Resilience and brain health of older adults during the COVID-19 pandemic

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Abstract: Exercise and mindfulness are believed to be effective stress reduction interventions, but research to date has not been able to assess their benefits while individuals are coping with a major stressor in real time. The COVID-19 pandemic is an unwanted natural experiment in the deleterious effects of stress – especially social isolation (social disconnectedness and loneliness), a stressor particularly strongly associated with the pandemic - on older Americans’ cognitive and emotional health and risk for Alzheimer’s Disease (AD). This project will elucidate whether exercise and mindfulness can mitigate the effects of pandemic stress on cognitive function and emotional health in later life, including neurobiological measures of risk for AD. We will leverage a unique resource: the NIH-funded trial, “Mindfulness-Based Stress Reduction and Exercise for Age-Related Cognitive Decline” (MEDEX). By leveraging MEDEX and following these participants, who continue to attend monthly booster sessions of their randomized condition remotely during the pandemic, we will have repeated sets of clinical, cognitive, molecular, and neuroimaging measures covering 7.5 years during the pre-, during-, and post-pandemic period. We can examine intervention effects, as well as individual factors such as resilience, on long-term outcomes. Among other innovative aspects of the project, we will analyze effects on two novel peripheral biomarkers: Senescence-Associated Secretory Phenotype (SASP), which measures mechanisms of biological aging, and plasma amyloid Aβ42 and Aβ40, which measure AD risk. In the proposed project, (1) during the pandemic, we will use novel methods such as Ecological Momentary Assessment (EMA) to characterize social isolation both objectively (e.g., number of social contacts) and subjectively (e.g., loneliness), and its biological mechanisms on aging (such as elevations in SASP and plasma amyloid); (2) post-pandemic, we will assess downstream effects on cognitive function, emotional well-being, and brain health, including AD risk, using neuropsychological assessments, EMA, and neuroimaging. Outcomes include (Aim 1) changes in cognitive performance and emotional well-being, and decline in emotional well-being measured by positive and negative affect and sleep quality; increases in biological aging and decreasing AΒ42/40 ratio in the post-pandemic phase, indicating higher risk of AD; atrophy in hippocampal and prefrontal volume (structural MRI) and reduced global functional connectivity (resting-state fMRI). Modifiers of these effects (Aim 2) include exercise and mindfulness; psychological resilience; COVID-19 exposure; medical morbidities; and APOE genotype. Mechanisms of cognitive, emotional, and brain health changes (Aim 3) include amyloid (Aβ40 and Aβ42), SASP, DNA methylation, and cortisol during the pandemic. This project will advance our knowledge of the impact of social isolation and other stressors on older adults, including mechanisms by which these stressors produce deleterious cognitive, emotional, and brain health changes over time, and whether exercise and mindfulness have durable protective effects.