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Alzheimer's Association International Conference 2026

July 12-15, 2026 | London, United Kingdom, and Online

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6359

AD Brain Signature And Regional Patterns Of Brain Atrophy In Superagers

Poster Presenter

Alaina Durant

Authors

Alaina Durant, Guray Erus, Yuhan Cui, Shubhabrata Mukherjee, Michael Lee, Seo-Eun Choi, Sam Albertson, Ali Asadollahi, Karen Velderrian-Lopez, Emily Trittschuh, Jesse Mez, Carlos Cruchaga, Jason Hassenstab, Walter Kukull, Sarah Biber, Adam Naj, Li-San Wang, Andrew Saykin, Michael Cuccaro, Brian Kunkle, Margaret Pericak-Vance, Eden Martin, David Bennett, Lisa Barnes, Julie Schneider, William Bush, Johnathan Haines, Paul Thompson, Emily Mahoney, Aditi Sathe, Angela Jefferson, Logan Dumitrescu, Alzheimer's Disease Genetic Consortium (ADGC), Alzheimer's Disease Sequencing Project (ADSP), Paul Crane, Christos Davatzikos, Derek Archer, Timothy Hohman, Leslie Gaynor

Affiliations

, Vanderbilt Memory & Alzheimer's Center, Vanderbilt Health, Nashville, TN, USA, Department of Radiology, Section of Biomedical Image Analysis, University of Pennsylvania, Philadelphia, PA, USA, Department of Medicine, University of Washington, Seattle, WA, USA, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA; VA Puget Sound Health Care System, GRECC, Seattle, WA, USA, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA, Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA; NeuroGenomics and Informatics Center, Washington University in St. Louis, St. Louis, MO, USA, Department of Neurology and Department Psychological & Brain Sciences, Washington University in St Louis, St. Louis, MO, USA, Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA, Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA, Department of Radiology and Imaging Services, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, USA, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA, Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Vanderbilt Memory & Alzheimer's Center, Vanderbilt Health, Nashville, TN, USA; Department of Neurology, Vanderbilt Health, Nashville, TN, USA, Vanderbilt Memory & Alzheimer's Center, Vanderbilt Health, Nashville, TN, USA; Department of Neurology, Vanderbilt Health, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt Health, Nashville, TN, USA, Vanderbilt Memory & Alzheimer's Center, Vanderbilt Health, Nashville, TN, USA; Division of Geriatric Medicine, Department of Medicine, Vanderbilt Health, Nashville, TN, USA

Part of Topic

Background:
SuperAgers are oldest individuals (ages 80+) whose exceptional memory performance tests resemble those of adults in their mid 50s to 60s.
Previous neuroimaging research suggests that SuperAgers exhibit preserved brain volume in regions associated with memory and executive function despite advanced aged.
 
Aim & Hypothesis:
We aimed to analyze the association of SuperAging with regional brain volume and brain signatures of aging and Alzheimer's disease. We hypothesized that SuperAgers would demonstrate superior brain volume in memory regions and lower SPARE-AD scores, compared to AD cases and controls.
 
Methods:
Data were collected from non-Hispanic White (NHW) and non-Hispanic Black (NHB) participants across six well-established longitudinal cohorts of aging.
Harmonized T1-weighted magnetic resonance imaging (MRI) scans and cognitive scores were obtained through the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC).
Cognitive domain scores were estimated using latent variable modeling.
Regional brain volume was obtained using Multi-atlas region Segmentation using Ensembles (MUSE).
Machine learning was used to derive brain signatures of AD (Spatial Pattern of Abnormality for Recognition of Early Alzheimer’s Disease, or SPARE-AD) and brain aging (SPARE-BA).
Linear regression analyses were used to compare regional brain volume and signatures of AD and brain aging across SuperAgers and their counterparts.
 
Results:
SuperAgers demonstrated significantly lower SPARE-AD values compared to both cognitively normal controls and AD dementia cases.
SuperAgers also showed significantly younger SPARE-Brain Age values compared to both AD dementia cases and cognitively normal controls.
Findings suggest that, through lower SPARE AD and BA values, SuperAgers exhibit a more favorable AD-related neuroanatomical profile despite advanced age.
SuperAgers showed greater temporal, parietal, and total white matter volume compared to both cognitively normal controls and AD dementia cases,
SuperAgers demonstrated larger anterior insula volumes compared to AD dementia cases and cognitively normal controls.
Aligned with previous studies, SuperAgers demonstrated larger anterior cingulate gyrus and hippocampal volumes than AD dementia cases.
The findings also suggest that structural brain integrity across distributed cortical and medial temporal systems may support exceptional memory performance in advanced aging. Future work will expand to additional image processing methods to solidify regions of interest relevant in SuperAging.

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