{"doi":"10.1002/alz.70920","title":"Putaminal hypermetabolism identifies Lewy body co‐pathology in Alzheimer's disease","abstract":"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, 18 F‐fluorodeoxyglucose positron emission tomography (PET), and cerebrospinal fluid tau phosphorylated at threonine 181 (pTau 181 )/Aβ 42 plus α‐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 (Aβ 42 ). Its interaction with pTau 181 /Aβ 42 influenced MOG SUVR, showing increased MOG SUVR with higher pTau 181 /Aβ 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. Highlights LB co‐pathology in AD alters regional brain metabolism. SRP analyses capture putaminal hypermetabolism for SAA positivity. SUVR analyses emphasize occipital hypometabolism for SAA positivity. Occipital metabolism correlates positively with AD severity in mixed AD‐LB. Putaminal, not occipital, metabolism predicts cognitive change over AD‐related metabolism and SAA.","journal":"Alzheimer s & Dementia","year":2025,"id":548815,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":701793,"name":"Seun Jeon","orcid":"0000-0003-2817-3352","position":1,"is_corresponding":false},{"id":1442503,"name":"Yeo Ju Kim","orcid":"0000-0002-1783-8876","position":2,"is_corresponding":false},{"id":1442982,"name":"Su‐Hee Jeon","orcid":null,"position":3,"is_corresponding":false},{"id":1442983,"name":"Min-Sun Choi","orcid":null,"position":4,"is_corresponding":false},{"id":1403279,"name":"Young‐gun Lee","orcid":"0000-0003-0460-455X","position":5,"is_corresponding":false},{"id":1403281,"name":"Byoung Seok Ye","orcid":"0000-0003-0187-8440","position":6,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":7,"is_corresponding":false},{"id":1403280,"name":"Sung Woo Kang","orcid":"0000-0001-9791-6899","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41273227","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}