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Largest Super-Ager Study Ties APOE Gene Variants to Alzheimer’s Resilience

The Vanderbilt-led analysis presents the super-ager phenotype as a practical route to investigate protective biology in late-life cognitive health.

Overview

  • Published in Alzheimer's & Dementia, the study pooled harmonized data on 18,080 participants from eight U.S. aging cohorts through the ADSP-PHC, led by Vanderbilt researchers.
  • Super agers were 68% less likely to carry the high-risk APOE-ε4 allele than 80+ adults with Alzheimer’s dementia and 19% less likely than cognitively normal peers of the same age.
  • They were 28% more likely to carry the protective APOE-ε2 allele than cognitively normal controls and 103% more likely than those with Alzheimer’s dementia.
  • Super agers were defined as people aged 80 or older whose memory performance exceeded the average of cognitively normal adults aged 50 to 64, yielding the largest super-ager sample to date.
  • Researchers stress the results are associative and call for replication across diverse populations to help identify mechanisms that may confer resistance to Alzheimer’s disease.