| Title: |
Evaluating the association of APOE genotype and cognitive resilience in SuperAgers |
| Authors: |
Durant, Alaina; Mukherjee, Shubhabrata; Lee, Michael L.; Choi, Seo-Eun; Scollard, Phoebe; Klinedinst, Brandon S.; Trittschuh, Emily H.; Mez, Jesse; Farrer, Lindsay A.; Gifford, Katherine A.; Cruchaga, Carlos; Hassenstab, Jason; Naj, Adam C.; Wang, Li-San; Johnson, Sterling C.; Engelman, Corinne D.; Kukull, Walter A.; Keene, C. Dirk; Saykin, Andrew J.; Cuccaro, Michael L.; Kunkle, Brian W.; Pericak-Vance, Margaret A.; Martin, Eden R.; Bennett, David A.; Barnes, Lisa L.; Schneider, Julie A.; Bush, William S.; Haines, Jonathan L.; Mayeux, Richard; Vardarajan, Badri N.; Albert, Marilyn S.; Thompson, Paul M.; Jefferson, Angela L.; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer’s Disease Genetics Consortium (ADGC); The Alzheimer’s Disease Sequencing Project (ADSP); Crane, Paul K.; Dumitrescu, Logan; Archer, Derek B.; Hohman, Timothy J.; Gaynor, Leslie S. |
| Contributors: |
Radiology and Imaging Sciences, School of Medicine |
| Source: |
PMC |
| Publisher Information: |
medRxiv |
| Publication Year: |
2025 |
| Collection: |
Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| Subject Terms: |
SuperAgers; Older adults; Exemplary aging; APOE‐ε2 alleles; APOE‐ε4 alleles |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Durant A, Mukherjee S, Lee ML, et al. Evaluating the association of APOE genotype and cognitive resilience in SuperAgers. Preprint. medRxiv. 2025;2025.01.07.25320117. Published 2025 Jan 7. doi:10.1101/2025.01.07.25320117; https://hdl.handle.net/1805/46046 |
| Availability: |
https://hdl.handle.net/1805/46046 |
| Rights: |
Attribution-NonCommercial-NoDerivatives 4.0 International ; https://creativecommons.org/licenses/by-nc-nd/4.0 |
| Accession Number: |
edsbas.D75077A4 |
| Database: |
BASE |