Physical activity, cognitive decline and biomarkers of Alzheimer’s disease in adults with Down syndrome

Abstract

AbstractBackgroundAdults with Down Syndrome (DS) are at high risk for Alzheimer's disease (AD), which is characterized by the early accumulation of amyloid‐beta (Aβ), followed by neurofibrillary tangles of tau, and subsequent pathology. There is variability in the age of AD onset in DS, which may mean that non‐genetic factors impact AD timing. Physical activity is associated with less age‐related cognitive declines and lower risk of AD in non‐DS populations. The goal of this study was to examine the association between physical activity and cognitive performance and AD biomarkers (Aβ PET, tau PET, and white matter (WM)) in non‐demented adults with DS.Methods66 adults with DS from the Alzheimer Biomarker Consortium Down Syndrome participated. Participants wore an actigraph accelerometer on their non‐dominant wrist for 7‐days. Cognitive performance was assessed via measures of memory, executive functioning, visuospatial ability, and dementia symptoms. Participants underwent MRI and PET scans to assess the standard uptake value ratio of [11C]PiB (15 mCi) in the neocortex and striatum and [18F]AV‐145 across braak regions I‐VI. WM integrity was assessed using DTI mean diffusivity and fractional anisotrophy in major association tracts.ResultsGreater sedentary activity was associated with more dementia symptoms (r = ‐0.298, p<.05). Higher moderate‐to‐vigorous activity was associated with better memory (r = 0.309, p<.01), executive functioning (r = 0.270, p<.05), visuospatial ability (r = 0.311, p<.05), and fewer dementia symptoms (r = 0.356, p<.01). Models controlled for age and level of intellectual disability. Neither sedentary nor moderate‐to‐vigorous activity were significantly related to PET Aβ or tau PET. However, both were associated with WM integrity in the superior longitudinal fasciculus (r = ‐0.445, p<.05; r = 0.393, p<.05) and sedentary was associated with inferior longitudinal fasciculus tracts (r = ‐0.362, p<.05), after controlling for age and intellectual disability.ConclusionPhysical activity might have a protective effect against age‐related cognitive declines in in DS. However, the reverse time‐order could also be true. Physical activity was not associated with PET Aβ or tau PET cross‐sectionally. In contrast, physical activity was associated with WM integrity, Longitudinal studies are needed to understand mechanisms driving associations, including the cardiovascular impairment