Life Events, Psychophysiological Mediators, Cognitive Decline and Dementia

描述（由申请人提供）：拟议的研究将对心血管健康研究（CHS）的10波数据进行二次数据分析。CHS包括来自美国几个地区的5，888名社区居住老年人。在基线时，CHS参与者进行了磁共振成像扫描和其他测量。那些痴呆症患者从痴呆症的随访样本中筛选出来，但在其他措施上进行了重新测试。10年后，对无痴呆的参与者进行了重新测试，并观察了480例痴呆事件和577例轻度认知障碍（MCI）。我们将使用这个样本来满足我们的主要目标，即检查事件生活事件作为认知下降，MCI和事件痴呆的危险因素。我们的具体目标是使用压力的理论模型来测试关于四个事件压力生活事件（SLEs）（即，亲人去世、护理、亲人生病、与亲人关系不佳）与认知能力下降/痴呆症;以及狼疮性红斑狼疮、介体和认知能力下降/痴呆症的间接关系。调解人有理论和经验支持。它们包括心理社会（社会支持，生活质量，抑郁症，睡眠问题），行为（饮酒，吸烟，运动，饮食）和生理（代谢综合征，炎症）措施，以及偶发疾病（高血压，糖尿病等）。我们还将研究调节因子，即SLE与假定的病因因素（上述介质）以及与遗传（APOE），物理（疾病）和化学（药物）的相互作用。由于这些措施在10年内重复了几次，因此CHS允许进行双重前瞻性分析。这种分析在SLE文献中很少见。它们提供了关于个体在经历SLE之前以及在经历认知下降和/或痴呆事件之前的重要信息。例如，如果心理生理学指标介导SLE事件与认知能力下降/痴呆的关系，我们将能够估计这是否受到SLE本身、SLE之前的假定介质或两者相互作用的影响。我们还将能够评估某些SLE是急性还是慢性（例如，复发），以及慢性经历是否与急性事件相互作用，以加剧彼此对结局的影响。这些关系可能有重大影响的程序设计的人暴露于潜在的有害压力。未来20年，美国65岁以上人口的增长速度将远远快于35岁以下人口的增长速度。鉴于年龄与痴呆症之间的关系，政府机构已经警告痴呆症的流行。痴呆症给受害者和家庭造成痛苦，医疗费用非常昂贵。为了缓解这一危机，我们必须了解发展认知问题/痴呆症的风险。遗传环境风险已被确定为痴呆症，但对SLE的关注有限。这是令人惊讶的，因为SLE和痴呆症与认知，心理生理和行为问题有关。

DESCRIPTION (provided by applicant): The proposed research will perform secondary data analyses on 10 waves of data from the Cardiovascular Health Study (CHS). The CHS includes 5,888 community-dwelling older adults sampled from several US regions. At baseline, CHS participants had magnetic resonance imagining scans and other measures. Those with dementia were screened from the follow-up sample for dementia, but were retested on other measures. After 10 years, the dementia-free participants were retested and 480 cases of incident dementia and 577 of Mild Cognitive Impairment (MCI) were observed. We will use this sample to meet our primary goal which is to examine incident life events as risk factors for cognitive decline, MCI, and incident dementia. Our specific aims are to use theoretical models of stress to test hypotheses about direct relationships of four incident stressful life events (SLEs) (i.e., death of a loved one, caregiving, illness of a loved one, poor relationship with loved one) with cognitive decline/incident dementia; and indirect relationships of SLEs, mediators, and cognitive decline/dementia. The mediators have theoretical and empirical support. They include psychosocial (social supports, quality of life, depression, sleep problems), behavioral (drinking, smoking, exercise, diet), and physiological (metabolic syndrome, inflammation) measures, as well as incident illnesses (hypertension, diabetes, etc). We will also examine moderators, namely interactions of SLEs with putative etiologic factors (the above cited mediators) and with genetic (APOE), physical (illnesses) and chemical (medications). Because these measures were repeated several times over the course of 10 years, the CHS allows doubly- prospective analyses. Such analyses are rare in the SLE literature. They provide important information about individuals before they experience a SLE and before they experience cognitive decline and/or incident dementia. For example, if psychophysiological measures mediate relationships of incident SLEs with cognitive decline/dementia, we will be able to estimate whether this was influenced by the SLE itself, the putative mediators before the SLE, or the interaction of the two. We will also be able to assess whether some SLE are acute or chronic (e.g. caregiving) and whether chronic experiences interact with acute events to exacerbate the influence of each other on the outcomes. These relationships could have major implications for the design of programs for persons exposed to potentially harmful stressors. In the next 20 years, the US population over 65 years old will grow much faster than the proportion that is less than 35 years old. Given the relationship between age and dementia, government agencies have warned of a dementia epidemic. Dementia causes suffering for victims and families and is very costly to health care. To mitigate this crisis, we must understand the risks for developing cognitive problems/dementia. Genetic-environmental risks have been identified for dementia, but limited attention has been given to SLEs. This is surprising because SLEs and dementia are associated with cognitive, psychophysiological, and behavioral problems.