Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.
Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, California, USA.
J Gerontol A Biol Sci Med Sci. 2024 Nov 1;79(11). doi: 10.1093/gerona/glae206.
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.
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.
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.
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.
慢性疼痛会导致 tau 积累和海马体萎缩，而这可能会受到炎症的影响。在老年男性中，我们研究了慢性疼痛与阿尔茨海默病（AD）相关血浆生物标志物以及海马体体积之间的关系，同时还考虑了系统性炎症的调节作用。
参与者均为没有痴呆症的男性。慢性疼痛的定义为在平均年龄为 56、62 和 68 岁的 2 次以上研究波次中出现中度至重度疼痛。在 68 岁时，我们测量了血浆中的淀粉样蛋白-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），后者是系统性炎症的标志物。一个亚组接受了结构磁共振成像（MRI）检查，以测量海马体体积（n=385）。分析调整了医疗合并症、抑郁症状和阿片类药物使用情况。
慢性疼痛与较高的 Aβ40 相关（β=0.25，p=0.009），但 hs-CRP 与 AD 相关生物标志物无关（p＞0.05）。存在显著的交互作用，即患有慢性疼痛且 hs-CRP 水平较高的老年男性的 Aβ42 水平更高（β=0.36，p=0.001），Aβ40 水平也更高（β=0.29，p=0.003）。慢性疼痛和 hs-CRP 没有交互作用来预测 Aβ42/Aβ40、t-tau 或 NfL 的水平。此外，存在显著的交互作用，表明 Aβ42 和 Aβ40 与较低的海马体体积相关，尤其是当 hs-CRP 水平升高时（hs-CRP×Aβ42：β=-0.19，p=0.002；hs-CRP×Aβ40：β=-0.21，p=0.001），而无论慢性疼痛状态如何。
慢性疼痛与较高的血浆 Aβ水平相关，尤其是当 hs-CRP 也升高时。较高的 hs-CRP 和 Aβ 水平都与海马体体积较小有关。慢性疼痛，如果伴有系统性炎症，可能会增加 AD 易损区域发生神经退行性变的风险。
