MCI, APOE and Sleep Apnea: Effects on Cognition

描述(由申请人提供)：这是一项调查睡眠障碍呼吸、载脂蛋白E基因和认知之间关系的提案的重新提交。睡眠呼吸障碍随着年龄的增长而增加，并与认知障碍有关。APOE e4等位基因最近被认为与睡眠呼吸障碍，特别是阻塞性睡眠呼吸暂停综合征(OSAS)有关。E4等位基因是认知能力下降和痴呆症发展的既定风险因素。这提出了一个重要的问题：APOE e4等位基因对认知和痴呆风险的负面影响是否源于OSAS？具体地说，在一个已经易受认知功能减退加速影响的人群中，载脂蛋白e4基因状态、阻塞性睡眠呼吸暂停综合征的存在或发展以及载脂蛋白e4基因状态和阻塞性睡眠呼吸暂停综合征的组合如何进一步加速认知功能减退？据我们所知，没有任何研究直接研究这些问题。为了有效地解决这一知识鸿沟，需要纵向收集数据和分析技术，专门为识别认知衰退的“调节者”和“中介者”而设计。我们建议在150名60岁及以上的老年人中调查这一问题，他们将被纵向跟踪4年。认知功能和阻塞性睡眠呼吸暂停综合征的评估将在基线和每年进行，APOE状态将在基线确定。以下假设将得到检验。假设1：在老年人中，睡眠呼吸紊乱、apoE e4基因和年龄三个危险因素及其相互作用将预测认知能力的下降速度。假设2：apoe e4缓解睡眠呼吸障碍对认知功能下降的影响。假设3：睡眠呼吸障碍会调节apoe e4对认知功能下降的任何负面影响。目前还没有有效的治疗认知衰退或MCI的方法，但有治疗OSAS的有效方法。减少认知功能障碍、延缓AD发病具有显著的临床和经济效益。因此，这个问题的答案可以显著提高我们对老年人认知障碍的治疗方法。

DESCRIPTION (provided by applicant): This is a resubmission of a proposal to investigate the relationships among sleep disordered breathing, APOE genotype and cognition. Sleep disordered breathing increases with age and is associated with impaired cognition. The APOE e4 allele has recently been associated with sleep disordered breathing, particularly Obstructive Sleep Apnea Syndrome (OSAS). The e4 allele is an established risk factor for cognitive decline and the development of dementia. This raises an important issue: is the negative impact of APOE e4 allele on cognition and risk for dementia risk due to OSAS? Specifically, in a population already susceptible to accelerated cognitive decline, how do APOE e4 genotype status, presence or development of OSAS and the combination of APOE e4 status and OSAS further accelerate cognitive decline? We are aware of no studies which have directly examined these issues. To address this knowledge gap effectively requires longitudinal collection of data and analytic techniques designed specifically to identify "moderators" and "mediators" of cognitive decline. We propose to investigate this issue in a group of 150 older adults, 60 years of age and older who will be followed longitudinally for 4 years. Assessments of cognitive function and OSAS will be conducted at baseline and annually, with APOE status determined at baseline. The following hypotheses will be tested. Hypothesis 1: In older adults, 3 risk factors, sleep disordered breathing, APOE e4 genotype and age and their interactions will predict rate of decline in performance on measures of cognition. Hypothesis 2: APOE e4 moderates the effect of sleep disordered breathing on cognitive decline. Hypothesis 3: Sleep disordered breathing will mediate any negative impact of APOE e4 on cognitive decline. There are currently no effective treatments for cognitive decline or MCI, but there are effective treatments for OSAS. Reducing cognitive impairment and delaying the onset of AD has significant clinical and economic benefits. Thus, the answer to this question could significantly enhance our therapeutic approach to cognitive impairment in older adults.