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5888名居住在社区的老年人。在基线时，CHS参与者进行了磁共振成像扫描和其他测量。那些患有痴呆症的人被从痴呆症的后续样本中筛选出来，但在其他方面进行了重新测试。10年后，无痴呆的参与者再次接受测试，观察到480例痴呆和577例轻度认知障碍（MCI）。我们将使用这个样本来实现我们的主要目标，即检查偶发性生活事件作为认知能力下降、轻度认知障碍和偶发性痴呆的风险因素。我们的具体目的是使用压力的理论模型来检验关于四种突发压力生活事件（即，亲人死亡，照顾，亲人生病，与亲人关系不良）与认知能力下降/偶发性痴呆的直接关系的假设；以及SLEs、介质和认知能力下降/痴呆之间的间接关系。中介有理论和实证支持。它们包括社会心理（社会支持、生活质量、抑郁、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，以及突发疾病（高血压、糖尿病等）。我们还将研究调节因子，即SLEs与假定的病因（上述介质）以及与遗传（APOE），物理（疾病）和化学（药物）的相互作用。因为这些测量在10年的过程中重复了几次，CHS允许双重前瞻性分析。这样的分析在SLE文献中是罕见的。它们提供了个体在经历SLE和经历认知能力下降和/或偶发性痴呆之前的重要信息。例如，如果心理生理测量调节偶发SLE与认知能力下降/痴呆之间的关系，我们将能够估计这是由SLE本身、SLE之前的假定介质还是两者的相互作用影响的。我们还将能够评估一些SLE是急性的还是慢性的（例如护理），以及慢性经历是否与急性事件相互作用，从而加剧彼此对结果的影响。这些关系可能对暴露于潜在有害压力源的人的方案设计具有重要意义。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。考虑到年龄和痴呆症之间的关系，政府机构已经警告过痴呆症的流行。痴呆症给受害者和家属带来痛苦，对医疗保健的成本也很高。为了缓解这一危机，我们必须了解发生认知问题/痴呆症的风险。遗传-环境风险已被确定为痴呆症，但对SLEs的关注有限。这是令人惊讶的，因为SLEs和痴呆与认知、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. PUBLIC HEALTH RELEVANCE: Despite a great interest in psychosocial and physical reactions to stressful life events (SLEs), there has been limited to no interest in cognitive functioning in response to such events/experiences. This is surprising because some life experiences produce chronic stress which has been shown to be related to compromised cognition. This study will assess 1) the degree to which SLEs increase the risk for cognitive decline, Mild Cognitive Impairment and dementia in older adults; 2) the degree to which incident SLEs predict: a) psychosocial/behavioral factors (e.g., depression, social supports, sedentary behavior), b) physiological factors (e.g., insulin, CRP); and, c) incident Illnesses and events (e.g., diabetes, obesity, hypertension, MIs); and, 3) whether psychosocial, behavioral, physiological and incident illnesses/events predict cognitive decline/MCI/dementia. In cases where such predictions hold, we will examine whether the prediction of cognitive decline/MCI/dementia is mediated by psychophysiological, behavioral function and incident illness. We will also examine interactions between SLEs with putative etiologic factors (psychophysiological, behavioral and incident illness), as well as with chemical (medications) and genetic (APOE) factors.