Weissová Kamila, Bartoš Aleš, Sládek Martin, Nováková Marta, Sumová Alena
Department of Neurohumoral Regulations, Institute of Physiology, the Czech Academy of Sciences, Prague, Czech Republic.
Charles University in Prague, Third Faculty of Medicine, Department of Neurology, Prague, Czech Republic.
PLoS One. 2016 Jan 4;11(1):e0146200. doi: 10.1371/journal.pone.0146200. eCollection 2016.
Alzheimer's disease (AD) is a neurodegenerative disease often accompanied with disruption of sleep-wake cycle. The sleep-wake cycle is controlled by mechanisms involving internal timekeeping (circadian) regulation. The aim of our present pilot study was to assess the circadian system in patients with mild form of AD in their home environment. In the study, 13 elderly AD patients and 13 age-matched healthy control subjects (the patient's spouses) were enrolled. Sleep was recorded for 21 days by sleep diaries in all participants and checked by actigraphy in 4 of the AD patient/control couples. The samples of saliva and buccal mucosa were collected every 4 hours during the same 24 h-interval to detect melatonin and clock gene (PER1 and BMAL1) mRNA levels, respectively. The AD patients exhibited significantly longer inactivity interval during the 24 h and significantly higher number of daytime naps than controls. Daily profiles of melatonin levels exhibited circadian rhythms in both groups. Compared with controls, decline in amplitude of the melatonin rhythm in AD patients was not significant, however, in AD patients more melatonin profiles were dampened or had atypical waveforms. The clock genes PER1 and BMAL1 were expressed rhythmically with high amplitudes in both groups and no significant differences in phases between both groups were detected. Our results suggest moderate differences in functional state of the circadian system in patients with mild form of AD compared with healthy controls which are present in conditions of their home dwelling.
阿尔茨海默病(AD)是一种神经退行性疾病,常伴有睡眠-觉醒周期紊乱。睡眠-觉醒周期受包括内部计时(昼夜节律)调节在内的机制控制。我们目前这项初步研究的目的是评估轻度AD患者在家中环境下的昼夜节律系统。在该研究中,招募了13名老年AD患者和13名年龄匹配的健康对照者(患者的配偶)。所有参与者通过睡眠日记记录21天的睡眠情况,并对4对AD患者/对照者采用活动记录仪进行检查。在相同的24小时时间段内,每4小时采集一次唾液和颊黏膜样本,分别检测褪黑素和时钟基因(PER1和BMAL1)的mRNA水平。AD患者在24小时内的静息间隔明显更长,白天小睡次数明显多于对照组。两组褪黑素水平的每日变化曲线均呈现昼夜节律。与对照组相比,AD患者褪黑素节律的振幅下降不显著,然而,AD患者中更多的褪黑素变化曲线变平缓或呈现非典型波形。时钟基因PER1和BMAL1在两组中均有高振幅的节律性表达,且两组之间在相位上未检测到显著差异。我们的结果表明,与健康对照者相比,轻度AD患者的昼夜节律系统功能状态存在适度差异,这些差异存在于他们在家居住的条件下。