アルツハイマー型認知症患者における前頭葉機能と介護負担の関係

AIM: Understanding of the relationship between caregiver burden and the degree of behavioural deficits in patients with Alzheimer's disease (AD) is relatively limited. Therefore, it is worthwhile to examine the correlations between the various relevant factors to improve the efficacy of care for patients with AD. The aim of this study was to investigate the specific contributions of frontal lobe dysfunction in AD patients to caregiver burden, while controlling for other predictor variables. METHODS: Participants included 30 pairs of caregivers and patients with AD. The Zarit Burden Interview and Frontal Assessment Battery were used to measure the caregiver burden and patients' frontal lobe function, respectively. To investigate the effects of frontal lobe dysfunction on caregiver burden, hierarchical regression equations with steps incorporating additional predictor variables were fitted. We also performed a correlation analysis between the individual subdomains of the Zarit Burden Interview and the predictor variables. RESULTS: Our study suggests that the degree of frontal lobe dysfunction in AD patients predicts their caregiver burden, when other factors of daily functional limitations and neuropsychiatric symptoms are controlled. Daily functional limitations and neuropsychiatric symptoms affected caregivers' psychosocial burden, whereas frontal lobe dysfunction affected caregivers' burden due to the increase in the dependency of the patients. CONCLUSION: Our findings indicate that to ameliorate the disabilities of patients and reduce caregiver burden, there is a need for interventions that focus on psychosocial burdens, as shown in previous studies, as well as on excessive dependency due to frontal lobe dysfunction.博士（医学）・甲第661号・平成29年3月15日© 2017 Japanese Psychogeriatric SocietyThis is the pre-peer reviewed version of the following article: http://dx.doi.org/10.1111/psyg.12231, which has been published in final form at http://dx.doi.org/10.1111/psyg.12231. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving

気分状態に依存しない双極性障害と大うつ病性障害における脳梁の白質微細構造の差異

OBJECTIVE: It is difficult to distinguish between bipolar disorder and major depressive disorder (MDD) in patients lacking a clear history of mania. There is an urgent need for an objective biomarker for differential diagnosis. Using diffusion tensor imaging, this study investigated the differences in the brain white matter microstructure between patients with bipolar disorder and MDD. METHODS: Participants included 16 patients with bipolar disorder and 23 patients with MDD having depressed or euthymic states based on DSM-IV-TR criteria and 23 healthy volunteers. Whole-brain voxel-based morphometric analysis was used to detect any significant differences in fractional anisotropy between patients with bipolar disorder and MDD. The study was conducted between August 2011 and July 2015. RESULTS: We found a significant decrease in fractional anisotropy values in the anterior part of the corpus callosum in patients with bipolar disorder compared with MDD (P < .001), which did not depend on the patients' affective state. This decrease was associated with increased radial diffusivity values (P < .05), which was also found in patients with bipolar disorder when compared with healthy volunteers (P < .05). We predicted bipolar disorder and MDD in all patients using the fractional anisotropy values, with a correct classification rate of 76.9%. CONCLUSIONS: The present study revealed that patients with bipolar disorder have microstructural abnormalities in the corpus callosum during depressed or euthymic states, which may deteriorate the exchange of emotional information between the cerebral hemispheres, resulting in emotional dysregulation. Our results indicate the possible use of diffusion tensor imaging as a differential diagnostic tool.博士（医学）・甲第662号・平成29年3月15日© Copyright 2017 Physicians Postgraduate Press, Inc.発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.4088/JCP.15m09851" （※全文閲覧は学内限定

