{"doi":"10.1093/gerona/glae206","title":"Elevated C-Reactive Protein in Older Men With Chronic Pain: Association With Plasma Amyloid Levels and Hippocampal Volume","abstract":"BACKGROUND: Chronic pain leads to tau accumulation and hippocampal atrophy, which may be moderated through inflammation. In older men, we examined associations of chronic pain with Alzheimer's disease (AD)-related plasma biomarkers and hippocampal volume as moderated by systemic inflammation. METHODS: Participants were men without dementia. Chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, we measured plasma amyloid-beta (Aβ42, n = 871), Aβ40 (n = 887), total tau (t-tau, n = 841), and neurofilament light chain (NfL, n = 915), and serum high-sensitivity C-reactive protein (hs-CRP, n = 968), a marker of systemic inflammation. A subgroup underwent structural MRI to measure hippocampal volume (n = 385). Analyses adjusted for medical morbidities, depressive symptoms, and opioid use. RESULTS: Chronic pain was related to higher Aβ40 (β = 0.25, p = .009), but hs-CRP was unrelated to AD-related biomarkers (ps > .05). There was a significant interaction such that older men with both chronic pain and higher levels of hs-CRP had higher levels of Aβ42 (β = 0.36, p = .001) and Aβ40 (β = 0.29, p = .003). Chronic pain and hs-CRP did not interact to predict levels of Aβ42/Aβ40, t-tau, or NfL. Furthermore, there were significant interactions such that Aβ42 and Aβ40 were associated with lower hippocampal volume, particularly when levels of hs-CRP were elevated (hs-CRP × Aβ42: β = -0.19, p = .002; hs-CRP × Aβ40: β = -0.21, p = .001), regardless of chronic pain status. CONCLUSIONS: Chronic pain was associated with higher plasma Aβ, especially when hs-CRP was also elevated. Higher hs-CRP and Aβ levels were both related to smaller hippocampal volumes. Chronic pain, when accompanied by systemic inflammation, may elevate the risk of neurodegeneration in AD-vulnerable regions.","journal":"The Journals of Gerontology Series A","year":2024,"id":445342,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":264626,"name":"Carol E. Franz","orcid":"0000-0002-8987-1755","position":1,"is_corresponding":false},{"id":316753,"name":"Kelsey R. Thomas","orcid":"0000-0003-4277-8876","position":2,"is_corresponding":false},{"id":750515,"name":"Mc Kenna E. Williams","orcid":null,"position":3,"is_corresponding":false},{"id":109306,"name":"Lisa T. Eyler","orcid":"0000-0002-7783-8798","position":4,"is_corresponding":false},{"id":805751,"name":"Imanuel Lerman","orcid":"0000-0002-6564-7222","position":5,"is_corresponding":false},{"id":585575,"name":"Christine Fennema‐Notestine","orcid":"0000-0002-6527-6361","position":6,"is_corresponding":false},{"id":585574,"name":"Olivia K. Puckett","orcid":"0000-0002-5073-2563","position":7,"is_corresponding":false},{"id":823052,"name":"Stephen M Dorros","orcid":null,"position":8,"is_corresponding":false},{"id":279709,"name":"Matthew S. Panizzon","orcid":null,"position":9,"is_corresponding":false},{"id":586308,"name":"Rahul C. Pearce","orcid":null,"position":10,"is_corresponding":false},{"id":281334,"name":"Donald J. Hagler","orcid":"0000-0002-0331-3294","position":11,"is_corresponding":false},{"id":264628,"name":"Michael J. Lyons","orcid":"0000-0001-6516-9219","position":12,"is_corresponding":false},{"id":486270,"name":"Jeremy A. Elman","orcid":"0000-0002-5840-1769","position":13,"is_corresponding":false},{"id":264627,"name":"William S. Kremen","orcid":"0000-0002-8629-5609","position":14,"is_corresponding":false},{"id":463718,"name":"Tyler Bell","orcid":"0000-0001-5702-5995","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:01:42.089235Z","pmid":"39169831","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":[]}