The impact of a 12-month randomized exercise intervention on cognitive function and brain volume in adults with down syndrome

BACKGROUND: Adults with Down syndrome (DS) have a high risk for Alzheimer's disease (AD). While exercise improves cognition and brain health in the general population, few long-term studies have evaluated its effects in DS. OBJECTIVE: We examined the impact of a 12-month remotely delivered exercise program on cognitive function and brain volume in adults with DS. METHODS: 81 adults with DS (mean age = 27 years) were randomized to high-frequency remote exercise (3 sessions/week, RH), low-frequency remote exercise (1 session/week, RL), or a support and education control (SE). Cognitive function was assessed using the DS-adapted Cambridge Neuropsychological Test Automated Battery (CANTAB), and brain volumes were measured via MRI at baseline and 12 months. RESULTS: There were no significant changes in any group in executive function or episodic memory (all p > 0.05), but the RH arm significantly improved processing speed across the 12-month intervention (EMM change: 0.17; p = 0.04). No between-group differences were observed for changes in overall cognitive scores. The RL group showed a decrease in total grey matter volume (EMM change -0.82; p = 0.02) and the RH group had no change (EMM change: 0.08; p = 0.72), yielding a significant group effect across time (EMM: 0.90; p = 0.04). Additionally, the RH arm had an increase in right hippocampal volume over 12 months (EMM change: 0.004; p = 0.04). CONCLUSION: The improvements in reaction time, right hippocampal volume, and grey matter preservation suggest that structured exercise may influence cognition and brain health in adults with DS. CLINICAL TRIALS REGISTRATION: NCT04048759.