せん妄の遷延化に関連する因子についての後方視研究

Background: It has been reported that delirium causes various problems. Many researchers have reported the risk factors associated with the onset of delirium; however, there are few reports focused on persistent delirium. This study aimed to identify the risk factors associated with persistent delirium. Methods: A total of 573 patients hospitalised in Nara Prefecture General Medical Centre from October 2014 through September 2017 who were referred to the psychiatry consultation service were included in this study. Persistent delirium was defined as delirium lasting for 14 days or more. A retrospective study was carried out based on the patients' records. The relationship between various background factors and persistent delirium was statistically analysed. Results: Of the 573 hospitalised patients, 295 were diagnosed as having delirium. Forty-six patients with persistent delirium and 181 patients with nonpersistent delirium were included in this study. Multivariable logistic regression analyses revealed that male gender, opioid analgesics use, non-opioid analgesics use, and low serum sodium were significantly and independently associated with persistent delirium. Ramelteon or trazodone was used significantly more in persistent delirium, although each use was not significant. Conclusion: This is the first study to reveal that male gender and use of analgesics were associated with persistent delirium in general hospital. However, as this is a case-control study and may contain bias, future cohort studies and intervention studies are needed. It is also necessary to investigate the relevance of the 'degree of pain' behind the use of analgesics.博士（医学）・乙第1516号・令和3年12月21日© 2021 Japanese Psychogeriatric Society.This is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/psyg.12655], which has been published in final form at [https://doi.org/10.1111/psyg.12655]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited

近赤外線スペクトロスコピィを用いた覚醒剤精神病と統合失調症の鑑別

Despite some slight differences in symptomatology, differential diagnosis of methamphetamine-induced psychosis (MAP) versus schizophrenia can be challenging because both disorders present a large overlap in their clinical symptoms. However, a recent study has shown that near-infrared spectroscopy (NIRS) performed during a cognitive task can be a powerful tool to differentiate between these two disorders. Here, we evaluated verbal fluency task performance during NIRS in 15 patients diagnosed with MAP and 19 with schizophrenia matched for age and sex. We used prefrontal probes and a 24-channel NIRS machine to measure the relative concentrations of oxyhaemoglobin every 0.1 s during the task. For each patient, the neurocognitive function and clinical psychopathology were evaluated using the Positive and Negative Symptom Scale (PANSS), and the Brief Assessment of Cognition in Schizophrenia (BACS). Oxyhaemoglobin changes in the prefrontal cortex were significantly higher in the MAP group compared to those in the schizophrenia group, particularly in the right dorsolateral prefrontal cortex. In contrast, we found no significant difference in PANSS and BACS scores. Our findings suggest that NIRS measurement could be applied to differentiate patients with MAP from those with schizophrenia, even in cases where clinical symptoms are similar.博士（医学）・甲第645号・平成28年3月15日This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0

Positron emission tomography assessments of phosphodiesterase 10A in patients with schizophrenia

[Background and hypothesis] Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been reported previously, but the status of this molecule in the living patients with schizophrenia remains elusive. Therefore, this study aimed to investigate the central PDE10A status in patients with schizophrenia and examine its relationship with psychopathology, cognition, and corticostriatal glutamate levels. [Study design] This study included 27 patients with schizophrenia, with 5 antipsychotic-free cases, and 27 healthy controls. Positron emission tomography with [18F]MNI-659, a specific PDE10A radioligand, was employed to quantify PDE10A availability by measuring non-displaceable binding potential (BPND) of the ligand in the limbic, executive, and sensorimotor striatal functional subregions, and in the pallidum. BPND estimates were compared between patients and controls while controlling for age and gender. BPND correlations were examined with behavioral and clinical measures, along with regional glutamate levels quantified by the magnetic resonance spectroscopy. [Study results] Multivariate analysis of covariance demonstrated a significant main effect of diagnosis on BPND (p = .03). A posthoc test showed a trend-level higher sensorimotor striatal BPND in patients, although it did not survive multiple comparison corrections. BPND in controls in this subregion was significantly and negatively correlated with the Tower of London scores, a cognitive subtest. Striatal or dorsolateral prefrontal glutamate levels did not correlate significantly with BPND in either group. [Conclusions] The results suggest altered striatal PDE10A availability and associated local neural dysfunctions in patients with schizophrenia

Spatially distinct neural mechanisms differentially linking tau aggregations, oxidative stress, and neuronal loss to apathic phenotypes in progressive supranuclear palsy

