Physical activity as a resistance or resilience mechanism in Down syndrome Alzheimer's disease

Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD). Lifestyle factors such as engagement in moderate-to-vigorous physical activity (MVPA) reduce risk or delay the onset of AD. This study aimed to determine whether MVPA confers a resistance (AD pathology) or resilience (cognitive decline) effect on the relationship between AD pathology and cognitive decline in DS.

Analyses included 69 adults with DS (aged 26-58) who participated in a longitudinal study across 3.29 years. An actigraphy accelerometer assessed MVPA across 7 days. Directly administered and informant-reported measures assessed cognitive functioning, specifically memory and dementia symptoms. Neuroimaging biomarkers quantified amyloid beta (Aβ) burden, as assessed via positron emission tomography imaging.

In regression models, baseline MVPA was not associated with baseline level or change in global Aβ burden across 32 months. However, baseline MVPA (β = -0.005 to -0.004, p < 0.05) significantly moderated the association between increases in Aβ burden and declines in cognitive functioning. Adults with DS who engaged in greater MVPA experienced less cognitive decline compared to adults with DS who engaged in less MVPA, who had similar Aβ load.

MVPA may help maintain cognitive functioning early in the progression of AD pathology in adults with DS.

Adults with Down syndrome are genetically at risk for Alzheimer's disease (AD).Timing of AD clinical onset spans 30+ years.Physical activity has been linked to less cognitive decline and dementia symptoms.Physical activity may protect against dementia through resilience mechanisms.Physical activity could be a low-cost intervention to help prevent cognitive decline.