Abstract INTRODUCTION Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection (“early phase”) reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid‐negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early‐phase 18 F‐florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD. METHODS One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual‐phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion. RESULTS Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism‐associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions. DISCUSSION EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual‐phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment. Highlights Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism. Parkinson's disease (PD) is a predominantly amyloid‐negative condition. Early‐phase florbetaben (eFBB) in PD was associated with cognitive performance. eFBB uptake reflects hypometabolism‐related cognitive decline in PD. eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion. eFBB distinguished dementia from normal cognition and mild cognitive impairment. Findings were independent of late‐phase Aβ burden. Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion.

Early‐phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease