O4‐11‐03: U.S. Pointer: Study Design and Launch

There is an urgent need to expand the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) results in geographically and culturally diverse populations to test the generalizability, adaptability and sustainability. U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), the first such study to be conducted in large group of individuals across the U.S, is a 2-year RCT to evaluate whether lifestyle interventions that simultaneously target many risk factors for cognitive decline and dementia can protect cognitive function in older adults (60-79 years old) at increased risk for cognitive impairment and dementia. U.S. POINTER will enroll 2,000 older adults (60-79 years) who may be at increased risk for cognitive decline owing to first degree family history of significant memory impairment, sedentary lifestyle, poor diet, and suboptimum cardio-metabolic health status. Enrolled participants will be randomized to one of two lifestyle intervention groups that differ in intensity and format. The local chapters of the Alzheimer's Association together with lifestyle specialists will be instrumental in delivering and monitoring intervention uptake and adherence. The primary outcome will be 2-year cognitive trajectory using a global composite score that will allow harmonization with FINGER, and its other progenies across the globe through Worldwide-FINGERS, and with large pharmacologic prevention trials in cognitively normal older adults (e.g., A4) and with single domain lifestyle intervention studies in adults with early stage cognitive impairment (e.g., EXERT). Intervention effects on vascular and metabolic health, physical function, mood, sleep, healthcare utilization and quality of life will also be assessed. The trial has launched at one vanguard site in January 2019, and at two to three other sites in Summer 2019. U.S. POINTER provides an unprecedented opportunity to test whether intensive lifestyle modification can protect cognitive function in older Americans who are at increased risk of cognitive decline and dementia. The lessons learned in U.S. POINTER will inform the design and implementation of future studies, studies that may one day push pharmacologic approaches to include lifestyle modification with the goal of improving brain health and thus responsivity to an investigational agent.