睡眠较差与皮层淀粉样蛋白负荷有关联

Dr. Kate Sprecher

明尼阿波利斯——据联合专业睡眠协会年会上报告的一项队列研究，主诉感觉较困倦及休息不充分的人群脑区淀粉样蛋白的水平升高，而这种体征通常见于阿尔茨海默病。

在本研究中，威斯康星–麦迪逊大学神经科学培训项目的在读博士、本研究的第一作者Kate Sprecher及其合作者们对98例来自WRAP（威斯康星阿尔茨海默病预防登记处）项目的无症状且认知功能正常的中老年人进行了探究，其中大多数因存在家族史而具有较高的阿尔茨海默病风险。这些受试者平均年龄为63岁、2/3为女性；总共有76%有阿尔茨海默病的家族史，34%存在与患病风险增高有关的APOE4等位基因；完成了医疗结局研究（MOS）睡眠量表和Epworth嗜睡量表（ESS）的评测。其脑部淀粉样蛋白的沉积水平是利用匹兹堡复合物B正电子发射计算机断层扫描测量的。

结果显示，主诉嗜睡、睡眠质量较差以及有睡眠问题与整个皮层内以及4个亚区内淀粉样蛋白沉积水平较高具有显著的相关性（P<0.05），而该指标是阿尔茨海默病的典型表现。研究者表示，淀粉样蛋白负荷与嗜睡之间看起来确实存在相关性，这种关联在认知功能正常但今后罹患阿尔茨海默病风险较高的成人中亦存在，这部分人在淀粉样蛋白病理学方面处于极早期；在机理方面，根据这些数据无法判断睡眠是否会促成淀粉样蛋白沉积，或是淀粉样蛋白的沉积是否会干扰睡眠。不过，从睡眠可以作为我们预防或延缓阿尔茨海默病的一个手段这个意义上说，这种情况还是很值得关注的。在疾病早期进行干预可能具有一定的可行性，在这个阶段人们实际上能够对治疗有效果，而目前常用的药物都是针对晚期病变，也就是已经发生严重的神经变性的阶段。

针对可能的混杂因素调整的分析表明，MOS睡眠量表显示的嗜睡（困倦、很难保持清醒和小睡的平均分）与左缘上回（相关系数[r]）=0.22、左侧额内眶皮层（r = 0.21）以及左侧额下眶皮层（r = 0.21）内的淀粉样蛋白负荷具有相关性。睡眠质量较差与整个皮层内以（r=0.25）及左右楔前叶（r = 0.23 和 0.25）、右缘上回（r = 0.23）、左右侧额内眶皮层（r = 0.29 和0.29）和左右侧额下眶皮层（r = 0.26和0.25）内的淀粉样蛋白负荷有关（P≤0.05）。睡眠问题指数评分也与上述部分皮层区内的负荷较大相关。ESS评分与MOS评分具有显著的相关性，但与所研究的任何脑区内淀粉样蛋白负荷均无直接的相关性。研究者表示，这可能是因为这两份调查问卷在嗜睡方面的针对性略有不同：ESS调查的是你在看电视时或开车时等多种常见的场合下入睡的几率有多大，而MOS调查的是你是在白天是否会小睡、感觉困倦，或是在夜间睡眠是否充足，因此MOS在判断睡眠量充足程度方面可能更胜一筹，即便你在白天努力保持清醒。

研究者们计划使用睡眠和阻塞性睡眠呼吸暂停的客观指标进一步探讨所观察到的相关性。并且也会对这个队列做一些纵向的随访研究，以观察睡眠改变是否会导致疾病发生实际性的进展。

Sprecher女士无相关的经济利益冲突披露。

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MINNEAPOLIS – People who report feeling more sleepy and less rested have elevated levels of amyloid in regions of the brain that are commonly involved in Alzheimer’s disease, finds a cohort study reported at the annual meeting of the Associated Professional Sleep Societies.

Researchers studied 98 asymptomatic, cognitively healthy late-middle-age adults from the WRAP (Wisconsin Registry for Alzheimer’s Prevention) program, the majority of whom were at elevated risk for the disease because of family history.

Self-reported somnolence, poorer sleep quality, and sleep problems were significantly correlated with higher levels of amyloid deposition in the cortex overall and in four subregions that are typically affected in Alzheimer’s disease (P less than .05).

"It does appear that there is an association between amyloid burden and sleepiness, and that relationship is present in adults who are cognitively healthy but who are at risk of developing Alzheimer’s disease in the future. They are fairly young in terms of amyloid pathology," commented first author Kate Sprecher, a PhD candidate in the neuroscience training program at the University of Wisconsin–Madison. She acknowledged that the findings may differ in a cohort not enriched for people at elevated risk.

"In terms of mechanisms, we can’t say from these data whether sleep is driving amyloid deposition or whether amyloid deposition is disrupting sleep," she added. "Nonetheless, it’s kind of tantalizing that sleep may be a tool that we can use to prevent or delay Alzheimer’s pathology. We may be able to intervene early in the disease, when people are actually able to respond to treatment, because typically, current drugs are targeting later disease, when a great deal of neurodegeneration has already taken place. So sleep may be something that we can target really early."

The investigators plan to further investigate the observed association using objective measures of sleep and obstructive sleep apnea (OSA), according to Ms. Sprecher. "And we’ll do some longitudinal follow-up as well in our cohort to see how sleep changes might relate to actual progression of the disease," she said.

Study participants completed the Medical Outcomes Study (MOS) Sleep Scale and the Epworth Sleepiness Scale (ESS). Amyloid deposition in the brain was measured by positron emission tomography performed with Pittsburgh Compound B.

The participants were 63 years old, on average, and two-thirds were female, reported Ms. Sprecher, who disclosed no conflicts of interest relevant to the research. Overall, 76% had a family history of Alzheimer’s disease, and 34% were positive for the APOE4 allele, which is associated with risk of this disease.

Analyses adjusted for these and other potential confounders showed a correlation (P less than or equal to .05) between somnolence on the MOS Sleep Scale – the average of scores for drowsiness, trouble staying awake, and napping – and the burden of amyloid in the left supramarginalgyrus (correlation [r] = 0.22), the left frontal medial orbital cortex (r = 0.21), and the left frontal inferior orbital cortex (r = 0.21).

Poorer quality of sleep was correlated (P less than or equal to .05) with amyloid burden in the cortex overall (r = 0.25) as well as in the left and right precuneus (r = 0.23 and 0.25), the right supramarginalgyrus (r = 0.23), the left and right frontal medial orbital cortex (r = 0.29 and 0.29), and the left and right frontal inferior orbital cortex (r = 0.26 and 0.25).

Scores on the Sleep Problem Index were also associated with greater burden in some of these cortical areas.

Although ESS scores were significantly correlated with MOS scores, they were not directly correlated with amyloid burden in any of the regions studied.

"This could be because the two questionnaires probe slightly different aspects of sleepiness," Ms. Sprecher proposed in an interview. "The ESS asks how likely you are to fall asleep in several common situations such as while watching TV or driving a car. The MOS asks whether you take naps, feel sleepy during the day, or feel that you get enough sleep at night. Therefore, the MOS may be better at probing how adequate your sleep is, even if you are managing to stay awake during the day."

Ms. Sprecher disclosed no relevant conflicts of interest.