Open Access Highly Accessed Research article

Different associations of white matter lesions with depression and cognition

Jun-Young Lee12, Philip Insel1, R Scott Mackin3, Norbert Schuff14, Helena Chui5, Charles DeCarli6, Kee Hyung Park17, Susanne G Mueller1 and Michael W Weiner18*

Author Affiliations

1 Center for Imaging of Neurodegenerative Diseases, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA

2 Department of Psychiatry, Seoul National University Boramae Hospital, Seoul, Korea

3 Department of Psychiatry, University of California, San Francisco, CA, USA

4 Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA

5 Department of Neurology, University of Southern California, Los Angeles, CA, USA

6 Department of Neurology and Center for Neuroscience, University of California, Davis, Sacramento, CA, USA

7 Department of Neurology, Gachon University Gil Hospital, Incheon, Korea

8 Department of Radiology, Psychiatry, Neurology, and Medicine, University of California, San Francisco, CA, USA

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BMC Neurology 2012, 12:83  doi:10.1186/1471-2377-12-83

Published: 25 August 2012



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.


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.


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.


These findings suggest that the neurobiological mechanisms underpinning depressive symptoms and cognitive dysfunction in older adults may differ.

Leukoaraiosis; Depression; Cognition; Frontal lobe; Mediation