Manabu Ikeda

Kumamoto University, Kumamoto, Kumamoto, Japan

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Publications (112)242.36 Total impact

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    ABSTRACT: The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial. This 52-week study consisted of 16-week randomized placebo-controlled (RCT) and 36-week open-label extension phases. Of 142 DLB patients enrolled in the RCT phase (three arms: placebo, 5 mg, and 10 mg), 110 entered the extension phase. The placebo group of the RCT phase initiated active treatment at week 16, and the active groups maintained allocated treatment and dosages until week 24. After week 24, all patients received 10 mg. Dose reduction to 5 mg for safety concerns was allowed. Efficacy measures included Mini-Mental State Examination (MMSE) for cognitive function and Neuropsychiatric Inventory (NPI) for behavioral symptoms. Safety evaluations included adverse events (AEs) and the unified Parkinson disease rating scale. In total, 100 subjects completed the study. Cognitive function improvement was sustained for 52 weeks (MMSE at week 52 in 10 mg: 2.8 ± 3.5 (mean ± standard deviation); P <0.001, Student paired t test)). Those who received placebo in the RCT phase showed an improvement after starting active treatment. NPI improved in all the groups throughout the study, including the placebo period. In the subgroup of the 5 mg group without remarkable cognitive or behavioral improvement at week 24, further improvement was observed after a dose increase to 10 mg. After week 24, 21 patients experienced dose reduction. The incidence of any AEs did not increase over time. The long-term administration of donepezil at 10 mg/day improved cognitive function for up to 52 weeks in patients with DLB without increasing the risk of clinically significant safety events. NCT01278407. Trial registration date: January 14, 2011.
    Alzheimer's Research and Therapy 12/2015; 7(1):5. DOI:10.1186/s13195-014-0081-2 · 3.50 Impact Factor
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    ABSTRACT: It is generally thought that people with dementia are not able to attempt suicide because of impaired executive function. Little research is available about suicidal ideation among dementia patients. The present study examines 1) the sociodemographic and clinical features of dementia patients with suicidal ideation and 2) the effect of suicidal ideation on caregiver burden. A total of 634 dementia outpatients and their family caregivers participated in this study. Comparisons of variables were made among three groups: patients with suicidal ideation, patients with depression without suicidal ideation, and patients with neither suicidal ideation nor depression. Data were collected between April 2007 and July 2013. Suicidal ideation was seen in 64 patients (10.1%). Patients with suicidal ideation had a significantly higher rate of behavioural and psychological symptoms of dementia (BPSD) (P<0.001). Caregivers of patients with suicidal ideation felt a higher caregiver burden, even after adjusting for BPSD score (P<0.01). Suicidal ideation was assessed by interview with caregivers, so we may have overlooked people who had suicidal ideation but did not express it to their caregivers. Suicidal ideation among dementia patients should receive greater attention. Adequate assessment of suicidal ideation and psychological support for both patients with suicidal ideation and their caregivers are needed. Copyright © 2015. Published by Elsevier B.V.
    Journal of Affective Disorders 06/2015; 178. DOI:10.1016/j.jad.2015.02.019 · 3.76 Impact Factor
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    ABSTRACT: Assessing driving aptitude in dementia patients is critically important for both patient and public safety. However, there have been only a few reports on the driving behaviours and accident risk of patients with dementia, especially frontotemporal lobar degeneration (FTLD). Therefore, we compared the characteristics of driving behaviours in patients with FTLD and those with Alzheimer's disease (AD). The subjects were 28 FTLD and 67 AD patients who visited the Department of Psychiatry, Kochi Medical School Hospital. We conducted semi-structured interviews with their families and caregivers about traffic accident history and changes in patient driving behaviours after dementia onset and then compared the findings between the two groups. Overall changes in driving behaviours were reported in 89% (25/28) and 76% (51/67) of the FTLD and AD patients, respectively (P = 0.17). In the FTLD group, difficulty in judging inter-vehicle distances, ignoring road signs and traffic signals, and distraction were reported in 50% (14/28), 61% (17/28), and 50% (14/28) of patients, respectively, and 75% (21/28) patients had caused a traffic accident after dementia onset. The risk of causing an accident was higher in the FTLD group than in the AD group (odds ratio = 10.4, 95% confidence interval = 3.7-29.1). In addition, the mean duration between dementia onset and a traffic accident was 1.35 years in the FTLD group compared with 3.0 years in the AD group (P < 0.01). Patients with FTLD were more likely to show dangerous driving behaviours than those with AD, and the risk of causing a traffic accident may be higher in patients with FTLD from an early disease stage. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.
