Effect of Exercise Training or Complex Mental and Social Activities on Cognitive Function in Adults With Chronic Stroke: A Randomized Clinical Trial

Abstract

Importance: A stroke doubles one's risk for dementia. How to promote cognitive function among persons with chronic stroke is unclear.

Objective: To evaluate the effect of exercise (EX) or cognitive and social enrichment activities (ENRICH) on cognitive function in adults with chronic stroke.

Design, setting, and participants: This was a 3-group parallel, single-blinded, single-site, proof-of-concept randomized clinical trial at a research center in Vancouver, British Columbia, Canada. Participants included community-dwelling adults with chronic stroke, aged 55 years and older, able to walk 6 meters, and without dementia. The trial included a 6-month intervention and a 6-month follow-up. Randomization occurred from June 6, 2014, to February 26, 2019. Measurement occurred at baseline, 6 months, and 12 months. Data were analyzed from January to November 2021.

Interventions: Participants were randomly allocated to twice-weekly supervised classes of: (1) EX, a multicomponent exercise program; (2) ENRICH, a program of cognitive and social enrichment activities; or (3) balance and tone (BAT), a control group that included stretches and light-intensity exercises.

Main outcomes and measures: The primary outcome was the Alzheimer Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus), which included the 13-item ADAS-Cog, Trail Making Test Parts A and B, Digit Span Forward and Backward, Animal Fluency, and Vegetable Fluency.

Results: One-hundred and twenty participants, with a mean (range) of 1.2 (1-4) strokes, a mean (SD) of 66.5 (53.8) months since the most recent stroke, mean (SD) baseline age of 70 (8) years, mean (SD) baseline ADAS-Cog-Plus of 0.22 (0.81), and 74 (62%) male participants, were randomized to EX (34 participants), ENRICH (34 participants), or BAT (52 participants). Seventeen withdrew during the 6-month intervention and another 7 during the 6-month follow-up. Including all 120 participants, at the end of the 6-month intervention, EX significantly improved ADAS-Cog-Plus performance compared with BAT (estimated mean difference: -0.24; 95% CI, -0.43 to -0.04; P = .02). This difference did not persist at the 6-month follow-up (estimated mean difference: -0.08; 95% CI, -0.29 to 0.12; P = .43). For the 13-item ADAS-Cog, the EX group improved by 5.65 points over the 6-month intervention (95% CI, 2.74 to 8.57 points; P < .001), exceeding the minimally clinical difference of 3.0 points.

Conclusions and relevance: These findings suggest that exercise can induce clinically important improvements in cognitive function in adults with chronic stroke. Future studies need to replicate current findings and to understand training parameters, moderators, and mediators to maximize benefits.

Trial registration: ClinicalTrials.gov identifier: NCT01916486.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Liu-Ambrose reported receiving grants from Canadian Institutes of Health Research, grants from Jack Brown and Family Alzheimer Research Foundation, and grants from Canada Foundation for Innovation during the conduct of the study; support from Canada Research Chair Program; and Dr Liu-Ambrose reported serving on the board of directors for the British Columbia Brain Wellness Foundation Inc and the executive team of Synaptitude Brain Health Inc (she does not receive personal fees for these roles). Drs Falck and Dao reported receiving funding from Michael Smith Health Research BC Funding for postdoctoral training during the conduct of the study. Dr Hsiung reported receiving research support as a clinical trials site investigator from Anavax, Biogen, Eli Lilly and Roche, and has received research grants from the Canadian Institute of Health Research, Alzheimer Society of Canada, and National Institute on Aging/National Institutes of Health. Dr Hsiung reported being supported by the Ralph Fisher Professorship in dementia research from the Alzheimer Society of British Columbia. Dr Middleton reported receiving grants from the Public Health Agency of Canada related to exercise as a therapeutic strategy for dementia and grants from the Alzheimer Society of Canada related to exercise as a therapeutic strategy for dementia outside the submitted work. Dr Eng reported being supported by the Canada Research Chair Program and being supported by a Canada Research Chair during the conduct of the study. No other disclosures were reported.

Figures

Figure.. Trial Flow Diagram