Published papers

© 2020 The Author(s). Background: Pisa syndrome (PS) is characterized by an abnormally sustained posture, with flexion of the body and head to one side and slight rotation of the trunk. Although PS most commonly arises as an adverse effect of antipsychotic drugs, choline-esterase inhibitors (ChEIs) are also sometimes known to induce PS. Despite the fact that the precise mechanism remains unclear, cholinergic-dopaminergic imbalance has been considered as a possible pathophysiologic mechanism underlying the genesis of PS. Case presentation: We hereby report the case of a 60-year-old woman with Alzheimer's disease who presented with the signs of PS after her treatment was switched to galantamine, a type of ChEI, even though she had received donepezil, another type of ChEI, for 5 years without any complications. To the best of our knowledge, this is the first report of PS associated with treatment switch from one to another type of ChEI. Galantamine, but not other ChEIs, can enhance striatal dopamine release through allosteric modulation of the nicotinic acetylcholine receptor, and has weaker muscarinic effects than donepezil. Therefore, we propose two novel hypotheses to explain the development of PS, as follows; galantamine, which enhances dopamine release, can induce imbalance of dopamine levels in the striatum of patients with dementia, resulting in PS, and the weaker muscarinic effects of the drug could be one of the factors predisposing to the development of PS. Conclusion: The present case suggests that treatment with galantamine is associated with a higher risk of development of PS than that with other ChEIs, such as donepezil, despite the pharmacological profile of galantamine as a dopamine modulator. Also, this report provides novel insight into another plausible mechanism underlying the development of PS, besides cholinergic-dopaminergic imbalance, namely, dopamine imbalance in the striatum with muscarinic-nicotinic imbalance.

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: To examine characteristics of placebo responders and seek optimal criteria of early improvement with placebo for predicting subsequent placebo response in patients with schizophrenia. Method: Data of 672 patients with schizophrenia randomized to placebo in nine double-blind antipsychotic trials were analyzed. Multiple logistic regression analyses were conducted to examine associations between placebo response at week 6 (i.e., a ≥ 25% reduction in the Positive and Negative Syndrome Scale [PANSS] score) and gender, age, study locations, baseline PANSS total or Marder 5-Factor scores, and per cent PANSS score reduction at week 1. Predictive power of improvement at week 1 for subsequent response was investigated; sensitivity and specificity of incremental 5% cutoff points between 5% and 25% reduction in the PANSS total score at week 1 were calculated. Results: Per cent PANSS total score reduction at week 1 and lower PANSS Marder disorganized thought scores at baseline were significantly associated with subsequent placebo response. A 10% reduction in a per-protocol analysis or a 15% reduction in last-observation-carried-forward analysis in the PANSS total score at week 1 showed the highest predictive power. Conclusion: These findings are informative to identify potential placebo responders at the earliest opportunity for optimal trial design for schizophrenia.

© 2019 Elsevier B.V. Introduction: Little attention has been paid to the contribution of individual residual symptom to predict relapse in patients with schizophrenia receiving oral or long-acting injectable (LAI) antipsychotics. Method: We used the data from the Preventing Relapse on Oral Antipsychotics Compared to Injectables - Evaluating Efficacy (PROACTIVE) study, in which 305 outpatients with schizophrenia were randomly allocated to either biweekly LAI-risperidone (LAI-R) or daily oral second-generation antipsychotics (SGA) and assessed for up to 30 months. Baseline individual symptoms that could predict subsequent relapse were identified, using a Cox proportional hazards model. Moreover, among those who relapsed during the study (n = 73), individual symptoms were compared between baseline and biweekly ratings 8 to 2 weeks before relapse, using the linear mixed model. Results: A greater score in grandiosity at baseline was significantly associated with subsequent relapse (adjusted HR = 1.24, p = 0.006). When the two treatment groups were separately analyzed, more severe grandiosity (adjusted HR = 1.43, p = 0.003) and less severe hallucinatory behavior (adjusted HR = 0.70, p = 0.013) at baseline were significantly associated with relapse in the oral SGA group, but none was identified in the LAI-R group. Emotional withdrawal was significantly worse 8 and 2 weeks before relapse compared to the baseline (p = 0.032 and p = 0.043, respectively). Discussion: More severe grandiosity and less hallucination may have led to more frequent relapses in patients with schizophrenia receiving oral antipsychotics, which was not a case in those receiving LAI-R. The exploratory analysis indicates an increase in emotional withdrawal before relapse may be a useful marker for earlier interventions to possibly avert relapse.