    Psychogeriatrics 03/2015; DOI:10.1111/psyg.12115 · 1.22 Impact Factor
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    ABSTRACT: The features of behavioural and psychological symptoms of dementia (BPSD) are influenced by dementia stage. In early-onset Alzheimer's disease (EOAD), the association between BPSD and dementia stage remains unclear because of the difficulty of recruiting subjects with a wide range of disease severity. We used a combination of community-based and hospital-based approaches to investigate the relationship between dementia severity and BPSD in EOAD patients. Sixty-three consecutive EOAD outpatients and 29 EOAD patients from a community-based survey were divided into three dementia severity groups according to the Clinical Dementia Rating scale (CDR): mild (CDR 0.5-1, n = 55), moderate (CDR 2, n = 17), and severe (CDR 3, n = 20). BPSD were rated using the Neuropsychiatric Inventory. Scores of the Neuropsychiatric Inventory subscales agitation, euphoria, apathy, disinhibition, irritability, and aberrant motor behaviour increased significantly with increased dementia severity. Hallucinations were greater in the moderate group than in the mild group. For delusions, depression, and anxiety, no significant differences were observed among the three severity groups. The pattern of apathy, agitation, disinhibition, irritability, and aberrant motor behaviour worsening with severity progression in EOAD is similar to the pattern in late-onset Alzheimer's disease. In contrast, hallucinations, depression, and anxiety showed different patterns in EOAD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.
    Psychogeriatrics 03/2015; DOI:10.1111/psyg.12108 · 1.22 Impact Factor
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    ABSTRACT: Post-stroke depression (PSD) is a serious and common complication of stroke. In this prospective study on the relationship between clinical PSD and physical recovery, we focused on (1) distinguishing between depression and apathy, (2) issues in assessment of PSD, and (3) timing of assessment. Japanese stroke patients (n=117) were studied. We used self-rating scales [Zung Self-Rating Depression Scale (SDS) for depression; Apathy Scale (AS) for apathy] and observer-rating scales [Montgomery-Åsberg Depression Rating Scale (MADRS) for depression; Neuropsychiatric Inventory-Nursing Home (NPI-NH) for apathy] to assess psychological state. We assessed physical disability using the Functional Independence Measurement (FIM). Two-way analysis of covariance was used to determine effects of depression and apathy on functional outcome. We evaluated PSD twice, within 10 days after hospitalization and four weeks later. Objective scales gave higher prevalence than subjective scales for both depression and apathy. A significant effect of apathy on FIM recovery was seen with objective scale assessment during hospitalization; there was a marginal effect of depression at the same time. We did not consider the stroke size and location. In addition, we excluded patients with severe comprehension deficits or with a history of stroke. Our findings indicate that depression and apathy could occur independently after stroke and could individually influence functional recovery. We obtained more accurate estimates of functional recovery using objective measures. Furthermore, our findings suggest that depression and apathy should be assessed not only at admission but also during hospitalization to estimate and enhance the functional recovery of stroke patients. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 01/2015; 176C:56-60. DOI:10.1016/j.jad.2015.01.020 · 3.76 Impact Factor
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    ABSTRACT: Klinefelter syndrome (KS) is widely associated with cognitive impairment and language problems. KS patients may also exhibit psychiatric symptoms. We present the case of an 18-year-old man with KS who experienced rapidly repeating relapses of manic episodes. He was unresponsive to the usual pharmacotherapies for bipolar disorders such as mood stabilizers and second-generation antipsychotics. Mood was eventually improved with testosterone therapy in addition to pharmacotherapy, with no relapse of manic episodes for 3years after discharge. Testosterone therapy may prevent relapsing manic episodes of bipolar disorder in patients with KS. Copyright © 2014 Elsevier Inc. All rights reserved.
    General Hospital Psychiatry 12/2014; DOI:10.1016/j.genhosppsych.2014.12.003 · 2.90 Impact Factor
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    ABSTRACT: Abstract Hirotaka Tanabe was a Japanese neuropsychiatrist engaged in neuropsychological research on cerebrovascular disease and dementia. He contributed widely to the symptomatology of dementia, especially in the field of frontotemporal dementia (FTD). He focused on clarifying the clinical features of a language disturbance, termed Gogi-aphasia by Imura (1943), in 7 patients with anterior temporal circumscribed atrophy. He attributed the nature of Gogi-aphasia to a selective impairment of semantic memory for words and proposed that the pathological process of lobar atrophy with temporal predominance might affect the semantic memory system. In addition, he described in detail the behavioral symptoms of FTD. In his later years, he adovocated a neuropsychological approach to psychiatry.
