Abstract

Introduction: This study examined longitudinal associations between self-reported exercise and cognition, with moderation by sex, in individuals with autosomal dominant Alzheimer's disease (ADAD) mutations. We also examined whether changes in exercise over time differed in ADAD mutation carriers versus non-carriers in the years preceding first cognitive symptom onset. Methods: Participants (n = 491) were ADAD mutation carriers (63%) and non-carriers (37%) from the Dominantly Inherited Alzheimer Network aged 37.6 ± 11.1 years. Participants reported their average time partaking in various leisure-time exercise activities over the past 12 months. Results: Greater baseline exercise predicted better longitudinal cognitive performance. Sex did not moderate these associations. In the years preceding first cognitive symptoms or last follow-up visit, mutation carriers showed a decline in their exercise engagement compared to mutation non-carriers. Discussion: Self-reported exercise is associated with preserved cognitive function in those with ADAD mutations; however, AD-related pathways may influence the level of engagement in exercise prior to cognitive symptom onset. Highlights: Greater weekly exercise predicts slower cognitive decline in ADAD mutation carriers. These associations varied dependent on closeness to estimated symptom onset. These associations were not moderated by sex. Weekly exercise declined in ADAD mutation carriers compared to non-carriers. Results may suggest a bidirectional relationship between exercise and AD risk.

Keywords

Autosomal dominant Alzheimer's disease, cognition, cognitive function, exercise

Document Type

Journal Article

Date of Publication

6-1-2025

Volume

21

Issue

6

PubMed ID

40534311

Publisher

Wiley

School

Centre of Excellence for Alzheimer's Disease Research and Care / Centre for Precision Health / School of Medical and Health Sciences

RAS ID

82503

Funding Information

SRRS is supported by a National Health and Medical Research Council (NHMRC) Investigator Grant (GNT1197315). BMB is supported by the Western Australian Future Health Research & Innovation Fund. Data collection and sharing for this project was supported by the Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA), the Alzheimer's Association (SG-20-690363-DIAN), the German Center for Neurodegenerative Diseases (DZNE), and Raul Carrea Institute for Neurological Research (FLENI). In addition, partial support was provided by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development (AMED), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea RS-2024-00344521, and Spanish Institute of Health Carlos III (ISCIII).

Funding received from the National Health and Medical Research Council (NHMRC)

GNT1197315

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Comments

Sewell, K. R., Doecke, J. D., Martins, R. N., Rainey‐Smith, S. R., Peiffer, J., Gardener, S. L., Sohrabi, H. R., Erickson, K. I., & Brown, B. M. (2025). Longitudinal associations between self‐reported exercise levels and cognition in ADAD. Alzheimer's & Dementia, 21(6). https://doi.org/10.1002/alz.70383

Recommended Citation

Sewell, K. R., Doecke, J. D., Martins, R. N., Rainey‐Smith, S. R., Peiffer, J., Gardener, S. L., Sohrabi, H. R., Erickson, K. I., & Brown, B. M. (2025). Longitudinal associations between self‐reported exercise levels and cognition in ADAD. Alzheimer's & Dementia, 21(6). https://doi.org/10.1002/alz.70383

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