Brain outcomes with lifestyle change in adults with Down syndrome: Rationale and design for a 12-month randomized trial.

Most adults with Down syndrome (DS) will develop pathology associated with Alzheimer's disease (AD). By age 65, the cumulative incidence of dementia exceeds 90%. The available data from trials in typically developed adults suggest the potential for intentional weight loss and changes in dietary intake to prevent or delay the development of AD. However, the potential of weight loss to prevent or delay AD in adults with DS has not been previously examined. In this article, we describe the methods and rationale for a randomized trial that will evaluate the impact of weight loss and dietary intake on factors that may delay the development of AD in adults with DS including cognition, plasma biomarkers, and brain structure. The results of this trial will provide information on if non-pharmacological approaches could delay onset of AD in adults with DS. Clinical Trials Registration: NCT05985486 HIGHLIGHTS: By the age of 65 the cumulative incidence of dementia exceeds 90% in adults with DS. There is a paucity of non-pharmacological interventions to delay AD in adults with DS. Clinical trials in adults without DS suggest that intentional weight loss may improve cognitive function and reduce the risk of developing AD. A randomized trial exploring the impact of weight loss on AD biomarkers in adults with DS is currently underway. This trial will explore if non-pharmacological approaches could delay onset of AD in adults with DS.