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 18 F-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 (F 1 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.

Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays

“…Although earlier work indicated that Aβ pathology may reach a plateau during the dementia phase of AD, 47 recent findings suggest that this may not be the case. 48 As such, we were not able to examine the effect of higher Aβ-PET SUVR values on p-tau isoforms but were nonetheless able to identify the significantly higher dynamic range of p-tau217 Lilly using the available Aβ-PET from participants with out dementia. Although we acknowledge the lack of Aβ-PET across all groups as a limitation, very high concordance is seen between CSF Aβ42/Aβ40 and Aβ-PET.…”

Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology

“…In this case, PVC substantially improved our flortaucipir-to-NFT correlation, and our laterality scores were more in line with the postmortem counts than without PVC. Previous reports have shown PVC improves detection and longitudinal measurement in real and simulated PET data [ 4 , 55 , 66 ], with one study finding it increased variability for amyloid PET [ 60 ].…”

Longitudinal amyloid and tau PET imaging in Alzheimer's disease: A systematic review of methodologies and factors affecting quantification

“…125 Such differences were also observed by Rullman et al, who found a significant effect of PVC on Aβ-positive subjects, but none on Aβ-negative subjects, 126 and a significant positive effect of PVC in MCI and AD groups in another study. 127 These results…”

“…106,107 Most studies found that PVC increases the change in tracer uptake but also increases the measurement uncertainty. 5,[124][125][126][127] Increases in rates of change due to PVC may affect subjects with higher amyloid more, as suggested by Brendel et al who found a decrease in percentage change over time in healthy controls and MCI subjects, versus an increase in AD subjects. 125 Such differences were also observed by Rullman et al, who found a significant effect of PVC on Aβ-positive subjects, but none on Aβ-negative subjects, 126 and a significant positive effect of PVC in MCI and AD groups in another study.…”