Evidence map›Paper›PMID 42493810›Full record

ArticleAlzheimer's research & therapy2026

SuperAging is not the inverse of common-variant Alzheimer's risk: evidence across genetic ancestries.

Ignazio Stefano Piras, Ana Werneck Capuano, Amanda Cook Maher, Rhiana Schafer, Anna Bonfitto, Serena Song, Francis Taguinod, Felicia Goldstein, Angela Roberts, Ozioma Okonkwo and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Ignazio Stefano Piras *Division of Early Detection and Prevention, The Translational Genomics Research Institute, a part of City of Hope, 445 N Fifth Street, Phoenix, AZ, USA. ipiras@tgen.org.
Ana Werneck Capuano *Department of Neurology, The Healthy Aging & Alzheimer's Research Care (HAARC) Center, University of Chicago, Chicago, IL, USA.
Amanda Cook MaherDepartment of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Rhiana SchaferDepartment of Neurology, The Healthy Aging & Alzheimer's Research Care (HAARC) Center, University of Chicago, Chicago, IL, USA.
Anna BonfittoDivision of Early Detection and Prevention, The Translational Genomics Research Institute, a part of City of Hope, 445 N Fifth Street, Phoenix, AZ, USA.
Serena SongDivision of Early Detection and Prevention, The Translational Genomics Research Institute, a part of City of Hope, 445 N Fifth Street, Phoenix, AZ, USA.
Francis TaguinodDivision of Early Detection and Prevention, The Translational Genomics Research Institute, a part of City of Hope, 445 N Fifth Street, Phoenix, AZ, USA.
Felicia GoldsteinDepartment of Neurology, Goizuetta Alzheimer's Disease Research Center, Emory University School of Medicine, 6 Executive Park Drive, Atlanta, NEGA, USA.
Angela RobertsDepartment of Computer Science, Western University, London, ON, Canada.
Ozioma OkonkwoWisconsin Alzheimer's Disease Research Center and Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, USA.
Adam MartersteckDepartment of Neurology, The Healthy Aging & Alzheimer's Research Care (HAARC) Center, University of Chicago, Chicago, IL, USA.
SuperAging Research Initiative
Matt J Huentelman *Division of Early Detection and Prevention, The Translational Genomics Research Institute, a part of City of Hope, 445 N Fifth Street, Phoenix, AZ, USA.
Emily Rogalski *Department of Neurology, The Healthy Aging & Alzheimer's Research Care (HAARC) Center, University of Chicago, Chicago, IL, USA.

Funding

Vascular and Behavioral Determinants of Superior Memory Performance from Continuous Monitoring of Everyday ActivitiesU19AG073153 · NIA · UNIVERSITY OF CHICAGO · PI GEULA, CHANGIZ, MESULAM, MAREK-MARSEL M · 2021 to 2025
$19.1M
Cognitive SuperAging: A model to explore resilience and resistance to aging and Alzheimers diseaseR01AG067781 · NIA · UNIVERSITY OF CHICAGO · PI GEULA, CHANGIZ, MESULAM, MAREK-MARSEL M · 2020 to 2025
$3.7M
Exceptional Cognitive Aging: Neuropsychologic, Anatomic and Pathologic CorrelatesR01AG045571 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GEULA, CHANGIZ, MESULAM, MAREK-MARSEL M · 2014 to 2019
$2.6M
Exceptional Cognitive Aging: Neuropsychologic, Anatomic and Pathologic CorrelatesR56AG045571 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GEULA, CHANGIZ, MESULAM, MAREK-MARSEL M · 2019 to 2019
$1.4M
NIA NIH HHS R01 AG045571NIA NIH HHS R01 AG067781NIA NIH HHS R56 AG045571NIA NIH HHS U19 AG073153
6 · The paper itself

Abstract

backgroundAs longevity increases and the population over age 65 expands, advancing age remains the most reliable predictor of cognitive decline, highlighting the need to identify biological mechanisms that support exceptional cognitive aging. We tested whether lower inherited risk of Alzheimer's disease (AD) dementia predicts SuperAger status (adults ≥ 80 years with episodic memory at least as good as middle-age adults) using prospectively enrolled SuperAgers and Cognitively Average Controls (Controls) from the multisite SuperAging Research Initiative.

methodsWe studied 231 participants (SuperAgers n = 142; Controls n = 89). We confirmed that the genetic ancestry structure across groups was comparable. We evaluated whether APOE status (ε2, ε3, ε4) and three AD polygenic risk scores (PRS) derived from large contemporary Genome-Wide Association Studies (GWAS) (PRS

resultsAPOE allele and genotype distributions did not differ between groups, and neither APOE nor any of the three PRS predicted SuperAger status. Results were unchanged when accounting for global non-European or African ancestry or principal components. In this well-characterized cohort, neither APOE nor contemporary PRS explained SuperAger status.

conclusionsThese findings suggest that the exceptional late-life memory phenotype that is characteristic of SuperAging is not explained by common-variant AD genetic risk captured by APOE or contemporary AD PRS, motivating a deeper investigation of potential rare genetic variations and experiential factors contributing to exceptional cognitive aging.

Indexed as

AgingAlzheimer DiseaseApolipoproteins EGenetic Predisposition to DiseaseLongevityAgedAged, 80 and overFemaleGenetic Risk ScoreGenome-Wide Association StudyGenotypeHumansMaleMemory, EpisodicApolipoproteins EAlzheimer’s diseaseAPOEGenetic ancestryPolygenic risk scoreResilienceResistanceSuperAger

Identifiers

PMID42493810
PMCPMC13397696

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.