Open Access Research article

Apathy/depression, but not subjective fatigue, is related with cognitive dysfunction in patients with multiple sclerosis

Masaaki Niino1*, Nobuhiro Mifune2, Tatsuo Kohriyama3, Masahiro Mori4, Takashi Ohashi5, Izumi Kawachi6, Yuko Shimizu7, Hikoaki Fukaura89, Ichiro Nakashima10, Susumu Kusunoki11, Katsuichi Miyamoto11, Kazuto Yoshida12, Takashi Kanda13, Kyoichi Nomura9, Takashi Yamamura14, Fumihito Yoshii15, Jun-ichi Kira16, Shunya Nakane17, Kazumasa Yokoyama18, Makoto Matsui19, Yusei Miyazaki20 and Seiji Kikuchi20

Author Affiliations

1 Department of Clinical Research, Hokkaido Medical Center, Yamanote 5jo 7chome, Nishi-ku, Sapporo 063-0005, Japan

2 School of Management, Kochi University of Technology, Kochi, Japan

3 Department of Neurology, Hiroshima City Hospital, Hiroshima, Japan

4 Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan

5 Department of Neurology, Tokyo Women’s Medical University Yachiyo Medical Center, Chiba, Japan

6 Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan

7 Department of Neurology, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan

8 Department of Neurology, Iwate Medical School, Morioka, Japan

9 Department of Neurology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

10 Department of Neurology, Tohoku University School of Medicine, Sendai, Japan

11 Department of Neurology, Kinki University School of Medicine, Osaka, Japan

12 Department of Neurology, Asahikawa Red Cross Hospital, Asahikawa, Japan

13 Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

14 Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan

15 Department of Neurology, Tokai University School of Medicine, Kanagawa, Japan

16 Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

17 Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan

18 Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan

19 Department of Neurology, Kanazawa Medical University, Ishikawa, Japan

20 Department of Neurology, Hokkaido Medical Center, Sapporo, Japan

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BMC Neurology 2014, 14:3  doi:10.1186/1471-2377-14-3

Published: 6 January 2014



Cognitive impairment could affect quality of life for patients with multiple sclerosis (MS), and cognitive function may be correlated with several factors such as depression and fatigue. This study aimed to evaluate cognitive function in Japanese patients with MS and the association between cognitive function and apathy, fatigue, and depression.


The Brief Repeatable Battery of Neuropsychological tests (BRB-N) was performed in 184 Japanese patients with MS and 163 healthy controls matched for age, gender, and education. The Apathy Scale (AS), Fatigue Questionnaire (FQ), and Beck Depression Inventory Second Edition (BDI-II) were used to evaluate apathy, fatigue, and depression, respectively. Student’s t-test was used to compare MS patients and healthy controls. Correlations between two factors were assessed using the Pearson correlation test, and multiple regression analysis was used to evaluate how much each factor affected the BRB-N score.


In all BRB-N tests, patients with MS scored significantly lower than controls, and the effect size of symbol digit modalities test was the highest among the 9 tests of the BRB-N. Patients with MS had higher AS (p < 0.001), FQ (p < 0.0001), and BDI-II (p < 0.0001) scores than controls. In patients with MS, scores on most of the BRB-N tests correlated with scores on the AS and BDI-II; however, there was little correlation between scores on the BRB-N tests and those on the FQ.


Cognitive function was impaired, particularly information-processing speed, and decreased cognitive function was correlated with apathy and depression in Japanese patients with MS. Despite the association between cognitive variables and depression/apathy, cognitive function was impaired beyond the effect of depression and apathy. However, subjective fatigue is not related with cognitive impairment. Taken together, this suggests that different therapeutic approaches are needed to improve subjective fatigue and cognition, and thereby quality of life, in patients with MS.

Multiple sclerosis; Cognition; Apathy; Fatigue; Depression; Japanese