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48/100

✓ Peer-reviewed alzhub usefulness score 48 out of 100. Genetics

Topic: Amyloid, tau and blood-test diagnosis

Background Stroke and APOE ε4 are established risk factors of dementia. However, it remains unclear whether stroke interacts with APOE genotypes to influence dementia occurrence. This study aims to investigate the associations of stroke and its interaction by APOE genotypes with incident risk of dementia, with a specific focus on peripheral clues for biological mechanisms. Methods This prospective cohort study included 336 903 participants (mean age: 56.3 years, stroke history: 1.3%, APOE ε4: 28.5%) from the UK Biobank, with a median follow‐up of 13 years. Cumulative incidence curves were constructed using Fine–Gray death competing risks analysis. The additive and multiplicative interaction of stroke (including ischemic and hemorrhagic stroke) with APOE genotypes on incident risk of all‐cause dementia (ACD) and Alzheimer disease were examined. Blood proteomics combined with bioinformatics analyses were used to explore the peripheral clues for biological mechanisms. Results Either ischemic or hemorrhagic stroke was significantly associated with elevated risk of ACD and Alzheimer disease ( P <0.001). A significant multiplicative interaction was observed between stroke and APOE ε4 ( P <0.001). The association of stroke with increased risk of dementia was stronger in APOE ε4 non‐carriers than carriers, for both ACD (hazard ratio [HR], 1.93 for carriers and 3.36 for non‐carriers, P <0.001) and AD (HR, 1.14 for carriers and 2.67 for non‐carriers, P <0.001). Inflammation‐related pathways could be mechanisms underpinning the association of stroke with ACD risk. We identified 191 functionally interconnected ( P <1.0×10 −16 ) proteins associated with both stroke and ACD only in APOE ε4 non‐carriers. CD4‐related and TGF‐beta (transforming growth factor beta) signaling pathway could mediate the strengthened relationship in APOE ε4 non‐carriers. Conclusions Stroke interacts with APOE ε4 to influence dementia, with the association being more pronounced in APOE ε4 non‐carriers. Future studies are needed to verify the underpinning mechanisms to guide precise prevention.

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APA 7th

Zhang, C., Huang, L., Feng, Y., Tan, C., Tan, L., & Xu, W. (2025). APOE Genotype Modulates the Relationship of Stroke With Dementia Risk: Associations and Peripheral Clues for Biological Mechanisms. Journal of the American Heart Association. https://doi.org/10.1161/jaha.125.043446

Vancouver

Zhang C, Huang L, Feng Y, Tan C, Tan L, Xu W. APOE Genotype Modulates the Relationship of Stroke With Dementia Risk: Associations and Peripheral Clues for Biological Mechanisms. Journal of the American Heart Association. 2025. doi:10.1161/jaha.125.043446. PMID: 41404739.

BibTeX

@article{zhang2025-41404739,
  author  = {Zhang, Chong‐Hui and Huang, Liang‐Yu and Feng, Yu‐Gong and Tan, Chen‐Chen and Tan, Lan and Xu, Wei},
  title   = {{APOE Genotype Modulates the Relationship of Stroke With Dementia Risk: Associations and Peripheral Clues for Biological Mechanisms}},
  journal = {Journal of the American Heart Association},
  year    = {2025},
  doi     = {10.1161/jaha.125.043446},
  pmid    = {41404739},
  url     = {https://doi.org/10.1161/jaha.125.043446}
}

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Key findings

Results Either ischemic or hemorrhagic stroke was significantly associated with elevated risk of ACD and Alzheimer disease ( P <0.001).
A significant multiplicative interaction was observed between stroke and APOE ε4 ( P <0.001).
The association of stroke with increased risk of dementia was stronger in APOE ε4 non‐carriers than carriers, for both ACD (hazard ratio [HR], 1.93 for carriers and 3.36 for non‐carriers, P <0.001) and AD (HR, 1.14 for carriers and 2.67 for non‐carriers, P <0.001).
We identified 191 functionally interconnected ( P <1.0×10 −16 ) proteins associated with both stroke and ACD only in APOE ε4 non‐carriers.

Why it matters

In this UK Biobank cohort of over 336,000 participants, both ischemic and hemorrhagic stroke were significantly associated with elevated risk of all-cause dementia and Alzheimer disease. The association of stroke with increased dementia risk was stronger in APOE ε4 non-carriers than carriers, with a significant interaction between stroke and APOE ε4.

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Study details

Study designcohort study
Participants336
Effect size1.3%; 28.5%
Evidence strengthModerate

How this study scored 48/100

Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Journal of the American Heart Association)
Journal's citation record	2 / 4	Journal of the American Heart Association: journal h-index 200 (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	2 / 4	336 participants
Effect reported	2 / 3	Effect reported as a number, without an interval or test
Studied in people	3 / 3	Studied in people (participant count stated)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	0 / 7	Cited 0 times (OpenAlex, 2026-10-10)
Citations per year	0 / 5	0.0 citations a year over 3 year(s) since 2025
Impact for its field and year	0 / 6	Cited 0.0× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	0 / 4	Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Wei Xu: h-index 42 (OpenAlex, whole career)
Institution's track record	0 / 3	Qingdao University: institution h-index 430 (OpenAlex)
Multicenter collaboration	2 / 3	OpenAlex lists 4 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 41404739)
Free to read	2 / 2	Free to read
Total	48 / 100	—

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