  • Alzheimer's and Dementia 07/2014; 10(4):P533-P534. DOI:10.1016/j.jalz.2014.05.847 · 17.47 Impact Factor
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    ABSTRACT: Background Sense of coherence (SOC) is associated with a reduced risk of various health problems and is thought to be a major factor related to the ability to cope with stress. In the present study, we examined the association between caregiver burden and SOC among caregivers to persons with dementia. Methods Participants included 274 caregivers or family members of community-dwelling elderly dementia patients. To assess the cognitive function of patients, neuropsychological tests (e.g. Mini-Mental State Examination, Clinical Dementia Rating) were conducted by a clinical psychologist who was well trained in interviewing participants; the tests used a semi-structured interview protocol. Senior neurologists and psychiatrists also independently evaluated the dementia status of patients. To assess the SOC and caregiver burden, a social welfare counsellor asked questions from a 13-item version of the SOC scale and the short, eight-item Japanese version of the Zarit Caregiver Burden Interview (ZBI). Results Among 78 caregivers of elderly subjects with cognitive impairment due to dementia, the ZBI score was significantly associated with SOC (r=-0.38, P=0.001). Multiple regression analyses revealed that SOC scores (=-0.42, P<0.001) and Mini-Mental State Examination scores (=-0.28, P=0.009) were significantly associated with ZBI scores (F(2, 76)=10.51, P<0.001). SOC was closely associated with personal strain in the ZBI (=-0.41, P<0.001; F(3, 75)=8.53, P<0.001). Conclusion Caregivers with a strong SOC may be less prone to experiencing personal strain from their burden. These results suggest that reinforcement of SOC would contribute to reducing the personal strain.
    Psychogeriatrics 06/2014; 14(2). DOI:10.1111/psyg.12050 · 1.22 Impact Factor
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    ABSTRACT: Background In responses to self-reported depression screening questionnaires, item non-response, which refers to the absence of answers to specific questions, is problematic. The objective of this study were (1) to clarify the features of respondents with item non-response on a self-reported elderly depression screening questionnaire (15-item geriatric depression scale; GDS-15) as compared to respondents with full responses, and (2) to compare positive depression screening rates calculated using two methods: excluding respondents with item non-response (complete case analysis; CCA) and estimating by multiplying mean scores from valid responses by the total number of GDS-15 items for respondents with item non-response. Methods This was a cross-sectional study conducted from 2010 to 2012. Of 4794 elderly subjects (65 years and older) living in one town in Japan 2836 community-dwelling elderly people (59.2%) were included in the analysis. Results Item non-response was observed in 25.0% of respondents. Respondents with item non-response had a higher rate of depression and mental and physical problems. Respondents with depression (estimated GDS-15 score ≥6) and suicidal ideation both had a 1.6-times higher risk of item non-response on the GDS-15. The positive depression screening rate on GDS-15 by CCA was 16.5%, compared with 18.9% when calculated by the estimated GDS-15 score. Limitations Our survey was conducted in one rural area and targeted only elderly people. Conclusion The incidence of item non-response among community-dwelling elderly people was associated with depression of the respondent. Excluding subjects with item non-response when calculating positive depression screening rates in elderly individuals causes the rate to be underestimated.
    Journal of Affective Disorders 06/2014; 162:30–33. DOI:10.1016/j.jad.2014.03.022 · 3.76 Impact Factor
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    ABSTRACT: Purposes The Japanese word “ronin-sei” refers to a student who has failed their university entrance examination and is preparing to re-take the examination in the following year. We aimed to determine how sleep duration is associated with daytime sleepiness or depression in ronin-sei because impaired daytime performance is known to result from sleep deprivation. Methods The participants in this cross-sectional study were 1075 ronin-sei and 285 university students. Sleepiness and depressive symptoms were assessed using the Epworth Sleepiness Scale (ESS) and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Results Ronin-sei had significantly shorter sleep duration and earlier bed- and rise-times than university students. There was no significant difference in CES-D between the groups; however, the ESS score of university students was significantly higher than of ronin-sei. Ronin-sei who slept for 5 to less than 6 hours had higher ESS scores than those who slept for 6 to less than 7 hours. The mean CES-D score in ronin-sei who slept less than 5 hours was significantly higher than in those who slept for 5 to less than 6 hours, from 6 to less than 7 hours, and from 7 to less than 8 hours. Ronin-sei who slept for more than 8 hours also had higher depression scores. Conclusions Sleep deprivation appears to be common among ronin-sei. Furthermore, a U-shaped relationship was found between sleep duration and depressive symptoms, revealing that ronin-sei who had too little or too much sleep were more likely to exhibit an increase in depressive symptoms.
