Article Dans Une Revue medRxiv : the preprint server for health sciences Année : 2025

Evaluating the association of APOE genotype and cognitive resilience in SuperAgers

Alaina Durant
  • Fonction : Auteur
Shubhabrata Mukherjee
  • Fonction : Auteur
Michael L Lee
  • Fonction : Auteur
Seo-Eun Choi
  • Fonction : Auteur
Brandon S Klinedinst
  • Fonction : Auteur
Emily H Trittschuh
  • Fonction : Auteur
Jesse Mez
  • Fonction : Auteur
Lindsay A Farrer
  • Fonction : Auteur
Katherine A Gifford
  • Fonction : Auteur
Carlos Cruchaga
  • Fonction : Auteur
Jason Hassenstab
  • Fonction : Auteur
Adam C Naj
  • Fonction : Auteur
Li-San Wang
  • Fonction : Auteur
Sterling C Johnson
  • Fonction : Auteur
Corinne D Engelman
  • Fonction : Auteur
Walter A Kukull
  • Fonction : Auteur
C Dirk Keene
  • Fonction : Auteur
Andrew J Saykin
  • Fonction : Auteur
Michael L Cuccaro
  • Fonction : Auteur
Brian W Kunkle
  • Fonction : Auteur
Margaret A Pericak-Vance
  • Fonction : Auteur
Eden R Martin
  • Fonction : Auteur
David A Bennett
  • Fonction : Auteur
Lisa L Barnes
  • Fonction : Auteur
Julie A Schneider
  • Fonction : Auteur
William S Bush
  • Fonction : Auteur
Jonathan L Haines
  • Fonction : Auteur
Richard Mayeux
  • Fonction : Auteur
Badri N Vardarajan
  • Fonction : Auteur
Marilyn S Albert
  • Fonction : Auteur
Paul M Thompson
  • Fonction : Auteur
Angela L Jefferson
  • Fonction : Auteur
Paul K Crane
  • Fonction : Auteur
Logan Dumitrescu
  • Fonction : Auteur
Derek B Archer
  • Fonction : Auteur
Timothy J Hohman
  • Fonction : Auteur
Leslie S Gaynor
  • Fonction : Auteur

Résumé

IMPORTANCE: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary memory are underexplored in large, racially diverse cohorts. OBJECTIVE: To determine the frequency of APOE genotypes in non-Hispanic Black and non-Hispanic White SuperAgers compared to middle-aged (ages 50-64), old (ages 65-79), and oldest-old (ages 80+) controls and Alzheimer's disease (AD) dementia cases. DESIGN: This multicohort study selected data from eight longitudinal cohort studies of normal aging and AD. SETTING: Variable recruitment criteria and follow-up intervals, including both population-based and clinical-based samples. PARTICIPANTS: Inclusion in our analyses required APOE genotype, that participants be age 50+, and are identified as either non-Hispanic Black or non-Hispanic White. In total, 18,080 participants were included in the present study with a total of 78,549 datapoints. MAIN OUTCOMES AND MEASURES: Harmonized, longitudinal memory, executive function, and language scores were obtained from the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC). SuperAgers, controls, and AD dementia cases were identified by cognitive scores using a residual approach and clinical diagnoses across multiple timepoints when available. SuperAgers were compared to AD dementia cases and cognitively normal controls using age-defined bins (middle-aged, old, oldest-old). RESULTS: Across racialized groups, SuperAgers had significantly higher proportions of APOE-ε2 alleles and lower proportions of APOE-ε4 alleles compared to cases. Similar differences were observed between SuperAgers and middle-aged and old controls. Non-Hispanic White SuperAgers had significantly lower proportions of APOE-ε4 alleles and significantly higher proportions of APOE-ε2 alleles compared to all cases and controls, including oldest-old controls. In contrast, non-Hispanic Black SuperAgers had significantly lower proportions of APOE-ε4 alleles compared to cases and younger controls, and significantly higher proportions of APOE-ε2 alleles compared only to cases. CONCLUSIONS AND RELEVANCE: In the largest study to date, we demonstrated strong evidence that the frequency of APOE-ε4 and -ε2 alleles differ between non-Hispanic White SuperAgers and AD dementia cases and cognitively normal controls. Differences in the role of APOE in SuperAging by race underlines distinctions in mechanisms conferring resilience across race groups given likely differences in genetic ancestry.
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hal-04951932 , version 1 (17-02-2025)

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Alaina Durant, Shubhabrata Mukherjee, Michael L Lee, Seo-Eun Choi, Phoebe Scollard, et al.. Evaluating the association of APOE genotype and cognitive resilience in SuperAgers. medRxiv : the preprint server for health sciences, 2025, ⟨10.1101/2025.01.07.25320117⟩. ⟨hal-04951932⟩

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