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An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial

Nature Medicine volume 31, pages 565–573 (2025)Cite this article

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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.

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Fig. 1: Overall trial procedure for both intervention and control participants.
Fig. 2: Flow chart from recruitment to randomization.
Fig. 3: Change in cognition (z score) from baseline to 3 years by group (n = 6,104).
Fig. 4: Mean change and relative rate of change in other health-related outcomes from baseline to 3 years by group (n = 6,104).

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Data availability

Deidentified data collected for the trial, including individual participant data and data dictionaries, will be made available upon review and approval. Proposals need to be scientifically valid and methodologically sound. A signed data access agreement is needed to access data as per Ethics Committee requirements. Please contact MED CHeBA Data ([email protected]). The trial protocol is published16.

Code availability

The code for the data analysis is also available upon request to MED CHeBA Data ([email protected]).

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Acknowledgements

This trial was funded by a National Health and Medical Research Council (NHMRC) Dementia Research Team Grant (APP1095097). The funder had no role in the study design, data collection, data analysis, data interpretation or writing of the manuscript. This research was completed using data collected through the 45 and Up Study (www.saxinstitute.org.au). The 45 and Up Study is managed by the Sax Institute in collaboration with major partner Cancer Council NSW and partners the Heart Foundation and the NSW Ministry of Health. We thank the many thousands of people participating in the 45 and Up Study, particularly those who made the MYB trial possible. We acknowledge the contributions of the MYB Collaborative Team (N. Bosler, C. Boulamatsis, H. Christensen, I. Chuprov, L. Cobiac, K. Cox, J. Gunn, F. Harrison, A. Hayen, M. Hobbs, M. Kivipelto, H. Lapsley, J. Meiklejohn and S. Redman) and the MYB DSMB (J. Close, R. Day and M. Law). MYB used software developed by CogState, Creyos, NeuroNation and This Way Up. We also sought permission from Amsterdam Centrum to use the Amsterdam Instrumental Activity of Daily Living Questionnaire short version (A-IADL-Q-SV). MYB thanks Signs Publishing for a nonexclusive license to use traditional Mediterranean recipes from Food as Medicine: Cooking for Your Best Health by S.R.-V. and Adventist Media Network for the production and use of cooking videos. M.V. is supported by an NHMRC career development fellowship (APP1112813). K.J.A. is funded by ARC FL190100011. P.S.S. is supported by an NHMRC Investigator Grant.

Author information

Author notes

  1. Juan Carlo San Jose

    Present address: Centre for Healthy Brain Ageing (CHeBA), School of Clinical Medicine, UNSW Sydney, Sydney, New South Wales, Australia

  2. These authors contributed equally: Maria Fiatarone Singh, Michael Valenzuela.

Authors and Affiliations

  1. Centre for Healthy Brain Ageing (CHeBA), School of Clinical Medicine, UNSW Sydney, Sydney, New South Wales, Australia

    Henry Brodaty, Tiffany Chau, Megan Heffernan, Perminder S. Sachdev, Nicole A. Kochan & Michael Valenzuela

  2. School of Computer, Data and Mathematical Sciences, Western Sydney University, Sydney, New South Wales, Australia

    Jeewani A. Ginige

  3. Clinical Research Unit for Anxiety and Depression, School of Psychiatry, UNSW Sydney, Sydney, New South Wales, Australia

    Gavin Andrews & Michael Millard

  4. School of Psychology, UNSW Sydney, Sydney, New South Wales, Australia

    Kaarin J. Anstey

  5. UNSW Ageing Futures Institute, UNSW Sydney, Sydney, New South Wales, Australia

    Kaarin J. Anstey

  6. Neuroscience Research Australia, Sydney, New South Wales, Australia

    Kaarin J. Anstey

  7. Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia

    Nicola T. Lautenschlager & Amit Lampit

  8. Royal Melbourne Hospital Mental Health Services, Royal Melbourne Hospital, Parkville, Victoria, Australia

    Nicola T. Lautenschlager

  9. School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

    John J. McNeil

  10. Centre for Big Data Research in Health, UNSW Sydney, Sydney, New South Wales, Australia

    Louisa Jorm & Heidi Welberry

  11. College of Nursing and Health Sciences, Flinders University, Adelaide, South Australia, Australia

    Anthony Maeder

  12. Research Technology Services (ResTech), UNSW Sydney, Sydney, New South Wales, Australia

    Juan Carlo San Jose

  13. Stats Central, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, New South Wales, Australia

    Nancy E. Briggs & Gordana Popovic

  14. School of Health Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia

    Yorgi Mavros, Carolina Almendrales Rangel, Yian Noble, Sue Radd-Vagenas, Victoria M. Flood & Maria Fiatarone Singh

  15. Heat and Health Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Noth South Wales, Australia

    Yorgi Mavros

  16. University Centre for Rural Health, Northern Rivers, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia

    Victoria M. Flood

  17. Susan Wakil School of Nursing and Midwifery, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia

    Fiona O’Leary

  18. The Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia

    Fiona O’Leary

  19. Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, Victoria, Australia

    Courtney C. Walton

  20. School of Psychological Science, University of Bristol, Bristol, UK

    Polly Barr

  21. Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA

    Maria Fiatarone Singh

  22. Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia

    Maria Fiatarone Singh

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  1. Henry Brodaty
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Contributions

H.B., M.H. and T.C. wrote the first draft of the manuscript. H.B., M.V., M.F.S., P.S.S., K.J.A., N.T.L., J.J.M., L.J., G.A. and A.M. contributed to the design of the trial. M.F.S. led the physical activity and nutrition modules assisted by Y.M., S.R.-V., V.M.F., Y.N., F.O’.L. and C.A.R. M.V. led the brain training module assisted by P.B., C.C.W. and A.L. G.A. developed This Way Up, the peace of mind intervention module. T.C. led the control modules and curated the information for the control group. M.H. coordinated the trial. N.K. led the design of cognitive assessments and validation. N.E.B. and G.P. performed the statistical analyses. M.H. and H.W. contributed to statistical analyses. M.H., T.C. and J.C.S.J. had full access and managed all data in the trial. A.M. and J.A.G. led the development of the MYB digital platform, which was managed by J.C.S.J. All authors had final responsibility for the decision to submit for publication. They reviewed and contributed to drafts of the manuscript and approved the final manuscript. M.H., N.E.B. and G.P. directly accessed and verified the underlying data reported in the manuscript. H.B. is the chief investigator.

Corresponding author

Correspondence to Henry Brodaty.

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Competing interests

H.B. has been an advisory board member or consultant to Biogen, Eisai, Eli Lilly, Medicines Australia, Roche, Skin2Neuron Pty, Cranbrook Care and Montefiore Homes. P.S.S. was a member of expert panels for Biogen and Roche in 2020 and 2021. M.V. has a financial interest in and is cofounder and CEO of Skin2Neuron Pty, unrelated to this work. The other authors declare no competing interests.

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Nature Medicine thanks Tao Chen, Gill Livingston and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Jerome Staal, in collaboration with the Nature Medicine team.

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Brodaty, H., Chau, T., Heffernan, M. et al. An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial. Nat Med 31, 565–573 (2025). https://doi.org/10.1038/s41591-024-03351-6

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