Objectives: Although progressive supranuclear palsy (PSP) patients are known to exhibit apathy frequently, neuropathological processes leading to this phenotype remains elusive. The current study was aimed to examine the involvement of tau aggregations, oxidative stress (OS), and neuronal loss in the apathic manifestation of PSP patients.Methods: Twenty PSP patients and 23 healthy controls (HCs) were enrolled. We evaluated tau depositions by PET with a specific probe, 18F-PM-PBB3, and brain volumes by MRI. Glutathione (GSH) levels as resilience measures against OS were also quantified by MRS in the anterior and posterior cingulate cortices (ACC and PCC).Results: Tau pathologies were noted in the subcortical and cortical structures of the patient brains. Among these areas, tau accumulations were positively correlated with apathy scale (AS) in the angular gyrus (AG). Although PSP cases did not show alterations of GSH relative to HCs, GSH levels in PCC but not ACC were correlated with AS and tau depositions in AG. Marked atrophy was observed in the subcortical but not neocortical regions of PSP subjects, while gray matter (GM) volumes of the inferior frontal gyrus (IFG) and ACC were positively correlated with AS but had no relations to PET-detectable tau depositions and GSH. Finally, path analysis highlighted synergistic contributions of PET-detectable tau pathologies and GSH reductions in the posterior brain regions to AS, in parallel with associations of GM volume loss in the anterior brain regions with AS.Conclusions: Our findings have indicated neural mechanisms underlying apathy in PSP may consist of PET-detectable tau aggregation and OS without marked neuronal loss in the posterior cortex and neuronal loss with neither PET-detectable tau pathologies nor OS in the anterior cortex.The 8th JHBI Talk Serie

Treatment‐related neuroendocrine prostate cancer with BRCA2 germline mutation treated with olaparib

Introduction The efficacy of olaparib for treatment‐related neuroendocrine prostate cancer is unknown. Here, we report a case of treatment‐related neuroendocrine prostate cancer with a BRCA2 mutation that was treated with olaparib with 1‐year efficacy. Case presentation A 75‐year‐old man initially diagnosed with prostate adenocarcinoma developed treatment‐related neuroendocrine prostate cancer after 10‐year androgen deprivation therapy. Despite the initial temporary effects of etoposide and carboplatin, the patient experienced prostate bed tumor recurrence 1 year after chemotherapy cessation. FoundationOne® detected a BRCA2 gene mutation, and olaparib was initiated after repeating one chemotherapy course using the same chemotherapeutic agents. The patient received olaparib with sustained tumor regression for 1 year without severe side effects. Conclusion Olaparib may be the treatment of choice for treatment‐related neuroendocrine prostate cancer in patients with BRCA mutations

自閉スペクトラム症における幼少期逆境体験と白質微小構造障害の関連性についての検討

Individuals with autism spectrum disorder (ASD) have an increased risk of adverse childhood experiences (ACEs) than typically developed (TD) children. Since multiple lines of studies have suggested that ACEs are related to myelination in the frontal lobe, an exposure to ACEs can be associated with white matter microstructural disruption in the frontal lobe, which may be implicated in subsequential psychological deficits after the adulthood. In this study, we investigated the relationship between ACEs and microstructural integrity on frontal lobe-related white matter tracts using diffusion tensor imaging in 63 individuals with ASD and 38 TD participants. Using a tractography-based analysis, we delineated the uncinate fasciculus (UF), dorsal cingulum (Ci), and anterior thalamic radiation (ATR), which are involved in the neural pathology of ASD, and estimated each diffusion parameter. Compared to the TD participants, individuals with ASD displayed significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the left ATR. Then, ASD individuals exposed to severe ACEs displayed higher RD than those exposed to mild ACEs and TD participants in the left ATR. Moreover, the severity of ACEs, particularly neglect, correlated with lower FA and higher RD in the left UF and ATR in individuals with ASD, which was not observed in TD participants. These results suggest that an exposure to ACEs is associated with abnormality in the frontal lobe-related white matter in ASD.博士（医学）・甲第843号・令和4年6月29日Copyright © 2022 Yoshikawa, Kitamura, Matsuoka, Takahashi, Ishida, Kishimoto, Yasuno, Yasuda, Hashimoto, Miyasaka, Kichikawa, Kishimoto and Makinodan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY: https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms