Evaluating the association of APOE genotype and cognitive resilience in SuperAgers

medRxiv [Preprint]. 2025 Jun 25:2025.01.07.25320117. doi: 10.1101/2025.01.07.25320117.

Abstract

Introduction: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined 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 resilience differ across race groups.

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