© Georg Thieme Verlag KG Stuttgart.New York. Introduction Therapeutic drug monitoring is necessary for lithium, but clinical application of several prediction strategies is still limited because of insufficient predictive accuracy. We herein proposed a suitable model, using creatinine clearance (CLcr)-based lithium clearance (Li-CL). Methods Patients receiving lithium provided the following information: serum lithium and creatinine concentrations, time of blood draw, dosing regimen, concomitant medications, and demographics. Li-CL was calculated as a daily dose per trough concentration for each subject, and the mean of Li-CL/CLcr was used to estimate Li-CL for another 30 subjects. Serum lithium concentrations at the time of sampling were estimated by 1-compartment model with Li-CL, fixed distribution volume (0.79 L/kg), and absorption rate (1.5/hour) in the 30 subjects. Results One hundred thirty-one samples from 82 subjects (44 men; mean±standard deviation age: 51.4±16.0 years; body weight: 64.6±13.8 kg; serum creatinine: 0.78±0.20 mg/dL; dose of lithium: 680.2±289.1 mg/day) were used to develop the pharmacokinetic model. The mean±standard deviation (95% confidence interval) of absolute error was 0.13±0.09 (0.10-0.16) mEq/L. Discussion Serum concentrations of lithium can be predicted from oral dosage with high precision, using our prediction model.

© 2019 Elsevier Ltd Objective: The purpose of the present study was to compare important patient questionnaire items by creating a random forest model for predicting deficiency-excess pattern diagnosis in six Kampo specialty clinics. Design: A multi-centre prospective observational study. Setting: Participants who visited six Kampo specialty clinics in Japan from 2012 to 2015. Main outcome measure: Deficiency-excess pattern diagnosis made by board-certified Kampo experts. Methods: To predict the deficiency-excess pattern diagnosis by Kampo experts, we used 153 items as independent variables, namely, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We extracted the 30 most important items in each clinic's random forest model and selected items that were common among the clinics. We integrated participating clinics’ data to construct a prediction model in the same manner. We calculated the discriminant ratio using this prediction model for the total six clinics’ data and each clinic's independent data. Results: Fifteen items were commonly listed in top 30 items in each random forest model. The discriminant ratio of the total six clinics’ data was 82.3%; moreover, with the exception of one clinic, the independent discriminant ratio of each clinic was approximately 80% each. Conclusions: We identified common important items in diagnosing a deficiency-excess pattern among six Japanese Kampo clinics. We constructed the integrated prediction model of deficiency-excess pattern.

© 2017 International Psychogeriatric Association. Background: Caregivers of people with dementia are likely to have psychological distress that sometimes results in mental health problems, such as depression. The objective of this study was to examine some predictive factors that are thought to be associated with psychological distress of caregivers of people with dementia in Japan. Methods: Design: A cross-sectional study. Sample: As part of a study to estimate the cost of dementia in Japan, 1,437 people with dementia-caregiver dyads were enrolled in the current informal care time study. The measurements in the study included were the basic characteristics of the caregivers and the people with dementia, and the informal care time during a week.Analysis: Factors that predict caregivers' psychological distress, which was measured by Kessler's Psychological Distress scale (K6) score, were evaluated using univariate and multivariate regression analyses. Results: Approximately 69% of the caregivers recorded a K6 score higher than 4, while 18% scored higher than 12. According to the results of the logistic regression analysis (cut-off 4/5), the K6 score was associated with mental and comorbid diseases of people with dementia, informal care time, its lower number of caregivers, and the level of nursing care. According to the results of logistic regression analysis (cut-off 12/13), the K6 score was associated with mental symptoms and comorbid disease of people with dementia, sex of caregivers, informal care time, and its lower number of caregivers. Conclusion: Our findings indicated that the psychological distress of the caregivers is quite high and that informal care time and behavioral and psychological symptoms of dementia are associated with it. These results corroborate with previous findings.

