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BACKGROUND/AIMS: We developed an idiopathic normal-pressure hydrocephalus grading scale (iNPHGS) to classify a triad of disorders (cognitive impairment, gait disturbance and urinary disturbance) of iNPH with a wide range of severity. The purpose of this study was to assess the reliability and validity of this scale in 38 patients with iNPH. RESULTS: The interrater reliability of this scale was high. The iNPHGS cognitive domain score significantly correlated with the cognitive test scores, including the Mini-Mental State Examination (MMSE), the gait domain score with the Up and Go Test and Gait Status Scale scores, and the urinary domain score with the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. The MMSE, Gait Status Scale and ICIQ-SF scores significantly improved in patients whose iNPHGS scores improved after CSF tapping but not in those whose iNPHGS scores did not improve after CSF tapping. Fourteen of the 38 patients received shunt operations. In these 14 patients, changes in the iNPHGS cognitive and urinary domains after CSF tapping were significantly associated with the changes after the shunt operation. [ABSTRACT FROM AUTHOR]

Background: In an earlier study we showed that a powerful emotional experience (the Kobe earthquake) reinforced memory retention in patients with Alzheimer's disease, but we could not control factors other than the emotional impact of the earthquake.Aims: To test our previous findings in a controlled experimental study.Method: Recall tests consisting of two short stories were administered to 34 patients with Alzheimer's disease and 10 normal subjects. The two stories were identical except for one passage in each story: one was emotionally charged (arousing story) and the other (neutral story) was not.Results: In both groups, the emotionally charged passage in the arousing story was remembered better than the counterpart in the neutral story. In addition, the extent of the memory improvement was similar in the subjects and in the controls.Conclusions: The results provide further evidence that emotional arousal enhances declarative memory in patients with Alzheimer's disease, and give a clue to the management of people with dementia. [ABSTRACT FROM AUTHOR]

Describes patients with motor neglect following surgical ablation restricted to the supplementalry motor area. Details of medical case reports; Results of pre-operative neurological and neuropsychological examinations; Explanations for the decrease of voluntary movement in the left hand.

Abstract Background The cerebrospinal fluid (CSF) tap test (TT) has been regarded as an important test for the prediction of shunt effectiveness in patients with suspected idiopathic normal pressure hydrocephalus (iNPH). Although its specificity and sensitivity are reportedly high, there remains some disagreement over this point. Herein, the TT as a test for predicting shunt effectiveness was investigated in our multicenter prospective study named SINPHONI and strategies to increase its predictability were examined. Methods One hundred suspected iNPH patients with the following entry criteria were enrolled in the study: (1) 60 to 85 years old, (2) one or more of the NPH triad signs, (3) ventriculomegaly (Evans index > 0.3), (4) high convexity tightness in coronal-section MRI, and (5) no antecedent disorders. Changes in NPH triad symptoms were assessed using the iNPH grading scale and other measures before and after removal of 30 ml lumbar CSF. A positive response to TT was pre-defined by specific improvements on the grading and other scales. A ventriculoperitoneal shunt was performed with a programmable valve. The sensitivity and specificity of the TT was calculated with a contingency table. A decision tree analysis was performed to increase the predictability of the TT. Results Among 100 patients, 80 were shunt responders. A statistically-significant variable between shunt responders and non-responders was CSF pressure. The changes in single variables in the iNPH grading scale after TT showed high specificity with low sensitivity. In contrast, change of the total score in the iNPH grading scale showed a relatively high sensitivity of 71.3% with specificity of 65%. A decision tree analysis revealed that using the iNPH grading scale total score and pre-shunt CSF pressure ≥ 15 cmH20, sensitivity increased to 82.5%, without a decrease in specificity. Conclusions The sensitivity and specificity of the TT for predicting shunt responsiveness were optimum when improvement on any iNPH grading scale was combined with CSF pressure ≥ 15 cmH20. To increase the sensitivity of the TT, further effort is necessary. Trial Registration This study is registered with ClinicalTrials.gov, with the number NCT00221091.

