Abstract INTRODUCTION Down syndrome (DS) is associated with elevated risk for Alzheimer’s disease (AD) due to beta amyloid (Aβ) lifelong accumulation. We hypothesized that the spatial distribution of brain Aβ predicts future dementia conversion in individuals with DS. METHODS We acquired 18 F-Florbetapir PET scans from 19 nondemented individuals with DS at baseline and monitored them for four years, with five individuals transitioning to dementia. Machine learning classification determined features on 18 F-Florbetapir standardized uptake value ratio (SUVR) maps that predicted transition. RESULTS In addition to “AD signature” regions including the inferior parietal cortex, temporal lobes, and the cingulum, we found that Aβ cortical binding in the prefrontal and superior frontal cortices distinguished subjects who transitioned to dementia. Classification did well in predicting transitioners. DISCUSSION Our study suggests that specific regional profiles of brain amyloid in older adults with DS may predict cognitive decline and are informative in evaluating the risk for dementia. Highlights Regional [18F]-Florbetapir PET predicts future transition to dementia in Downs Syndrome. Increased amyloid in prefrontal, inferior parietal, superior frontal, rostral middle frontal, and posterior cingulate cortices detect transitioiners, with prefrontal and superior frontal being best overall. Amyloid PET-based classification able to discriminate between transitioners and non-transitioners.

Brain Amyloid and the Transition to Dementia in Down Syndrome