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.