Effects of amyloid beta and dopaminergic depletion on perfusion and clinical symptoms

Abstract

Introduction: Although mixed pathologies are common in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), the effects of amyloid beta and dopaminergic depletion on brain perfusion and clinical symptoms have not been elucidated.

Methods: In 99 cognitive impairment patients due to AD and/or DLB and 32 controls, 18F-florbetaben (FBB) and dual-phase dopamine transporter (DAT) positron emission tomography (PET) were performed to measure the FBB standardized uptake value ratio (SUVR), striatal DAT uptakes, and brain perfusion.

Results: Higher FBB-SUVR and lower ventral striatal DAT uptake were intercorrelated and, respectively, associated with left entorhinal/temporo-parietal-centered hypoperfusion and vermis/hippocampal-centered hyperperfusion, whereas regional perfusion mediated clinical symptoms and cognition.

Discussion: Amyloid beta deposition and striatal dopaminergic depletion contribute to regional perfusion changes, clinical symptoms, and cognition in the spectrum of normal aging and cognitive impairment due to AD and/or LBD.

Highlights: Amyloid beta (Aβ) deposition was associated with ventral striatal dopaminergic depletion. Aβ deposition and dopaminergic depletion correlated with perfusion. Aβ deposition correlated with hypoperfusion centered in the left entorhinal cortex. Dopaminergic depletion correlated with hyperperfusion centered in the vermis. Perfusion mediated the Aβ deposition/dopaminergic depletion's effects on cognition.