MCI, APOE and Sleep Apnea: Effects on Cognition

描述（由申请人提供）：这是一项关于研究睡眠呼吸障碍、APOE基因型和认知之间关系的提案的再提交。睡眠呼吸障碍随着年龄的增长而增加，并与认知受损有关。APOE e4等位基因最近与睡眠呼吸障碍，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一个确定的危险因素。这就提出了一个重要的问题：APOE e4等位基因是否会对认知和OSAS痴呆风险产生负面影响？具体来说，在已经容易加速认知能力下降的人群中，APOE e4基因型状态、OSAS的存在或发展以及APOE e4状态与OSAS的结合如何进一步加速认知能力下降？据我们所知，没有任何研究直接审查了这些问题。为了有效地解决这一知识差距，需要纵向收集数据和专门设计的分析技术，以确定认知衰退的“调节者”和“中介者”。我们建议在150名60岁及以上的老年人中调查这个问题，他们将被纵向随访4年。将在基线和每年进行认知功能和OSAS评估，并在基线时确定APOE状态。以下假设将被检验。假设1：在老年人中，睡眠呼吸障碍、APOE e4基因型和年龄及其相互作用将预测认知能力下降的速度。假设2:APOE e4调节睡眠呼吸障碍对认知能力下降的影响。假设3：睡眠呼吸障碍会介导APOE e4对认知能力下降的负面影响。目前对认知能力下降或轻度认知障碍没有有效的治疗方法，但对阻塞性睡眠呼吸暂停症有有效的治疗方法。减少认知障碍和延缓AD的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.