PiB correlates of cerebral FDG metabolism in autosomal dominant AD

Objectives Autosomal dominant Alzheimer’s disease (ADAD) is a rare form of AD with early onset. This population has been studied longitudinally in the context of the DIAN consortium. This consortium has characterized the imaging pattern of the disease evolution using amyloid deposition (PiB-PET), PET glucose metabolism (FDG-PET) and volumetric MRI. For practical and safety aspects, it would be desirable to identify surrogate imaging biomarkers in order to reduce the participant burden of multiple imaging sessions and radiation dose. It has been proposed that early frames of PiB, corresponding to perfusion of the tracer, are well correlated with glucose metabolism (1). In order to evaluate the use of early PiB PET perfusion images as a surrogate for FDG in ADAD, we compared PiB with FDG-PET measures.

Methods Thirty participants underwent PIB, FDG PET and MRI. The PET images were co-registered with the MR images. Standard uptake values (SUVs) from early PiB frames (at 1min; for 7min) and late PiB frames (at 40min; for 30min) were compared with late FDG frames (at 40min; for 30min). SUVs were defined with cerebellar cortex as reference. Mean cortical binding potential with a threshold of 0.18 was used to define PiB positivity. Correlations were performed at the level of the whole brain. PiB (negative; positive), mutation (non-carriers; carriers), and cognitive (CDR0; CDR0.5; CDR1) status were considered.

Results The correlations are high between early PiB frames and late FDG frames (mean r=0.80±0.01) and are low between late PiB and late FDG frames (mean r=0.09±0.06). The high correlations are not affected by PiB, mutation or cognitive status. Low correlations of late frames are significantly different between PiB (p<0.05), mutation (p<0.005), and cognitive (p<0.005) status.

Conclusions These results suggest that combined measures of early and late frames of PiB could be sufficient to evaluate both perfusion and amyloid deposition in ADAD.

Research Support U01AG032438