Executive contributions to the “double jeopardy” of depressive symptoms and age on episodic memory in racially diverse adults - PROJECT SUMMARY/ABSTRACT Emerging evidence suggests that age and depression, even the modest levels common in aging, may interact to produce a “double jeopardy” for episodic memory impairment and may predict cognitive decline and Alzheimer’s disease (AD). The underlying cause/s of this double jeopardy is unknown. Even less is known about depression- related memory impairments in Black/African American and Mexican Americans, despite evidence of more disabling depression, and AD prevalence than in non-Hispanic Whites (NHWs). Multiple race-related proxy factors (e.g., discrimination, vascular burden, religiosity) that may exacerbate or reduce depression-related memory impairments but they have seldom been explored. Executive dysfunction may be an important contributor to depression-related episodic memory impairments but studies of depression-related memory and executive functioning impairments have been conducted in parallel. We propose a new conceptual framework in which depression-related executive and associated PFC dysfunction underlie depression-related memory impairments, double jeopardy effects, and ethnoracial disparities in these impairments. We will enroll 330 adults from Black, Mexican, and NHW groups across the adult lifespan. Consistent with an RDoC framework, we will assess depression along a continuum and examine depressive symptom dimensions (i.e., somatic, depressed mood, etc.), and consider age of onset and chronicity that may differ by age and race/ethnicity. We will use a combination of cognitive neuroscience and clinical neuropsychology approaches, innovative memory tasks manipulating executive functions, univariate, multivariate, and multimodal neuroimaging, and longitudinal clinical and cognitive assessments to identify the neural mechanisms underlying depression-related memory impairments. With 2 fMRI experiments that use different approaches to manipulate demands on executive functioning (Aim 1: inhibition of mnemonic interference and Aim 2: spontaneous and instructed emotion regulation), we bridge across diverse literatures with our unifying executive dysfunction framework. In Aim 3, we test racial/ethnic group differences in depression-related memory alterations, neural mechanisms underlying them, and psychosocial factors that may influence group differences. In exploratory Aim 4, we use cutting-edge analyses to explore multi-modal neuroimaging markers of depression-related memory impairment and decline in older adults. Should the neural mechanisms by which depression negatively impacts memory depend upon age, race/ethnicity and related psychosocial factors, it would suggest a need to update and advance current theories of depression-related cognitive impairment to incorporate the influence of these factors. These results may reveal who may be most sensitive to the negative cognitive effects of depression and identifying reasons why, informing future, personalized brain stimulation or lifestyle interventions, tailored to one’s age, race/ethnicity and related factors to reduce depression-related cognitive impairment.
