Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer's Disease.
Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer's Disease.
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DOI：
10.3389/fnagi.2017.00093
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发表时间：
2017
影响因子：
4.8
通讯作者：
Guinjoan SM
中科院分区：
文献类型：
--
作者：
Abulafia C;Duarte-Abritta B;Villarreal MF;Ladrón-de-Guevara MS;García C;Sequeyra G;Sevlever G;Fiorentini L;Bär KJ;Gustafson DR;Vigo DE;Guinjoan SM
迟发性阿尔茨海默病(LOAD)的早期神经病理改变涉及脑干和边缘结构，这些结构调节神经营养功能，包括睡眠-觉醒节律。事实上，睡眠模式是一种新兴的生物标志物，也是负荷的潜在病理生理机制。我们假设，LOAD(O-LOAD)患者的认知无症状的中年后代在客观认知改变开始之前会表现出一系列昼夜节律异常。我们对31名LOAD患者(O-LOAD)和19名没有阿尔茨海默病家族史的健康人(对照组，CS)进行了基本的认知功能测试，并对睡眠-觉醒节律、心脏自主神经功能和体温进行了活动测量。出乎意料的是，与CS相比，O-Load在言语情景记忆(雷伊听觉言语学习测验延迟回忆10.6±0.4vs.8.6±0.6，t=4.97，df=49，p<；0.01)和语言(韦氏词汇量51.4±1.3vs.44.3±1.5，t=2.49，df=49，p<；0.001)方面显示出轻微但显著的缺陷，即使所有参与者的结果都在临床正常范围内。氧负荷的体温节律呈相位延迟(2.56±0.47h比3.8±0.26h，t=2.48，df=40，p=0.031)。O-Load的认知表现与一系列心脏自主神经睡眠-觉醒变量有关；具体地说，夜间交感神经活动较强的指标与较差的认知有关。目前的结果表明，睡眠模式作为负荷的潜在神经生物学特征值得进一步研究，即使是在中年、高危人群中也是如此。
Early neuropathological changes characteristic of late-onset Alzheimer’s disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep–wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer’s disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep–wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 ± 0.4 vs. 8.6 ± 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler’s vocabulary 51.4 ± 1.3 vs. 44.3 ± 1.5, t = 2.49, df = 49, p < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 ± 0.47 h vs. 3.8 ± 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep–wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.