The association between cardiorespiratory fitness and resting-state functional connectivity in adults with Down syndrome.

Resting-state functional connectivity (FC) of the default mode network (DMN) is linked to Alzheimer’s disease in people with Down syndrome (DS). In adults without DS, cardiorespiratory fitness is associated with DMN FC; however, this has not been unexplored in DS. This analysis used baseline data from an intervention in adults with DS. Resting-state functional magnetic resonance imaging measured connectivity from the posterior cingulate cortex seed to DMN nodes. Fitness was measured by the maximal treadmill test. Pearson correlations and linear regressions were used to examine the associations between fitness and FC. Data from 40 adults with DS (26.0 years, 58% female) showed fitness was associated with overall DMN connectivity (r = 0.472, p = 0.004) and medial prefrontal cortex connectivity (r = 0.431, p = 0.010). The association between fitness and DMN FC remained significant after adjustment for age and sex (β = 0.0072, p = 0.04). Fitness may be associated with DMN FC in DS. In adults with DS, cardiorespiratory fitness was associated with overall DMN connectivity, which remained significant after adjusting for age and sex. No associations were found between moderate to vigorous physical activity and DMN connectivity. Increasing fitness may be a therapeutic strategy for AD prevention or delay in DS.