Elevated cerebral blood flow proxy with increased beta-amyloid burden in Alzheimer’s disease preclinical phase evaluated by dual-phase 18F-florbetaben positron emission tomography

This study investigated the earliest change of cerebral blood flow (CBF) and its relationship with β-amyloid (Aβ) burden in preclinical Alzheimer's disease (AD) employing dual-phase ¹⁸F-florbetaben (FBB) PET. Seventy-one cognitively normal (NC) individuals were classified as Aβ negative (Aβ^-NC) or positive (Aβ⁺NC) based on two different cutoff values: an SUVR of > 1.08 and a Centiloid scale of > 20. The PET scans were acquired in two phases: an early phase (0-10 min, eFBB) and a delayed phase (90-110 min, dFBB), which were averaged to generate single-frame images for each phase. Furthermore, an R1 parametric map was generated from the early phase data using a simplified reference tissue model. We conducted regional and voxel-based analyses to compare the eFBB, dFBB, and R1 images between the Aβ positive and negative groups. In addition, the correlations between the CBF proxy R1 and the dFBB SUVR were analyzed. The Aβ⁺NC group showed significantly higher dFBB SUVR in both the global cerebral cortex and target regions compared to the Aβ^-NC group, while no significant differences were observed in eFBB SUVR between the two groups. Furthermore, the Aβ⁺NC group exhibited significantly higher R1 values, a proxy for cerebral perfusion, in both the global cerebral cortex and target regions compared to the Aβ^-NC group. Significant positive correlations were observed between R1 and dFBB SUVR in both the global cerebral cortex and target regions, which remained significant after controlling for demographics and cognitive profiles, except for the medial temporal and occipital cortices. The findings reveal increased CBF in preclinical AD and a positive correlation between CBF and amyloid pathology. The positive correlation between R1 and amyloid burden may indicate a compensatory mechanism in the preclinical stage of Alzheimer's disease, but to elucidate this hypothesis, further longitudinal observational studies are necessary.