Abstract P67: Role of Genetic Variants in Predicting Cognitive Outcomes Following Small Vessel Ischemic Stroke

Abstract

Background: About 20% of patients with small vessel ischemic stroke (SVS) have cognitive impairment; however, the role of genetic factors in predicting cognitive outcomes following SVS has not been fully explored. APOE and ABCC9 have been associated with Alzheimer’s disease and hippocampal sclerosis respectively and play an important role in the neurovascular unit. We evaluated whether allelic variants in these genes influence cognitive outcomes following SVS. Methods: We conducted a retrospective analysis of a prospective cohort of patients enrolled in the ASA-Bugher Small Vessel Intracranial Disease Whole Genome Association Studies. Patients with SVS were categorized by APOE (presence or absence of ε4 allele) and ABCC9 SNP rs704180 (presence or absence of A allele) status. The primary outcomes were total score on the short form of the MoCA, which assesses global cognition, and time to complete Trails B, which is a measure of executive function that can be affected by stroke. Linear regression analyses were performed using the genetic exposures of interest, adjusting for age, education, sex, race/ethnicity, NIHSS score, burden of white matter disease (WMD; using the CHS validated score 0-9), and time between stroke and the cognitive assessment. Results: The sample included 145 patients who had SVS and available APOE and ABCC9 data. Among this cohort, 51.4% were men and 27.6% African American. The median age of the study participants was 63.4 years, the median years of education was 12, the median NIHSS was 2, and the median WMD burden score was 2. The mean time between stroke and the cognitive assessment was 75 days. The APOE ε4 allele was present in 35.0% and ABCC9 A allele in 74.8%. The presence of APOE ε4 allele was not associated with post-stroke MoCA scores (p=0.31) or Trails B (p=0.86). ABCC9 A allele was also not associated with post-stroke MoCA scores (p=0.34) or Trails B (p=0.31). Older age, higher NIHSS score, and greater burden of WMD were independently associated with longer times to complete Trails B (p<0.0001), but not with the MoCA score. Conclusion: Following SVS, several patient characteristics, including age, stroke severity, and WMD burden, rather than their APOE and ABCC9 allelic statuses, were associated with post-stroke measures of executive function.