ArticleNeurology2025
Statin Initiation and Dementia Incidence in a Large Health Care System From 1997 to 2020: A Target Trial Emulation Study.
Article in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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.
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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
5 citing papers in PubMed.
- Sodium-Glucose Cotransporter 2 Inhibitors and Dementia Risk in Patients With Psychiatric Disorders.JAMA network open · 2026Article
- The Use of Statins in Parkinson's and Alzheimer's Disease: A 2021-2025 State-of-the-Art Review of Clinical and Preclinical Evidence.Pharmacology research & perspectives · 2026Review
- The heterogeneous treatment effects of statins on dementia: a target trial emulation with causal machine learning using integrated genetic and real-world data.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Lipid-Lowering Therapies and Cognition in Older Adults: A Narrative Review and Clinical Considerations.Current cardiology reports · 2025Review
- Sociodemographic modifiers of effects of statin initiation on dementia incidence: An emulated trial design in a large health care member population with 10+ years of follow-up.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
BACKGROUND AND
objectivesPrevious research of associations between statins and Alzheimer disease and Alzheimer disease-related dementias (AD/ADRDs) has been limited by short follow-up, small samples, and confounding. We aimed to estimate the association between the 1st statin prescription and incident AD/ADRD among members of a large population-based cohort of older adults.
methodsWe used a cohort study design emulating a target trial using data from Kaiser Permanente Northern California (KPNC), an integrated health care delivery system. Participants were born before 1951 and KPNC members for 4+ years during 1997-2010. Embedded subsamples included sociodemographic and genetic data. Statin initiators were matched at first prescription ("baseline") with up to 5 "noninitiators" based on age and low-density lipoprotein cholesterol (LDL-C). Participants with extreme propensity scores were excluded. The outcome was time to incident AD/ADRD diagnosis, censoring, or the administrative end of study (December 31, 2020). Cox proportional hazard models were used to estimate hazard ratios for statin initiation on AD/ADRD incidence. Follow-up time was divided at the first year of follow-up to account for increased AD/ADRD detection in the first year due to increased interaction with the health care system after a statin prescription.
resultsAmong eligible participants (n = 705,061), 264,294 individuals (37.5% of eligible participants) initiated any statin during 2001-2010 ("initiators"), of whom 249,613 (94.4%) were matched with 255,937 unique noninitiators to create the analytic sample (322,358 unique participants; mean age at baseline = 67.4 years; 55.1% female). The average follow-up was 11.8 years. In the first year after initiating statins, AD/ADRD diagnoses were elevated by 46% (hazard ratio [HR] = 1.46, 95% CI 1.42-1.53) compared with noninitiators. After 1 year, statin initiators experienced no difference in AD/ADRD incidence (full sample: HR = 1.00, 95% CI 0.99-1.01; subsample with survey covariates: HR = 1.01, 95% CI 0.98-1.06; subsample with survey and genetic covariates: HR = 0.97, 95% CI 0.91-1.07). Adjustment for sociodemographic covariates and DISCUSSION: In this large emulated target trial, statin initiation was inconsistent with more than a 3% increase or decrease in the hazard of AD/ADRD after the first year of follow-up. This intent-to-treat analysis does not directly quantify effects of long-term exposure to statins. Associations in the first year likely reflect increased medical observation immediately after statin initiation. CLASSIFICATION OF EVIDENCE: This emulated trial provides Class II evidence that statin initiation is not associated with AD/ADRD or AD incidence after the first year of follow-up.
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