ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2024
Elevated C-Reactive Protein in Older Men With Chronic Pain: Association With Plasma Amyloid Levels and Hippocampal Volume.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Prospective study on physical activity and Alzheimer's disease-related biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- CRP Is a Key Indicator of Rheumatoid Arthritis-Associated Vascular Injury and Neurodegeneration.International journal of molecular sciences · 2026Review
- Potential correlation between chronic pain and amyloid beta in Alzheimer's disease.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Monomeric [CRP] and CRP-Controlled Stress and Pain Hypersensitization as Novel Predictors of Cognitive Disturbance and AD in Chronic Inflammatory Disease.International journal of molecular sciences · 2025Review
- Association between preoperative blood-brain barrier permeability and postoperative delirium in older patients undergoing cardiac surgery: a pilot study.Aging clinical and experimental research · 2025Observational
- Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases.Current issues in molecular biology · 2025Review
- Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.Journal of biochemical and molecular toxicology · 2025Review
- Causal Association of Alzheimer's Disease with Low Back Pain: A Mendelian Randomization Study.Journal of pain research · 2025Article
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Authors and funding
15 authors.
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Abstract
backgroundChronic 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.
methodsParticipants 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.
resultsChronic 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.
conclusionsChronic 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.
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