Depression, Inflammation, Biological Age and Cognitive Function

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ABSTRACT - PROJECT 2 The incidence of Alzheimer’s disease and related dementias (ADRD) are rapidly rising as the world population is aging. The majority of past research to identify risk factors for dementia has focused on the predictive value of one factor at a time. This has resulted in a long list of factors that relate to the precursors of ADRD (i.e., cognitive decline and mild cognitive impairment [MCI]) with little guidance as to which to prioritize or which targets might be most suitable for intervention. Our approach will address this problem by considering many factors simultaneously and in interaction. This project will focus on the role of three interrelated factors: major depressive disorder (and depressive symptomatology), systemic inflammation, and accelerated biological aging (e.g., DNA methylation age, telomere length). All three are known to be risk factors for MCI and subsequent ADRD, but the degree to which they have unique impact is unclear, as is the degree to which they accumulate or interact to confer risk. In addition, this project will help unpack underpinnings of cognitive health disparities by examining how race and gender moderate connections between depressive symptoms and biological measures with ADRD, and the relevance of perceived discrimination, lifetime adversity, and socioeconomic status (SES). Rich assessment at multiple time points in older adults, and determination of inter-relationships between multiple key risk factors, will enable greater ability to predict not only who is at greatest risk but also to illuminate specific targets for future intervention. The proposed project is part of a renewal of the Einstein Aging Study (EAS). For this renewal, 767 racially diverse men and women aged 60 and older will complete up to 5 annual waves of data collection. Each wave will include a two week “burst” of daily and ecological momentary assessments (EMAs) to examine psychosocial and behavioral factors as they are experienced, as well as an in-depth assessment of cognitive function level, mild cognitive impairment (MCI), and depression. A blood draw will occur at the end of each EMA burst to capture inflammatory load and enable classification of biological age, as well as plasma-based neurodegenerative biomarkers that will further inform study endpoints. This project will help clarify the effects of depression, inflammation, and biological age on individual risk for cognitive decline and MCI, using more nuanced and integrative models than in past research. Innovation includes leveraging an existing cohort of diverse older adults to explore disparities in ADRD risk attributable to race, ethnicity, SES, and psychosocial factors (e.g., perceived discrimination), and the use of multiple biological measures that have not previously been integrated in biopsychosocial models. This work will ultimately pave the way for tailored interventions to reduce risk of cognitive aging and decline.