Putaminal hypermetabolism identifies Lewy body co-pathology in Alzheimer&apos;s disease

1 2

Cited 0 times in

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

Authors: Kang, Sungwoo ; Jeon, Seun ; Kim, Yeoju ; Jeon, Su-Hee ; Choi, Minsun ; Lee, Young-Gun ; Ye, Byoung Seok

MeSH: Aged ; Aged, 80 and over ; Alzheimer Disease* / diagnostic imaging ; Alzheimer Disease* / metabolism ; Alzheimer Disease* / pathology ; Amyloid beta-Peptides / cerebrospinal fluid ; Brain* / diagnostic imaging ; Brain* / metabolism ; Brain* / pathology ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lewy Body Disease* / diagnostic imaging ; Lewy Body Disease* / metabolism ; Lewy Body Disease* / pathology ; Male ; Positron-Emission Tomography ; Putamen* / diagnostic imaging ; Putamen* / metabolism ; Putamen* / pathology ; alpha-Synuclein / cerebrospinal fluid ; tau Proteins / cerebrospinal fluid

Keywords: Alzheimer&apos ; s disease ; Lewy body disease ; metabolic imaging ; seeding amplification assays

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.