Hypertensive Disorders of Pregnancy and Subsequent Risk of Vascular Dementia, Alzheimer's Disease, or Related Dementia: A Retrospective Cohort Study Taking into Account Mid-Life Mediating Factors.

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PROJECT SUMMARY/ABSTRACT This is an application for a K01 award for Dr. Karen Schliep, a tenure-line Assistant Professor of Public Health at the University of Utah. Dr. Schliep is establishing herself as a young investigator in women’s life-course epidemiology, specifically in a novel area of aging research—to improve our understanding of women’s increased risk of Alzheimer’s disease (AD) and related dementias (RD) and create women-specific interventions to mitigate risk and improve outcomes. This award will allow Dr. Schliep to achieve her goal of research independence by providing her support to accomplish the following training aims: 1) develop expertise in biomedical informatics and population-based research methods; 2) gain experience in the conduction of clinical cognitive health assessments; 3) enhance knowledge of modifiable factors affecting women’s mid- and late-life cognitive health; and 4) expand skills to independently lead and manage a successful research program. Dr. Schliep has assembled a mentoring team comprising a primary mentor, Dr. Michael Varner, an obstetrician and nationally renowned maternal-fetal medicine investigator with expertise in pregnancy complications including hypertensive disorders of pregnancy (HDP), and two co-mentors: Dr. Norman Foster, a cognitive neurologist and geriatric neurologist and recognized leader in dementia research, and Dr. Ken Smith, an internationally known expert in population-based analyses and genetic/family epidemiology. Dr. Schliep has five advisors with expertise in classification modeling, ADRD neuropsychology, mid-life women’s health, longitudinal and survival data analysis, and chronic disease epidemiology. Little is known regarding the association between HDP, estimated to complicate 2–8% of all pregnancies, and long-term adverse maternal neurological outcomes with similar inflammatory vascular etiologies, including ADRD. An estimated 5.4 million Americans currently suffer from ADRD, two-thirds of whom are women. As the US aging population increases, prevalence of dementia is expected to approach 13.2 to 16.0 million cases by 2050. Why ADRD disproportionately affects women is not known. Dr. Schliep’s research objective is to develop classification models for the various dementia subtypes (including AD, vascular dementia, Lewy body dementia, and frontotemporal dementia) to analyze longitudinal, individual-level data to better understand how HDP may increase a woman’s risk for ADRD. Dr. Schliep will accomplish this through the following research aims: 1) increase accuracy of ADRD diagnoses within health administrative databases; and 2) investigate the association between HDP and ADRD, and mid-life mediating factors. The proposal’s expected outcomes include 1) a novel method to accurately capture dementia cases within large linked health administrative databases; 2) clarity on how HDP may be linked with specific dementia subtypes; and 3) skills, experience, and preliminary data for Dr. Schliep to support future studies identifying other sex-specific risk factors for dementia and mediating factors amenable to interventions.