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Record W4406187173 · doi:10.1101/2025.01.07.25320117

Evaluating the association of <i>APOE</i> genotype and cognitive resilience in SuperAgers

2025· preprint· en· W4406187173 on OpenAlexfundno aff
Alaina Durant, Shubhabrata Mukherjee, Michael L. Lee, Seo‐Eun Choi, Phoebe Scollard, Brandon S. Klinedinst, Emily H. Trittschuh, Jesse Mez, Lindsay A. Farrer, Katherine A. Gifford, Carlos Cruchaga, Jason Hassenstab, Adam C. Naj, Li‐San Wang, Sterling C. Johnson, Corinne D. Engelman, Walter A. Kukull, C. Dirk Keene, Andrew J. Saykin, Michael L. Cuccaro, Brian W. Kunkle, Margaret A Pericak‐Vance, Eden R. Martin, David Bennett, Lisa L. Barnes, Julie A. Schneider, William S. Bush, Jonathan L. Haines, Richard Mayeux, Badri N. Vardarajan, Marilyn S. Albert, Paul M. Thompson, Angela L. Jefferson, Paul K. Crane, Logan Dumitrescu, Derek B. Archer, Timothy J. Hohman, Leslie S. Gaynor

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationPfizerNovartis Pharmaceuticals CorporationUniversity of Southern CaliforniaBiogenEli Lilly and CompanyBristol-Myers SquibbBioClinicaU.S. Department of DefenseAlzheimer's Disease Neuroimaging InitiativeMeso Scale DiagnosticsNational Institute on AgingHope Center for Neurological DisordersAlzheimer's Association
KeywordsResilience (materials science)Association (psychology)Apolipoprotein ECognitionGenotypePsychologyGeographyBiologyGeneticsMedicineNeuroscienceInternal medicineGenePsychotherapist

Abstract

fetched live from OpenAlex

Abstract INTRODUCTION “SuperAgers” are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined APOE allele frequency in non-Hispanic Black (NHB) and non-Hispanic White (NHW) SuperAgers compared to controls and Alzheimer’s disease dementia cases. METHODS In 18,080 participants from eight cohorts, harmonized clinical diagnostics and memory, executive function, and language domain scores were used to identify SuperAgers, cases, and controls across age-defined bins. RESULTS NHW SuperAgers had significantly lower frequency of APOE- ε4 alleles and higher frequency of APOE -ε2 alleles compared to all cases and controls, including oldest-old controls. Similar patterns were found in a small yet substantial sample of NHB SuperAgers; however, not all comparisons with controls reached significance. DISCUSSION We demonstrated strong evidence that APOE allele frequency relates to SuperAger status. Further research is needed with a larger sample of NHB SuperAgers to determine if mechanisms conferring resilience differ across race groups.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.039
GPT teacher head0.391
Teacher spread0.352 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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Same venuemedRxiv→Same topicDementia and Cognitive Impairment Research→French-language works237,207→