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Mechanisms of interventions targeting modifiable factors for dementia risk reduction
Anna Matton, Ruth Anna Stephen, Makrina Daniilidou, Mariagnese Barbera, Vilma Alanko, Marcel Ballin, Jamie Ford, Katri Hemiö et al.. Molecular Neurodegeneration, 2025-06-23
Topic: Risk, prevention and care in population studies
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.
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APA 7th
Matton, A., Stephen, R. A., Daniilidou, M., Barbera, M., Alanko, V., Ballin, M., et al. (2025). Mechanisms of interventions targeting modifiable factors for dementia risk reduction. Molecular Neurodegeneration. https://doi.org/10.1186/s13024-025-00845-w
Vancouver
Matton A, Stephen RA, Daniilidou M, Barbera M, Alanko V, Ballin M, et al. Mechanisms of interventions targeting modifiable factors for dementia risk reduction. Molecular Neurodegeneration. 2025. doi:10.1186/s13024-025-00845-w. PMID: 40551205.
BibTeX
@article{matton2025-40551205,
author = {Matton, Anna and Stephen, Ruth Anna and Daniilidou, Makrina and Barbera, Mariagnese and Alanko, Vilma and Ballin, Marcel and Ford, Jamie and Hemiö, Katri and others},
title = {{Mechanisms of interventions targeting modifiable factors for dementia risk reduction}},
journal = {Molecular Neurodegeneration},
year = {2025},
doi = {10.1186/s13024-025-00845-w},
pmid = {40551205},
url = {https://doi.org/10.1186/s13024-025-00845-w}
}
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Key findings
- The findings of this review underscore the potential of lifestyle-based interventions in modulating several different types of pathophysiological pathways associated with dementia.
Why it matters
This review examined how lifestyle interventions for dementia risk reduction may work, finding the most evidence for neuroimaging biomarkers and less conclusive evidence for fluid biomarkers, vascular markers, inflammatory markers and neurotrophins. Physical exercise consistently appeared to affect several of these pathways, but the review does not establish that any intervention prevents dementia.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular Neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 14 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 8.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Miia Kivipelto: h-index 107 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Imperial College London: institution h-index 1,744 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40551205) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-025-00845-w
- PubMed: 40551205
- Original source →
- Free full text: Molecular Neurodegeneration →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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