Reshaping the amyloid buildup curve in alzheimer disease? partial-volume effect correction of longitudinal amyloid pet data

Abstract

It was hypothesized that the brain β-amyloid buildup curve plateaus at an early symptomatic stage of Alzheimer disease (AD). Atrophy-related partial-volume effects (PVEs) degrade signal in hot-spot imaging techniques such as amyloid PET. The current study, a longitudinal analysis of amyloid-sensitive PET data, investigated the effect on the shape of the β-amyloid curve in AD when PVE correction (PVEC) is applied. Methods: We analyzed baseline and 2-y follow-up data for 216 symptomatic individuals on the AD continuum (positive amyloid status) enrolled in the Alzheimer's Disease Neuroimaging Initiative (17 with AD dementia and 199 with mild cognitive impairment), including 18F-florbetapir PET, MRI, and Mini Mental State Examination scores. For PVEC, the modified Müller-Gärtner method was performed. Results: Compared with non-PVE-corrected data, PVE-corrected data yielded significantly higher changes in regional and composite SUV ratio (SUVR) over time (P 5 0.0002 for composite SUVRs). Longitudinal SUVR changes in relation to Mini Mental State Examination decreases showed a significantly higher slope for the regression line in the PVE-corrected than in the non-PVE-corrected PET data (F1 5 7.1, P 5 0.008). Conclusion: These PVEC results indicate that the β-amyloid buildup curve does not plateau at an early symptomatic disease stage. A further evaluation of the impact of PVEC on the in vivo characterization of time-dependent AD pathology, including the reliable assessment and comparison of other amyloid tracers, is warranted.