Effect of APOE and LPA Genotypes on the Risk of Dementia after Myocardial Infarction: a Clinic-Based Cohort Study

Survivors of myocardial infarction (MI) face elevated risk of subsequent cognitive decline, yet the relative contributions of neurodegenerative susceptibility (APOE4) and lipid-mediated vascular burden (LPA risk variants) to post-MI dementia remain unclear, particularly in Asian populations historically underrepresented in dementia genetics research. We conducted a retrospective cohort study of 4,788 patients with confirmed MI enrolled in the China Medical University Hospital precision medicine program (January 1, 2004–December 31, 2021), with directly genotyped APOE (rs429358, rs7412) and LPA (rs10455872, rs3798220) variants linked to longitudinal electronic health records and the Taiwan National Death Registry. Patients were classified into four genetic risk groups: low-risk, LPA-only, APOE4-only, and dual-risk. The primary outcome was incident all-cause dementia within a fixed 5-year follow-up and was analyzed using Cox proportional hazards regression. Sensitivity analyses included a Fine–Gray subdistribution hazards model to describe the cumulative incidence of dementia in the presence of death as a competing event, along with subgroup analyses by age, sex, and cardiovascular comorbidity. The median age was 61.2 years (IQR 51.9–70.3). Compared with the low-risk reference, APOE4 carriers had substantially elevated dementia risk (APOE4-only: HR 2.49, 95