© 2019 The Author(s). Background: This study aimed to examine potential predictors of duration of sick leave due to mental disorders in Japan. Methods: A total of 207 employees at a manufacturing company in Japan with a past history of sick leave due to mental disorders participated in this study. Mental disorders were defined as those listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). All of the participants used the mental health program that the company provided. The predictive power of the variables was tested using a Cox proportional hazard analysis. The hazard ratios in the final model were used to identify the predictor variables of the duration of sick leave. We included socio-demographic (age, sex, tenure), clinical (diagnosis and number of previous sick leave), and work-related factors (employment rank) as possible predictors. Data on these variables were obtained through the psychiatrists and psychologists in the company's mental health program. Results: The results of the univariate analyses showed that the number of previous sick leave episodes, diagnosis and employee rank were significant predictors of the duration of sick leave due to mental disorders. A multivariate analysis indicated that age, number of previous sick leave and employee rank were statistically significant predictors of return to work. Conclusions: Diagnosis, number of previous sick leave episodes, and employee rank are predictors of the duration of sick leave due to mental disorders. This study's findings have implications in the development of effective interventions to prevent protracted sick leave.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: Synthetic glucocorticoids cause various psychiatric symptoms. Prescription of psychotropic drugs could be considered to be a proxy for manifestation of psychiatric symptoms. The aim of this study was to investigate the prescriptions of psychotropics in outpatients receiving synthetic glucocorticoids. Methods: We used the claims sampling data during January 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan made by the Ministry of Health, Labor, and Welfare in Japan. We compared the prescription rates of psychotropics between outpatients receiving oral synthetic glucocorticoids and age- and sex-matched controls and the prescription rates of psychotropics among the eight dosage groups of synthetic glucocorticoids by chi-squared test, and chlorpromazine/imipramine/diazepam equivalent doses (or daily defined doses) of respective psychotropics among these groups using Welch's t-test. Results: Synthetic glucocorticoids were prescribed to 3.1% (n = 18 122) of 581 990 patients. The prescription rates of psychotropics were significantly higher among the synthetic glucocorticoid recipients than among the non-recipients: antipsychotics, 1.8% (n = 321) vs. 1.1% (n = 201) (P = 1.4 × 10−7); antidepressants, 4.0% (n = 724) vs. 2.0% (n = 359) (P = 8.7 × 10−30); anxiolytics/hypnotics, 16.7% (n = 3029) vs. 10.2% (n = 1841) (P = 2.7 × 10−75); and mood stabilizers, 1.3% (n = 238) vs. 0.7% (n = 120) (P = 3.6 × 10−10) respectively. There was no significant difference in the prescription rates of any psychotropic drugs, other than anxiolytics/hypnotics, among the eight synthetic glucocorticoid dosage groups. Conclusion: Prescriptions of oral synthetic glucocorticoids were found to be associated with the use of any of the types of psychotropic drugs, other than anxiolytics/hypnotics, although a causal relationship could not be confirmed due to the retrospective and cross-sectional nature of this study.

© 2020, The Author(s). The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second ‘most important’ FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future.

