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A Precision Aging Approach to Cognitive Aging: Clustering Multiple Domains of Risk

Ryan, L.; Ortiz, O. S.; Pettigrew, C. A.; Soldan, A.; LaFleur, B.; Levin, B.; Lah, J. J.; Hay, M.; Moghekar, A.; Doyle, K. P.; Barnes, C. A.; Huentelman, M. J.

2026-08-21 neurology
10.64898/2026.08.18.26360626 medRxiv
Show abstract

The term Precision Aging describes an approach that focuses on multi-domain profiles of risks impacting individual trajectories of age-related cognitive functioning. The goal of the present study was to identify profiles of risk within a sample of 555 adults, ages 50 to 79, without diagnosis of dementia. Using cluster analyses, we considered 38 risk factors associated with five categories of risk known to negatively impact cognitive aging - cardiovascular insufficiency, glucose dysregulation, inflammation, immune dysfunction, and neuropathology. Results yielded five profiles, including a group with low risk in all five risk categories, and four groups with prominent risks in specific domains. Importantly, all four high risk groups performed more poorly relative to the low risk group on multiple memory measures from a well-established neuropsychological test, the Auditory Verbal Learning Test. The results highlight the importance of considering multiple domains of risk within the same cohort to predict age-related cognitive functioning.

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