Altered whole-brain white matter networks in preclinical Alzheimer's disease
Open accessAbstract
Surrogates of whole-brain white matter (WM) networks reconstructed using diffusion tensor imaging (DTI) are novel markers of structural brain connectivity. Global connectivity of networks has been found impaired in clinical Alzheimer's disease (AD) compared to cognitively healthy aging. We hypothesized that network alterations are detectable already in preclinical AD and investigated major global WM network properties. Other structural markers of neurodegeneration typically affected in prodromal AD but seeming largely unimpaired in preclinical AD were also examined. 12 cognitively healthy elderly with preclinical AD as classified by florbetapir-PET (mean age 73.4 ± 4.9) and 31 age-matched controls without cerebral amyloidosis (mean age 73.1 ± 6.7) from the ADNI were included. WM networks were reconstructed from DTI using tractography and graph theory. Indices of network capacity and the established imaging markers of neurodegeneration hippocampal volume, and cerebral glucose utilization as measured by fludeoxyglucose-PET were compared between the two groups. Additionally, we measured surrogates of global WM integrity (fractional anisotropy, mean diffusivity, volume). We found an increase of shortest path length and a decrease of global efficiency in preclinical AD. These results remained largely unchanged when controlling for WM integrity. In contrast, neither markers of neurodegeneration nor WM integrity were altered in preclinical AD subjects. Our results suggest an impairment of WM networks in preclinical AD that is detectable while other structural imaging markers do not yet indicate incipient neurodegeneration. Moreover, these findings are specific to WM networks and cannot be explained by other surrogates of global WM integrity.
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Clinical studies have noted decreased network efficiency in patients with AD.
“Clinical studies have also noted decreased network efficiency in patients with AD (Daianu et al., 2013; Fischer et al., 2015; Lo et al., 2010; Reijmer et al., 2013)”
From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Fischer et al., 2015
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“Clinical studies have also noted decreased network efficiency in patients with AD (Daianu et al., 2013; Fischer et al., 2015; Lo et al., 2010; Reijmer et al., 2013), which we did not observe.”
BackgroundTucholka, A., Grau-Rivera, O., Falcon, C., Rami, L., Sánchez-Valle, R., Lladó, A., Gispert, J. D., Molinuevo, J. L., & Initiative, F. T. A. D. N. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170553 · Cited by 29 · see citing works
- Authors
- Fischer, F. U., Wolf, D., Scheurich, A., & Fellgiebel, A.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Fischer, Florian Udo
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2015
- Volume
- 8
- Pages
- 660-666
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC4536470
- OpenAlex
- W804767602
- Cited by
- 105
- References
- 14
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 10 · 2022: 10 · 2021: 10 · 2020: 10 · 2019: 14 · 2018: 17 · 2017: 8 · 2016: 8 · 2014: 1
- FWCI
- 8.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Gutenberg Open Science (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Gutenberg Open Science
- Funders
- Alzheimer's Disease Neuroimaging Initiative (ADNI)
- National Institutes of Health (U01 AG024904)
- DOD ADNI
- Department of Defense (W81XWH-12-2-0012)
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- EISAI Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- F Hoffmann-La Roche Ltd.
- Genentech, Inc.
- GE Healthcare
- Innogenetics, N.V.
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research and Development, LLC
- Johnson and Johnson Pharmaceutical Research and Development LLC
- Medpace, Inc.
- Merck & Co., Inc.
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- servier
- Synarc Inc.
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- preclinical Alzheimer's disease, white matter networks, structural brain connectivity, global efficiency, shortest path length, graph theory, neurodegeneration, hippocampal volume, brain glucose metabolism, fractional anisotropy, mean diffusivity, cerebral amyloidosis, florbetapir PET
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Brain, Ethylene Glycols, Female, Glucose, Hippocampus, Humans, Male, Nerve Net, Biomarkers, Amyloid beta-Peptides, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography, Diffusion Tensor Imaging, White Matter
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