SynthesisJournal of neurology2025
The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.
Synthesis in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- Article
- Return of genetic results to persons with Parkinson's disease: Blessing or foe?Journal of Parkinson's disease · 2026Review
- Liver Fibrosis and the Risks of Impaired Cognition and Dementia: Mechanisms, Evidence, and Clinical Implications.Medical sciences (Basel, Switzerland) · 2026Review
- Prevention of cognitive decline and dementia: Current evidence on lifestyle factors and dietary patterns.EXCLI journal · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundThe ε4 allele of the apolipoprotein E gene (APOE ε4) is the strongest genetic risk factor for dementia. However, it remains unclear whether APOE ε4 status modulates the associations of non-genetic risk factors and dementia risk. This study aims to comprehensively evaluate this potential modulating role.
methodsA systematic search of electronic databases was conducted up to June 2023. Population-based longitudinal studies were included if they reported associations of risk factors with all-cause dementia (ACD) or Alzheimer's disease (AD) stratified by APOE ε4 status. Subgroup and meta-regression analyses were performed to test stratification effects by APOE ε4.
resultA total of 170 studies (173 factors) were included, with 48 factors for meta-analyses. Meta-regression confirmed significant modification effect by APOE ε4 status for nine risk factors. Stronger associations in APOE ε4 carriers were found for nonsteroidal anti-inflammatory drugs, statins, frequent drinking, and high systolic blood pressure; in noncarriers, stronger associations were observed for light-to-moderate alcohol consumption, female sex, physical activity, diabetes, and loneliness. Diabetes specifically increased AD risk only in APOE ε4 noncarriers. Additionally, the subgroup analyses stratified by APOE ε4 status indicated that nine other factors may influence risk differentially between carriers and noncarriers, though the associations were not significant in meta-regression (vitamin E intake, heart failure, serum neurofilament light chain, serum testosterone, agitation, air NO
conclusionEvidence from the current investigation suggests that APOE ε4 defines distinct etiological pathways for dementia, underscoring the promise of genotype-tailored prevention strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.