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Alzheimer's Association International Conference 2026
July 12-15, 2026 | London, United Kingdom, and Online
9797
Regional White Matter Injury Modifies Associations Of ί-amyloid With Cognition And Cortical Thickness
Poster Presenter
Authors
Sarah Royse, Alexandria Reese, Beth Snitz, James Hengenius, Paul Crane, Shubhabrata Mukherjee, Seo-Eun Choi, Daniel Willie-Permor, Cynthia Felix, Theodore Huppert, Rebecca Roush, Geraldine Cisneros, Katey Potopenko, Brian Lopresti, Ann Cohen, C. Elizabeth Shaaban
Affiliations
University of Pittsburgh, University of Washington, Universitaire Sainte-Justine
Part of Topic
WHAT DID WE FIND?
• The combined influence of co-localized white matter injury and β-amyloid on cognition varies by brain region, but these differences are not readily explained by underlying neurodegeneration.
WHY IS IT IMPORTANT?
• Parietal white matter injury and β-amyloid may act synergistically to influence lower cognition and more neurodegeneration.
• The anterior cingulate may support a compensatory mechanism for preserving cognition, despite greater pathological burden in AD.
BACKGROUND
• White matter injury is common in Alzheimer’s disease (AD).
• Examining synergistic relationships of co-localized white matter injury and AD pathology on cognition and neurodegeneration is difficult with current white matter injury indices.
• Our objective was to determine if co-localized white matter injury (indexed using our spatially precise measurement) and β-amyloid (Aβ) interact on (1) memory, executive functioning, and language and (2) co-localized cortical thickness.
METHODS
• Study Population: Connectomics in Brain Aging (CoBRA) participants who underwent neuroimaging and a standardized neuropsychological test battery at one time point
• Predictors: (1) Regional unhealthy white matter connectivity (UWMC): The proportion of white matter connections between two brain regions that pass through white matter hyperintensities; (2) Regional [11C]Pittsburgh Compound-B ([11C]PiB) standardized uptake value ratios (SUVRs)
• Outcomes: (1) Memory, executive functioning, language domain composite scores, created via item-response theory; (2) Regional cortical thickness
• Statistical analyses: Individual robust regression models tested interactions between corresponding pairs of regional UWMC and [11C]PiB SUVR with each cognitive domain score. Repeated replacing cognitive domain scores à corresponding cortical thickness. Covariates: age, sex, racialized group, education, APOE*4, hypertension, diabetes, and high cholesterol
RESULTS
• The relationship between more parietal UWMC and worse memory, executive functioning (P=0.01), and language (P=0.01) composite scores was stronger with higher [11C]PiB SUVR.
• Greater anterior cingulate UWMC was associated with better memory composite score in those with higher, versus lower, [11C]PiB SUVR.
• Parietal UWMC and [11C]PiB SUVR did not interact on co-localized cortical thickness.
• The association between more anterior cingulate UWMC and lower cortical thickness was stronger with higher [11C]PiB SUVR.
CONCLUSIONS
• Strengths: More spatially precise index of white matter injury allowed us to more closelyinterrogate its combined influence with Aβ on cognition and co-localized cortical thickness
• Limitations: Sample of participants is fairly small and healthier than the general older adult population
• Future directions: Explore interactions of regional white matter injury with other AD markers
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