Evidence map›Paper›PMID 41748529›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

The heterogeneous treatment effects of statins on dementia: a target trial emulation with causal machine learning using integrated genetic and real-world data.

Yongjie Lai, Qoua L Her, Yue Zhang, Hong Xu, Anna Kucharska-Newton, Dongze Ji, Guorong Wu, Gwenn Garden, Til Stürmer, Tiansheng Wang and 1 more

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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. 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

11 authors.

Yongjie LaiDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Qoua L HerDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Yue ZhangDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Hong XuDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Anna Kucharska-NewtonDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Dongze JiDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Guorong WuDepartment of Psychiatry, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Gwenn GardenDepartment of Neurology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Til StürmerDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Tiansheng WangDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Yang XuDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.ORCID https://orcid.org/0000-0002-1074-608X

Funding

National Natural Science Foundation of China 82304245the Key Laboratory of Epidemiology of Major Diseases (Peking University) grant from the Ministry of Education of China
6 · The paper itself

Abstract

introductionGiven the complexity of dementia, the inconsistent evidence on statins and dementia highlights the need for robust methods to assess heterogeneous treatment effects (HTEs).

methodsWe emulated a target trial using UK Biobank comparing statin initiators and non-initiators aged ≥55 years. Marginal structural models were fitted to estimate 5-year adjusted risk difference (aRD). We used iterative causal forest, a causal machine learning subgrouping algorithm, to identify subgroups with HTEs.

resultsAmong 18,366 participants, the overall aRD for all-cause dementia was -1.0‰ (95% CI: -4.2‰ to 2.3‰). We identified subgroups by polygenic risk score for Alzheimer's disease (AD) excluding apolipoprotein E (APOE) genotype ("non-APOE PRS"). Participants with high non-APOE PRS showed cognitive benefit (all-cause dementia: aRD -5.9‰, 95% CI: -8.1‰ to 1.2‰; AD: aRD -5.0‰, 95% CI: -8.2‰ to -0.2‰). DISCUSSION: Participants with high non-APOE PRS may benefit from statins, suggesting genetic susceptibility beyond APOE could modify statins' cognitive effects.

Indexed as

DementiaHydroxymethylglutaryl-CoA Reductase InhibitorsMachine LearningAgedAlzheimer DiseaseApolipoproteins EFemaleGenetic Risk ScoreHumansMaleMiddle AgedTreatment Effect HeterogeneityUnited KingdomApolipoproteins EHydroxymethylglutaryl-CoA Reductase Inhibitorsdementiaheterogeneous treatment effectsiterative causal forestpolygenic risk scorestatins

Identifiers

PMID41748529
PMCPMC12945722

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.