Putaminal hypermetabolism identifies Lewy body co-pathology in Alzheimer's disease

Abstract

INTRODUCTION: The clinical implications of brain hypermetabolism remain unexplored in Lewy body disease (LBD) co-pathology in Alzheimer's disease (AD). METHODS: We investigated cognition, F-18-fluorodeoxyglucose positron emission tomography (PET), and cerebrospinal fluid tau phosphorylated at threonine 181 (pTau(181))/A beta(42) plus alpha-synuclein seeding amplification assays (SAA) in controls, 217 SAA-negative AD (AD(SAA-)), and 124 SAA-positive AD (AD(SAA+)). Brain metabolism was assessed using subject residual profile (SRP) and standardized uptake value ratio (SUVR). RESULTS: Compared to AD(SAA-), AD(SAA+) showed putamen SRP hypermetabolism and middle occipital gyrus (MOG) SUVR hypometabolism. SAA positivity correlated with putamen SRP hypermetabolism independently of pTau(181)/amyloid beta 42 (A beta(42)). Its interaction with pTau(181)/A beta(42) influenced MOG SUVR, showing increased MOG SUVR with higher pTau(181)/A beta(42) in AD(SAA+). Putamen SRP hypermetabolism predicted faster cognitive decline and greater variability in both groups. MOG SUVR hypometabolism correlated with them only in AD(SAA-). Adding putamen SRP hypermetabolism to models, including SAA positivity and AD signature hypometabolism, improved the prediction of cognitive decline/variability, whereas MOG SUVR did not. DISCUSSION: Putaminal hypermetabolism may serve as a robust metabolic marker of LBD co-pathology in AD.