Low-density lipoprotein cholesterol levels and risk of incident dementia: a distributed network analysis using common data models.
Level 3 - non-randomized controlled study
Retrospective propensity score-matched cohort study using multi-center electronic health records.
PubMed 40169354 · doi:10.1136/jnnp-2024-334708
What was done
Researchers conducted a retrospective cohort study across 11 university hospitals using the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Participants with prior dementia, fewer than 180 days of pre-cohort observation, or presence in both exposure cohorts were excluded. Using 1:1 propensity score matching, they analyzed a cohort of 108,980 patients comparing individuals with LDL-C <70 mg/dL (1.8 mmol/L) against those with LDL-C >130 mg/dL (3.4 mmol/L). The primary outcome was incident all-cause dementia, and the secondary outcome was Alzheimer's disease-related dementia (ADRD). Secondary analyses evaluated LDL-C <55 mg/dL (1.4 mmol/L) and the role of statin use.
What was found
LDL-C levels <70 mg/dL were associated with a 26% reduction in all-cause dementia risk and a 28% reduction in ADRD risk compared with levels >130 mg/dL. For LDL-C levels <55 mg/dL, there was an 18% risk reduction for both dementia outcomes. Among individuals with LDL-C <70 mg/dL, statin use was associated with a 13% reduction in all-cause dementia risk and a 12% decrease in ADRD risk compared with non-users.
Why it matters
This study provides large-scale multi-hospital observational evidence supporting lower LDL-C levels and statin therapy as potentially protective factors against incident dementia, reinforcing lipid management in neurodegenerative risk reduction.
Limits
The study is retrospective and observational, leaving residual confounding possible despite propensity score matching. The abstract does not provide exact effect estimates with confidence intervals, p-values, follow-up duration, or specific demographic details. Diagnoses relied on routine medical record coding rather than standardized prospective cognitive evaluations.
Cited by
- partial Failing to lower LDL cholesterol below 100 mg/dL or 70 mg/dL places individuals at higher risk for dementia.