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Background: People with Down syndrome are at ultra-high risk of developing Alzheimer’s dementia. At present, there are no preventative or curative treatments. Evidence from sporadic Alzheimer’s disease literature suggests that lifestyle factors including physical activity may help maintain cognitive and functional skills and reduce dementia risk. Our study aimed to explore the association between regular exercise undertaken by participants with Down syndrome and changes in dementia-related domains of cognition and function. This was to consider whether physical activity may be a protective measure to delay cognitive decline and dementia in Down syndrome. Methods: Demographic, lifestyle, and health information was collected at baseline and at a two year follow up from 214 adults with Down syndrome without dementia, who also underwent assessment using the Cambridge Examination for Mental Disorders of Older People with Down Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) and genetic analysis. Logistic regression models were used to examine the potential associations between decline in CAMDEX-DS domains and exercise whilst controlling for key variables. Results: At baseline, engaging in moderate intensity exercise was associated with a 47% reduced risk of everyday skills decline and engaging in high intensity exercise was associated with a 62% reduced risk of decline in personality and behaviour. At follow-up, high levels of exercise were associated with an 87% reduced risk of decline in personality and behaviour. Moderate intensity exercise at baseline was associated with a 62% reduction in risk of decline during the follow-up period in memory and orientation. Discussion: Based on our data it appears that regular moderate and high intensity exercise could reduce the risk of clinically detectable decline in a Down syndrome population with possible long-term benefits. People with Down syndrome may engage in less physical activity than their peers, and barriers remain which can prevent people with Down syndrome engaging in exercise. Our work highlights how important it is that people with Down syndrome are supported to be physically active, and to promote exercise as part of a healthy ageing plan. Clinical trials in this area would be justified to determine if engaging in exercise can lead to realistic improvements in maintaining functioning and delaying dementia onset in Down syndrome and to help develop guidance in this area.

The Association between Physical Activity and CAMDEX-DS Changes Prior to the Onset of Alzheimer’s Disease in Down Syndrome