None listed
Conditions
Brief summary
Mild cognitive impairment (MCI) affects at least 10% of older adults globally, and in this cohort the risk of incident dementia is greatly increased from 1-2% per annum to 10-15%. Exercise has been shown to be beneficial for some cognitive outcomes in MCI, although results are heterogeneous, and the optimum exercise dose and modality for preservation or improvement of cognition is not fully defined. Progressive resistance training (PRT) has been shown to have larger effects on cognition than aerobic training in meta-analyses. The limited benefit of some aerobic training studies may be due to insufficient intensities of the intervention, which have produced suboptimal changes in aerobic capacity or other physiological adaptations potentially mechanistic for improved brain function. High intensity interval training (HIIT) results in more beneficial cardiovascular adaptations compared to standard moderate intensity aerobic training. The wealth of data linking aerobic fitness to cognition suggests that HIIT, which approximately doubles the average improvement in aerobic fitness compared to standard training, is of potentially great interest in MCI therefore. However, HIIT has never been tested alone or directly compared to PRT for cognitive benefits in any cohort. We hypothesize that PRT and HIIT will be robust, alternative exercise interventions to improve cognition in MCI. We will conduct a multi-national, randomised controlled trial over 4 years in which we randomise 210 older adults with MCI in Australia and Canada to PRT, HIIT or a sham exercise control group for 12 months. Executive function is the primary cognitive outcome. Secondary outcomes include other cognitive domains, biomarkers for cognitive decline and distinct mediators of benefit for PRT (e.g., anabolic hormones, lean mass) vs. HIIT (e.g., arterial stiffness, aerobic fitness), functional status, brain structure and connectivity, and psychological wellbeing. The study is powered for our primary hypothesis that both PRT and HIIT will improve Executive Function Domain relative to the control. We will recruit 70 participants per group for a total sample size of 210 across the three sites. This sample size will allow to demonstrate a relative ES of 0.48 (PRT vs. Control or HIIT vs. Control) assuming alpha less than 0.05 and beta of 0.2. Sample size has not been inflated for loss to follow-up, as we will utilise linear repeated measures mixed models and/or General Linear Models in intention-to-treat analyses including all randomised participants irrespective of dropout or adherence. We do not intend to compare PRT to HIIT as we hypothesise both to be effective, therefore the comparisons are for intervention vs. control only. BRAIN will be the first trial of HIIT for cognition in any cohort, and the largest and only multi-national study of exercise for Mild Cognitive Impairment ever conducted.
Interventions
1. Study Sites:
This multi-site randomised control trial will take place across 3 study sites: University of Sydney (Australia), University of Queensland (Australia), and University of British Columbia (Canada).
2. Intervention Arms and Training Location:
Eligible and consenting participants at each study site will be randomly allocated to one of three study arms; progressive-resistance training (PRT), high-intensity interval training (HIIT) or a balance, toning & mobility (SHAM) sham-control g
1. Study Sites: This multi-site randomised control trial will take place across 3 study sites: University of Sydney (Australia), University of Queensland (Australia), and University of British Columbia (Canada). 2. Intervention Arms and Training Location: Eligible and consenting participants at each study site will be randomly allocated to one of three study arms; progressive-resistance training (PRT), high-intensity interval training (HIIT) or a balance, toning & mobility (SHAM) sham-control group. Participants will train supervised 2-3 days per week (depending on study arm), for 52 weeks. Trainers will have a background in exercise and sports science, exercise physiology, kinesiology or physiotherapy. The location of the exercise sessions will vary according to the study site as follows: - University of Sydney and University of British Columbia: PRT and HIIT training sessions will be performed in university-based gymnasiums; BTM sessions will be performed in separate rooms to the PRT and HIIT training groups. - University of Queensland: PRT training sessions will be performed in a gymnasium based in a retirement village; HIIT and BAT will be performed in separate rooms within the same retirement village. Resident of the retirement village and members of the community will have access to the training areas. 2.1. Intervention Arm 1: Progressive Resistance Training (PRT) The PRT intervention will be performed 2 session per week for 52 weeks and consist of 7 exercises performed using pneumatic resistance machines for 3 sets of 8 repetitions at 80% of 1 repetition maximum (1RM). Participants will be instructed to contract concentrically ‘as fast as possible’ and then take 3-4 seconds through the eccentric phase. Rest between repetitions will be 10-15 seconds, and 1 to 2 minutes between sets. Exercises will be performed in the following order: bilateral leg press, bilateral chest press, unilateral knee extension, bilateral seated row, bilateral knee flexion, bilateral triceps pushdown, unilateral hip abduction. Total session time will be approximately 60 minutes, with a ratio of 1 trainer to 4 participants. Weeks 1 and 2 of the intervention will include familiarisation (session 1), assessment of 1RM (session 2) and gradual increase in target intensity from 50% (session 3), 60% (session 4), 70% (session 5) until 80% of 1RM is reached in session 6. Thereafter training intensity will be set at 80% 1RM and progressed by a projected gain in strength of 3% 1RM each session, used in conjunction with daily ratings of perceived exertion (15-18/20 on the Borg Scale). At the start of every 7th session, 1RM will be re-tested and target weight at 80% 1RM will be recalculated based on the new 1RM. Muscle visualisation and mental imagery: Prior to each set, and during the rest intervals, participants will be shown a poster depicting the exercise being performed and the muscles targeted. The instructor will show participants where these muscles are located and encourage participants to feel the area. During the contraction phase of each repetition, participants will be asked to visualise and focus on the contracting muscles as they perform the movement 'as fast as they can'. 