{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T15:58:04Z","timestamp":1788191884999,"version":"build-2803163510"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Aging at the National Institutes of Health","award":["AG050595"],"award-info":[{"award-number":["AG050595"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["AG022381"],"award-info":[{"award-number":["AG022381"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["AG076838"],"award-info":[{"award-number":["AG076838"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["AG064955"],"award-info":[{"award-number":["AG064955"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["P01 AG055367"],"award-info":[{"award-number":["P01 AG055367"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["K01 AG063805"],"award-info":[{"award-number":["K01 AG063805"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["K01 AG081559"],"award-info":[{"award-number":["K01 AG081559"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["RF1 AG082726"],"award-info":[{"award-number":["RF1 AG082726"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["R03 AG070435"],"award-info":[{"award-number":["R03 AG070435"]}]},{"name":"VA Department of Veterans Affairs","award":["IK2CX001865"],"award-info":[{"award-number":["IK2CX001865"]}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","award":["AARG-22-723000"],"award-info":[{"award-number":["AARG-22-723000"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2019s disease (AD)-related plasma biomarkers and hippocampal volume as moderated by systemic inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 (A\u03b242, n\u2005=\u2005871), A\u03b240 (n\u2005=\u2005887), total tau (t-tau, n\u2005=\u2005841), and neurofilament light chain (NfL, n\u2005=\u2005915), and serum high-sensitivity C-reactive protein (hs-CRP, n\u2005=\u2005968), a marker of systemic inflammation. A subgroup underwent structural MRI to measure hippocampal volume (n\u2005=\u2005385). Analyses adjusted for medical morbidities, depressive symptoms, and opioid use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chronic pain was related to higher A\u03b240 (\u03b2 = 0.25, p\u2005=\u2005.009), but hs-CRP was unrelated to AD-related biomarkers (ps\u2005&amp;gt;\u2005.05). There was a significant interaction such that older men with both chronic pain and higher levels of hs-CRP had higher levels of A\u03b242 (\u03b2 = 0.36, p\u2005=\u2005.001) and A\u03b240 (\u03b2 = 0.29, p\u2005=\u2005.003). Chronic pain and hs-CRP did not interact to predict levels of A\u03b242\/A\u03b240, t-tau, or NfL. Furthermore, there were significant interactions such that A\u03b242 and A\u03b240 were associated with lower hippocampal volume, particularly when levels of hs-CRP were elevated (hs-CRP \u00d7 A\u03b242: \u03b2 = \u22120.19, p\u2005=\u2005.002; hs-CRP \u00d7 A\u03b240: \u03b2 = \u22120.21, p\u2005=\u2005.001), regardless of chronic pain status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Chronic pain was associated with higher plasma A\u03b2, especially when hs-CRP was also elevated. Higher hs-CRP and A\u03b2 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/gerona\/glae206","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T17:57:26Z","timestamp":1723744646000},"source":"Crossref","is-referenced-by-count":11,"title":["Elevated C-Reactive Protein in Older Men With Chronic Pain: Association With Plasma Amyloid Levels and Hippocampal Volume"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5702-5995","authenticated-orcid":false,"given":"Tyler R","family":"Bell","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]},{"name":"Center for Behavior Genetics of Aging, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-1755","authenticated-orcid":false,"given":"Carol E","family":"Franz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]},{"name":"Center for Behavior Genetics of Aging, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4277-8876","authenticated-orcid":false,"given":"Kelsey R","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]},{"name":"Research Service, VA San Diego Healthcare System , San Diego, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McKenna E","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa T","family":"Eyler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imanuel","family":"Lerman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Fennema-Notestine","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]},{"name":"Department of Radiology, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia K","family":"Puckett","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]},{"name":"Center for Behavior Genetics of Aging, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M","family":"Dorros","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S","family":"Panizzon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]},{"name":"Center for Behavior Genetics of Aging, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul C","family":"Pearce","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego , La Jolla, California ,","place":["USA"]},{"name":"Center for Behavior Genetics of Aging, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Donald J","family":"Hagler","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of California, San Diego , La Jolla, California ,","place":["USA"]},{"name":"Department of Radiology, University of California, San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Lyons","sequence":"additional","affiliation":[{"name":"Department of Psychology, Boston University , Boston, Massachusetts 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