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Background  We investigated regional amyloid staging characteristics in  11 C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled in the Wisconsin Registry for Alzheimer’s Prevention.    Methods  We analyzed partial volume effect-corrected  11 C-PiB-PET distribution volume ratio maps from 220 participants (mean age = 61.4 years, range 46.9–76.8 years). Regional amyloid positivity was established using region-specific thresholds. We used four stages from the frequency-based staging of amyloid positivity to characterize individual amyloid deposition. Longitudinal PET data was used to assess the temporal progression of stages and to evaluate the emergence of regional amyloid positivity in participants who were amyloid-negative at baseline. We also assessed the effect of amyloid stage on longitudinal cognitive trajectories.    Results  The staging model suggested progressive accumulation of amyloid from associative to primary neocortex and gradually involving subcortical regions. Longitudinal PET measurements supported the cross-sectionally estimated amyloid progression. In mixed-effects longitudinal analysis of cognitive follow-up data obtained over an average period of 6.5 years following the baseline PET measurement, amyloid stage II showed a faster decline in executive function, and advanced amyloid stages (III and IV) showed a faster decline across multiple cognitive domains compared to stage 0.    Conclusions  Overall, the  11 C-PiB-PET-based staging model was generally consistent with previously derived models from  18 F-labeled amyloid PET scans and a longitudinal course of amyloid accumulation. Differences in longitudinal cognitive decline support the potential clinical utility of in vivo amyloid staging for risk stratification of the preclinical phase of AD even in middle-aged to older individuals at risk for AD.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13195-021-00918-0.

In vivo staging of regional amyloid progression in healthy middle-aged to older people at risk of Alzheimer’s disease