血浆p-tau217及神经退行相关生物标志物预测阻塞性睡眠呼吸暂停中新发认知障碍：一项前瞻性队列研究
Plasma p-tau217 and neurodegeneration-related biomarkers predict incident cognitive impairment in obstructive sleep apnea: a prospective cohort study.
文献信息
| PMID | 42862512 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Chaofan Geng |
| 作者单位 | Henan Provincial Clinical Research Center for Cardiovascular Disease, Henan Cardiovascular Disease Center (Central China Subcenter of National Center for Cardiovascular Diseases), Henan Provincial Cardiovascular Hospital, Fuwai Central China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, 451464, Zhengzhou, China. |
| 期刊 | Sleep & breathing = Schlaf & Atmung |
| SCI 分区 | Q3 |
| IF | 2.8 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 阻塞性睡眠呼吸暂停（OSA）与认知功能下降相关，但用于识别未来风险增加的认知未受损患者的生物标志物仍然有限。我们评估了与神经轴索损伤和阿尔茨海默病相关生物学有关的血浆生物标志物在OSA中的预后价值。
方法： 在这项前瞻性队列研究中，286名经多导睡眠图确诊OSA且认知未受损的成年人接受了基线血浆NfL、GFAP、p-tau181、p-tau217、Aβ42和Aβ40测量，并随访新发认知障碍。采用Cox回归、预测性能分析和线性混合效应模型。
结果： 在中位随访4.18年期间，68名参与者（23.78%）出现新发认知障碍。在完全校正的Cox模型中，NfL每增加1个标准差与新发认知障碍风险升高46%相关（HR=1.46，95% CI 1.17-1.83，P=0.001），p-tau217每增加1个标准差与风险升高58%相关（HR=1.58，95% CI 1.25-2.00，P<0.001）。联合建模时，NfL（HR=1.34，95% CI 1.06-1.69，P=0.014）和p-tau217（HR=1.47，95% CI 1.14-1.89，P=0.003）仍与新发认知障碍相关。在纵向分析中，联合建模时较高的基线NfL和p-tau217也与MoCA评分更快的年度下降相关（NfL×时间：β=-0.10，95% CI -0.18至-0.02，P=0.014；p-tau217×时间：β=-0.16，95% CI -0.25至-0.07，P=0.001）。将这两种生物标志物加入临床模型后，C指数从0.72提高至0.81，4年时间依赖AUC提高至0.81；乐观校正后的C指数为0.79。
结论： 在认知未受损的OSA患者中，较高的血浆NfL和p-tau217水平与新发认知障碍和更快的纵向认知下降独立相关。
英文摘要
BACKGROUND: Obstructive sleep apnea (OSA) is associated with cognitive decline, but biomarkers for identifying cognitively unimpaired patients at increased future risk remain limited. We evaluated the prognostic value of plasma biomarkers associated with neuroaxonal injury and Alzheimer's disease-related biology in OSA.
METHODS: In this prospective cohort study, 286 cognitively unimpaired adults with polysomnography-confirmed OSA underwent baseline measurement of plasma NfL, GFAP, p-tau181, p-tau217, Aβ42, and Aβ40 and were followed for incident cognitive impairment. Cox regression, predictive performance analyses, and linear mixed-effects models were used.
RESULTS: During a median follow-up of 4.18 years, 68 participants (23.78%) developed incident cognitive impairment. In fully adjusted Cox models, each 1-SD increase in NfL was associated with a 46% higher risk of incident cognitive impairment (HR = 1.46, 95% CI 1.17-1.83, P = 0.001), and each 1-SD increase in p-tau217 was associated with a 58% higher risk (HR = 1.58, 95% CI 1.25-2.00, P < 0.001). When modeled jointly, both NfL (HR = 1.34, 95% CI 1.06-1.69, P = 0.014) and p-tau217 (HR = 1.47, 95% CI 1.14-1.89, P = 0.003) remained associated with incident cognitive impairment. In longitudinal analyses, higher baseline NfL and p-tau217 were also associated with faster annual declines in MoCA scores when modeled jointly (NfL × time: β = -0.10, 95% CI - 0.18 to - 0.02, P = 0.014; p-tau217 × time: β = -0.16, 95% CI - 0.25 to - 0.07, P = 0.001). Adding both biomarkers to the clinical model increased the C-index from 0.72 to 0.81 and the 4-year time-dependent AUC to 0.81; the optimism-corrected C-index was 0.79.
CONCLUSIONS: Higher plasma NfL and p-tau217 levels were independently associated with incident cognitive impairment and faster longitudinal cognitive decline in cognitively unimpaired patients with OSA.