Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease

Abstract

Introduction: Cross-sectional findings using the tau tracer [¹⁸F]THK5317 (THK5317) have shown that [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single PET study can provide both functional and molecular information.

Methods: We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change.

Results: Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317.

Discussion: Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.

Keywords: Alzheimer's disease; Alzheimer's disease dementia; FDG; Hypometabolism; Longitudinal study; Mild cognitive impairment; Neurofibrillary tangles; Perfusion SUVR; Perfusion imaging; Positron emission tomography (PET); Prodromal Alzheimer's disease; R(1); THK5317; Tau imaging.