The chitinase 3-like 1 (CHI3L1) gene acts as a cellular survival factor in response to several environmental and psychosocial stresses. The expression level of CHI3L1 was increased in the hippocampus and prefrontal cortex regions of patients with schizophrenia. Genetic variants of the CHI3L1 gene have been significantly associated with schizophrenia in two distinct ethnic groups, the Chinese and Irish populations. The aims of this study are to confirm the association between the CHI3L1 gene and schizophrenia in a Japanese population using the largest sample size to date (1463 cases and 1795 controls) and perform a meta-analysis of the combined samples (3005 cases, 3825 controls and 601 trios). We found significant associations between single nucleotide polymorphism (SNP) 4/rs4950928 (p=0.009), which is located in the promoter region of the CHI3L1 gene, and haplotypes including this SNP and schizophrenia (the most significant global p<0.001). As the meta-analysis of the combined samples showed significant heterogeneity among studies of SNP3/rs10399805 (p=0.026) and SNP4 (p<0.001), we performed meta-analyses separately in the Japanese (2033 cases and 2365 controls) and Chinese populations (412 cases, 464 controls and 601 trios), the major groups analyzed in association studies of the CHI3L1 gene. The meta-analysis in Japanese populations showed stronger evidence for the association of schizophrenia with SNP4 (p=0.003), while the meta-analysis in Chinese populations showed an association with a different variant (SNP3) (p=0.003). We conclude that the genetic variants in the CHI3L1 gene have ethnic heterogeneity and confer a susceptibility to schizophrenia in Asian populations. [ABSTRACT FROM AUTHOR]

In Alzheimer's disease (AD), reports on the association between false recognition and brain structure have been inconsistent. In dementia with Lewy bodies (DLB), no such association has been reported. This study aimed to identify brain regions associated with false recognition in AD and DLB by analyzing regional gray matter volume (rGMV). We included 184 patients with AD and 60 patients with DLB. The number of false recognitions was assessed using the Alzheimer's Disease Assessment Scale' word recognition task. Brain regions associated with the number of false recognitions were examined by voxel-based morphometry analysis. The number of false recognitions significantly negatively correlated with rGMV in the bilateral hippocampus, left parahippocampal gyrus, bilateral amygdala, and bilateral entorhinal cortex in patients with AD (p < 0.05, family-wise error [FEW] corrected) and in the bilateral hippocampus, left parahippocampal gyrus, right inferior frontal gyrus, right middle frontal gyrus, right basal forebrain, right insula, left medial and lateral orbital gyri, and left fusiform in those with DLB (p < 0.05, FWE corrected). Bilateral hippocampus and left parahippocampal gyrus were associated with false recognition in both diseases. However, we found there were regions where the association between false recognition and rGMV differed from disease to disease., (© 2024. The Author(s).)

