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To realize an individual-level risk evaluation of progression of early Alzheimer's disease (AD), we applied an AD resemblance atrophy index (AD-RAI) to differentiate the subjects at risk of progression from normal subjects (NC) to mild cognitive impairment (MCI) and from MCI to AD. We included 183 subjects with a two-year follow-up: 50 NC stable (NCs), 23 NC-to-MCI converters (NCc), 50 MCI stable (MCIs), 35 MCI-to-AD converters (MCIc), 25 AD stable (ADs). ANCOVA analyses were used to identify baseline brain atrophy in converters compared with non-converters. To explore the relative merits of AD-RAI over individual regional volumetric measures in prediction of disease progression, we searched for the optimal cutoff for each measure in logistic regressions and plotted the longitudinal trajectories of these brain volumetric measures in converters and non-converters. Baseline AD-RAI performed the best in differentiating NCc from NCs (odds ratio 26.35, AUC 0.740) and MCIc from MCIs (odds ratio 8.91, AUC 0.771). The AD-RAI presented greater increase in the second year for NCc vs. NCs but not for MCIc vs. MCIs. Baseline AD-RAIs were also associated with CSF-based and PET-based AD biomarkers. These results showed the potential of AD-RAI in early risk estimation before progression to MCI/AD at an individual-level.

Risk estimation before progression to mild cognitive impairment and Alzheimer’s disease: an AD resemblance atrophy index