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Multilevel white matter degeneration associated cognitive dysfunction in mild cognitive impairment
Yu Chen1, Tiantian Liu2, Li-Zhi Cao1
1School of Medical Technology, Beijing Institute of Technology, Haidian District, Beijing, China.
Molecular Psychiatry
|August 27, 2025
Summary
Mild cognitive impairment (MCI) involves white matter (WM) damage impacting cognitive function. This study reveals how WM microstructure changes mediate cognitive decline in prodromal dementia.
Area of Science:
- Neuroimaging
- Neuroscience
- Neurology
Background:
- Mild cognitive impairment (MCI) is the preclinical stage of dementia, marked by cognitive deficits and white matter (WM) alterations.
- Understanding WM microstructure changes and their impact on cognition is crucial for early diagnosis and intervention in prodromal dementia.
Purpose of the Study:
- To investigate WM microstructure degeneration at multiple scales in individuals with MCI.
- To analyze the mediating role of structural connectome in the relationship between WM alterations and cognitive dysfunction.
Main Methods:
- Fixel-based analysis (FBA) using fixelwise and fiberwise measures in 50 MCI patients and 75 healthy controls.
- Structural connectome analysis to examine network-level effects on WM-cognition associations.
Main Results:
- Patients with MCI showed widespread fiber-specific WM disruptions, including decreased fiber density and cross-section in commissural and association fibers.
- WM microstructural degeneration was associated with multi-domain cognitive impairments.
- The structural connectome between visual and salience networks mediated the link between WM damage and impaired language and memory functions.
Conclusions:
- WM microstructure damage at different scales contributes to cognitive decline in MCI.
- Network-level interactions, particularly involving visual and salience networks, are critical in mediating the effects of WM alterations on specific cognitive domains.
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