The effects of cognitive and physical exercise interventions on cognition in Huntington’s disease: A systematic review

Abstract Background Cognitive and physical exercise interventions demonstrate efficacy in improving cognition in several populations but have not been reviewed in Huntington’s disease (HD). This systematic review aims to examine the effects of cognitive and physical interventions in HD. Method Electronic databases (MEDLINE, EMBASE, PsycINFO, CENTRAL) were searched from inception through till 10 May 2021 for interventional studies of cognitive or physical exercise interventions in HD, with any control or no control. Clinical trial registries, theses databases and organisational websites were additionally searched. The primary outcome was change on objective measures of cognition. Additional outcomes included change in psychosocial, functional and neuroimaging outcomes. Risk of bias for each outcome domain was assessed independently by two reviewers using the Cochrane RoB 2 and ROBINS‐I tools. As studies reported multiple eligible outcomes in cognitive and psychosocial domains, composite effect sizes were calculated as standardized mean differences (Hedges’ g) with 95% CI. Result Fifteen studies (three cognitive, five physical, seven multidomain interventions) were included. There were five randomized controlled trials, two non‐randomized controlled trials and eight single arm studies. Most studies were therefore considered at serious risk of bias due to confounding. Interventions that included cognitive training (alone or combined with exercise) tended to report larger cognitive effect sizes, whereas studies of physical exercise (alone or combined with cognitive rehabilitation or stimulation) reported negligible benefits. Studies of multidomain interventions had larger effects on psychosocial functioning. Functional outcomes were only available from studies of multidomain interventions, which had negligible benefits. Across interventions, structural brain changes were reported in cortical and subcortical regions, but regions of interest and analyses were heterogeneous. No studies reported functional brain changes. Conclusion Our review indicates that cognitive training may benefit cognition in HD, while multidomain interventions may improve psychosocial function. Cognitive and physical interventions may promote structural brain changes, but functional brain changes are unclear. Larger randomised controlled trials are required to confirm the effects of cognitive or physical interventions in HD.