Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment: A Randomized Clinical Trial

Key Points Question Does a multidomain intervention of aerobic-resistance exercises with cognitive training and vitamin D improve cognition in older adults with mild cognitive impairment? Findings In this randomized clinical trial including 175 Canadian adults aged 65 to 84 years, a 20-week multidomain intervention of aerobic-resistance exercises with computerized cognitive training had a larger effect in improving cognition than exercise interventions alone, and these improvements were maintained at 12-month follow-up. Vitamin D addition did not enhance the effect. Meaning These findings suggest that pairing aerobic and resistance exercises with sequential computerized cognitive training may improve cognition in older adults with mild cognitive impairment. This randomized clinical trial examines the effectiveness of aerobic-resistance exercise with and without computerized cognitive training and vitamin D supplements to improve cognition among older adults with mild cognitive impairment (MCI). Importance Exercise, cognitive training, and vitamin D may enhance cognition in older adults with mild cognitive impairment (MCI). Objective To determine whether aerobic-resistance exercises would improve cognition relative to an active control and if a multidomain intervention including exercises, computerized cognitive training, and vitamin D supplementation would show greater improvements than exercise alone. Design, Setting, and Participants This randomized clinical trial (the SYNERGIC Study) was a multisite, double-masked, fractional factorial trial that evaluated the effects of aerobic-resistance exercise, computerized cognitive training, and vitamin D on cognition. Eligible participants were between ages 65 and 84 years with MCI enrolled from September 19, 2016, to April 7, 2020. Data were analyzed from February 2021 to December 2022. Interventions Participants were randomized to 5 study arms and treated for 20 weeks: arm 1 (multidomain intervention with exercise, cognitive training, and vitamin D), arm 2 (exercise, cognitive training, and placebo vitamin D), arm 3 (exercise, sham cognitive training, and vitamin D), arm 4 (exercise, sham cognitive training, and placebo vitamin D), and arm 5 (control group with balance-toning exercise, sham cognitive training, and placebo vitamin D). The vitamin D regimen was a 10000 IU dose 3 times weekly. Main Outcomes and Measures Primary outcomes were changes in ADAS-Cog-13 and Plus variant at 6 months. ResultsAmong 175 randomized participants (mean [SD] age, 73.1 [6.6] years; 86 [49.1%] women), 144 (82%) completed the intervention and 133 (76%) completed the follow-up (month 12). At 6 months, all active arms (ie, arms 1 through 4) with aerobic-resistance exercise regardless of the addition of cognitive training or vitamin D, improved ADAS-Cog-13 when compared with control (mean difference, -1.79 points; 95% CI, -3.27 to -0.31 points; P=.02; d=0.64). Compared with exercise alone (arms 3 and 4), exercise and cognitive training (arms 1 and 2) improved the ADAS-Cog-13 (mean difference, -1.45 points; 95% CI, -2.70 to -0.21 points; P=.02; d=0.39). No significant improvement was found with vitamin D. Finally, the multidomain intervention (arm 1) improved the ADAS-Cog-13 score significantly compared with control (mean difference, -2.64 points; 95% CI, -4.42 to -0.80 points; P=.005; d=0.71). Changes in ADAS-Cog-Plus were not significant. Conclusions and Relevance In this clinical trial, older adults with MCI receiving aerobic-resistance exercises with sequential computerized cognitive training significantly improved cognition, although some results were inconsistent. Vitamin D supplementation had no effect. Our findings suggest that this multidomain intervention may improve cognition and potentially delay dementia onset in MCI. Trial Registration ClinicalTrials.gov Identifier: NCT02808676