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Updated: May 19, 2026

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
Published on: April 23, 2021
Different associations of white matter lesions with depression and cognition
Jun-Young Lee1, Philip Insel, R Scott Mackin
1Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Background:
To test the hypothesis that white matter lesions (WML) are primarily associated with regional frontal cortical volumes, and to determine the mediating effects of these regional frontal cortices on the associations of WML with depressive symptoms and cognitive dysfunction.
Methods:
Structural brains MRIs were performed on 161 participants: cognitively normal, cognitive impaired but not demented, and demented participants. Lobar WML volumes, regional frontal cortical volumes, depressive symptom severity, and cognitive abilities were measured. Multiple linear regression analyses were used to identify WML volume effects on frontal cortical volume. Structural equation modeling was used to determine the MRI-depression and the MRI-cognition path relationships.
Results:
WML predicted frontal cortical volume, particularly in medial orbirtofrontal cortex, irrespective of age, gender, education, and group status. WML directly predicted depressive score, and this relationship was not mediated by regional frontal cortices. In contrast, the association between WML and cognitive function was indirect and mediated by regional frontal cortices.
Conclusions:
These findings suggest that the neurobiological mechanisms underpinning depressive symptoms and cognitive dysfunction in older adults may differ.
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