Sprecher Kate E, Koscik Rebecca L, Carlsson Cynthia M, Zetterberg Henrik, Blennow Kaj, Okonkwo Ozioma C, Sager Mark A, Asthana Sanjay, Johnson Sterling C, Benca Ruth M, Bendlin Barbara B
From the Department of Medicine and Neuroscience Training Program (K.E.S.) and Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), University of California, Irvine.
Neurology. 2017 Aug 1;89(5):445-453. doi: 10.1212/WNL.0000000000004171. Epub 2017 Jul 5.
To determine the relationship between sleep quality and CSF markers of Alzheimer disease (AD) pathology in late midlife.
We investigated the relationship between sleep quality and CSF AD biomarkers in a cohort enriched for parental history of sporadic AD, the Wisconsin Registry for Alzheimer's Prevention. A total of 101 participants (mean age 62.9 ± 6.2 years, 65.3% female) completed sleep assessments and CSF collection and were cognitively normal. Sleep quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed for biomarkers of amyloid metabolism and plaques (β-amyloid 42 [Aβ42]), tau pathology (phosphorylated tau [p-tau] 181), neuronal/axonal degeneration (total tau [t-tau], neurofilament light [NFL]), neuroinflammation/astroglial activation (monocyte chemoattractant protein-1 [MCP-1], chitinase-3-like protein 1 [YKL-40]), and synaptic dysfunction/degeneration (neurogranin). To adjust for individual differences in total amyloid production, Aβ42 was expressed relative to Aβ40. To assess cumulative pathology, CSF biomarkers were expressed in ratio to Aβ42. Relationships among sleep scores and CSF biomarkers were assessed with multiple regression, controlling for age, sex, time between sleep and CSF measurements, and CSF assay batch.
Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater AD pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42. There were no significant associations between sleep and NFL or neurogranin.
Self-report of poor sleep was associated with greater AD-related pathology in cognitively healthy adults at risk for AD. Effective strategies exist for improving sleep; therefore sleep health may be a tractable target for early intervention to attenuate AD pathogenesis.
确定中年后期睡眠质量与阿尔茨海默病（AD）病理的脑脊液标志物之间的关系。
在一个因散发性AD家族史而富集的队列——威斯康星州阿尔茨海默病预防登记处，我们研究了睡眠质量与脑脊液AD生物标志物之间的关系。共有101名参与者（平均年龄62.9±6.2岁，65.3%为女性）完成了睡眠评估和脑脊液采集，且认知正常。使用医学结局研究睡眠量表测量睡眠质量。检测脑脊液中的淀粉样蛋白代谢和斑块生物标志物（β-淀粉样蛋白42 [Aβ42]）、tau病理（磷酸化tau [p-tau] 181）、神经元/轴突变性（总tau [t-tau]、神经丝轻链 [NFL]）、神经炎症/星形胶质细胞活化（单核细胞趋化蛋白-1 [MCP-1]、几丁质酶-3样蛋白1 [YKL-40]）以及突触功能障碍/变性（神经颗粒素）。为校正总淀粉样蛋白产生的个体差异，Aβ42相对于Aβ40进行表达。为评估累积病理，脑脊液生物标志物以与Aβ42的比值表示。通过多元回归评估睡眠评分与脑脊液生物标志物之间的关系，同时控制年龄、性别、睡眠与脑脊液测量之间的时间以及脑脊液检测批次。
较差的主观睡眠质量、更多的睡眠问题和日间嗜睡与更严重的AD病理相关，表现为脑脊液中较低的Aβ42/Aβ40以及较高的t-tau/Aβ42、p-tau/Aβ42、MCP-1/Aβ42和YKL-40/Aβ42。睡眠与NFL或神经颗粒素之间无显著关联。
在有AD风险的认知健康成年人中，睡眠不佳的自我报告与更严重的AD相关病理有关。存在改善睡眠的有效策略；因此，睡眠健康可能是早期干预以减轻AD发病机制的一个可处理的靶点。