© Author(s) (or their employer(s)) 2018. Introduction Suicide attempt is the most important risk factor for later suicide. A randomised-controlled, multicentre trial of postsuicide attempt case management for the prevention of further suicide attempts in Japan, named ACTION-J, has established effective interventions for prevention of suicide reattempts. The ACTION-J assertive case management intervention programme was adopted by the Japanese Ministry of Health, Labour and Welfare in 2016, when medical fees were revised. This nationwide programme is provided to patients who attempt suicide and who are admitted to emergency departments in Japan. The aim of the present study is to examine the current implementation status of the ACTION-J programme. The present study also aims to clarify which patients' and hospitals' factors affect the implementation of the programme. Methods and analysis This is a prospective, multicentre, patient registry cohort study. Participants will be suicide attempters admitted to the emergency departments of medical facilities with both psychiatry and emergency departments. The assertive case management programme will be delivered to participants by a case manager for up to 24 weeks, based on psychiatric diagnoses, social risks and patient needs. The core feature of the programme is to encourage patients to participate in psychiatric treatment. The primary outcome will be the proportion of patients still participating in the case management intervention at 24 weeks after registration. The secondary outcomes will include measures of the fidelity of the case management intervention. The fidelity will be evaluated using a fidelity assessment manual developed by the study group. Ethics and dissemination This observational study has been approved by the ethics board of Sapporo Medical University. Enrolment began in October 2016 and will continue until December 2018. Dissemination plans include presentations at scientific conferences and scientific publications.

© 2019 American Academy of Ophthalmology Purpose: To determine the association of retinal thickness with cognitive function in Japanese persons. Design: Cross-sectional, population-based survey. Participants: A total of 1293 Japanese persons aged 65 to 86 years who resided in the Saku area in the Japan Public Health Center–Based Prospective Study participated in the eye and mental health screening. Methods: Participants underwent comprehensive ophthalmic assessment, including fundus photography, measurement of intraocular pressure, and determination of refraction status. We assessed the thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GC-IPL), and ganglion cell complex (GCC, which includes the retinal nerve fiber layer and GC-IPL), and the full thickness in the macula and peripapillary retinal nerve fiber layer (ppRNFL) using spectral-domain (SD) OCT. Cognitive tests consisted of the Mini-Mental State Examination, Wechsler Memory Scale Revised logical memory I/II subtest, clock drawing test, and Clinical Dementia Rating Scale. These were used to designate the participants in the following 3 groups: Normal, those with mild cognitive impairment (MCI), and those with dementia. Multivariable logistic regression models were used to analyze associations between retinal thickness and cognitive function after adjusting potential confounding factors. Main Outcome Measures: Association of retinal thickness with cognitive function. Results: Among the 1293 potential subjects, 114 were excluded for a diagnosis of depression, 64 were excluded for retinal disease, and 140 were excluded for scanning errors or suboptimal OCT images. The remaining 975 participants (mean age, 73.2 years) were included in this analysis. Significant differences were found in the 3 groups in all layers and GCC thickness, but not in ppRNFL thickness. After adjusting for age, sex, educational status, and refraction, full macular thickness and GCC thickness were inversely associated with the presence of dementia, but ppRNFL thickness was not. Furthermore, GC-IPL, GCC, and full macular thicknesses were all associated with the presence of dementia in the inferior sectors. Conclusions: Macular thickness was associated with the presence of dementia, but ppRNFL was not. Our results suggest that OCT measurements of the macula could be superior to those of the ppRNFL in assessing neurodegenerative changes and a potentially useful diagnostic biomarker of cognitive function.

© 2018 John Wiley & Sons, Ltd. Objectives: The present study investigated the usefulness of evaluating the existence of volume reduction in brain regions using voxel-based morphometry (VBM) to dissociate major depressive disorder (MDD) from bipolar disorder (BD). Methods/Design: This study enrolled 92 individuals with MDD, 32 individuals with BD, and 43 healthy controls (HCs). We focused on gray matter volume (GMV) of the subgenual anterior cingulate cortex (sgACC), subcallosal area (SCA), and hippocampus. The degree of volume reduction in these brain regions was calculated as the z score, and the differences of z scores in these regions were investigated among the MDD, BD, and HC groups. We then performed a receiver operating characteristic curve analysis to dissociate the individuals with MDD and BD from the HCs based on the z scores in the GMV of these brain regions. Results: While there were no significant differences in the z scores of the hippocampus among the three groups, the z score of the sgACC was significantly higher in the MDD group than in the BD and HC groups, and the SCA z score was significantly higher in the MDD and BD groups than in the HC group. Conclusions: Our findings suggest that VBM evaluation of GMV reduction in the sgACC may be useful as an objective adjunctive tool to distinguish between MDD and BD.

