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

NHW SuperAgers had significantly lower frequency of APOE-ε4 alleles compared to all cases and controls, including oldest-old controls.

• Study included 18,080 participants from eight cohorts
• Participants were non-Hispanic Black (NHB) and non-Hispanic White (NHW) oldest-old adults (ages 80+)
• Comparisons were made across age-defined bins using harmonized clinical diagnostics
• The lower ε4 frequency in NHW SuperAgers held when compared specifically to oldest-old controls, not just younger comparison groups

NHW SuperAgers had significantly higher frequency of APOE-ε2 alleles compared to all cases and controls, including oldest-old controls.

• APOE-ε2 enrichment was observed in NHW SuperAgers across multiple comparison groups
• This pattern held when compared to oldest-old controls, suggesting the ε2 association is not simply an age survival artifact
• Memory, executive function, and language domain scores were used to identify SuperAgers

NHB SuperAgers showed similar patterns of APOE allele frequency differences, but not all comparisons with controls reached statistical significance.

• The NHB SuperAger sample was described as 'small yet substantial'
• The directional pattern of lower ε4 and higher ε2 frequencies was similar to NHW SuperAgers
• Failure to reach significance in some comparisons was attributed at least in part to smaller NHB sample size
• Authors concluded that further research is needed with a larger NHB SuperAger sample

SuperAgers were defined as oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults.

• Eight cohorts contributed to the total sample of 18,080 participants
• Harmonized clinical diagnostics and cognitive domain scores (memory, executive function, and language) were used to identify SuperAgers, cases, and controls
• Participants were classified across age-defined bins
• SuperAgers were compared to both Alzheimer's disease dementia cases and cognitively normal controls

The study demonstrated strong evidence that APOE allele frequency relates to SuperAger status.

• Results were consistent across NHW and NHB groups in terms of directionality
• The association was present even when SuperAgers were compared to oldest-old controls, ruling out simple survivorship as an explanation
• Authors noted the relationship of APOE and NHB SuperAger status remains unclear due to sample size limitations
• The findings suggest APOE genetic variation may play a role in conferring cognitive resilience in the oldest-old