medRxiv [Preprint]. 2026 Apr 14:2026.04.12.26350734. doi: 10.64898/2026.04.12.26350734.
ABSTRACT
BACKGROUND: Coronary artery bypass graft (CABG) is a widely performed procedure for coronary artery disease (CAD), yet its association with Impaired Cognition (IC), i.e., mild-cognitive impairment or all-cause dementia, while accounting for APO (ε) genotype, remains unclear.
METHODS: We analyzed AllofUS participants with CAD (Age≥60 yrs) from 2017-2023. We defined CAD as a history of angina/myocardial infarction/chronic ischemic heart disease or having percutaneous coronary intervention/CABG, and IC as mild cognitive impairment or all-cause dementia using ICD/SNOMED codes. We performed logistic regression analyses to assess the association between CABG and IC, adjusting for clinical factors (age, sex, hypertension, diabetes, hyperlipidemia, depression, stroke, smoking, alcohol use, statin/antihypertensive/antidiabetic use), social determinants (self-reported race/ethnicity, income, employment), and APO (ε) genotypes. We further performed stratified analyses across APO (ε) genotypes (ε2/ε2, ε2/ε3 ε3/ε3, ε2/ε4, ε3/ε4, ε4/ε4). We defined significance at p ≤ 0.05.
RESULTS: We included 22,349 with CAD and identified 908 with IC after CAD till 2023. 40% were females, 70% were White, 12% were Black, and 9% were Hispanic. The proportion of IC was higher ( 5.1% vs 3.5%, p=1e-08 ) in CABG (n=8,135) vs non-CABG (n=14,214). After adjusting for clinical factors, social determinants, and APO (ε) genotypes, CABG ( 1.23;1.06-1.41, p = 0.005 ) was associated with IC. In APO (ε) stratified analysis, the association of CABG with IC was strongest in the APO ε2/ε3 group ( 1.91;1.21-3.02, p = 0.005 ).
CONCLUSION: In the AllofUS cohort, we observed an association between CABG and IC in CAD participants, with the strongest association in the APO ε2/ε3 group.
KEY MESSAGE: What is already known on this topic: Coronary artery disease (CAD) and Impaired Cognitive (IC) disease, i.e., mild cognitive impairment and all-cause dementia, share genetic, sociodemographic, and clinical factors, including cardiovascular conditions like coronary artery bypass grafting (CABG) procedure.What this study adds: We observed an association between CABG and IC in CAD participants after adjusting for sociodemographic, clinical factors, and APO (ε) effects. Further, when CAD participants were stratified across APO (ε) groups, CABG was significantly associated with IC in the APO ε2/ε3 group.How this study might affect research, practice or policy: Our observations highlight the role of APO (ε) genotype evaluation in CAD patients for IC risk assessment.
PMID:42064926 | PMC:PMC13127513 | DOI:10.64898/2026.04.12.26350734