Delineating the topography of amyloid-associated cortical atrophy in Down’s syndrome

Abstract Objective Older adults with Down Syndrome (DS) often have Alzheimer’s disease (AD) neuropathologies. While PET imaging studies of amyloid deposition (Aβ) have been associated with worse clinical prognosis and cognitive impairment, their relationships with cortical thickness remain unclear in people with DS. Methods In a sample of 44 DS adults who underwent cognitive assessments, [ 11 C]-PiB PET and T1-MPRAGE, we used mixed effect models to evaluate the spatial relationships between Aβ binding with patterns of cortical thickness. Partial Spearman correlations were used to delineate the topography of local Aβ-associated cortical thinning. Results [ 11 C]-PiB BP ND was negatively associated with decreased cortical thickness. Locally, regional [ 11 C]-PiB retention was negatively correlated with cortical thickness in widespread cortices, predominantly in temporo-parietal regions. Conclusion Contrary to the prevailing evidence in established AD, we propose that our findings implicate Aβ in spatial patterns of atrophy that recapitulated the “cortical signature” of neurodegeneration in AD, conferring support to recent recommendations for earlier disease- interventions.