The effect of white matter signal abnormalities on default mode network connectivity in mild cognitive impairment

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Default mode network (DMN) dysfunction is implicated in Alzheimer's disease, but its mechanisms in mild cognitive impairment (MCI) remain unclear.
• White matter lesions (WMLs) are linked to vascular issues, while cortical atrophy is associated with neurodegeneration, both potentially affecting DMN connectivity.

Purpose of the Study:

• To investigate the associations between DMN functional connectivity (FC), WML load, and cortical atrophy in individuals with MCI and healthy controls.
• To differentiate the contributions of WMLs and cortical atrophy to DMN alterations in MCI.

Main Methods:

• Seed-based functional connectivity analysis of the DMN using resting-state fMRI.
• Quantification of white matter lesion volume and cortical thickness.
• Comparison of DMN FC, WMLs, and cortical thickness between MCI and control groups.

Main Results:

• MCI patients exhibited decreased DMN FC compared to controls, particularly between the precuneus and lateral temporal cortex, medial prefrontal cortex, posterior cingulate cortex, and inferior parietal lobe.
• Controlling for WML volume reduced DMN connectivity differences in the lateral temporal cortex but revealed increased connectivity in the medial prefrontal cortex in MCI, linked to WMLs.
• Controlling for cortical thickness showed similar DMN FC decreases across both MCI and control groups.

Conclusions:

• White matter lesions and cortical atrophy differentially impact DMN functional connectivity in MCI.
• The findings highlight a significant vascular contribution of white matter lesions to DMN alterations and cognitive impairment in MCI.