    Asian Journal of Psychiatry 06/2014; DOI:10.1016/j.ajp.2014.01.006
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    ABSTRACT: ABSTRACT Background: Previous studies in western countries have shown that about 30%-50% of patients with frontotemporal lobar degeneration (FTLD) have a positive family history, whereas the few epidemiological studies on FTLD done in Asia reported much lower frequencies. It is not clear the reason why the frequencies of FTLD with positive family history were lower in Asia. Furthermore, these findings were not from studies focused on family history. Therefore, it is necessary to conduct further studies on the family history of FTLD in Asia. This international multi-center research aims to investigate the family histories in patients with FTLD and related neurodegenerative diseases such as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and motor neuron diseases in a larger Asian cohort. Methods: Participants were collected from five countries: India, Indonesia, Japan, Taiwan, and Philippines. All patients were diagnosed with behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive non-fluent aphasia (PA), frontotemporal dementia with motor neuron disease (FTD/MND), PSP, and corticobasal degeneration (CBD) according to international consensus criteria. Family histories of FTLD and related neurodegenerative diseases were investigated in each patient. Results: Ninety-one patients were included in this study. Forty-two patients were diagnosed to have bvFTD, two patients had FTD/MND, 22 had SD, 15 had PA, one had PA/CBS, five had CBS and four patients had PSP. Family history of any FTLD spectrum disorder was reported in 9.5% in bvFTD patients but in none of the SD or PA. Conclusion: In contrast to patients of the western countries, few Asian FTLD patients have positive family histories of dementia.
    International Psychogeriatrics 04/2014; 26(12):1-5. DOI:10.1017/S1041610214000635 · 1.89 Impact Factor
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    ABSTRACT: To identify patient-related factors associated with depressive state in caregivers of patients with dementia, we investigated the caregivers' and patients' characteristics in relation to the depressive state in their caregivers. Prospective hospital-based cohort study. Two memory clinics in Japan. Outpatients with dementia (n = 135) and their caregivers at home. The outpatients and their caregivers were divided into 2 groups according to the Center for Epidemiologic Studies Depression Scale for caregivers. To identify the patient-related factors that cause depressive state in caregivers, Mini-Mental State Examination (MMSE), the Physical Self-Maintenance Scale for fundamental activities of daily living (ADL), and the instrumental ADL scale (IADL) scores for instrumental ADL and the neuropsychiatric inventory (NPI) subscale score for behavioral and psychological symptoms of dementia were compared between the 2 groups. We used logistic regression to determine the independent predictors of caregiver depressive state. There was no significant difference in MMSE score between the 2 groups. Logistic regression analysis revealed that the depressive state in caregivers was related with IADL score and delusion in NPI subscale of patients. Depressive state in caregivers was independent of the decline in cognitive function in patients with dementia but was associated with decline in instrumental ADL and severity of delusion.
    Journal of the American Medical Directors Association 03/2014; 15(5). DOI:10.1016/j.jamda.2014.02.007 · 5.30 Impact Factor
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    ABSTRACT: In the Japanese education system, students who fail university entrance exam often go to special preparatory schools to prepare for the following year's exam. These students are called ronin-sei. The purpose of this study was to clarify: (i) depression and somatic complaints in ronin-sei; and (ii) the association between depression, examination-related stressors, and sense of coherence (SOC). A total of 914 ronin-sei from two preparatory schools were asked to answer a self-rating questionnaire. Depression was measured using the Center for Epidemiologic Studies Depression Scale (CES-D) and SOC was measured using the SOC-13 Scale. Overall, 57.9% of subjects were considered to have depression (CES-D ≥ 16) and 19.8% had severe depression (CES-D ≥ 26). Higher CES-D scores were associated with a higher rate of somatic complaints. In hierarchical logistic regression analysis, having no one to talk to about his/her worries and having parents who disagree about the first-choice of university and faculty were independent risk factors for depression and severe depression, respectively, even after controlling for SOC. Preparatory school students have various somatic complaints, and their depression is in part related to examination-related stressors. To maintain mental health, it is important to enhance SOC, to understand their examination-related stressors and to provide adequate support for these students.
