18 Jan Vanderbilt Study Provides Most Definitive Evidence To Date that APOE Contributes to SuperAging

MedicalResearch.com Interview with:

Dr. Gaynor

Leslie S. Gaynor, PhD
Clinical Neuropsychologist & Assistant Professor of Medicine
Division of Geriatric Medicine
Department of Medicine
Vanderbilt University Medical Center
Nashville, TN 37203

MedicalResearch.com: What is the background for this study?

Response: The US population is rapidly aging, and the oldest members of our population are also the most vulnerable to developing clinical dementia. We are interested in studying older adults ages 80+ who display cognitive resilience despite this increased risk of dementia and actually display exceptional memory performance compared to their same-aged, typically performing peers. These “SuperAgers,”—i.e., 80+-year-old adults with memory performance that is comparable to or surpasses that of adults 20 to 30 years their junior—may hold the key to uncovering genetic factors that predict exceptionally healthy longevity.

MedicalResearch.com: What are the main findings?

Response:  We leveraged the harmonized data from the 18,000 participants in the Alzheimer’s Disease (AD) Sequencing Project Phenotype Harmonization Consortium to retrospectively identify 1,623 SuperAgers. We then performed the largest evaluation of the strongest genetic risk factor for sporadic AD, APOE, in the context of SuperAging. APOE includes an allele that increases risk for AD (ɛ4) and an allele that protects against disease (ɛ2). Fascinatingly, these SuperAgers not only have a lower frequency of ɛ4 and a higher frequency of ɛ2 when compared to people with AD dementia, but also when compared to cognitively normal controls of their same age.

Response: How might this genotype influence longevity and cognition?

Response:  APOE has a known relationship with longevity and cognition. Carrying an ɛ4 allele, specifically, is related to increased mortality and greater risk of AD dementia. We used to think this effect was most profound before age 70. Our study suggests that having an ɛ4 allele continues to influence both cognition and longevity well past age 70.

MedicalResearch.com: What should readers take away from your report?

Response:  This is the most definitive evidence to date that APOE contributes to SuperAging.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: We are excited to continue this work by exploring other genetic and brain factors that may underlie the superior memory performance on SuperAgers. This research will contribute significantly to our understanding of factors that relate to exceptionally healthy aging well into late life.

No disclosures

Citation:

Durant A, Mukherjee S, Lee ML, et al. Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers. Alzheimer’s Dement. 2026; 22:e71024. https://doi.org/10.1002/alz.71024

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Last Updated on January 18, 2026 by Marie Benz MD FAAD