An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial Link to DOI → Authors: Brodaty, H. and Chau, T. and Heffernan, M. and Ginige, J. A. and Andrews, G. and Millard, M. and Sachdev, P. S. and Anstey, K. J. and Lautenschlager, N. T. and McNeil, J. J. and Jorm, L. and Kochan, N. A. and Maeder, A. and Welberry, H. and San Jose, J. C. and Briggs, N. E. and Popovic, G. and Mavros, Y. and Almendrales Rangel, C. and Noble, Y. and Radd-Vagenas, S. and Flood, V. M. and O'Leary, F. and Lampit, A. and Walton, C. C. and Barr, P. and Fiatarone Singh, M. and Valenzuela, M. Year: 2025 Journal: Nat Med Vol/Issue: Vol. 31, No. 2 Pages: 565-573 Study Characteristics Lifestyle Pillars NutritionPhysical Activity Study Design RCT Abstract Effective, scalable dementia prevention interventions are needed to address modifiable risk factors given global burden of dementia and challenges in developing disease-modifying treatments. A single-blind randomized controlled trial assessed an online multidomain lifestyle intervention to prevent cognitive decline over 3 years. Participants were dementia-free community-dwelling Australians aged 55-77 years with modifiable dementia risk factors. Eligible participants (n = 6,104, 64% female) were randomized 1:1 to a personalized schedule of online coaching in two to four modules (targeting physical activity, nutrition, cognitive activity and depression or anxiety) or a control group that received module-eligible information only. At 3 years, the mean change in a global cognitive composite, the primary outcome, was met. The mean changes in z scores were 0.28 (95% confidence interval (CI): 0.25-0.32) for intervention, 0.10 (95% CI: 0.07-0.13) for control and 0.18 (95% CI: 0.13-0.23, P < 0.001) for the between-group difference. Trial-related adverse events occurred in 19 (0.60%) intervention and 1 (0.03%) control participant. Randomization of this internet-delivered lifestyle intervention tailored to individual dementia risk factors resulted in significantly better cognition in older adults over 3 years. This intervention is scalable with the potential for population-level rollout that may delay cognitive decline in the general community. Australian New Zealand ClinicalTrials.gov registration: ACTRN12618000851268.