Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers

Abstract

Introduction: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined apolipoprotein E (APOE) allele frequency in non-Hispanic Black (NHB) and non-Hispanic White (NHW) SuperAgers compared to controls and Alzheimer's disease dementia cases. Methods: In 18,080 participants from eight cohorts, harmonized clinical diagnostics and memory, executive function, and language domain scores were used to identify SuperAgers, cases, and controls across age-defined bins. Results: NHW SuperAgers had significantly lower frequency of APOE-ε4 alleles and higher frequency of APOE-ε2 alleles compared to all cases and controls, including oldest-old controls. Similar patterns were found in a small yet substantial sample of NHB SuperAgers; however, not all comparisons with controls reached significance. Discussion: We demonstrated strong evidence that APOE allele frequency relates to SuperAger status. Further research is needed with a larger sample of NHB SuperAgers to determine if mechanisms conferring cognitive resilience differ across race groups. Highlights: Apolipoprotein E (APOE) allele frequency differs between SuperAgers and cases APOE allele frequency differs between non-Hispanic White SuperAgers and controls The relationship of APOE and non-Hispanic Black SuperAger status is unclear.