Evidence mapPaperPMID 33435977Full record

SynthesisBMC medicine2021

Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews.

Alexios-Fotios A Mentis, Efthimios Dardiotis, Vasiliki Efthymiou, George P Chrousos

Erratum issuedOpen access · goldAbstract readSystematic Review
In one paragraph

Synthesis in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 5 pooled it
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 5 syntheses or guidelines pooled it, 63 citations in OpenAlex.

  1. Pooled it
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  6. Article
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  9. Unraveling the molecular mechanisms of aluminium chloride-induced Alzheimer's disease.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
  10. Article
  11. Personalized prevention of neurodegenerative diseases: scoping review and evidence gap map.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  12. Towards effective interventions: scoping review on prevention and modifiable risk factors of neurodegenerative diseases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Article
  13. Review
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  15. Article
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  19. Genome-wide association studies of coffee intake in UK/US participants of European ancestry uncover cohort-specific genetic associations.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Alexios-Fotios A MentisPublic Health Laboratories, Hellenic Pasteur Institute, Athens, Greece; and, Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece. amentis1@jhu.edu.ORCID http://orcid.org/0000-0002-1480-390X
Efthimios DardiotisDepartment of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece.
Vasiliki EfthymiouUniversity Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece.
George P ChrousosUniversity Research Institute of Maternal and Child Health and Precision Medicine, and UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Athens, Greece.
National and Kapodistrian University of Athens · GRUniversity of Thessaly · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases.

methodsWe performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified.

resultsWe identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia.

conclusionsWe identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).

Indexed as

BiomarkersDiet, MediterraneanExerciseHumansHypertensionNervous System DiseasesProtective FactorsRisk FactorsBiomarkersBrain diseasesMeta-analysisNervous system diseasesProtective factorsRisk factorsSystematic reviewUmbrella review

Identifiers

PMID33435977
PMCPMC7805241
OpenAlexW3118471424

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.