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 = 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 = 7.1, P = 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.