Wednesday, January 15, 2025
1/15/2025
ABSTRACT Substantial research demonstrates dispositional optimism is related to reduced mortality; fewer studies evaluate optimism specifically in relation to cognitive health - despite the critical importance of cognitive aging to healthspan. Alzheimer's disease and related dementias (ADRD) are a leading cause of death, and with limited availability of treatment, prevention must be a priority. Given prior work showing optimism is associated with longevity and is also modifiable, identifying a relationship between optimism and less cognitive decline and obtaining greater understanding of mechanisms underlying the associations may help to identify new targets for interventions to improve cognitive aging. We previously identified physical activity as a promising mediator of optimism's association with longevity but did not find evidence to support posited biological pathways (e.g., telomere shortening, epigenetic age). Research on physical activity as a pathway linking higher optimism and cognitive health could provide key details for targeting interventions and demonstrating the full range of ways optimism may alter health. As prior studies of optimism and physical activity were based on self- reported activity, findings lack granularity and may not adequately portray activity levels in aging populations. Also, research on relevant biologic mechanisms linking optimism to better health remains limited; recent findings linking psychological factors with the gut microbiome suggest this may be a promising pathway. We will examine the relationship of optimism to traditional long-term cognitive trajectories in 4 cohorts (Aim 1), focusing on memory as a domain strongly linked to ADRD, as well as associations of optimism with novel, high frequency testing via smartphones to assess cognition in the “natural environment” among 2500 adults ages 60-69 years in a fifth cohort (Aim 2). Together, this will facilitate fuller understanding of associations of optimism with cognitive health across middle and older ages. To pursue research on pathways, we will leverage the mobile app used in Aim 2 to collect intensive physical activity data via accelerometer, to deeply characterize optimism in relation to physical activity (Aim 3). Finally, we will conduct exploratory analyses of optimism and the gut microbiome, leveraging existing stool metagenomic data (n=4500) (Aim 4). We will utilize cohorts with men and women, and multiple diversity groups: Women's Health Initiative Memory Study, Multi- Ethnic Study of Atherosclerosis, Jackson Heart Study, Health and Retirement Study, Nurses' Health Study II (NHSII). We will rigorously harmonize/co-calibrate the cognitive batteries in Aim 1 to compare findings across diverse groups represented in the cohorts; we will collect new data only in NHSII (Aims 2, 3). IMPACT: These Aims, leveraging cohorts spanning both sexes and diverse racial groups, provide new directions for building a science of psychological resilience in ADRD prevention. Findings will reiterate the value of shifting the focus of traditional disease paradigms from reducing risks/deficits to enhancing resilience and building strengths.
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