The effect of white matter signal abnormalities on default mode network connectivity in mild cognitive impairment
Open accessAbstract
Regions within the default mode network (DMN) are particularly vulnerable to Alzheimer's disease pathology and mechanisms of DMN disruption in mild cognitive impairment (MCI) are still unclear. White matter lesions are presumed to be mechanistically linked to vascular dysfunction whereas cortical atrophy may be related to neurodegeneration. We examined associations between DMN seed-based connectivity, white matter lesion load, and cortical atrophy in MCI and cognitively healthy controls. MCI showed decreased functional connectivity (FC) between the precuneus-seed and bilateral lateral temporal cortex (LTC), medial prefrontal cortex (mPFC), posterior cingulate cortex, and inferior parietal lobe compared to those with controls. When controlling for white matter lesion volume, DMN connectivity differences between groups were diminished within bilateral LTC, although were significantly increased in the mPFC explained by significant regional associations between white matter lesion volume and DMN connectivity only in the MCI group. When controlling for cortical thickness, DMN FC was similarly decreased across both groups. These findings suggest that white matter lesions and cortical atrophy are differentially associated with alterations in FC patterns in MCI. Associations between white matter lesions and DMN connectivity in MCI further support at least a partial but important vascular contribution to age-associated neural and cognitive impairment.
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Executive function performance is dependent on both intact white matter pathway connectivity and pathologic integrity of the cortical regions themselves.
“Indeed, the present findings support the hypothesis that executive function performance is dependent on both intact white matter pathway connectivity, as well as pathologic integrity of the cortical regions themselves [12,45,46]”
From Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function (2023) · cites this paper as [45]
The Introduction (page unavailable) says functional connectivity depends on intact white matter pathways and cortical structural integrity. The Results (page unavailable) associate medial prefrontal connectivity with executive-function test performance. The paper does not establish that executive performance itself depends on both structural factors, so the claim extends its connectivity finding to performance. (LLM, conf=0.84)
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Ali, D. G., Abner, E. L., Bahrani, A. A., El Khouli, R., Gold, B. T., Jiang, Y., Wilcock, D. M., & Jicha, G. A. (2023) · Brain Sciences · doi:10.3390/brainsci13020218 · Cited by 7 · see citing works
“Indeed, the present findings support the hypothesis that executive function performance is dependent on both intact white matter pathway connectivity, as well as pathologic integrity of the cortical regions themselves [12,45,46] and that there is a synergistic interaction between baseline biomarkers of pathology on lo…”
- Authors
- Wang, Z., Williams, V. J., Stephens, K. A., Kim, C., Bai, L., Zhang, M., & Salat, D. H.
- Affiliations
- Massachusetts General Hospital (US)
- Xi'an Jiaotong University (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- VA Boston Healthcare System (US)
- Corresponding author
- Wang, Zhuonan
- ORCID
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2019-11-19
- Volume
- 41
- Issue
- 5
- Pages
- 1237-1248
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC7267894
- OpenAlex
- W2990515946
- Cited by
- 28
- References
- 85
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 4 · 2021: 3 · 2020: 3 · 2018: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Human Brain Mapping (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Foundation for the National Institutes of Health (R01 NR010827)
- National Natural Science Foundation of China (81571640, 81571752, 81771914)
- 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 › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- mild cognitive impairment, default mode network, white matter lesions, cortical atrophy, functional connectivity, seed-based functional connectivity, vascular dysfunction, Alzheimer's disease, medial prefrontal cortex, lateral temporal cortex, posterior cingulate cortex, inferior parietal lobule, precuneus, cortical thickness
- MeSH terms
- Default Mode Network, Aged, Aged, 80 and over, Atrophy, Brain Mapping, Cerebral Cortex, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Neuropsychological Tests, Cognitive Dysfunction, White Matter
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