Purpose <p>Clinical staging in individuals with Alzheimer’s disease (AD) typically relies on neuropsychological testing. Recognizing the imperative for an objective measure of clinical AD staging, regional perfusion in early-phase β-amyloid-PET may aid as a cost-efficient index for the assessment of neurodegeneration severity in patients with Alzheimer’s disease.</p> Methods <p>Regional perfusion deficits in early-phase β-amyloid-PET as well as neuropsychological testing (max. 90 days delay) were evaluated in 82 patients with biologically defined AD according to the ATN classification. In reference to the Braak staging system patients were classified into the groups stage⁰, stage^I−II+, stage^I−IV+, stage^I−VI+, and stage^atypical+ according to regional perfusion deficits in regions of interest (ROIs) published by the Alzheimer’s Disease Neuroimaging Initiative. Multiple regression analysis controlling for age, gender, and education was used to evaluate the association of regional z-scores on perfusion-phase PET with clinical scores for all patients and with annual decline of cognitive performance in 23 patients with follow-up data.</p> Results <p>Patients classified as stage⁰ and stage^I−II+ demonstrated significantly superior neuropsychological performance compared to those classified as stage^I−IV+ and stage^I−VI+. Lower cognitive performance was associated with decreased perfusion in early-phase β-amyloid-PET globally and regionally, with the most pronounced association identified in the left temporal lobe. Mean z-scores on early-phase PET in temporal and parietal regions offered a robust prediction of future annual decline in MMSE and sum scores of the CERAD-Plus (Consortium to Establish a Registry for Alzheimer’s Disease) test battery.</p> Conclusion <p>Regional and global perfusion deficits in early-phase β-amyloid-PET can serve as an objective index of neurodegeneration severity and may act as prognostic markers of future cognitive decline in AD.</p>