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

项目摘要 阿尔茨海默病及其相关痴呆（ADRD）是潜伏期延长的疾病， 有效的治疗。中年血管疾病被认为是ADRD的主要原因， 是早期干预的一个有希望的目标。性别特异性风险因素特别重要，因为 老年妇女比男性更容易发生ADRD，并且痴呆症的寿命更长。 先兆子痫（PEC）和其他妊娠并发症（PC），包括早产、胎儿生长 限制和死产是母亲心血管风险的早期成年标志。PEC的历史 与慢性高血压、中风、心力衰竭和认知障碍的风险较高有关。 在生活中，在怀孕后5至15年， 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和ADRD相关的神经放射学和神经病理学病变。 成人思想变化（ACT）研究自1986年以来一直招募参与者， 老化研究的学习实验室，在西方的综合保健服务系统内设置 华盛顿。ACT的独特设置允许无与伦比的联系，行政，药房，临床 实验室，账单和摘要医疗记录数据，可追溯到1950年。在美国，ACT是 联合收割机将详细的生命过程暴露数据与世界级的临床痴呆症相结合的能力是无与伦比的 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与详细的产科表型，以及2）探索 中年PC与女性ADRD发展之间的关联。 这将是第一个纵向研究，以探讨PC与临床ADRD和相关疾病的关系。 女性神经放射学和神经病理学病变。我们将创造一个新的，无与伦比的资源， 研究人员测试了广泛的假设，从早期的性别特异性暴露的影响， 成年至中年，女性ADRD。识别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， 预防性战略，以阻止或减缓这一弱势群体认知能力下降的进展。

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.