Unique Regional Patterns of Amyloid Burden Predict Progression to Prodromal and Clinical Stages of Alzheimer's Disease

Although beta-amyloid (A beta) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of A beta deposition measured with F-18-florbetapir may serve as biomarker for progression risk in A beta-positive cognitively normal (CN) and MCI patients, including clinical follow-up data and cerebrospinal fluid (CSF) biomarkers. Voxel-wise group comparisons between age and sex-matched A beta-positive groups (i.e., CN-stables [n = 38] vs. CN-to-MCI/AD progressors [n = 38], MCI-stables [n = 104] versus MCI-toAD progressors [n = 104]) revealed higher A beta burden in precuneus, subcortical, and parietal regions in CN-to-MCI/AD progressors and cingulate, temporal, and frontal regions in MCI-to-AD progressors. Importantly, these regional patterns predicted progression to advanced stages on the AD spectrum in the short and the long-term beyond global A beta burden and CSF biomarkers. These results suggest that distinct regional patterns of A beta burden are a valuable biomarker for risk of disease progression in CN and MCI. (C) 2021 The Authors. Published by Elsevier Inc.