Sleep moderates the effects of exercise on cognition in chronic stroke: secondary analysis of a randomized trial

Background: Exercise (EX) or cognitive and social enrichment (ENRICH) are two promising strategies for promoting cognitive function post-stroke. Sleep may moderate the effects of these interventions on cogntion, whereby intervention effects may be more robust among individuals suffering from poor sleep. We examined whether sleep moderates the effects of EX or ENRICH on cognitive function in adults with chronic stroke. Methods: Secondary analysis of a three-arm parallel, single-blinded, randomized clinical trial among community-dwelling adults aged 55+ years with chronic stroke (i.e., ≥12 months since stroke). Participants were randomized to 2x/week EX, ENRICH, or balance and tone control (BAT). At baseline, device-measured sleep duration and efficiency were measured using MotionWatch8 wrist-worn actigraphy; self-reported quality was measured by Pittsburgh Sleep Quality Index (PSQI). Participants were categorized at baseline as having good or poor: 1) device-measured duration; 2) device-measured efficiency; or 3) self-reported quality. The primary cognitive outcome was Alzheimer's Disease Assessment Scale Plus (ADAS-Cog-Plus) measured at baseline, 6 months (end of intervention), and 12 months (6-month follow-up). Linear mixed models examined if baseline sleep categorizations (i.e., good/poor) moderated the effects of EX or ENRICH on ADAS-Cog-Plus. Results: We enrolled 120 participants in the trial (EX=34; ENRICH=34; BAT=52). Baseline sleep categorization did not moderate the effect of ENRICH on ADAS-Cog-Plus; however, it moderated the effect of EX. EX participants with poor baseline sleep efficiency (estimated mean difference: -0.48; 95% CI:[-0.85, -0.10]; p=0.010) or self-reported sleep quality (estimated mean difference: -0.38; 95% CI:[-0.70, -0.07]; p=0.014) had significantly better ADAS-Cog-Plus performance at 6 months compared with BAT participants with poor sleep. There was no effect of EX on ADAS-Cog-Plus for participants with good baseline sleep. Conclusion: The effects of EX on cognitive function in adults with chronic stroke is moderated by sleep, whereby poor sleepers benefit more. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ClinicalTrials.gov identifier: [NCT01916486][1] ### Funding Statement This study was funded by the Canadian Institutes of Health Research (MOP-126130) and the Jack Brown and Family Alzheimer Research Foundation Society. Dr. Falck is a Michale Smith Health Research BC postdoctoral fellow. Dr. Liu-Ambrose is a Canada Research Chair (Tier 1) in Healthy Aging. Dr. Davis is a Canada Research Chair (Tier 2) in Applied Health Economics and a Michael Smith Health Research BC Career Scholar. Dr. Eng is a Canada Research Chair (Tier 1) in Neurological Rehabilitation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was provided by University of British Columbia?s Clinical Research Ethics Board (H13-00715) and Vancouver Coastal Health Research Institute (V13-00715). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes De-identified participant data will be made available by the corresponding author to others who propose a reasonable scientific request and obtain appropriate ethics. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01916486&atom=%2Fmedrxiv%2Fearly%2F2024%2F01%2F17%2F2024.01.16.24301392.atom