The Impact of Early and Later-life Stress on Later-life Cognition and Plasma Biomarkers of Alzheimer's Disease and Related Dementias - PROJECT SUMMARY/ABSTRACT By 2050, the estimated cost of Alzheimer’s disease and related dementias (ADRD) in the US is estimated at 1.6 trillion dollars. Thus, it is crucial to understand the factors contributing to the development of ADRD to identify strategies for prevention or intervention. Stress is a multidimensional construct that can occur at various points across the life course (early and later-life), either accumulating gradually over time or manifesting suddenly with an immediate impact. Although stress has been associated with the risk of cardiovascular disease, there is limited research on the potential association between stress and the risk of cognitive decline and ADRD, or on biomarkers of ADRD pathology. Moreover, few studies have assessed sex differences even though both stress and ADRD differ by sex. In this proposal, stress will be defined as occurring across the life-course as well as an individual's perception of psychological stress. The overarching goal of this proposal is to examine the associations of early and later-life stress on later-life cognition and plasma biomarkers of ADRD pathology including Abeta 40 [Aβ40], Abeta 42 [Aβ42], Glial Fibrillary Acidic Protein [GFAP], and Neurofilament light [NfL], phosphorylated tau181 (p-tau181), and phosphorylated tau217 (p-tau217), and whether associations are modified by sex. To examine these associations, we will cross-sectionally examine the relationship between life course stress and cognition (Aim 1) or plasma biomarkers of ADRD pathology (Aim 2). We will also assess whether sex modifies the association. Moreover, we will examine these associations among participants without dementia, recruited into the Wake Forest Alzheimer’s Disease Research Center (ADRC). The ADRC consists of community-dwelling individuals, who are clinically well-characterized, have completed seven different stress questionnaires, and provided a blood sample. The applicant will receive training in advanced methods in epidemiology, biostatistics, sex differences, and how life course stress impacts health. Additionally, they will also develop an understanding of ADRD clinical diagnosis and cognitive outcomes, while acquiring the necessary skills to interpret plasma ADRD biomarkers – all of which are essential for achieving the proposed aims. Mentorship will be provided by a multidisciplinary team of researchers and physicians at Wake Forest University School of Medicine. The team will provide the applicant with feedback regarding project implementation, data collection and analysis, and manuscript preparation. The proposed aims have the potential to provide essential insight into the impact of life course stress on later-life cognition and by understanding which measures of stress influence ADRD markers. Future interventions can be targeted towards those at highest risk.
