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.

中文翻译：

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老年慢性疼痛男性 C 反应蛋白升高：与血浆淀粉样蛋白水平和海马体积的相关性


背景 慢性疼痛导致 tau 蛋白积累和海马萎缩，这可能通过炎症来缓解。在老年男性中，我们检查了慢性疼痛与阿尔茨海默病 （AD） 相关血浆生物标志物和海马体积的相关性，这些关联受全身炎症调节。方法 参与者是无痴呆的男性。慢性疼痛被定义为平均年龄为 56 、 62 和 68 岁的 2+ 研究波中的中度至重度疼痛。在 68 岁时，我们测量了血浆淀粉样蛋白-β （Aβ42， n = 871）、Aβ40 （n = 887）、总 tau （t-tau， n = 841） 和神经丝轻链 （NfL， n = 915），以及血清高敏 C 反应蛋白 （hs-CRP，n = 968），全身炎症的标志物。一个亚组接受结构 MRI 测量海马体积 （n = 385）。分析根据医学发病率、抑郁症状和阿片类药物的使用进行了调整。结果 慢性疼痛与较高的 Aβ40 相关 （β = 0.25，p = .009），但 hs-CRP 与 AD 相关生物标志物无关 （ps > .05）。存在显着的相互作用，因此患有慢性疼痛和 hs-CRP 水平较高的老年男性具有更高水平的 Aβ42 （β = 0.36，p = .001） 和 Aβ40 （β = 0.29，p = .003）。慢性疼痛和 hs-CRP 不相互作用预测 Aβ42/Aβ40 、 t-tau 或 NfL 的水平。此外，存在显着的相互作用，使得 Aβ42 和 Aβ40 与较低的海马体积相关，特别是当 hs-CRP 水平升高时 （hs-CRP × Aβ42：β = -0.19，p = .002;hs-CRP × Aβ40：β = -0.21，p = .001），无论慢性疼痛状态如何。结论 慢性疼痛与较高的血浆 Aβ 相关，尤其是当 hs-CRP 也升高时。较高的 hs-CRP 和 Aβ 水平均与较小的海马体积有关。 慢性疼痛伴有全身炎症时，可能会增加 AD 易感区域神经退行性变的风险。