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

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