Results from the Systematic Multi‐domain Alzheimer’s Risk Reduction Trial (SMARRT): A Personalized Approach

Background Modifiable risk factors are hypothesized to account for 30‐40% of dementia; yet, few trials have demonstrated that risk reduction interventions, especially multi‐domain, improve risk factors or cognition. We conducted the Systematic Multi‐domain Alzheimer’s Risk Reduction Trial (SMARRT), a 2‐year personalized, pragmatic risk reduction intervention. Methods We recruited 172 adults at elevated risk for dementia (age 70‐89 and ≥ 2 targeted risk factors) from primary care clinics of Kaiser Permanente Washington. Participants were randomly assigned to the SMARRT intervention (personalized risk reduction goals with health/nurse coaching) or to Health Education (HE) control. The primary outcome was change in a composite modified Neuropsychological Test Battery (mNTB); pre‐planned secondary outcomes were change in risk factors and quality of life. Outcomes were assessed at baseline, 6, 12, 18, and 24 months (initially in person, then due to COVID‐19, by phone). We used linear mixed models to compare, by intention‐to‐treat, changes from baseline averaged over the four follow‐up assessments. Results Participants had a mean age of 75.7 years (sd 4.8), 63% were women and 81% non‐Hispanic White. After 2 years, compared to the 90 in the HE control, the 82 adults assigned to SMARRT demonstrated larger improvements in the composite cognitive score (average treatment effect 0.15 SD; 95% CI 0.04‐0.26, p = 0.008; an 80% improvement compared to HE change), better composite risk factor score (average treatment effect 0.11 SD; 95% CI 0.02‐0.21, p = 0.02) and improved quality of life (average treatment effect 1.11 points; 95% CI 0.08‐2.14, p = 0.03). There were no between‐group differences in serious adverse events or SAEs (HE = 23, SMARRT = 24, p = 0.59), but the intervention group had greater treatment related AEs such as musculoskeletal pain (14 vs. 0, p