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Precision Aging: Profiles of Risk Related to Cognitive Impairment Among Older Adults

Poster Session A - Saturday, March 7, 3:00 – 5:00 pm, Fairview/Kitsilano Ballrooms

Lee Ryan¹ (ryant@arizona.edu), Olivia Ortiz¹, Matthew Huentelman²; ¹University of Arizona, ²Translational Genomics Institute

Numerous factors are associated with increased risk for age-related cognitive impairment, including cardiovascular risks such as hypertension, obesity, and heart disease, as well as diabetes, inflammation, and immune dysfunction, among many others. But each factor generally explains only a small portion of the variance in cognitive functioning, and few studies have considered combinations of risk factors in order to understand their collective impact on age-related cognitive functioning (Ryan et al. 2019, 2025). Drawing on data from 555 participants, ages 50-79, enrolled in the Precision Aging Network study (https://precisionagingnetwork.org/), we employed cluster analysis methods to determine profiles of factors (including genetics, blood biomarkers, medical diagnoses, and medication use) from five risk categories: cardiovascular health, glucose regulation, neuropathology, immune function, and inflammation. We identified four relatively independent clusters that reflected high risk for glucose dysregulation, immune dysfunction, neuropathology, and inflammation. Interestingly, cardiovascular risks did not cluster separately, but instead were spread relatively equally across the four high risk clusters, as well as a 'low risk' cluster with few risks relative to the other groups. Importantly, each of the high risk clusters differed from the low risk group on measures of memory, executive functions (working memory, switching inhibition), and choice reaction time, controlling for age, education, and sex. The results highlight the importance of taking an individualized approach to determining factors that impact brain aging and risk for age-related cognitive impairment, in order to develop personalized interventions that optimize brain health and cognitive health across the adult lifespan.

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