Matton, A. orcid.org/0000-0002-7819-0495, Stephen, R. orcid.org/0000-0002-3380-9530, Daniilidou, M. orcid.org/0000-0002-5460-9802 et al. (15 more authors) (2025) Mechanisms of interventions targeting modifiable factors for dementia risk reduction. Molecular Neurodegeneration, 20 (1). 75. ISSN 1750-1326
Abstract
The global prevalence of dementia is increasing. With no widely available and accessible treatments to halt or reverse the progression of dementia, exploring preventative strategies is critical. Lifestyle-based interventions show promise in preventing or delaying dementia onset. However, understanding the complex and multifactorial mechanisms underlying dementia, and how interventions target these pathways, is essential for developing personalized and effective strategies. In this review, we examined the current evidence of the mediating pathways in dementia risk reduction. We focused on mechanisms investigated in single-domain interventions on physical exercise, cognitive training, diet, metabolic/cardiovascular or psycho-social risk factors in line with those combined in the landmark FINGER trial. Additionally, we synthesized existing literature on mechanisms of action in multimodal interventions combining multiple lifestyle changes. Most evidence was identified in relation to neuroimaging biomarkers with positive effects for all intervention components. The evidence among fluid biomarkers of Alzheimer’s disease and related disorders (ADRD) (amyloid-beta peptide (Aβ), tau and neurofilament light chain (Nfl)) vascular markers, inflammatory markers, and neurotrophins were less conclusive, though physical exercise consistently appeared to impact several of these pathways. The findings of this review underscore the potential of lifestyle-based interventions in modulating several different types of pathophysiological pathways associated with dementia. As the number of dementia cases reach epidemic proportions, a multifaceted approach is needed. We propose that the next critical step in dementia prevention/risk reduction is to refine existing intervention tools and develop an adaptive platform that integrates different lifestyle interventions tailored to individual risk profiles and needs. Understanding the underlying mechanisms and biomarkers related to modifiable risk factors will be instrumental to optimising these interventions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2025. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Jun 2025 15:36 |
Last Modified: | 30 Jun 2025 15:36 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1186/s13024-025-00845-w |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:228530 |