Specific white matter tracts and diffusion properties predict conversion from mild cognitive impairment to Alzheimer’s disease.
Open accessAbstract
Identifying biomarkers that can assess the risk of developing Alzheimer's Disease (AD) remains a significant challenge. In this study, we investigated the integrity levels of brain white matter in 34 patients with mild cognitive impairment (MCI) who later converted to AD and 53 stable MCI patients. We used diffusion tensor imaging (DTI) and automated fiber quantification to obtain the diffusion properties of 20 major white matter tracts. To identify which tracts and diffusion measures are most relevant to AD conversion, we used support vector machines (SVMs) to classify the AD conversion and non-conversion MCI patients based on the diffusion properties of each tract individually. We found that diffusivity measures from seven white matter tracts were predictive of AD conversion with axial diffusivity being the most predictive diffusion measure. Additional analyses revealed that white matter changes in the central and parahippocampal terminal regions of the right cingulate hippocampal bundle, central regions of the right inferior frontal occipital fasciculus, and posterior and anterior regions of the left inferior longitudinal fasciculus were the best predictors of conversion from MCI to AD. An SVM based on these white matter tract regions achieved an accuracy of 0.75. These findings provide additional potential biomarkers of AD risk in MCI patients.
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Patients with preclinical AD have widespread white matter abnormalities at a stage similar to those reported in AD.
“patients with preclinical AD have widespread white matter abnormalities at a stage similar to those reported in AD (Marquez and Yassa, 2019; Stone et al., 2021).”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Stone et al., 2021
The Introduction says white-matter changes may appear early in AD, and the Discussion reports that specific tracts can be affected years before symptoms. But Stone et al. studied patients with mild cognitive impairment and identified specific tract changes; it does not establish widespread abnormalities in preclinical AD comparable to those in AD. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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Li, Y., Tang, Z., Yao, M., Ran, Y., & Qiu, Z. (2026) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00006
Sathe, A., Chatterjee, A., Shashikumar, N., Pechman, K., Schilling, K. G., Landman, B., Bolton, C. J., Zhang, P.-P., Bender, A. R., Hohman, T., et al. (2025) · medRxiv · doi:10.1101/2025.05.29.25328528
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Magalhães, T. N. C., Casseb, R. F., Moraes, A. S., Teixeira, C. V. L., Carletti, A. M., de Rezende, T. J. R., Joaquim, H. P. G., Talib, L. L., Forlenza, O., Cendes, F., et al. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261467065
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- Authors
- Stone, D. B., Ryman, S. G., Hartman, A. P., Wertz, C. J., Vakhtin, A. A., & Initiative, A. D. N.
- Affiliations
- Mind Research Network (US)
- Corresponding author
- Stone, David B.
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2021-07-23
- Volume
- 13
- Pages
- 711579-711579
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC8343075
- OpenAlex
- W3183527235
- Semantic Scholar
- 38afbd94a541fbdbced4bf4044594df8ce78b3c1
- Cited by
- 28
- References
- 61
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 6
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Funders
- U.S. Department of Defense (U01 AG024904, W81XWH, W81XWH-12-2-, W81XWH-12, W81XWH1220012, AG024904)
- Foundation for the National Institutes of Health (W81XWH-12-2-0012, P30GM122734, U01AG024904, Grant U01 AG024904, AG024904)
- Alzheimer's Association (U01 AG024904, W81XWH-12-2-0012)
- Bristol-Myers Squibb (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Eli Lilly and Company (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Pfizer (AG024904, W81XWH-12-2-0012, U01 AG024904)
- Biogen (W81XWH-12-2-0012, U01 AG024904, AG024904)
- University of Southern California (W81XWH-12-2-0012, U01 AG024904)
- F. Hoffmann-La Roche (W81XWH-12-2-0012, AG024904, U01 AG024904)
- Meso Scale Diagnostics (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-, Department of Defense award number W81XWH-12-2-0012)
- BioClinica (U01 AG024904, W81XWH-12-2-0012, AG024904)
- Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Northern California Institute for Research and Education (U01 AG024904, W81XWH-12-2-0012)
- Eisai (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Servier (AG024904, W81XWH-12-2-0012, U01 AG024904)
- H. Lundbeck A/S (U01 AG024904, AG024904, W81XWH-12-2-0012)
- IXICO (AG024904, W81XWH-12-2-0012, U01 AG024904)
- National Institutes of Health (3u01ag024904-10s2, W81XWH, W81XWH-12-2-0012, U01-AG024904, Grant U01 AG024904, AG024904)
- Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
- Canadian Institutes of Health Research (U01 AG024904, W81XWH-12-2-0012)
- National Institute on Aging (U01-AG-024904, W81XWH-12-2–0012, AG 024904)
- National Institute of General Medical Sciences (W81XWH-12-2-0012, U01 AG024904, P30GM122734)
- National Institute of Biomedical Imaging and Bioengineering (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, mild cognitive impairment, conversion to Alzheimer's disease, white matter tracts, diffusion tensor imaging, axial diffusivity, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, white matter integrity, support vector machine classification
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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