Closer correlations between florbetapir PET measurements of amyloid plaque burden using a cerebral white matter reference region and Alzheimer’s disease‐related hypometabolism

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is associated with amyloid‐β (Aß) plaque deposition and a characteristic pattern of cerebral glucose hypometabolism. While a cerebellar reference region is commonly used to characterize cerebral Aβ burden, we demonstrated improvements in the ability of florbetapir PET to track Aβ burden using a cerebral white matter reference region (Chen, et al., 2015). Here, we compare associations between cerebral‐to‐reference region florbetapir PET standard value uptake ratios (SUVRs) using cerebral white matter versus cerebellar reference regions to two FDG PET indices of AD‐related cerebral hypometabolism: “hypometabolic convergence index” (HCI) and “statistical region‐of‐interest” (sROI) (Chen et al, 2010; 2011).MethodWe analyzed 1722 florbetapir and FDG PET scan pairs from the AD Neuroimaging Initiative, including 267 with probable AD dementia (pAD), 592 with MCI and 379 cognitively unimpaired (CU). Florbetapir SUVRs were computed using measures from the cerebral regions‐of‐interest with the cerebral white matter or cerebellar reference regions. HCI and sROI were generated from the FDG PET images. Pearson’s correlations and the Steiger statistical test were used to characterize and compare the extent to which florbetapir SUVRs using cerebellar versus cerebral white matter reference regions were associated with HCI or sROI in the overall group, the pAD, MCI and CU sub‐groups.ResultCorrelations between florbetapir SUVRs using the white matter reference region and HCI (0.59, 0.41, 0.45, and 0.40 in the overall, pAD, MCI and CU groups) were significantly stronger than those using the cerebellar reference region (0.40, 0.23, 0.26, and 0.20, P=1.1e‐16, 3.6e‐06, 1.3e‐09, and 1.0e‐11, respectively). Similarly, inverse correlations between florbetapir SUVR measurements using the white matter reference region and sROI measurements (‐0.51, ‐0.32, ‐0.38, and ‐0.28 in the overall, pAD, MCI and CU groups) were significantly stronger than those using the cerebellar reference region (‐0.34, ‐0.09, ‐0.24, and ‐0.13, P=2.0e‐15, 3.2e‐07, 1.7e‐0, and 4.0e‐07, respectively).ConclusionFlorbetapir PET Aβ plaque measures are more closely associated with the AD‐related pattern of cerebral hypometabolism when SUVRs are generated using a white matter rather than cerebellar reference regions. Additional research is needed to examine if our results are generalizable for other Aβ PET tracers and longitudinal change measures.