{"doi":"10.1007/s11357-025-01567-z","title":"Plasma homocysteine level and trajectories in association with longitudinal increase in plasma neurofilament light among urban adults","abstract":"Abstract We tested whether homocysteine (Hcy) was linked to longitudinal change in plasma neurofilament light chain (NfL) overall and differentially across sex and race in a sample of middle-aged urban adults. We used data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study [ n = 690, Age at visit 1 (v 1 :2004–2009): 30-66y, 42.1% male, 55.4% African American] to evaluate relationships between NfL levels and both visit 1 Hcy (Hcy v1 ) and time-dependent Hcy concentrations (Hcy td ). Specifically, we examined the relationship between these measures and visit 1 NfL (NfL v1 ) as well as annualized change in NfL (δNfL) over the study period of ~ 8y [2004–2009 (v 1 ), 2009–2013 (v 2 ) and/or 2013–2017 (v 3 )] using mixed effects linear regression models. Hcy v1 was positively associated with NfL v1 , but not with δNfL. However, when Hcy td was considered along with time-dependent covariates on multiple-imputed data, both NfL v1 and δNfL were associated with Hcy td , with some significant sex difference in the longitudinal association, whereby this relationship was stronger among males. The Hcy exposure obtained from group-based trajectory models, indicated that individuals belonging to the \"High increasing\" group were consistently associated with both higher NfL v1 and faster increase in NfL (overall, fully adjusted, High vs . Low: γ 0gbtm = + 0.226 ± 0.058, P < 0.001; γ 1gbtm = + 0.022 ± 0.007, P < 0.010). Dynamic Hcy exposures (Hcy td and Hcy gbtm ) were associated with faster rate of increase in NfL over time, reflecting potentially faster rate of axonal degeneration. Further studies are needed in comparable populations to replicate our findings.","journal":"GeroScience","year":2025,"id":543179,"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":0.7082,"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":345471,"name":"Nicole Noren Hooten","orcid":"0000-0002-1683-3838","position":1,"is_corresponding":false},{"id":902645,"name":"Michael F. Georgescu","orcid":"0000-0002-2619-2675","position":2,"is_corresponding":false},{"id":247988,"name":"Hind A. Beydoun","orcid":"0000-0002-9704-328X","position":3,"is_corresponding":false},{"id":422676,"name":"Marie Fanelli Kuczmarski","orcid":"0000-0001-6903-3386","position":4,"is_corresponding":false},{"id":48759,"name":"Jordan Weiss","orcid":"0000-0002-0392-3535","position":5,"is_corresponding":false},{"id":108724,"name":"Michele K. Evans","orcid":"0000-0002-8546-2831","position":6,"is_corresponding":false},{"id":22038,"name":"Alan B. Zonderman","orcid":"0000-0002-6523-4778","position":7,"is_corresponding":false},{"id":247987,"name":"May A. Beydoun","orcid":"0000-0002-1050-4523","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:53:04.088079Z","pmid":"39969743","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":[]}