Abstract
BACKGROUND: Multidomain lifestyle interventions hold promise as approaches to slow aging. Deficit accumulation frailty indices (FIs) are increasingly used to capture aging processes. Frailty is highly associated with increased mortality and chronic disease risk, but the degree to which multidomain lifestyle changes impact frailty is not clear. METHODS: The U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) was a 2-year randomized clinical trial to compare two multidomain lifestyle interventions designed to increase exercise, improve diet, and promote social and cognitive stimulating activities and health monitoring. The Structured intervention incorporated greater structure, intensity, and accountability than the Self-Guided intervention. A modified FI (mFI) was developed from data collected at baseline, 12, and 24 months. RESULTS: The trial enrolled 2111 adults (ages 60-79 years) who were at increased risk for accelerated cognitive decline. At 24 months, the mean (standard error) changes from baseline of a 31-component mFI were -0.009 (0.002) for Self-Guided and -0.024 (0.002) for Structured participants, a difference averaging -0.014 [-0.019, -0.008] (P < .0001). Group differences were similar across subgroups based on age, sex, body mass index, diabetes, and baseline mFI. Changes in mFI did not account for the relative cognitive benefits provided by the Structured intervention compared to the Self-Guided intervention. CONCLUSIONS: Multidomain lifestyle interventions may decrease frailty and slow aging processes with greater structure and intensity, resulting in greater benefits. CLINICAL TRIAL REGISTRATION NUMBER: NCT03688126.