MELATONIN AND COGNITION IN MILD COGNITIVE IMPAIRMENT (MCI)

褪黑激素与轻度认知障碍 (MCI) 中的认知

• 批准号: 7717885
• 负责人: Ruth M O'Hara
• 金额: $ 0.07万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717885
• 关键词: Age; Age-associated memory impairment; Aging-Related Process; Alzheimer' s Disease; Amyloid beta-Protein; Appearance; Attention; Circadian Rhythms; Clinical Trials; Cognition; Cognitive; Collection; Communities; Computer Retrieval of Information on Scientific Projects Database; Condition; Data; Dementia; Deposition; Development; Elderly; End Point; Exhibits; Experimental Designs; Funding; Goals; Grant; Home environment; Hour; Human; Hydrocortisone; Hypothalamic structure; Impaired cognition; Institution; Investigation; Light; Longitudinal Studies; Measurement; Measures; Mediating; Melatonin; Memory; Numbers; Output; Parents; Patient Self-Report; Pattern; Performance; Personal Satisfaction; Phase; Pineal gland; Production; Questionnaires; Range; Rate; Recruitment Activity; Reporting; Research; Research Personnel; Resources; Rest; Role; Saliva; Signal Transduction; Sleep; Sleep Wake Cycle; Source; Stress; System; Testing; Time; United States National Institutes of Health; Urine; Variant; Visit; actigraphy; age related; circadian pacemaker; day; follow-up; mild neurocognitive impairment; processing speed; suprachiasmatic nucleus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: We hypothesize that, during the aging process, a decrease in melatonin secretion and the appearance of a circadian rhythm disturbance will be associated with a more rapid rate of cognitive decline. Goals: Age-related cognitive decline is well documented, leading to cognitive impairment ranging from age-associated memory impairment (AAMI) to dementia. Recent data suggest that melatonin may protect against cognitive decline and the deposition of beta-amyloid that is associated with the development of Alzheimer's Disease (AD). However, most studies to date have focused on the use of exogenous melatonin and the role of endogenous melatonin in contributing to cognitive decline and the onset of dementia is unclear. Melatonin is secreted by the pineal gland and its production has a distinct circadian rhythm, which is generated within the hypothalamic suprachiasmatic nuclei (SCN), the master circadian clock. In humans melatonin exhibits a clear day/night variation with a rise at the beginning of the dark period, its peak during the dark phase, and a decrease with the morning light. The melatonin rhythm is synchronized to 24 hour by ocular light, which is conveyed via the retino-hypothalamic tract to the SCN. One significant aspect of the aging process is deconsolidation of the circadian system. As a result, clock-output signals, such as melatonin, exhibit age-related changes in both amplitude and timing. An extensive number of reports describe changes in melatonin rhythm related to age with most of them suggesting a decline in the magnitude of the nocturnal melatonin peak with age. Experimental Design: This study builds upon an ongoing NIA-funded longitudinal study on stress, cortisol and cognitive decline in older adults (PI Dr. O'Hara). From this ongoing investigation, we will recruit 