Abstract Body: Background and Objective: Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive dysfunction in the elderly, and frequently coexists with Alzheimer’s disease (AD) and tau pathology. Dual-phase ¹¹C-PiB PET can determine amyloid deposition and cerebral perfusion changes, and may have diagnostic value for detecting tau in CAA. This study aimed to assess the diagnostic utility of combining early- and late-phase PiB PET images in predicting tau pathology in CAA.
Methods: We prospectively enrolled patients with probable CAA for dynamic PiB and AV1451 scans. Tau positivity was defined as a standardized uptake value ratio (SUVR) > 1.26 in the meta-temporal region on static AV1451 PET. We compared early-stage (0-6 minutes after tracer injection) and late-phase (40-70 minutes) PiB PET between the tau(+) and tau(-) groups. Relationships between PiB PET parameters and tau burden were assessed using a linear regression model. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of PET parameters.
Results: No significant differences in age, sex, educational years, ApoE2 or ApoE4 carrier status were observed between the CAA/tau(+) vs. CAA/tau(-) groups. As expected, the CAA/tau(+) group had lower MMSE scores (p=0.021) and was associated with a lower hippocampal volume (p=0.036). On PET analysis, CAA/tau(+) was associated with lower early-phase temporal lobe PiB uptake than CAA/tau(-) (SUVR 0.87 [0.81-0.93] vs. 0.92 [0.89-0.98], p=0.014) and higher late-phase PiB uptake in the whole cortex and temporal and parietal lobes (all p<0.05). Early-phase temporal lobe PiB SUVR significantly correlated with tau burden (r=-0.34, p=0.038). Using Youden’s cutoff, early-phase temporal lobe SUVR had a sensitivity of 55% and specificity of 85% and late-phase temporal lobe SUVR had a sensitivity of 80% and specificity of 65% for detecting tau pathology. Together, combining early- and late-phase temporal lobe SUVRs provided a rule-out sensitivity of 90% and rule-in specificity of 100% for tau pathology in CAA.
Conclusions: AD-signature tau in CAA is associated with a higher amyloid load and reduced perfusion in the temporal lobe, suggestive of neurodegeneration. The combination of early- and late-phase amyloid PET scans may provide a reliable approach to detect concomitant tau in CAA, and could help reduce the radiation exposure and avoid additional scans or the expense of imaging for tau biomarkers.