Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease
Open accessAbstract
INTRODUCTION: White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. METHOD: Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN). RESULTS: WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. CONCLUSIONS: High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.
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Those fibre tracts connect regions of the default mode network (DMN) and their degeneration may contribute to the impairment of the DMN and other functional networks in Alzheimer's disease.
“Those fibre tracts connect regions of the default mode network (DMN) and their degeneration may thus contribute to the impairment of the DMN and other functional networks in Alzheimer’s disease (Taylor et al., 2017).”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Taylor et al., 2017
The Methods identify fiber tracts connecting DMN regions, and the Discussion links tract-specific white matter hyperintensities to reduced DMN functional connectivity. The extension to other functional networks is not supported: the Results report no association between tract hyperintensities and connectivity in the two other networks tested. The paper also cautions that its atlas-based approach cannot assure the tracts always connected the DMN regions. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCallosal white matter degeneration may contribute to functional disruption of functional networks such as the default mode network.
“our findings support the possibility that callosal white matter degeneration contribute to functional disruption of functional networks such as the default mode network (Chhatwal et al., 2013; Mueller and Weiner, 2017; Taylor et al., 2017)”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Taylor et al., 2017
The Discussion reports that tract-specific white matter hyperintensities were associated with reduced functional connectivity in the default mode network, supporting the proposed network disruption. But the Methods say the study excluded the interhemispheric forceps minor and major, and the Discussion identifies the inferior fronto-occipital fasciculus—not callosal fibers—as the tract driving the reported association. No page numbers are available in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredHigher vascular burden represented by white matter hyperintensities is associated with a reduced functional connectome in AD.
“Higher vascular burden represented by white matter hyperintensities (WMHs) also have been shown to be associated with a reduced functional connectome in AD (Taylor et al., 2017).”
From Effects of Alzheimer’s and Vascular Pathologies on Structural Connectivity in Early- and Late-Onset Alzheimer’s Disease (2021) · cites this paper as Taylor et al., 2017
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- Authors
- Taylor, A. N. W., Kambeitz-Ilankovic, L., Gesierich, B., Simon-Vermot, L., Franzmeier, N., Araque Caballero, M. Á., Müller, S., Hesheng, L., Ertl-Wagner, B., Bürger, K., Weiner, M. W., Dichgans, M., Duering, M., Ewers, M., & (ADNI), A. D. N. I.
- Affiliations
- Institut für Schlaganfall- und Demenzforschung (DE)
- Department of Psychiatry and Psychotherapy Ludwig-Maximilians-Universität LMU Munich Germany
- Institute for Stroke and Dementia Research Klinikum der Universität München, Ludwig-Maximilians-Universität LMU Munich Germany
- Institute of Clinical Radiology, Klinikum der Universität München Ludwig-Maximilians-Universität LMU Munich Germany
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School Charlestown MA USA
- LMU Klinikum (DE)
- San Francisco VA Medical Center (US)
- Munich Cluster for Systems Neurology (DE)
- Corresponding author
- Ewers, Michael
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-07-15
- Volume
- 13
- Issue
- 3
- Pages
- 225-235
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5319922
- OpenAlex
- W2496219973
- Cited by
- 73
- References
- 56
- Citations by year
- 2026: 11 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 13 · 2021: 5 · 2020: 9 · 2019: 5 · 2018: 7 · 2017: 2
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc-nd)
- Funders
- European Commission (PCIG12-GA-2012-334259 VASCAMY)
- Merck
- U.S. Department of Defense (2U01AG024904, W81XWH-13-1-0259, W81XWH-12-2-0012, R01 AG10897, 1P41 EB015904, P01 AG19724, R01 AG032306, R01A G03879)
- Alzheimer's Disease Neuroimaging Initiative (2-12-233036, 20110506, R01 MH098062-01)
- National Institutes of Health
- National Institute of Mental Health
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- white matter hyperintensities, Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Nerve Net, Neuropsychological Tests, Positron-Emission Tomography, White Matter
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