© 2019 Elsevier Inc. Objective: This systematic review aimed to elucidate the relationship between polydipsia and antipsychotics. Methods: We systematically searched MEDLINE, Embase, and PsycINFO, and included clinical studies and case reports on polydipsia induced or improved by antipsychotics. Results: We identified 61 articles: 1 double-blind randomized controlled trial (RCT), 4 single-arm trials, 1 cross-sectional study, 3 case series, and 52 case reports. The double-blind RCT demonstrated no significant difference in improvement in polydipsia between olanzapine and haloperidol. Two single-arm trials showed that polydipsia improved during clozapine treatment, whereas the other 2 showed that risperidone did not improve polydipsia. The cross-sectional study showed the prevalence of hyponatremia with first-generation antipsychotics (FGAs: 26.1%) and second-generation antipsychotics (SGAs: 4.9%). Two case series reported that clozapine improved polydipsia; the other one indicated that patients with polydipsia who were treated with FGAs had schizophrenia (70.4%) and mental retardation (25.9%). Of 90 cases in the case reports, 67 (75.3%) were diagnosed with schizophrenia. Of 83 cases in which antipsychotic treatment started before the onset of polydipsia, 75 (90.3%) received FGAs, particularly haloperidol (n = 24, 28.9%), and 11 (13.3%) received risperidone. Among 40 cases in which polydipsia was improved following antipsychotic treatment, 36 (90.0%) received SGAs, primarily clozapine (n = 14, 35.0%). Conclusions: Although the causal relationship between polydipsia and antipsychotics remains unclear because of the paucity of high-quality studies, antipsychotics with high affinity to dopamine D2 receptors may be associated with an increased risk of polydipsia while clozapine may be effective for treating polydipsia.

© 2019 ElSalhy et al. Backgrounds and aims: While the Internet became an indispensable component of our contemporary life, public and academic attention is also gathered to its negative impact, namely Internet addiction (IA). Although clinicodemographic and behavioral factors are hypothetically implicated in the mechanism of IA, it still remains largely unknown how such factors are linked to IA severity. Thus, this study sought to examine relationships among IA severity and factors potentially associated with IA in Japanese students in different educational stages. Methods: We conducted a questionnaire-based survey, which included questions about types of online activities and clinicodemographic information, the IA test for IA severity, and the K6 scale for psychological distress in 3,224 students at elementary, junior, and senior high schools, and universities. A multiple regression analysis was performed to predict IA severity with clinicodemographic and behavioral factors. Results: IA severity was significantly positively related to the following factors: e-messaging, social networking services (SNS), games, holiday Internet usage, and K6 scores, while IA severity had negative correlation with using Internet for educational purposes, age of first exposure to the Internet, and sleep duration. Age was not related to IA severity among participants using both SNS and e-messaging. Conclusions: IA was linked to various online activities and the degree of psychological distress. This indicates the importance of comprehensive assessment of online behavior and psychological factors for further understanding of IA.

