Pregnancy complications and the development of Alzheimer's disease and related dementias in women in the Adult Changes in Thought study

项目总结 阿尔茨海默病及其相关痴呆(ADRD)是一种潜伏期延长的疾病，没有 有效的治疗方法。来自中年的血管疾病被认为是导致ADRD的主要因素，以及 是早期干预的一个有希望的目标。性别相关的风险因素尤其令人感兴趣，因为 老年女性比男性更有可能出现ADRD，并患痴呆症的时间更长。 子痫前期(PEC)和其他妊娠并发症(PC)，包括早产、胎儿生长 节制和死产是母体心血管风险的成年期早期标志。PEC的历史已经 以后患慢性高血压、中风、心力衰竭和认知障碍的风险更高 在生活中，怀孕5至15年后脑部小血管疾病(CSVD)的MRI负担更高 这些女人。然而，缺乏关于PEC和其他PC对发展的影响的数据 临床ADRD及ADRD相关的神经放射学和神经病理损害。 成人思维变化(ACT)研究自1986年以来一直招募参与者，并以此为生， 老龄化研究学习实验室，设在西部的综合医疗保健提供系统中 华盛顿。ACT的独特设置允许无与伦比的管理、药房、临床 实验室、账单和提取的医疗记录数据，最早可以追溯到1950年。在美国，ACT是 其将详细的生命过程暴露数据与世界级临床痴呆症相结合的能力无与伦比 诊断、神经放射学和神经病理学测量。我们的总体目标是：1)扩大现有的 ACT研究中的生殖表型数据和详细的产科表型，以及2)探索 中年个人计算机与女性ADRD发生的关系 这将是第一项关于PC与临床ADRD及相关疾病之间关系的纵向研究 女性的神经放射学和神经病理损害。我们将创建一个新的、无与伦比的资源 研究人员测试了一系列关于性别暴露影响的假设，从早期开始 成年到中年，女性的ADRD。确定与ADRD相关的功能和结构变化 有PC病史的女性可以帮助我们在生命早期识别出有ADRD风险的女性，并开发 预防战略，以阻止或减缓这一弱势群体中认知能力下降的进程。

PROJECT SUMMARY Alzheimer's disease and its related dementias (ADRD) are diseases with extended latency periods and no effective treatments. Vascular disease from midlife is recognized as a major contributor to ADRD, and represents a promising target for early intervention. Sex-specific risk factors are of particular interest, since older women are more likely to experience ADRD onset and live more years with dementia than men. Preeclampsia (PEC) and other pregnancy complications (PC), including preterm birth, fetal growth restriction, and stillbirth, are early adulthood markers of maternal cardiovascular risk. A history of PEC has been associated with a higher risk of chronic hypertension, stroke, heart failure and cognitive impairment later in life, and a higher burden of cerebral small vessel disease (CSVD) on MRI 5 to 15 years after pregnancy in these women. However, data are lacking regarding the effects of PEC and other PC on the development of clinical ADRD and ADRD-related neuroradiological and neuropathological lesions. The Adult Changes in Thought (ACT) study has enrolled participants since 1986 and is a living, learning laboratory of aging research, set within an integrated health care delivery system in Western Washington. ACT's unique setting allows for unparalleled linkages to administrative, pharmacy, clinical laboratory, billing, and abstracted medical records data, extending back as far as 1950. In the US, ACT is unmatched in its ability to combine detailed life-course exposure data with world-class clinical dementia diagnoses, neuroradiological, and neuropathology measures. Our overall goals are to: 1) augment existing reproductive phenotypic data in the ACT study with detailed obstetric phenotyping, and 2) explore the association between mid-life PC and development of ADRD in women. This would be the first longitudinal study to explore the association of PC with clinical ADRD and related neuroradiological and neuropathological lesions in women. We will create a new, unparalleled resource for researchers to test a wide range of hypotheses regarding the effects of sex-specific exposures, from early adulthood to midlife, on ADRD in women. Identifying functional and structural ADRD-related changes in women with a history of PC could help us identify women early in life who are at risk of ADRD, and develop preventive strategies to thwart or slow the progression of cognitive decline in this vulnerable population.