Tau mediates the impact of amyloid and vascular disease burden on the trajectory of clinical symptoms
Longer amyloid (A) and vascular disease (V) chronicity were associated with faster cognitive decline, emphasizing the importance of considering chronic exposure to these pathologies. Individuals with higher V burden experienced a steeper decline in cognition in the presence of A pathology, highlighting the interaction between V and neurodegenerative processes. Progression from early to mild dementia was faster with greater white matter hyperintensity chronicity, even when A duration was held constant, supporting the idea that V pathology amplifies the clinical impact of amyloid in Alzheimer's disease. Tau accumulation played a significant mediating role in linking A and V burden to cognitive decline, suggesting that tau pathology is a critical downstream factor in symptom progression. Person-level chronicity estimates of A and V provide a more precise understanding of cognitive decline trajectories, offering insights for early intervention strategies.
Authors
- Bruce P. Hermann (ORCID: https://orcid.org/0000-0003-0133-4427)
- Tobey J. Betthauser (ORCID: https://orcid.org/0000-0001-8856-1352)
- Bradley Christian (ORCID: https://orcid.org/0000-0001-5072-3512)
- Rebecca L. Koscik (ORCID: https://orcid.org/0000-0003-0025-744X)
- Lianlian Du
- Robert V. Cadman (ORCID: https://orcid.org/0000-0001-7685-1977)
- Aaron S. Field (ORCID: https://orcid.org/0000-0003-4349-1009)
- Erin M. Jonaitis (ORCID: https://orcid.org/0009-0004-5091-8255)
- Karly Alex Cody (ORCID: https://orcid.org/0000-0001-5996-2560)
- Leonardo A. Rivera‐Rivera (ORCID: https://orcid.org/0000-0001-5629-8721)
- Laura B. Eisenmenger (ORCID: https://orcid.org/0000-0001-6764-4239)
- Nathaniel A. Chin (ORCID: https://orcid.org/0000-0001-8008-9356)
- Sterling C. Johnson (ORCID: https://orcid.org/0000-0002-8501-545X)
- Kevin M. Johnson
- Sanjay Asthana (ORCID: https://orcid.org/0000-0002-3298-6324)
Institutions
- Rush University Medical Center (US)
- University of Wisconsin–Madison (US)
- University of Wisconsin Health (US)
- Wisconsin Division of Public Health (US)
- Stanford University (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1002/alz.70831
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00