Analysis of 22,089 coronary artery disease patients from the All of Us database reveals statin users showed 70% higher odds of cognitive impairment compared to non-users, with the strongest association in APOE ε3/ε3 carriers (2.04-fold increased odds) and women (2.20-fold increase). The relationship was most pronounced among patients experiencing HDL increases above 10 mg/dL on statin therapy. This counterintuitive finding challenges the assumed safety profile of statins for brain health, particularly given that these cholesterol-lowering drugs are widely prescribed for cardiovascular protection. The APOE genotype dependency suggests genetic factors may influence individual susceptibility to statin-associated cognitive effects. However, this observational design cannot establish causation—sicker patients requiring statins may have inherently higher dementia risk, or detection bias could inflate associations if statin users receive more medical monitoring. The female-specific vulnerability warrants particular attention given sex differences in statin metabolism and cardiovascular disease presentation. As this remains an unreviewed preprint, these provocative results require peer scrutiny and replication before influencing clinical practice, though they add to growing concerns about statin cognitive effects in vulnerable populations.