Lifestyle medicine and brain health: Insights from the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) and the promise of personalization

The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) trial demonstrates that complex, multidomain interventions are feasible, acceptable, and capable of producing measurable cognitive benefits across large, heterogenous populations.While effective, U.S. POINTER produced modest effect sizes, suggesting that some components may not have been sufficiently potent or specific to elicit maximal benefits.To advance beyond feasibility, future multidomain lifestyle interventions should (1) tailor interventions to drive physiological adaptations; (2) leverage the synergistic potential of related behavioral domains; and (3) target sleep and circadian health as central intervention components.