Age, Multidomain Lifestyle Intervention, and White Matter Integrity

Importance: Multidomain lifestyle interventions slow cognitive decline in at-risk older adults, but effects on cerebrovascular injury and whether any effect differs by age or across magnetic resonance imaging (MRI) markers remain unclear. Objectives: To test whether a structured multidomain lifestyle intervention, vs a self-guided program, alters trajectories of cerebrovascular MRI markers and whether baseline diffusion MRI estimates subsequent vascular injury. Design, Setting, and Participants: POINTER Imaging was a prespecified secondary imaging analysis of the US POINTER (US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk) randomized clinical trial conducted at multiple US sites. Starting August 1, 2020, and continuing until March 1, 2023, all newly enrolled US POINTER trial participants who met criteria, including being 60 to 79 years of age and at increased risk for cognitive decline, were given the opportunity to enroll in POINTER Imaging. Annual MRIs were performed at baseline and up to 2 follow-up visits at 12 and 24 months. The imaging study ended May 14, 2025. Interventions: Structured multidomain lifestyle arm (supervised exercise, dietary counseling, cognitive and social engagement, and health coaching) vs self-guided educational arm. Main Outcomes and Measures: Primary outcomes were cerebrovascular MRI markers of global white matter free water (FW), fractional anisotropy (FA), peak width of skeletonized mean diffusivity (PSMD), analysis along the perivascular space (ALPS) index, white matter hyperintensity (WMH) volume, and incident cerebral microbleeds (CMBs). Age-group analyses (