Prioritizing Modifiable Risk Factors for Dementia Prevention across the Spectrum of Genetic Susceptibility: A Prospective Cohort Study
Tian F, Zhao J, Chen L, Wei S, Lin H. Annals of Neurology, 2025-10-14
Topic: Risk, prevention and care in population studies
Objective Various modifiable risk factors have been identified for dementia, but it remains unclear whether these associations and importance vary according to genetic predisposition. Methods We included 182,473 dementia-free individuals from United Kingdom (UK) Biobank cohort. We calculated the hazard ratios (HRs) and population-attributable fractions (PAF) of 11 modifiable risk factors (smoking status, drinking status, diet, physical activity, hypertension, diabetes, waist-to-hip ratio, education, depression, social contact, and air pollution) for dementia in general population and across various genetic groups based on APOE genotypes and a weighted polygenic-risk score (PRS). Results During 12.42-year follow-up, a total of 2,065 incident all-cause dementia (ACD) cases were documented. Low social contact, diabetes, and abdominal obesity were top 3 modifiable risk factors associated with an increased risk of dementia, especially in low APOE risk (ε2ε2 or ε2ε3) group. The HRs associated with low social contact, diabetes, and abdominal obesity were 3.86 (95% CI: 2.08-7.17), 2.18 (95% CI: 1.43-3.32) and 1.29 (95% CI: 0.88-1.89) for dementia in the low APOE risk. The same patterns were also observed in PRS groups. In terms of PAFs, abdominal obesity contributed the most in low genetic risk groups (PAF: 13.68 to 15.73%). In contrast, less education was the largest contributor in high APOE and high PRS groups (PAF: 11.35% [95% CI: 5.32-17.38%] and 11.24% [95% CI: 4.40-18.07%], respectively), followed by hypertension (PAF: 9.09% [95% CI: 2.01-16.17%] and 5.29% [95% CI: -2.72 to 13.29%], respectively). Overall, the total PAF decreased with increasing genetic risk, particularly for metabolic risk factors. Interpretation Our findings highlight the importance of personalized risk assessments and the development of tailored interventions based on genetic background to prevent dementia more effectively. ANN NEUROL 2025;98:1210-1221.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tian, F., Zhao, J., Chen, L., Wei, S., & Lin, H. (2025). Prioritizing Modifiable Risk Factors for Dementia Prevention across the Spectrum of Genetic Susceptibility: A Prospective Cohort Study. Annals of Neurology. https://doi.org/10.1002/ana.78060
Vancouver
Tian F, Zhao J, Chen L, Wei S, Lin H. Prioritizing Modifiable Risk Factors for Dementia Prevention across the Spectrum of Genetic Susceptibility: A Prospective Cohort Study. Annals of Neurology. 2025. doi:10.1002/ana.78060. PMID: 41085200.
BibTeX
@article{tian2025-41085200,
author = {Tian, F. and Zhao, J. and Chen, L. and Wei, S. and Lin, H.},
title = {{Prioritizing Modifiable Risk Factors for Dementia Prevention across the Spectrum of Genetic Susceptibility: A Prospective Cohort Study}},
journal = {Annals of Neurology},
year = {2025},
doi = {10.1002/ana.78060},
pmid = {41085200},
url = {https://doi.org/10.1002/ana.78060}
}
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Key findings
- Results During 12.42-year follow-up, a total of 2,065 incident all-cause dementia (ACD) cases were documented.
- Low social contact, diabetes, and abdominal obesity were top 3 modifiable risk factors associated with an increased risk of dementia, especially in low APOE risk (ε2ε2 or ε2ε3) group.
- The HRs associated with low social contact, diabetes, and abdominal obesity were 3.86 (95% CI: 2.08-7.17), 2.18 (95% CI: 1.43-3.32) and 1.29 (95% CI: 0.88-1.89) for dementia in the low APOE risk.
- Overall, the total PAF decreased with increasing genetic risk, particularly for metabolic risk factors.
- Interpretation Our findings highlight the importance of personalized risk assessments and the development of tailored interventions based on genetic background to prevent dementia more effectively.
Why it matters
Among 182,473 UK Biobank participants, low social contact, diabetes, and abdominal obesity were the top three modifiable risk factors associated with increased dementia risk, especially in the low APOE risk group. Abdominal obesity contributed the most in low genetic risk groups, while less education was the largest contributor in high genetic risk groups.
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Study details
- Study designcohort
- Participants182,473
- Effect sizeLow social contact HR 3.86 (95% CI 2.08-7.17) in low APOE risk group; less education PAF 11.35% in high APOE risk group
- Evidence strengthModerate
Limitations
UK Biobank volunteers are healthier and less diverse than the general population; risk factors measured once at baseline; subgroup estimates have wide intervals; PAFs assume causality.
How this study scored 58/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 57 of the 98 points we could judge it on, which is 58 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of Neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 4 / 4 | 182,473 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Hualiang Lin: h-index 43 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Sun Yat-sen University: institution h-index 851 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41085200) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 57 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 57 of the 98 points we could judge it on is 58 out of 100. |
| Total | 58 / 100 | — |
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