Copyright © 2018 John Wiley & Sons, Ltd. Background: Despite a steady increase in life expectancy, a few studies have investigated cross-sectional correlates and longitudinal predictors of cognitive function, a core domain of the successful aging, among socio-clinico-demographic factors in the oldest-old exclusively. Objectives: The aims of this study were to examine socio-clinico-demographic characteristics associated with global cognition and its changes in the oldest-old. Methods: We reanalyzed a dataset of cognitively preserved community-dwelling subjects aged 85 years and older in the Tokyo Oldest Old Survey on Total Health, a 6-year longitudinal observational study. This study consisted of (1) baseline cross-sectional analyses examining correlates of global cognition (n = 248) among socio-clinico-demographic factors and (2) longitudinal analyses examining baseline predictors for changes of global cognition in 3-year follow-up (n = 195). The Mini-Mental State Examination was used as a screening test to assess global cognition. Results: At baseline, higher weights were related to higher cognitive function in the oldest-old. The baseline predictors of global cognitive decline in 3-year follow-up were higher global cognition, shorter education period, and lower sociocultural activities and lower instrumental activity of daily living, in this order. Conclusions: The present study suggests that it is crucial to attain higher education during early life and avoid leanness or obesity, participate in sociocultural cognitive activities during late life, and maintain instrumental activity of daily living to preserve optimal cognitive function in the oldest-old, which will facilitate developing prevention strategies for cognitive decline and promoting successful aging in this increasing population.

Copyright: © 2020 Kitagawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The purpose of this study was to develop the Glasgow Antipsychotic Side effects Scale for Clozapine Japanese version (GASS-C-J) and examine its reliability to assess clozapine-related side effects. We developed the GASS-C-J using forward and backward translation. Semantic equivalence of the GASS-C-J to the GASS-C was confirmed by the original author. We then administered the GASS-C-J twice to 109 patients on clozapine treatment at two psychiatric hospitals in Japan. We assessed the internal consistency and test-retest reliability of the GASS-C-J using Cronbach's alpha and weighted kappa coefficient, respectively. We also examined if discrepancies in each GASS-C-J item score between the first and second rating were correlated with items of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD). The Cronbach's alpha coefficient of the GASS-C-J at the first and second rating was 0.78 (95% CI: 0.72 to 0.84) and 0.82 (95% CI: 0.76 to 0.88), respectively. The weighted kappa coefficient of individual and total GASS-C-J item scores ranged from 0.45 to 0.88. Some symptom domains were correlated with discrepancies in specific items of the GASS-C-J: psychotic symptoms and nausea/vomiting (rs = 0.27), thirst (rs = 0.31), and appetite/weight gain (rs = 0.27); disorganized thinking and urinary incontinence (rs = 0.26); depression/anxiety and myoclonus (rs = 0.25), hypersalivation (rs = -0.27), and blurred vision (rs = -0.22). These findings demonstrate that the GASS-C-J can be used in clinical and research settings as a reliable scale to assess clozapine-related side effects.

© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: The impact of religious/spiritual activities on clinical outcomes in patients with serious mental illnesses remains controversial, which was addressed in this international cross-sectional study. Method: Three-hundred sixty-nine subjects were recruited from Austria (n = 189) and Japan (n = 180), consisting of 112 outpatients with paranoid schizophrenia, 120 with bipolar I disorder (DSM-IV), and 137 healthy controls. Religiosity was assessed in terms of attendance and importance of religious/spiritual activities, while resilience was assessed using the 25-item Resilience Scale. General linear models were used to test whether higher religiosity will be associated with higher resilience, higher social functioning, and lower psychopathology. The association between levels of spiritual well-being and resilience was also examined. Results: Attendance of religious services (F [4,365] = 0.827, P = 0.509) and importance of religion/spirituality (F [3,365] = 1.513, P = 0.211) did not show significant associations with resilience. Regarding clinical measures, a modest association between higher importance of religion/spirituality and residual manic symptoms was observed in bipolar patients (F [3,118] = 3.120, P = 0.029). In contrast to the findings regarding religiosity, spiritual well-being showed a strong positive correlation with resilience (r = 0.584, P < 0.001). Conclusion: The protective effect of religiosity in terms of resilience, social functioning, and psychopathology was not evident in our sample. Spiritual well-being appears more relevant to resilience than religiosity.

