Although beta-amyloid (Aβ) 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 Aβ deposition measured with 18 F-florbetapir may serve as biomarker for progression risk in Aβ-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 Aβ-positive groups (i.e., CN-stables [n = 38] vs. CN-to-MCI/AD progressors [n = 38], MCI-stables [n = 104] versus MCI-to-AD progressors [n = 104]) revealed higher Aβ 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 Aβ burden and CSF biomarkers. These results suggest that distinct regional patterns of Aβ burden are a valuable biomarker for risk of disease progression in CN and MCI.

Background Regional differences in amyloid‐beta burden were examined between healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and its prognostic value was compared to other biomarkers. Method ADNI data (http://adni.loni.usc.edu/) of four age‐matched amyloid‐beta‐positive groups were included: cognitively stables (CN‐CN, n=38), CN to MCI or AD progressors (CN‐MCI/AD, n=38), MCI stables (MCI‐MCI, n=104), and MCI to AD progressors (MCI‐AD, n=104). Baseline 18F‐florbetapir scans were pre‐processed including normalization and intensity‐standardization (reference: cerebellum). To assess regional differences in amyloid‐beta burden, voxel‐wise group‐wise comparisons (FWE‐corrected) were performed between CN‐CN vs. CN‐MCI/AD and MCI‐MCI vs. MCI‐AD, respectively. Mean amyloid‐beta burden of resulting significant regions was subsequently used in logistic regression analyses together with global amyloid, genetic risk, and CSF biomarkers to determine the best predictive biomarker for progression. Result CN to MCI/AD progression was predicted by amyloid deposition in the precuneus, lingual and angular gyrus, pallidum, caudate, middle and superior temporal gyrus. MCI to AD progression was predicted by amyloid deposition in the anterior cingulate gyrus, medial frontal cortex, precuneus, middle and superior temporal gyrus, posterior and anterior insula. Conclusion Regional amyloid‐beta burden is a more sensitive predictor of progression to MCI or AD than global amyloid‐beta burden, pointing towards its usefulness as prognostic biomarker.