    Psychiatry and Clinical Neurosciences 02/2014; 68(6). DOI:10.1111/pcn.12146 · 2.04 Impact Factor
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    ABSTRACT: Abstract Objective: The Cognitive Fluctuation Inventory (CFI) was developed to evaluate cognitive fluctuation in patients with dementia with Lewy bodies (DLB). The objective of this study was to assess the content validity and inter-rater reliability of the CFI. Subjects and Methods: Nine specialists in DLB treatment were invited to participate in the survey to assess the content validity of the CFI. They were asked to assess the relevance and comprehensibility of the question items. In the validation study, inter-rater reliability was assessed using the intraclass correlation coefficient (ICC). Results: Regarding content validity, all nine specialists considered the main question and sub-questions to be relevant to cognitive fluctuation in patients with DLB. Eight out of nine specialists considered the CFI to be a comprehensive measure for detecting cognitive fluctuation in patients with DLB. In the analysis, which used data from 29 patients and their caregivers, the ICC of the CFI was 0.746, which suggests good inter-rater reliability. Conclusion: We found that the CFI showed good content validity and inter-rater reliability for evaluating cognitive fluctuation in patients with DLB. (Received April 5, 2013; Accepted September 20, 2013; Published February 1, 2014).
    Brain and nerve = Shinkei kenkyū no shinpo 02/2014; 66(2):175-83.
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    ABSTRACT: In Japan, the government and media have become aware of the issues of early onset dementia (EOD), but policies for EOD have not yet been established and support systems are inadequate. To provide practical data about EOD, a two-step postal survey was performed. A questionnaire requesting information on EOD cases was sent to target institutions in five catchment areas in Japan. According to the answers from the institutions, we estimated the prevalence of EOD using census data and determined the illnesses causing EOD. As a quality control study, the authors reviewed every diagnosis in a quarter of the reported cases using the medical and psychiatric records and neuroimaging data. This study was conducted from 2006 to 2007. Information from 2469 patients was collected from 12 747 institutions, and 2059 subjects with EOD were identified. The estimated prevalence of EOD was 47.6 per 100 000 (95% confidence interval, 47.1-48.1) for all of Japan. Of the illnesses causing EOD, vascular dementia (VaD) was the most frequent (39.8%), followed by Alzheimer's disease. The prevalence of EOD in Japan appeared to be similar to that in Western countries. However, unlike previously reported international experience, VaD was the most frequent cause of EOD in all catchment areas in Japan.
    Psychiatry and Clinical Neurosciences 12/2013; 68(3). DOI:10.1111/pcn.12127 · 2.04 Impact Factor
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    ABSTRACT: We assessed the value of combining (123)I-IMP brain perfusion SPECT and (123)I-MIBG myocardial scintigraphy for the discrimination of dementia with Lewy bodies (DLB) from other types of dementia. We subjected 252 consecutive patients with clinically suspected DLB to both (123)I-IMP brain perfusion SPECT and (123)I-MIBG myocardial scintigraphy. Patients with Parkinson's disease were included. The 252 patients were randomly assigned to an estimation (n = 152) or a validation group (n = 100). Using univariate analysis, we first analyzed the relationship between various variables and the presence or absence of DLB in estimation group and then proceeded to multivariate analysis to obtain a combined index that predicted the likelihood of DLB. The diagnostic value of the index was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC) with the cutoff value selected from the ROC curve. We then tested the predictive accuracy of the index in validation group. The combined index was an arithmetic expression that combined the age, early (123)I-MIBG heart-to-mediastinum uptake (E-H/M) ratio, and the parietal lobe hypoperfusion score. Values for the AUC of the combined index, the E-H/M ratio, the parietal lobe hypoperfusion score, and the patient age in validation group were 0.95, 0.90, 0.72, and 0.73, respectively. There was a significant difference in the AUC of the combined index among other indices (p < 0.05). The sensitivity, specificity, and accuracy of the combined index for a diagnosis of probable DLB in validation group were 88, 87, and 87 %, respectively. The combinational diagnosis based on (123)I-IMP brain perfusion SPECT, (123)I-MIBG myocardial scintigraphy, and the patient age is a simple and reliable means for predicting probable DLB.