© 2018 Japanese Psychogeriatric Society Adult-onset leucoencephalopathy with axonal spheroids and pigmented glia (ALSP), also known as hereditary diffuse leucoencephalopathy with spheroids (HDLS), is a progressive neurocognitive disorder that predominantly affects the cerebral white matter, mainly the frontal subcortical areas and the corpus callosum. Patients with ALSP are clinically characterized by a gradual onset of cognitive and behavioural dysfunction and personality changes, followed by motor impairments such as gait disturbance and bradykinesia. Given the disease-related degenerative changes of the frontal white matter, it is no wonder that patients with ALSP present with behavioural symptoms and non-fluent aphasia, which are found in patients with frontotemporal lobar degeneration. However, behavioural symptoms and non-fluent aphasia in a patient with ALSP have rarely reported in detail. Here, we describe a patient with ALSP who initially presented with remarkable behavioural signs and non-fluent primary progressive aphasia, which resembled symptoms of frontotemporal lobar degeneration. The present case suggests that ALSP should be included in the differential diagnosis for frontotemporal lobar degeneration.

© The Author(s) 2019. Introduction: Studies have demonstrated the high agreement of several remote neuropsychological tests using video teleconferencing (VTC) with face-to-face (FTF) tests. However, the reliability of the remotely administered Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog), one of the most commonly used neuropsychological tests to detect cognitive decline, has not been substantially elucidated, particularly in Japanese populations. Therefore, this study aimed to evaluate the reliability of the remotely administered ADAS-cog compared with FTF-administered ADAS-cog among elderly Japanese participants. Methods: Participants aged ≥60 years with and without cognitive impairment, i.e. those with mild cognitive impairment (MCI), those with dementia and healthy controls (HCs), were assessed with the ADAS-cog using VTC and FTF testing at an interval of >2 weeks and <3 months. The assessment order (VTC or FTF) was randomized by participants. Participants’ scores were compared among the entire sample, as well as subgroups, using intra-class correlation coefficients (ICCs) in a mixed-effects model. Results: A total of 73 participants were included in the study (36 men; age, 76.3 ± 7.6 years). The ICC for the ADAS-cog total score was high in the entire sample (0.86), whereas ICCs were moderate to high for the subgroups (MCI: 0.63, dementia: 0.80 and HC: 0.74). Discussion: The results indicate that a VTC-administered ADAS-cog could be an alternative for an FTF-administered ADAS-cog, although further replication studies with larger sample sizes and a wider range of cognitive functionalities are warranted.

© 2019 Objective: While exposure to endogenous estrogen may be associated with better cognitive performance, it is still unclear whether it has an association with mild cognitive impairment (MCI) or dementia. The aim of this study was to clarify the effects of reproductive history, as a surrogate marker of exposure to endogenous estrogen, on the risk of cognitive impairment (MCI or dementia) in women. Study design: A total of 747 women aged 40–59 years in the Saku area (Nagano Prefecture) were followed as part of the Japan Public Health Center-based Prospective (JPHC) Study, which started in 1990. Participants had undergone a mental health examination in 2014–2015. Main outcome measures: We used multiple logistic regression to analyze the association between reproductive history, obtained at baseline and 10-year follow-up, with current cognitive impairment diagnosed by a trained psychiatrist, adjusting for various lifestyle factors. Results: Among 670 eligible women, current cognitive impairment was diagnosed in 227, 196 of whom had MCI and 31 dementia. A longer reproductive period had a significantly inverse association with cognitive impairment (P-trend = 0.032). In particular, women with a reproductive period ≥38 years compared with ≤33 years had a significantly lower risk of cognitive impairment (multivariable adjusted odds ratio=0.62, 95% confidence interval=0.40–0.96). Conclusions: A longer reproductive period was associated with a lower risk of cognitive impairment, which suggests that a longer exposure to endogenous estrogen may have a protective effect against cognitive impairment.