Association of longitudinal cognitive decline with diffusion MRI in gray matter, amyloid, and tau deposition
Abstract
Extracellular amyloid plaques in gray matter are the earliest pathological marker for Alzheimer's disease (AD), followed by abnormal tau protein accumulation. The link between diffusion changes in gray matter, amyloid and tau pathology, and cognitive decline is not well understood. We first performed cross-sectional analyses on T1-weighted imaging, diffusion MRI, and amyloid and tau PETs from the ADNI 2/3 database. We evaluated cortical volume, free-water, fractional anisotropy (FA), and amyloid and tau SUVRs in 171 cognitively normal, 103 MCI, and 44 AD individuals. When the 3 groups were combined, increasing amyloid burden was associated with reduced extracellular free-water in the entorhinal cortex and hippocampus in those with amyloid-negative status whereas increasing tau burden was associated with increased extracellular free-water regardless of amyloid status. Next, we found that for the MCI subjects, diffusion measures (free-water, FA) alone predicted MMSE score 2 years later with a high r-square value (87%), as compared to tau SUVRs (27%), T1 volume (36%), and amyloid SUVRs (75%). Diffusion measures represent a potent non-invasive marker for predicting cognitive decline.
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Recent longitudinal work suggests that diffusion-derived axonal-density measures may detect early, spatially selective degeneration related to clinical decline in Alzheimer's disease.
“Recent longitudinal work further suggests that diffusion-derived axonal-density measures may detect early, spatially selective degeneration related to clinical decline in Alzheimer’s disease (Gong et al., 2026; Wang et al., 2023).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Wang et al., 2023
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Le Bihan, D. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1858655 · Cited by 1 · see citing works
40 Years of diffusion MRI in the brain: From history to emerging frontiers
Le Bihan, D. (2026) · Imaging Neuroscience · doi:10.1162/imag.a.1365
- Authors
- Wang, W.-E., Chen, R., Mayrand, R. P., Adjouadi, M., Fang, R., DeKosky, S. T., Duara, R., Coombes, S. A., & Vaillancourt, D. E.
- Affiliations
- University of Florida Health (US)
- University of Florida (US)
- Florida International University (US)
- Corresponding author
- Vaillancourt, David E.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2023-01
- Volume
- 121
- Pages
- 166-178
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W4308190831
- Cited by
- 20
- References
- 11
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 3 · 2023: 3
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH-12-2-0012, CNS-1920182)
- National Institutes of Health (U01 AG024904, P30AG066506)
- National Science Foundation (NSF 1908299)
- National Institute on Aging
- University of Florida (P30AG066506)
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Disease Neuroimaging Initiative
- Northern California Institute for Research and Education
- University of Southern California
- Alzheimer's Disease Research Center, Emory University
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- Alzheimer's disease, cognitive decline, diffusion MRI, fractional anisotropy, extracellular free water, amyloid deposition, tau deposition, gray matter, entorhinal cortex, hippocampus, mild cognitive impairment, amyloid PET, tau PET, cortical volume
- MeSH terms
- Alzheimer Disease, Amyloid, Amyloidosis, Cross-Sectional Studies, Humans, Water, Biomarkers, Amyloid beta-Peptides, tau Proteins, Diffusion Magnetic Resonance Imaging, Amyloidogenic Proteins, Cognitive Dysfunction, Gray Matter
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