40 community-dwelling older adults over 70 yrs of age, who have mild cognitive impairment (MCI). As a part of the parent study, at baseline and annual follow-ups all subjects undergo an extensive cognitive battery including measures of memory, attention, and processing speed since these cognitive domains display particularly robust age-related declines. Self-reported sleep questionnaires as well as objective sleep-wake cycle measures via actigraphy will be assessed over the course of 7 days following the annual cognitive assessment. Melatonin levels will be assessed in two different ways: in urine over the course of 24-hr at the subjects' homes, i.e. under naturalistic conditions; and in saliva and urine over the course of 24-hr under controlled conditions at the Stanford GCRC. All measurements will be repeated at one annual follow-up during the two-yr study period, at the same timepoints used for cortisol collection as part of the parent study. 1) Assessment of the Circadian Sleep-Wake Cycle: The circadian sleep-wake cycle will be assessed using actigraphy and self-report questionnaires on the quality and timing of sleep, as well as on chronotype. These measures will be performed at baseline and one annual follow-up visit. 2) The stability of the circadian patterning of rest and activity over several days (interdaily stability, IS), and 3) its level of fragmentation (intradaily variability, IV). Endpoints: This is an observational, longitudinal study in community-dwelling older adults with MCI, not a treatment study or a clinical trial. The study will proceed until all subjects have completed the testing. We believe that measurements taken during this study will allow us to determine: 1) if changes in levels of endogenous melatonin, i.e. the circadian amplitude, are correlated with changes in cognitive performance, over a one-yr period; and 2) if the impact of changes in endogenous melatonin on cognitive performance is mediated by changes in the sleep-wake cycle, over a one-year period.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 假设： 我们假设，在衰老过程中，褪黑素分泌的减少和昼夜节律紊乱的出现将与认知下降的更快速度有关。 目标： 与年龄相关的认知下降是有充分证据的，导致认知障碍，从年龄相关的记忆障碍(AAMI)到痴呆症。最近的数据表明，褪黑素可以防止认知能力下降和与阿尔茨海默病(AD)发展相关的β-淀粉样蛋白的沉积。然而，到目前为止，大多数研究都集中在外源性褪黑素的使用以及内源性褪黑素在认知能力下降中的作用，而痴呆的发病尚不清楚。 褪黑素是由松果体分泌的，它的产生有明显的昼夜节律，这种节律是在下丘脑的视交叉上核(SCN)产生的，SCN是生物钟的主时钟。在人体内，褪黑激素表现出明显的昼夜变化，在黑暗时期开始时上升，在黑暗阶段达到峰值，并随着早晨的光线而下降。褪黑激素的节律由眼光同步到24小时，通过视网膜-下丘脑束传送到SCN。 衰老过程的一个重要方面是昼夜节律系统的解固。因此，时钟输出信号，如褪黑素，在幅度和时序上都表现出与年龄相关的变化。大量的报告描述了褪黑素节律与年龄有关的变化，其中大多数都表明夜间褪黑激素峰值的幅度随着年龄的增加而下降。 实验设计： 这项研究建立在NIA资助的一项关于老年人压力、皮质醇和认知能力下降的纵向研究的基础上(皮奥哈拉博士)。从这项正在进行的调查中，我们将招募40名70岁以上社区居住的老年人，他们有轻度认知障碍(MCI)。作为父母研究的一部分，在基线和年度随访中，所有受试者都会经历广泛的认知电池，包括记忆、注意力和处理速度的测量，因为这些认知领域显示出与年龄相关的特别明显的下降。在年度认知评估之后的7天内，将评估自我报告的睡眠问卷以及通过活动记录仪进行的客观睡眠-觉醒周期测量。褪黑素水平将通过两种不同的方法进行评估：在受试者家中的24小时尿液中，即在自然条件下；在斯坦福GCRC受控条件下的24小时内唾液和尿液中。所有测量将在两年研究期间的一次年度随访中重复进行，时间与作为父研究一部分的皮质醇收集所用的时间点相同。 1)昼夜睡眠-觉醒周期的评估：将使用关于睡眠质量和时间以及时型的活动记录仪和自我报告问卷来评估昼夜睡眠-觉醒周期。这些措施将在基线上执行，并每年进行一次后续访问。 2)几天内休息和活动的昼夜节律模式的稳定性(日间稳定性，IS)，以及3)其碎片化程度(日内变异性，IV)。 终端： 这是一项针对患有MCI的社区老年人的观察性纵向研究，而不是治疗研究或临床试验。这项研究将继续进行，直到所有受试者完成测试。我们相信，在这项研究中进行的测量将使我们能够确定：1)内源性褪黑素水平的变化，即昼夜节律幅度，是否与一年期间认知表现的变化相关；以及2)内源性褪黑素对认知表现的影响是否通过一年期间睡眠-觉醒周期的变化来调节。