TY - JOUR T1 - Principal components analysis based measures of PET data closely reflect neuropathological staging schemes JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.120.252783 SP - jnumed.120.252783 AU - Ganna Blazhenets AU - Lars Frings AU - Arnd Sörensen AU - Philipp T Meyer Y1 - 2020/10/01 UR - http://jnm.snmjournals.org/content/early/2020/10/23/jnumed.120.252783.abstract N2 - Voxel-based principal components analysis allows for an identification of patterns of glucose metabolism and amyloid deposition related to the conversion from mild cognitive impairment (MCI) to Alzheimer’s dementia (ADCRP). Present study aimed to validate these ADCRPs against neuropathological findings. Methods We included patients from the Alzheimer’s disease (AD) neuroimaging initiative who underwent autopsy and for whom 18F-FDG [30 AD dementia, 6 MCI, 2 cognitively normal (CN)] and amyloid-beta (Aβ) [17 AD dementia, 3 MCI, 2 CN] PET were available. Pattern expression scores (PES) of the FDG- and Aβ-ADCRP were compared to Braak tangle stage and Thal amyloid phase, respectively. Mean 18F-FDG uptake and mean 18F-AV-45 standardized uptake value ratio (SUVr) in regions of hypometabolism and elevated amyloid load typical for AD, respectively, were employed as volume of interest (VOI)-based PET measures. The diagnostic performance for identifying none-to-low vs. intermediate-to-high AD neuropathological change (ADNC) was assessed for all biomarkers. Results We observed significant associations between PES of FDG-ADCRP and Braak stage (ρ>0.48, P<0.005) and between PES of Aβ-ADCRP and Thal phase (ρ>0.66, P<0.001). PES of FDG-ADCRP, PES of Aβ-ADCRP, and their combination identified intermediate-to-high ADNC with an area under receiver operating characteristic curve (AUC) of 0.80, 0.95, and 0.98 (n = 22), respectively. Mean 18F-FDG uptake and mean 18F-AV-45 SUVr in AD-typical regions were also significantly associated with Braak stage (|ρ|>0.45, P<0.01) and Thal phase (ρ>0.55, P<0.01), respectively. VOI-based PET measures discriminated between ADNC stages with an AUC of 0.79, 0.88, and 0.90, for mean 18F-FDG uptake, mean 18F-AV-45 SUVr, and their combination (n = 22), respectively. Contemplating all subjects with available 18F-FDG PET/neuropathology information (n = 38), PES of FDG-ADCRP was a significant predictor of intermediate-to-high ADNC (AUC=0.72), while mean 18F-FDG uptake was not (AUC=0.66), albeit the difference between methods was not significant. Conclusion PES of FDG-ADCRP, a measure of neurodegeneration, shows close correspondence with the extent of tau pathology, as assessed by Braak tangle stage. PES of Aβ-ADCRP is a valid biomarker of underlying amyloid pathology, as demonstrated by its strong correlation with Thal phase. The combination of ADCRPs performed superior to FDG-ADCRP alone, albeit there was only negligible improvement compared to Aβ-ADCRP. ER -