Evidence map›Paper›PMID 41342141›Full record

SynthesisEuropean journal of neurology2025

Evidence for Causal Links Between Known Modifiable Risk Factors and Dementia: A Systematic Review of Mendelian Randomisation Studies.

Roopal Desai, Amber John, Emma Anderson, Jean Stafford, Aysha Mohamed Rafik Patel, Natalie L Marchant, Georgina Charlesworth, Verena Zuber, Joshua Stott

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Roopal DesaiADAPT Lab, Research Department of Clinical Educational and Health Psychology, University College London, London, UK.ORCID 0000-0003-4221-1546
Amber JohnADAPT Lab, Research Department of Clinical Educational and Health Psychology, University College London, London, UK.ORCID 0000-0002-8207-7698
Emma AndersonDivision of Psychiatry, University College London, London, UK.
Jean StaffordMRC Unit for Lifelong Health and Ageing at UCL, London, UK.
Aysha Mohamed Rafik PatelADAPT Lab, Research Department of Clinical Educational and Health Psychology, University College London, London, UK.
Natalie L MarchantDivision of Psychiatry, University College London, London, UK.
Georgina CharlesworthADAPT Lab, Research Department of Clinical Educational and Health Psychology, University College London, London, UK.
Verena ZuberDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.
Joshua StottADAPT Lab, Research Department of Clinical Educational and Health Psychology, University College London, London, UK.ORCID 0000-0003-1361-053X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe aimed to systematically review the evidence for associations between the known modifiable risk factors and dementia based on Mendelian randomisation (MR) studies.

methodFive databases were searched from inception to April 2024 investigating the association between the 12 risk factors identified in the Lancet Commission and dementia. Evaluable analyses were categorized into one of four levels (robust, probable, suggestive, insufficient) based on estimate significance level and concordance of direction of effect between main and sensitivity analyses. Evidence from clinically diagnosed dementia outcomes was synthesized separately from proxy outcomes. A post hoc sensitivity analysis excluded estimates with concerns over construct validity.

resultsA total of 47 studies were included, representing 240 MR associations (185 unique and evaluable). Over half (73.5%) of evaluable analyses were graded as providing insufficient evidence for a causal association. Among clinically diagnosed outcomes, the strongest evidence was for educational attainment (mainly probable evidence in a protective direction) and type 2 diabetes-related dysfunction (probable evidence in the risk direction). Smoking showed probable evidence of a protective association. Other risk factors, produced inconclusive or insufficient evidence. Proxy outcome analyses yielded weaker findings; in particular, the association between education and Alzheimer's disease reversed direction.

conclusionMR evidence for most Lancet Commission risk factors remains insufficient or inconclusive. The most consistent support for causal associations was observed for lower educational attainment and type 2 diabetes. Null findings should be interpreted cautiously given limitations in GWAS phenotyping, sample composition, and MR methodology.

Indexed as

DementiaMendelian Randomization AnalysisDiabetes Mellitus, Type 2HumansRisk Factorsdementiamendelian randomisationmodifiable risk factorssystematic literature review

Identifiers

PMID41342141
PMCPMC12676184

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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 OpenQuestion graph.