Aim: This study aimed to investigate the improvement in gait velocity variability after cerebrospinal fluid (CSF) elimination, and the association between gait velocity variability and gait and cognitive impairment in patients with idiopathic normal pressure hydrocephalus., Methods: The gait velocity of 44 patients with idiopathic normal pressure hydrocephalus was measured using the Timed Up and Go Test (TUG) for a total of 10 times over 3 days each before and after CSF elimination. The coefficient of variation (CV) in the time required for the sequence of actions in TUG (TUG-CV) was calculated using 10 TUG data, and used for measuring intraindividual gait velocity variability. Gait quality was evaluated with the Gait Status Scale Revised (GSSR), and cognitive function was evaluated with the Mini-Mental State Examination and the Frontal Assessment Battery., Results: The TUG, TUG-CV, GSSR and Frontal Assessment Battery results improved significantly after CSF elimination. The analyses using pre-CSF elimination results showed that the TUG-CV significantly and positively correlated with the TUG and GSSR results, and negatively with Mini-Mental State Examination results, but not with age and the Frontal Assessment Battery results. The stepwise multiple regression analysis indicates that the TUG, GSSR and Mini-Mental State Examination results were significant predictors of the TUG-CV. The analysis using data of change after CSF elimination showed that ΔTUG and ΔGSSR were significant predictors of ΔTUG-CV., Conclusions: Gait velocity variability improved after CSF elimination, and gait velocity variability was associated with gait disturbances and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Geriatr Gerontol Int 2024; 24: 693-699., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Dementia and mild cognitive impairment (MCI) represent significant health challenges in an aging population. As the search for noninvasive, precise and accessible diagnostic methods continues, the efficacy of electroencephalography (EEG) combined with deep convolutional neural networks (DCNNs) in varied clinical settings remains unverified, particularly for pathologies underlying MCI such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and idiopathic normal-pressure hydrocephalus (iNPH). Addressing this gap, our study evaluates the generalizability of a DCNN trained on EEG data from a single hospital (Hospital #1). For data from Hospital #1, the DCNN achieved a balanced accuracy (bACC) of 0.927 in classifying individuals as healthy (n = 69) or as having AD, DLB, or iNPH (n = 188). The model demonstrated robustness across institutions, maintaining bACCs of 0.805 for data from Hospital #2 (n = 73) and 0.920 at Hospital #3 (n = 139). Additionally, the model could differentiate AD, DLB, and iNPH cases with bACCs of 0.572 for data from Hospital #1 (n = 188), 0.619 for Hospital #2 (n = 70), and 0.508 for Hospital #3 (n = 139). Notably, it also identified MCI pathologies with a bACC of 0.715 for Hospital #1 (n = 83), despite being trained on overt dementia cases instead of MCI cases. These outcomes confirm the DCNN's adaptability and scalability, representing a significant stride toward its clinical application. Additionally, our findings suggest a potential for identifying shared EEG signatures between MCI and dementia, contributing to the field's understanding of their common pathophysiological mechanisms., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takufumi Yanagisawa reports financial support was provided by Japan Agency for Medical Research and Development. Takufumi Yanagisawa reports financial support was provided by Japan Science and Technology Agency. Takufumi Yanagisawa reports financial support was provided by Japan Society for the Promotion of Science. Takufumi Yanagisawa reports financial support was provided by Council of State Secretariats for Science Technology and Innovation. Takufumi Yanagisawa reports financial support was provided by National Institute of Biomedical Innovation Health and Nutrition. Takufumi Yanagisawa reports a relationship with PGV inc that includes: consulting or advisory. Takufumi Yanagisawa has patent #Information processing device, determination method, and determination program (WO 2020/218,013 A1) pending to Osaka University. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Work schedules can make it challenging for professional care workers to participate in long-term training programs on managing behavioural and psychological symptoms of dementia (BPSD). Simultaneously, it is necessary to prevent caregivers' negative responses to BPSD, provide a positive environment for people with dementia, and create a system for new management plans, since the initial one is often unsuccessful. Therefore, we developed a short manual-based training system for functional analysis including positive behaviour support and strategies when management plans do not function well. This study aimed to preliminarily examine the usefulness of this system., Methods: Thirty-five staff members from 12 care facilities participated in the training. For each facility, off-the-job training was performed in two 120-min sessions held over 2 days. Then, care plans were implemented by staff members for a month, during which on-the-job training was provided. The study included 14 people with dementia and BPSD. This was a single-arm study without a control group. Pre- and post-tests were conducted to examine the effects of the training system using the Neuropsychiatric Inventory-Nursing Home Version., Results: The results of the pre- and post-tests for the total scores on severity and occupational disruptiveness significantly improved, with large effect sizes. Regarding symptom domains, delusions, agitation/aggression, and aberrant motor behaviour significantly improved in both severity and occupational disruptiveness. Depression/dysphoria and anxiety significantly improved in severity; however, there were trends of improvement in occupational disruptiveness. In addition, the effect sizes for severity and occupational disruptiveness of delusions and agitation/aggression were large., Conclusions: This preliminary study suggests that the training system is promising. A randomised controlled trial with a larger sample size is necessary to confirm the findings., (© 2023 Japanese Psychogeriatric Society.)

Japanese guidelines for idiopathic normal pressure hydrocephalus (iNPH) (iNPHGL) are the first and only guidelines in the world that were revised following subsequent developments in iNPH research. We first discuss the virtuous cycle in which the development and revision of the iNPHGL and how the implementation of two consecutive multicenter prospective studies conducted in Japan, SINPHONIs, have worked together to advance iNPH practices. Subsequently, we explained the most characteristic features of the iNPHGL, such as "Positioning of iNPH," "Diagnostic Criteria," and "Algorithms for Diagnosis and Treatment." To classify iNPH, we categorized chronic adult-onset normal pressure hydrocephalus (NPH) as iNPH, secondary NPH, Congenital/Developmental NPH, and Familial NPH. In the diagnostic criteria and algorithm, we classified iNPH into four categories: Suspected iNPH, Possible iNPH, Probable iNPH, and Definite iNPH, depending on the certainty of the diagnosis. In addition, a positioned disproportionately enlarged subarachnoid space hydrocephalus (DESH) on head computed tomography and magnetic resonance imaging is an important finding for the diagnosis of iNPH. Finally, we presented the results of a survey on the treatment status of patients with suspected iNPH, awareness of DESH, and use of this iNPHGL among medical centers for dementia in Japan.

