The Apolipoprotein E ε4 Allele Increases the Odds of Chronic Cerebral Infarction Detected at Autopsy in Older Persons

Abstract

Background and Purpose— Studies investigating the relation of the apolipoprotein E (apoE) ε4 allele to clinical stroke and to vascular changes on magnetic resonance imaging have been conflicting. Little data are available regarding the relation of apoE ε4 to cerebral infarctions documented on postmortem examination. Methods— We studied the apoE ε4 allele in 214 deceased members of the Religious Orders Study, a longitudinal clinical–pathologic study of aging and Alzheimer disease. The apoE genotype was determined using DNA from lymphocytes. Brains were removed a median of 5 hours (interquartile range, 5.5) after death. At postmortem examination, age, location, and size of macroscopic chronic cerebral infarctions were recorded from 1-cm coronal slabs after paraformaldehyde fixation. We also examined 20-μm paraffin-embedded sections of midfrontal and calcarine cortex for amyloid angiopathy on a scale of 1 to 4. Results— Subjects included 96 males and 118 females with a mean age at death of 86 years (SD, 7). Sixty-five subjects (30.4%) had at least 1 apoE ε4 allele and 76 (35.5%) exhibited cerebral infarctions. More than 74% of the subjects exhibited amyloid angiopathy with a mean score of 1.4±1.2. After controlling for age and sex, apoE ε4 increased the odds of cerebral infarction by 2.3-fold (95% CI, 1.2 to 4.2). apoE ε4 increased the odds of cortical 3.2-fold (95% CI, 1.3 to 7.7) and subcortical infarctions 2.3-fold (95% CI, 1.2 to 4.5). The effect was unchanged after accounting for amyloid angiopathy. Conclusions— apoE ε4 increases the odds of chronic cerebral infarction detected at autopsy in older persons.