The Relative Contribution of Amyloid, Tau, Neurodegeneration, and Vascular Disease to Cognition and Cognitive Decline - ACross-National Study

Sep 30, 2026

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Recent in vivo biomarker advances have enabled biological diagnostic and staging criteria for Alzheimer’s disease based on amyloid (A), tau (T), and neurodegeneration (N). The added impact of comorbid vascular pathology (V) and how ATNV jointly relates to cognitive performance and decline remain unclear. This study evaluated neuroimaging-derived ATNV measures and their relative contribution to cognition using cross-national cohort data.

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DOI: 10. 1002/alz70856_106457 BIOMARKERS POSTER PRESENTATION NEUROIMAGING The Relative Contribution of Amyloid, Tau, Neurodegeneration, and Vascular Disease to Cognition and Cognitive Decline: ACross-National Study Jeremy A. Tanner1 Kacie D Deters5 Dong Young Lee3 Kwangsik Nho 11 Diefei Chen2 Min Soo Byun3 Ileana DeAnda-Duran4 Martine Elbejjani6 Evan Fletcher7 A. Zarina Kraal8 Silvia Mejia-Arango9 Stefanie D Pina-Escudero 10 Talia L. Robinson 12 C. Elizabeth Shaaban 13 Adam M. Staffaroni 10 Meichen Yu 11 Andrew J. Saykin 14 Paul K Crane 15 Dahyun Yi3 Shannon L Risacher 11 ADNI, KBASE 1 University of Texas Health San Antonio, San Antonio, TX, USA 2 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA 3Seoul National University Medical Research Center, Seoul, Korea, Republic of (South) 4 Celia Scott Weatherhead Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA 5 University of California, Los Angeles Integrative Biology and Physiology (IBP), Los Angeles, CA, USA 6American University of Beirut, Beirut, Lebanon 7 University of California, Davis, Davis, CA, USA 8 Columbia University Irving Medical Center, New York, NY, USA 9The University of Texas Rio Grande Valley School of Medicine, Harlingen, TX, USA 10 Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA 11 Indiana University School of Medicine, Indianapolis, IN, USA 12 Massachusetts General Hospital, Boston, MA, USA 13 University of Pittsburgh, Pittsburgh, PA, USA Abstract Background: Recent in vivo biomarker advancements have led to biological diagnostic and staging criteria for AD based on amyloid(“A”), tau(“T”), and neurodegeneration(“N”). However, the contribution of comorbid vascular(“V”) pathology and the relative influence of ATNV on cognitive performance and decline remains unclear, though is necessary to guide personalized diagnosis, prognosis, and care. We assessed the relative contribution of neuroimaging-based ATNV measures to cognition in cross-national studies. Method: Amyloid PET, tau PET, MRI, cognitive testing, and clinical evaluations were obtained in two prospective cohort studies with similar designs: ADNI3 in the US (n = 508; mean age=71±7, female=55%, education(yrs)= 16.5±2. 3) and KBASE in South Korea(n = 165;age=73±8,female=64%, education(yrs)= 11.0±4. 6). Continuous ATNV predictors included A=cortical centiloids, T=meta-temporal SUVR, N = ADsignature cortical thickness, and V=white matter hyperintensity volume. Clinical diagnoses of cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia were determined by clinical consensus. Cognitive testing was obtained annually with up to 4 years of follow-up, and factor scores in each cognitive domain were used as outcomes. Parallel cross-sectional analyses were performed within each cohort. ANOVA was performed to compare ATNV across clinical diagnoses. Multivariable linear mixed-effect models were used to assess the association of 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):e106457. [https://doi.org/10.1002/alz70856_106457](https://doi.org/10.1002/alz70856_106457) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of4 14 Indiana University School of Medicine, Department of Radiology and Imaging Sciences, Indianapolis, IN, USA 15 University of Washington, Seattle, WA, USA Correspondence Jeremy A. Tanner, University of Texas Health San Antonio, San Antonio, TX, USA. [Email:](Email: Tannerj1@uthscsa.edu)[ Tann

FAQs

What does the study evaluate regarding ATNV and cognition?

It assesses how neuroimaging-based ATNV measures relate to cognitive performance and cognitive decline. The goal is to clarify the relative contribution of amyloid, tau, neurodegeneration, and vascular disease.

Which biomarkers and imaging measures correspond to A, T, N, and V?

Amyloid uses cortical centiloids (A), tau uses meta-temporal SUVR (T), neurodegeneration uses ADsignature cortical thickness (N), and vascular pathology uses white matter hyperintensity volume (V).

What were the main findings across the US and South Korea cohorts?

Across both ADNI and KBASE, A, T, N, and V increased with clinical disease severity. In the US cohort, higher baseline T and A were linked to domain-specific decline, while in KBASE no ATNV factors were associated with cognitive decline over time.

Sep 30, 2026

Uploaded by Theodore