Background: Aggression, a common symptom of Alzheimer's disease (AD), can impose a significant burden on caregivers, necessitating early institutionalization., Objective: The current study examined the neural basis of aggression and its expression mechanism, to advance the development of effective treatment strategies for aggression in patients with AD., Methods: The study sample included 257 patients; 180 were diagnosed with AD and 77 with amnestic mild cognitive impairment (aMCI). Factor analysis of the neuropsychiatric inventory (NPI) aggression scores was performed, and the correlation between each factor and cerebral blood flow (CBF) was examined via diagnosis of AD or aMCI using statistical parametric mapping., Results: Refusal of care was correlated with reduced CBF in the right hippocampus of patients with AD while no specific related regions could be identified in patients with aMCI. Violent behavior was associated with decreased CBF in the right temporal pole and medial frontal lobe of patients with AD and aMCI., Conclusions: These findings suggest that aggression, measured using NPI includes two distinct symptoms, refusal of care and violent behavior, having different underlying neural bases.

Background: Neuropsychiatric symptoms (NPS) in patients with dementia lead to caregiver burdens and worsen the patient's prognosis. Although many neuroimaging studies have been conducted, the etiology of NPS remains complex. We hypothesize that brain structural asymmetry could play a role in the appearance of NPS., Objective: This study explores the relationship between NPS and brain asymmetry in patients with Alzheimer's disease (AD)., Methods: Demographic and MRI data for 121 mild AD cases were extracted from a multicenter Japanese database. Brain asymmetry was assessed by comparing the volumes of gray matter in the left and right brain regions. NPS was evaluated using the Neuropsychiatric Inventory (NPI). Subsequently, a comprehensive assessment of the correlation between brain asymmetry and NPS was conducted., Results: Among each NPS, aggressive NPS showed a significant correlation with asymmetry in the frontal lobe, indicative of right-side atrophy (r = 0.235, p = 0.009). This correlation remained statistically significant even after adjustments for multiple comparisons (p < 0.01). Post-hoc analysis further confirmed this association (p < 0.05). In contrast, no significant correlations were found for other NPS subtypes, including affective and apathetic symptoms., Conclusions: The study suggests frontal lobe asymmetry, particularly relative atrophy in the right hemisphere, may be linked to aggressive behaviors in early AD. These findings shed light on the neurobiological underpinnings of NPS, contributing to the development of potential interventions.

To date, electroencephalogram (EEG) has been used in the diagnosis of epilepsy, dementia, and disturbance of consciousness via the inspection of EEG waves and identification of abnormal electrical discharges and slowing of basic waves. In addition, EEG power analysis combined with a source estimation method like exact-low-resolution-brain-electromagnetic-tomography (eLORETA), which calculates the power of cortical electrical activity from EEG data, has been widely used to investigate cortical electrical activity in neuropsychiatric diseases. However, the recently developed field of mathematics "information geometry" indicates that EEG has another dimension orthogonal to power dimension - that of normalized power variance (NPV). In addition, by introducing the idea of information geometry, a significantly faster convergent estimator of NPV was obtained. Research into this NPV coordinate has been limited thus far. In this study, we applied this NPV analysis of eLORETA to idiopathic normal pressure hydrocephalus (iNPH) patients prior to a cerebrospinal fluid (CSF) shunt operation, where traditional power analysis could not detect any difference associated with CSF shunt operation outcome. Our NPV analysis of eLORETA detected significantly higher NPV values at the high convexity area in the beta frequency band between 17 shunt responders and 19 non-responders. Considering our present and past research findings about NPV, we also discuss the advantage of this application of NPV representing a sensitive early warning signal of cortical impairment. Overall, our findings demonstrated that EEG has another dimension - that of NPV, which contains a lot of information about cortical electrical activity that can be useful in clinical practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH)., Design: Case-control study., Setting: Osaka University Hospital., Participants: Patients with possible iNPH underwent a CSF tap test., Measurements: Concentrations of amyloid beta (Aβ) 1-40, 1-42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aβ1-42 to Aβ1-40 (Aβ 42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients., Results: We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ 42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aβ 42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ 42/40 ratio. The association between Aβ 42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline., Conclusions: A low CSF Aβ 42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.