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J Clin Psychiatry. 2018 Sep 4;79(5). pii: 17m11763. doi: 10.4088/JCP.17m11763.

Depression Plays a Moderating Role in the Cognitive Decline Associated With Changes of Brain White Matter Hyperintensities.

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Department of Psychiatry, Jeju National University School of Medicine, Jeju National University Hospital, Jejudo, Korea.
Department of Psychiatry, Dankook University College of Medicine, Dankook University Hospital, Chungcheongbukdo, Korea.
Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly, Gyeonggi-do, Korea.
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea.
Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, Korea University, Seoul, Korea.
The Geriatric Research, Education, and Clinical Center (GRECC), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University, Nashville, Tennessee, USA.
Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.
Department of Neuropsychiatry, Seoul National University Bundang Hospital, 300 Gumidong, Bundanggu, Seongnamsi, Gyeonggi-do, Korea 463-707.
Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea.



In the elderly, depression and white matter hyperintensities (WMH) are common and associated with cognitive impairment. This study investigated the possible interactions between depression and WMH in their influences on cognition of the elderly.


Using multiple neuropsychological tests, we evaluated the cognitive function of 122 community-dwelling elders with depression at baseline between November 2008 and February 2009. Major depressive disorder, dysthymic disorder, and minor depressive disorder were diagnosed according to DSM-IV criteria. Subsyndromal depressive disorder was operationally defined using a modification of DSM-IV criteria. We visually rated WMH severity according to the modified Fazekas scale and calculated WMH volume using an automated method. We defined WMH (+) as having a score of 2 or higher on the modified Fazekas scale. In the 3-year follow-up study, baseline participants were reassessed between November 2011 and February 2013 with the same methodology.


Baseline depression was associated with a decline over 3 years in the Categorical Verbal Fluency Test (VFT) (P = .001), Word List Memory Test (WLMT) (P = .019), Trail Making Test A (TMT-A) (P = .018), and Mini-Mental State Examination (MMSE) (P = .017), while baseline WMH (+) was associated with a decline in WLMT (P = .039) only. An increase of WMH volume over 3 years was associated with a decline in the performances of VFT (P = .044), WLMT (P = .044), Word List Recall Test (P = .040), Word List Recognition Test (P = .036), and TMT-A (P = .001) over the same period only in the subjects with depression at baseline.


Depressive disorder and WMH are interactively associated with the poor performance of multiple cognitive functions. Depressive disorder may moderate the cognitive decline associated with the changes of brain WMH.


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