhealthy, and 38 or more as a healthy diet).
Change in social and community activities involvement [Baseline and post-intervention at 12 months.]
Social and community involvement questionnaire (Score ranges from 0-200, with a higher score indicating more social and community involvement).
Change in self-reported physical activity [Baseline]
Physical Activity Scale for the Elderly questionnaire (Score ranges from 0-400, with a higher score indicating better level of physical activity).
Self-reported masculinity and femininity trait [Baseline]
Short Form Bem Sex-Role Inventory questionnaire (30 items questionnaire with 10 items assessing the femininity traits, 10 items assessing the masculinity traits, and 10 items neutral, not scored. Two scores are calculated for femininity and masculinity, respectively, and range from 10-70, whit a higher score indicating a higher femininity or masculinity trait).
Genetic biomarkers [Baseline]
Genotyping array to generate high quality genome-wide genotyping data that include the APOE and BDNF genes.
Cognitive Reserve [Baseline]
Rami and colleagues' cognitive reserve questionnaire (Scale ranges from 0-26, with a higher score indicating a greater cognitive reserve).
Baseline level of physical activity [Baseline]
Quantification of physical activity using an accelerometry recording of 7 days (minutes of moderate to vigorous activity).