Polygenic risk score and cluster-based analysis suggests links between type 2 diabetes and vascular dementia in the KARE study
Wanqing Dong, Zijian Tian, Jie Bai, Benrui Wu, Mengjie Zhao, Yingyu Zhang, Jian Shao, Tian Xie et al.. Nature communications, 2025-11-19
Topic: Genetics and APOE
Type 2 diabetes is an established risk factor for dementia. However, how its genetic heterogeneity affects different dementia subtypes remains unclear. In this study, we investigate the associations between genetic risk of type 2 diabetes and dementia subtypes among 33,136 older Chinese adults from the KARE cohort. We find that a higher overall polygenic risk score for type 2 diabetes is significantly associated with an increased risk of vascular dementia, but not Alzheimer's disease. Further analyses using cluster-specific partitioned polygenic score show that elevated genetic risk specific to the hyperinsulinemia pathway is strongly associated with increased incidence of vascular dementia. These findings highlight the potential role of insulin-related metabolic abnormalities in the pathogenesis of vascular dementia and provide genetic evidence to support the use of the hyperinsulinaemia pathway as a clinically relevant marker for early risk stratification and precision prevention strategies.
Key findings
- We find that a higher overall polygenic risk score for type 2 diabetes is significantly associated with an increased risk of vascular dementia, but not Alzheimer's disease.
- Further analyses using cluster-specific partitioned polygenic score show that elevated genetic risk specific to the hyperinsulinemia pathway is strongly associated with increased incidence of vascular dementia.
- These findings highlight the potential role of insulin-related metabolic abnormalities in the pathogenesis of vascular dementia and provide genetic evidence to support the use of the hyperinsulinaemia pathway as a clinically relevant marker for early risk stratification and precision prevention strategies.
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Study details
- Evidence strengthModerate
How this study scored 50/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 28 of the 56 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41258170) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 28 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 28 of the 56 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Dong, W., Tian, Z., Bai, J., Wu, B., Zhao, M., Zhang, Y., et al. (2025). Polygenic risk score and cluster-based analysis suggests links between type 2 diabetes and vascular dementia in the KARE study. Nature communications. https://doi.org/10.1038/s41467-025-65252-7
Vancouver
Dong W, Tian Z, Bai J, Wu B, Zhao M, Zhang Y, et al. Polygenic risk score and cluster-based analysis suggests links between type 2 diabetes and vascular dementia in the KARE study. Nature communications. 2025. doi:10.1038/s41467-025-65252-7. PMID: 41258170.
BibTeX
@article{dong2025-41258170,
author = {Dong, Wanqing and Tian, Zijian and Bai, Jie and Wu, Benrui and Zhao, Mengjie and Zhang, Yingyu and Shao, Jian and Xie, Tian and others},
title = {{Polygenic risk score and cluster-based analysis suggests links between type 2 diabetes and vascular dementia in the KARE study}},
journal = {Nature communications},
year = {2025},
doi = {10.1038/s41467-025-65252-7},
pmid = {41258170},
url = {https://doi.org/10.1038/s41467-025-65252-7}
}
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