PTSD, Sleep-Disordered Breathing and APOE Genotype: Effects on Cognition

描述（由申请人提供）： 研究是否睡眠呼吸障碍（SDB），载脂蛋白54（APOE 54）状态，年龄的增加及其相互作用将预测患有PTSD的退伍军人的认知下降率，这是一个已经存在认知缺陷风险的人群。具体目标：为了解决SDB和APOE状态如何影响PTSD患者样本中的认知下降的问题，将测试将APOE状态和SDB对认知下降的影响分开的特定假设。假设1：在PTSD患者中，三个风险因素（睡眠呼吸障碍，APOE 54基因型，年龄）及其相互作用将预测认知能力下降的速度。假设2：APOE 54调节睡眠呼吸障碍对认知能力下降的影响。假设3：睡眠呼吸障碍将介导APOE 54对认知能力下降的任何负面影响。与退伍军人健康/退伍军人事务部使命的相关性：一些退伍军人在战后生活中患有创伤后应激障碍。随着创伤后应激障碍退伍军人年龄的增长，他们患认知能力下降和痴呆症的风险更高。大多数越战老兵是男性，多达29%的成年男性患有某种程度的SDB（Young等人，1993年）。基于最近发现的新证据表明，创伤后睡眠障碍经常表现为失眠和高于预期的SDB患病率的组合（Lamarche & De Koninch，2007; Krakow等人，2002年）。这项拟议的研究将确定患有PTSD的退伍军人如果是APOE 54携带者和/或患有SDB，他们的认知能力下降的风险会增加到什么程度。仔细评估这些风险因素对认知功能障碍或痴呆症的发展，在这一人群中是特别及时的，因为有既定的治疗SDB和有重大的NIH倡议的诊断和治疗MCI的一般人群。在完成我们的研究后，我们将能够估计SDB治疗的潜在效果，并描述我们的退伍军人群体，以最好地估计对治疗的反应。这些信息可以为在具有类似认知障碍风险的退伍军人PTSD人群中进行随机临床试验提供坚实的基础。现在是开展这项工作的时候了，而脆弱的越战老兵在患上痴呆症之前仍然处于危险之中。这些努力可能有助于减轻退伍军人及其家人不必要的个人痛苦，并减少未来对退伍军人管理局医疗保健系统的需求。设计/分析：将采用随机回归模型进行纵向设计。环境：本研究将在VA Palo Alto Health Care System进行。参与者：我们的假设将在90名PTSD和90名55岁以上的非PTSD患者中进行纵向测试。测量值：将在基线和每年评估主要结局指标、Rey听觉言语学习测试、其他认知指标和SDB。仅在基线时采集APOE状态。 公共卫生相关性： 相当多的退伍军人要么患有PTSD，要么在战后的某个时候患有PTSD。我们认为，随着患有创伤后应激障碍的退伍军人年龄的增长，他们患认知能力下降和痴呆症的风险更高。我们强调，大多数退伍军人是男性，多达29%的成年男性有一定程度的SDB（Young等人，1993年）。此外，新出现的证据表明，创伤后睡眠障碍经常表现为失眠和高于预期的SDB患病率的组合（Lamarche & De Koninch，2007; Krakow等人，2002年）。这项拟议的研究将确定，如果他们是APOE 54携带者和/或患有SDB，那么患有PTSD的退伍军人群体的认知能力下降风险会增加到什么程度。研究完成后，我们将不仅能够估计SDB治疗的潜在影响，而且能够描述我们的退伍军人群体，并估计他们对治疗作出反应的可能性。

DESCRIPTION (provided by applicant): To examine whether sleep disordered breathing (SDB), Apolipoprotein 54 (APOE 54) status, increasing age and their interactions will predict rate of cognitive decline in veterans who have PTSD, a population already at risk for cognitive deficits. Specific Aims: To address the question of how SDB and APOE status affect cognitive decline in a sample of PTSD patients, specific hypotheses that tease apart the effects of APOE status and SDB on cognitive decline will be tested. Hypothesis 1: In individuals with PTSD, three risk factors (sleep disordered breathing, APOE 54 genotype, age) and their interactions will predict rate of decline in performance on measures of cognition. Hypothesis 2: APOE 54 moderates the effect of sleep disordered breathing on cognitive decline. Hypothesis 3: Sleep disordered breathing will mediate any negative impact of APOE 54 on cognitive decline. Relevance to Veterans' Health/VA Mission: A number of veterans suffer from PTSD during their post-war life. As PTSD veterans age, they are at higher risk for cognitive decline and dementia. Most Vietnam veterans are male and as many as 29% of adult males have some degree of SDB (Young et al., 1993). Emerging evidence based on recent findings indicate that posttraumatic sleep disturbance frequently manifests with a combination of insomnia and a higher-than-expected prevalence of SDB (Lamarche & De Koninch, 2007; Krakow et al., 2002). The proposed research will determine to what degree veterans with PTSD are at accelerated risk for cognitive decline if they are APOE 54 carriers and/or have SDB. Careful assessment of these risk factors for development of cognitive impairment or dementia in this population is especially timely since there are established treatments for SDB and there are major NIH initiatives on the diagnosis and treatment of MCI in the general population. After completing our study we will be in a position to estimate the potential effect of treatments for SDB, as well as characterize our veteran population to best estimate response to treatment. Such information could lead to a firm basis for proposing randomized clinical trials in the veteran PTSD population at similar risk for developing cognitive impairment. Now is the time to undertake such work, while vulnerable Vietnam-era veterans are still just at risk, before developing dementia. Such efforts might help mitigate unnecessary personal suffering in veterans and their families and reduce future demands on the VA health care system. Design/Analysis: A longitudinal design will be employed using a random regression model. Setting: The study will be conducted at the VA Palo Alto Health Care System. Participants: Our hypotheses will be tested longitudinally in 90 PTSD and 90 non-PTSD patients, 55 years or older. Measurements: The primary outcome measure, Rey Auditory Verbal Learning Test, other cognitive measures, and SDB will be assessed at baseline and annually. APOE status will be collected at baseline only. PUBLIC HEALTH RELEVANCE: A significant number of veterans either suffer from PTSD currently or have suffered from PTSD at some time during their post-war life. We argue that as the population of veterans with PTSD ages, they are at higher risk for cognitive decline and dementia. We emphasize that most veterans are male and that as many as 29% of adult males have some degree of SDB (Young et al., 1993). Furthermore, emerging evidence indicate that posttraumatic sleep disturbance frequently manifests with a combination of insomnia and a higher-than- expected prevalence of SDB (Lamarche & De Koninch, 2007; Krakow et al., 2002). The proposed research will determine to what degree this population of veterans with PTSD is at accelerated risk for cognitive decline if they are APOE 54 carriers and/or if they have SDB. On completion of the study, we will be in a position not only to estimate the potential effect of treatments for SDB, but also to be able to characterize our veteran population and estimate the likelihood of their responding to treatment.