Feedback mechanisms between physical frailty and cognitive declines in older community-dwelling adults: The Rancho Bernardo Study.

This study investigates bidirectional feedback mechanisms between physical frailty and cognitive decline in older adults using 12-year longitudinal data from the Rancho Bernardo Study. Frailty phenotypes were assessed through measures of body composition (appendicular lean mass, adjusted by BMI and height squared), weakness (handgrip strength), and physical functioning (Timed Up-and-Go test and 5-times chair stand test). Cognitive function was evaluated using the Mini-Mental State Examination (global cognitive function), Trail Making Test (executive function), Category Fluency Test (semantic memory), and Buschke-Fuld Selective Reminding Test (verbal episodic memory). We propose a mediation-based approach to model the temporal sequences within the complex system of frailty, and found significant reciprocal associations between physical and cognitive decline. For example, muscle strength fully mediated the association between prior body composition and subsequent cognitive functions, and vice versa. These findings advance the understanding of frailty as a dynamic, multifaceted syndrome by elucidating the direct and indirect pathways across its functional domains, highlighting muscle strength as a pivotal target for screening and interventions to mitigate frailty progression.