Brain age modifies the association between blood biomarkers of Alzheimer’s disease and cognitive function - Poster Presentation - BIOMARKERS (NON-NEUROIMAGING)

Sep 30, 2026

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Background: Alzheimer’s disease (AD) involves brain pathology accumulation, yet some individuals show preserved cognitive and day-to-day function. This study tests whether brain age moderates links between AD-related blood biomarkers and cognitive performance. Method: Baseline data from the IGNITE exercise trial used cognitively unimpaired older adults (n=648). T1-weighted MRI computed brain age with brainageR, deriving brain-PAD (brain-predicted age difference). Plasma assays measured phosphorylated tau (p-tau217) and neurofilament light (NfL) on SIMOA. Results: Brain-PAD moderated p-tau217 associations with episodic memory, processing speed, working memory, and executive function/attentional control after covariate adjustment, but not visuospatial processing. No significant brain-PAD moderation for NfL was found. Conclusion: Slower brain aging may help protect against AD pathology-related cognitive deficits.

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DOI: 10. 1002/alz70856_106538 BIOMARKERS POSTER PRESENTATION BIOMARKERS (NON-NEUROIMAGING) Brain age modifies the association between blood biomarkers of Alzheimer’s disease and cognitive function Kelsey R. Sewell1 Patricio Solis-Urra2, 3 Haiqing Huang4 George Grove5 Arthur F. Kramer6 Edward McAuley7 Jeffrey M. Burns8 Charles Hillman9 Eric D Vidoni 10 Anna Marsland5 Chaeryon Kang5 Lu Wan 11 Lauren Oberlin 11 Kirk I. Erickson2 1Advent Health, Orlando, FL, USA 2AdventHealth Research Institute, Orlando, FL, USA 3 Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada., Granada, Granada, Spain 4AdventHealth Research Institute, Neuroscience, Orlando, FL, USA 5 University of Pittsburgh, Pittsburgh, PA, USA 6 Center for Cognitive & Brain Health, Northeastern University, Boston, MA, USA 7 University of Illinois, Urbana, IL, USA 8 Department of Neurology, University of Kansas School of Medicine, Kansas City, KS, USA 9 Northeastern University, Boston, MA, USA 10 University of Kansas Medical Center, Alzheimer’s Disease Research Center, Fairway, KS, USA 11AdventHealth Neuroscience Institute, Orlando, FL, USA Correspondence Kelsey R. Sewell, Advent Health, Orlando, FL, USA. [Email:](Email: Kelsey.Sewell@AdventHealth.com)[ Kelsey.Sewell@AdventHealth.com](Email: Kelsey.Sewell@AdventHealth.com) Abstract Background: The development of Alzheimer’s disease (AD) involves accumulation of brain pathology; however, some individuals appear to maintain cognitive and dayto-day function in the presence of neuropathology better than others. One likely contributor to this resilience is the maintenance of structural brain integrity to a greater extent than expected based on age-related norms, i.e., a younger ‘brain age’. In this study we examined whether brain age moderated the association between AD-related blood biomarkers and cognitive function. Method: We utilized baseline data from the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) study. Cognitively unimpaired older adults (n = 648, aged 69.9±3.8, 71% female) completed a comprehensive cognitive assessment and an MRI scan where T1-weighted images were used to calculate brain age using brainageR. The difference between chronological age and brain age was used to calculate the brain-predicted age difference (brain-PAD). Assays were completed for plasma-based biomarkers phosphorylated tau (p-tau) 217 and neurofilament light (NfL) measured on the SIMOA platform. Result: After covarying for age, sex, site, BMI, image quality and education, brain-PAD moderated the association of p-tau217 with episodic memory (β=-0.09, SE = 0.04, p = .017), processing speed (β=-0.07, SE = 0.04, p = .046), working memory (β=-0.10, SE = 0.04, p = .005), and executive function/attentional control (β=-0.08, SE = 0.04, p = .035), but not visuospatial processing. The direction of these interactions was such that the association between higher p-tau217 and poorer cognitive performance was strongest in those with higher brain-PAD (i.e., accelerated brain aging). We do not find This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e106538. [https://doi.org/10.1002/alz70856_106538](https://doi.org/10.1002/alz70856_106538) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of2 BIOMARKERS evidence of a significant moderation effect of brain-PAD on the association between NfL and cognitive performance in any domain (all p >.05). Conclusion: Our results suggest that maintenance of structural brain integrity (slower brain aging) may help protect

FAQs

What was the study’s main goal?

To examine whether brain age moderates associations between AD-related blood biomarkers and cognitive function.

How were brain age and brain-PAD calculated?

T1-weighted MRI images were used to compute brain age with brainageR, and the difference between chronological age and brain age produced brain-PAD.

Which blood biomarkers showed moderation by brain-PAD?

Brain-PAD moderated the association of p-tau217 with multiple cognitive domains, while no significant moderation effect was found for NfL.

Sep 30, 2026

Upload by Jasmine