Racial/ethnic minority adults are at higher risk for Alzheimer's disease and related dementias (ADRD). Moreover, minority adults are not only exposed to more stressful situations in their daily lives but they also have fewer resources to manage these situations in healthy ways. Limited resources among these adults may lead to impaired physiologic stress responses (i.e., stress reactivity), specifically chronic activation of the physiologic stress response systems, including the sympathetic nervous system and the hypothalamic- pituitary-adrenocortical (HPA) axis. Our understanding of the impact of stress reactivity on ADRD risk comes from animal studies and experiments in humans using controlled, laboratory stressors. This is a major limitation because laboratory stressors cannot capture the variety, severity, or duration of stressors that individuals face in their daily lives. Thus, there remains a need to more rigorously evaluate relationships of stress reactivity with ADRD risk in natural settings. We propose to fill this critical gap in the literature by adding personalized (person-level) indicators of stress reactivity and rigorous measures of cognitive function to our NIA-funded ecological momentary assessment (EMA) study of 510 Chicago area Latinx, African-American, and White adults aged 40-64 years (R01AG062180). We will leverage planned EMA measurements of stressful experiences and negative affect (emotions) by adding continuous ECG monitoring and by measuring cognitive function and gait speed, which has been shown to precede and predict onset of cognitive impairment, in a subset of 350 participants. We will use data collected over a 14-day study period to develop personalized measures of autonomic and affective stress reactivity. We will then examine whether these personalized measures of stress reactivity are associated with cognitive function and gait speed. Finally, we will test whether racial/ethnic differences in cognitive function are mediated by differences in autonomic and affective stress reactivity. Recommendation 3, Priority 2 of the 2019 ADRD Summit Draft Recommendations is to test mechanistic pathways that may account for AD/ADRD disparities including psychosocial factors like stress. Thus, our proposed study in a multi-ethnic sample will lay the foundation for a research program focused on elucidating the contributions of stress reactivity to disparities in ADRD risk. Our findings will also provide key insights into the most salient targets for stress management interventions designed to prevent ADRD.
Greater exposure to stressful situations, coupled with limited access to the financial and social resources needed to manage stress in healthy ways are believed to contribute to persistent racial/ethnic disparities in Alzheimer's disease and related dementias (ADRD). Our overall goal is to generate personalized measures of how people respond to stressful experiences in their daily lives and relate these measures to cognitive function and gait speed. Our proposed study in a multi-ethnic sample will lay the foundation for a research program focused on elucidating the contributions of stress reactivity to disparities in ADRD risk.
