Background: Alzheimer's disease (AD) neuropathologic changes are β-amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual-phase amyloid-PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early-phase amyloid-PET scans provide a proxy for cerebral perfusion, which has shown good correlations with neural dysfunction measured through metabolic consumption, while the late frames depict amyloid distribution. Our study aims to assess the comparability between early-phase amyloid-PET scans and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-PET brain topography at the individual level, and their ability to discriminate patients.

Methods: 166 subjects evaluated at the Geneva Memory Center, ranging from cognitively unimpaired to Mild Cognitive Impairment (MCI) and dementia, underwent early-phase amyloid-PET - using either ¹⁸F-florbetapir (eFBP) (n = 94) or ¹⁸F-flutemetamol (eFMM) (n = 72) - and ¹⁸F-FDG-PET. Aβ status was assessed. Standardized uptake value ratios (SUVR) were extracted to evaluate the correlation of eFBP/eFMM and their respective ¹⁸F-FDG-PET scans. The single-subject procedure was applied to investigate hypometabolism and hypoperfusion maps and their spatial overlap by Dice coefficient. Receiver operating characteristic analyses were performed to compare the discriminative power of eFBP/eFMM, and ¹⁸F-FDG-PET SUVR in AD-related metaROI between Aβ-negative healthy controls and cases in the AD continuum.

Results: Positive correlations were found between eFBP/eFMM and ¹⁸F-FDG-PET SUVR independently of Aβ status and Aβ radiotracer (R>0.72, p<0.001). eFBP/eFMM single-subject analysis revealed clusters of significant hypoperfusion with good correspondence to hypometabolism topographies, independently of the underlying neurodegenerative patterns. Both eFBP/eFMM and ¹⁸F-FDG-PET SUVR significantly discriminated AD patients from controls in the AD-related metaROIs (AUCFBP = 0.888; AUCFMM=0.801), with ¹⁸F-FDG-PET performing slightly better, however not significantly (all p-value higher than 0.05), than others (AUCFDG=0.915 and 0.832 for subjects evaluated with ¹⁸F-FBP and ¹⁸F-FMM, respectively).

Conclusion: The distribution of perfusion was comparable to that of metabolism at the single-subject level by parametric analysis, particularly in the presence of a high neurodegeneration burden. Our findings indicate that eFBP/eFMM imaging can replace ¹⁸F-FDG-PET imaging, as they reveal typical neurodegenerative patterns, or allow to exclude the presence of neurodegeneration. The finding shows cost-saving capacities of amyloid-PET and supports the routine use of the modality for individual classification in clinical practice.