    Annals of Nuclear Medicine 12/2013; DOI:10.1007/s12149-013-0796-3 · 1.41 Impact Factor
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    ABSTRACT: Sense of coherence (SOC) is thought to be a major determinant in maintaining health. SOC gained attention recently in the fields of psychiatry after it was reported to be associated with a lowered risk of various health problems. However, the effect of SOC as a buffer against performance impairment caused by health problems is not well known. Thus, we aimed to examine the relationships among health problem, the degree of presenteeism (performance loss due to health problems), and SOC in adolescents. Participants were 2824 university students (1855 males, mean age; 18.35±0.84 years). SOC and self-reported health problems were assessed using an SOC scale (29 items) and the presenteeism scale for students, respectively. SOC scores differed between students with and without health problems (t(2822)=5.75, P<0.001). The effect size (Cohen's d) was 0.22 for this difference. In a multiple logistic regression analysis, male gender (odds ratio [OR]=0.62; 95% confidence interval [CI]=0.53-0.73), moderate SOC (within ±1 SD; OR=0.59; 95% CI=0.47-0.72), and high SOC (>1 SD; OR=0.43; 95% CI=0.33-0.58) were independently associated with a lower frequently of health problems. In addition, SOC showed a significant inverse correlation with presenteeism (r=-0.27, P<0.001). These results suggest that application of the concept of SOC might aid in the prevention of health problems among university students. Students with a strong SOC might be less prone to a decline in performance when health problems arise.
    10/2013; 6(5):369-72. DOI:10.1016/j.ajp.2013.03.008
  • Article: [Apathy].
    Ryuta Fukunaga, Noboru Fujise, Manabu Ikeda
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    ABSTRACT: Apathy includes aspontaneous, indifferent behavior, with loss of motor and affective drive. Apathy is related to the disruption, at various anatomical sites, of frontosubcortical pathways, such as anterior cingulate and bithalamic lesions. Apathy was frequently reported in patients with Alzheimer's disease, post-stroke, and frontotemporal dementia. It is very important to distinguish apathy from depression by the therapeutic view point.
    Nippon rinsho. Japanese journal of clinical medicine 10/2013; 71(10):1798-803.
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    ABSTRACT: We investigated the pathological features of frontotemporal lobar degeneration (FTLD) with fused in sarcoma protein (FUS) accumulation (FTLD-FUS) in the Japanese population. Only one out of nine FTLD-FUS cases showed pathology that corresponds to atypical FTLD with ubiquitin-positive inclusions (aFTLD-U). Five were basophilic inclusion body disease (BIBD) and two were neuronal intermediate filament inclusion disease. The last case was unclassifiable and was associated with dystrophic neurites (DNs) as the predominant FUS pathology. The results of this study indicate an ethnic difference from western countries. In Japan, BIBD is the most common subtype of FTLD-FUS and aFTLD-U is rare, a finding which contrasts with aFTLD-U being the most common form in western countries. Immunohistochemical analyses of these FTLD-FUS cases reveal that FUS abnormally accumulated in neuronal cytoplasmic inclusions (NCIs) and DNs has an immunohistochemical profile distinct from that of normal, nuclear FUS. NCIs and DNs are more readily stained than the nuclei by antibodies to the middle portion of FUS. Antibodies to the carboxyl terminal portion, on the other hand, stain the nuclei more readily than NCIs and DNs. Such an immunohistochemical profile of NCIs and DNs was similar to that of cytoplasmic granular FUS staining which we previously reported to be associated with dendrites and synapses. Redistribution of FUS from the nucleus to the cytoplasm could be associated with the formation of abnormal FUS aggregates in FTLD-FUS.
    Journal of the neurological sciences 09/2013; 335(1-2). DOI:10.1016/j.jns.2013.08.035 · 2.32 Impact Factor

Publication Stats

903 Citations
242.36 Total Impact Points

Institutions

  • 2007–2015
    • Kumamoto University
      • • Department of Neuropsychiatry
      • • Department of Psychiatry and Neuropathobiology
      Kumamoto, Kumamoto, Japan
  • 2001–2013
    • Ehime University
      • Department of Neuropsychiatry
      Matuyama, Ehime, Japan
  • 2010–2011
    • The Jikei University School of Medicine
      • Department of Psychiatry
      Tokyo, Tokyo-to, Japan