2.2. Intervention Arm 2: High Intensity Interval Training (HIIT) The HIIT intervention will be performed 3 sessions per week for 52 weeks and the heart rate (HR) target used during the intervention will be set based on the peak HRpeak achieved on the stress test at baseline. The HIIT intervention will be performed on a treadmill, recumbent cross trainer or bike, depending on feasibility, preference, and co-morbidities such as osteoarthritis or balance impairment. Each session will consist of an 8-minute warm up at 60% peak HR; one 4-minute interval with a progressive increase in intensity so as to achieve 85% peak HR by the end of minute 2, and maintain 85% to 95% peak HR during minutes 3 and 4 of the interval; and a 3-minute cool down at 60% peak HR. Heart rate will be monitored continuously during all sessions using a heart rate monitor to adjust the workload used (speed or slope of treadmill; resistance or revolutions per minute on cross trainer or bike) so as to keep the HR during the last 2 minutes of the interval at 85-95% of peak, and at 60% during warm-up and cool-down. Sessions 1 to 4 of the intervention will include familiarisation and gradual increase of the time spent at 85-95% peak HR during the interval from 30, 60, 90 to 120 seconds in each successive session. Individuals with atrial fibrillation or on beta-blockers will be included, but we will use the Borg Scale of Perceived Exertion (rating 16-17/20) to adjust the workload in addition to HR. Total session time will be 15 minutes, with a ratio of 1 trainer for 4 participants.
Sponsors
University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Mild Cognitive Impairment (MCI) defined as the presence of all four generally accepted criteria (*) 1.1. Absence of dementia: Clinical Dementia Rating scale (CDR) score below 1. 1.2. No or minimal functional impairment due to cognition: Amsterdam IADL Questionnaire score equal or greater than 40, rated by informant or participant if no informant available. 1.3. Subjective memory/cognitive complaint: a) Cognitive Change Index (CCI) scale: Participant or informant responds to 3 or more statements with a rating of 3, 4 or 5 (‘mild to severe problem’); OR b) Subjective memory complaint questionnaire: Participant or informant responds ‘yes’ to question (1): ‘Have you noticed difficulties with your memory?’ and ‘yes’ to questions 2 OR 3: (2)‘Have you been concerned about your memory?, (3)Have you mentioned any concerns about memory to anyone? respectively, as per recommendations for the assessment of subjective memory complaint. 1.4. Objective cognitive impairment: Score between 19 and 25 on the Montreal Cognitive Assessment (MoCA). 2. Age 60 or above 3. Ambulatory without the assistance of a person 4. If from non-English speaking background, must have completed some education in English. 5. Residing in the community, including retirement villages and other senior housing or activity sites (independent level of care) 6. Willing to participate in a study which involves attending supervised exercise sessions 3 days per week for 12 months There will be 3-stage screening, which includes: Telephone screen by research assistant of participant and informant (if available) for willingness to participate, sedentary status, no exclusionary medical history, no current mayor depression (PHQ-9 score of 9 or below), no planned move, no planned vacation for more than 4 consecutive weeks during the 12 month stuy period. This will be followed by In-person screen to assess criteria for mild cognitive impairment, and later on by In-person screen by physician to perform medical screen and stress testing (to ascertain unstable or unsuitable medical conditions). (*) Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment-beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004;256:240-6.
Exclusion criteria
1. Diagnosis of dementia 2. High level residential care 3. Non-ambulatory or requiring person to assist when walking 4. 1 stroke in the past 12 months or 2 or more strokes in a lifetime 5. Cardiovascular event/surgery in the past 6 months 6. Progressive neurological disease 7. Inability to read and identify objects on a computer screen and draw on a piece of paper due to vision impairment 8. Current major depressive episode (PHQ-9 score above 9) 9. Psychosis or substance abuse according to DSM-IV criteria. 10. Alcohol abuse (Responded ‘Yes’ to questions 3 and 4 of the CAGE, and reported risky drinking behaviour using NHMRC standard criteria) 11. From a non-English speaking background (NESB) without any education in English 12. Already practicing =150 min moderate intensity exercise, PRT or HIIT regularly 13. Medical contraindications to the planned exercise due to chronic or unstable or terminal diseases 14. Planned move, or planning to be away for 4 or more consecutive weeks during the study period 15. Traumatic brain injury or >2 seizures in the past 12 months
Outcome results
None listed