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.