This is a revised new investigator submission (AGO25119-01) in response to a PA on frailty. Over one-third of adults over age 65 report at least one severe disability. The concept of """"""""frailty"""""""" has been used to identify older adults with low physiological reserves at increased risk for disability. However, clinical and biological markers of early frailty in older adults are lacking. We plan to address this gap by building on an ongoing, prospective cohort study of older adults, the Einstein Aging Study. Subclinical functional loss in nondisabled older adults may not be apparent on routine evaluation, but may manifest in stress due to low reserves providing a clinically relevant approach to identify individuals at risk for disability. In this proposal, we define latent mobility abnormalities as subclinical mobility loss unmasked by physical and cognitive stresses. The specific hypothesis to be evaluated is that latent mobility abnormalities will identify frailty and predict disability in nondisabled older adults with normal mobility. Specifically, we will 1) Examine latent mobility abnormalities in response to physical and cognitive stress tests as predictors of disability. 2) Establish the biological basis of latent mobility abnormalities, focusing on inflammatory markers. 3). Since subclinical disease may lead to suboptimal mobility performance, we will also study daily intra-individual variability in mobility in six sessions over a two-week period in a subset of subjects as a marker of very early frailty. To achieve these aims, 300 initially nondisabled older adults participating in the Einstein Aging Study will be recruited and assessed with comprehensive qualitative and quantitative mobility assessments at six monthly intervals over five years. These studies will provide new and vital information about the cognitive and physical attributes of early frailty, their biological basis, and identify opportunities to introduce specific interventions very early in at-risk older adults to ameliorate disability and maintain functional independence.
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