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Abstract 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.

Abstract Background We investigated whether the treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers, along with their attending physicians’ perception of those treatment needs, differ according to the clinical department visited by the patients. Methods This was a subanalysis of a multicenter, cross-sectional, observational survey study. Data from the main study were classified according to the clinical department visited by the patient: psychiatric group (P-group), geriatric internal medicine group (G-group), and neurology group (N-group). The treatment needs of patients and caregivers were defined as “the symptom that causes them the most distress”, and the frequency of each answer was tabulated. Results This subanalysis included 134, 65, and 49 patient–caregiver pairs in the P-, G-, and N-groups, respectively. Statistically significant differences in patient background characteristics such as patient age; initial symptom domains; use of cholinesterase inhibitors, levodopa, antipsychotics, and Yokukansan; and total scores of the Mini-Mental State Examination, Neuropsychiatric Inventory-12, and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Parts II and III were shown among the three subgroups. While there were no differences in patients’ treatment needs among the subgroups, residual analysis showed that in the N-group, parkinsonism was more of a problem than other symptom domains (p = 0.001). There were significant differences in caregivers’ treatment needs among the three subgroups (p

Early detection methods for cognitive impairment are crucial for its effective treatment. Dual-task-based pipelines that rely on skeleton sequences can detect cognitive impairment reliably. Although such pipelines achieve state-of-the-art results by analyzing skeleton sequences of periodic stepping motion, we propose that their performance can be improved by decomposing the skeleton sequence into representative phase-aligned periods and focusing on them instead of the entire sequence. We present the phase-aligned periodic graph convolutional network, which is capable of processing phase-aligned periodic skeleton sequences. We trained it with a cross-modality feature fusion loss using a representative dataset of 392 samples annotated by medical professionals. As part of a dual-task cognitive impairment detection pipeline that relies on two-dimensional skeleton sequences extracted from RGB images to improve its general usability, our proposed method outperformed existing approaches and achieved a mean sensitivity of 0.9231 and specificity of 0.9398 in a four-fold cross-validation setup.

Abstract Background Delayed neuropsychiatric sequelae (DNS) is a syndrome that appears days to weeks after acute carbon monoxide (CO) poisoning. DNS shows various neuropsychiatric symptoms, such as mental deterioration and parkinsonism. Case Presentation Our case was a 37‐year‐old male with schizophrenia. He attempted suicide by CO poisoning and was brought to our emergency department (Day 0). He was ventilated with normobaric oxygen therapy for 3 days and moved to the psychiatric ward with clear consciousness. We restarted antipsychotics, and he gradually presented akinesia and rigidity. Additionally, around Day 32, he showed disorganized behaviors, mental deterioration, incontinence, and gait disturbance. Brain magnetic resonance imaging (MRI) showed slightly abnormal findings on Day 35. Although we suspected DNS on the clinical course and the MRI findings, catatonia and side‐effects of antipsychotics were also considered. Finally, electroencephalography (EEG) on Day 38 with apparent abnormalities, including diffuse slow waves, resulted in our diagnosis of DNS, and he underwent hyperbaric oxygen therapy. His condition was dramatically improved, and his diffuse slow waves on EEG disappeared on Day 83. We also followed his clinical presentations and brain MRI until 33 months. Throughout the whole follow‐up, his cognition, movement, and psychiatric symptoms remained stable. However, his brain MRI showed progressive atrophy in bilateral frontal lobes and increasing white matter lesions throughout the whole course. Conclusion EEG, as well as brain MRI, may be crucial in the differential diagnosis of DNS in patients with complex conditions involving medications and severe mental illnesses.

BackgroundThe current biomarker-supported diagnosis of Alzheimer’s disease (AD) is hindered by invasiveness and cost issues. This study aimed to address these challenges by utilizing portable electroencephalography (EEG). We propose a novel, non-invasive, and cost-effective method for identifying AD, using a sample of patients with biomarker-verified AD, to facilitate early and accessible disease screening.MethodsThis study included 35 patients with biomarker-verified AD, confirmed via cerebrospinal fluid sampling, and 35 age- and sex-balanced healthy volunteers (HVs). All participants underwent portable EEG recordings, focusing on 2-minute resting-state EEG epochs with closed eyes state. EEG recordings were transformed into scalogram images, which were analyzed using “vision Transformer(ViT),” a cutting-edge deep learning model, to differentiate patients from HVs.ResultsThe application of ViT to the scalogram images derived from portable EEG data demonstrated a significant capability to distinguish between patients with biomarker-verified AD and HVs. The method achieved an accuracy of 73%, with an area under the receiver operating characteristic curve of 0.80, indicating robust performance in identifying AD pathology using neurophysiological measures.ConclusionsOur findings highlight the potential of portable EEG combined with advanced deep learning techniques as a transformative tool for screening of biomarker-verified AD. This study not only contributes to the neurophysiological understanding of AD but also opens new avenues for the development of accessible and non-invasive diagnostic methods. The proposed approach paves the way for future clinical applications, offering a promising solution to the limitations of advanced diagnostic practices for dementia.

Abstract Associations between delirium and postoperative adverse events in cardiovascular surgery have been reported and the preoperative identification of high-risk patients of delirium is needed to implement focused interventions. We aimed to develop and validate machine learning models to predict post-cardiovascular surgery delirium. Patients aged ≥ 40 years who underwent cardiovascular surgery at a single hospital were prospectively enrolled. Preoperative and intraoperative factors were assessed. Each patient was evaluated for postoperative delirium 7 days after surgery. We developed machine learning models using the Bernoulli naive Bayes, Support vector machine, Random forest, Extra-trees, and XGBoost algorithms. Stratified fivefold cross-validation was performed for each developed model. Of the 87 patients, 24 (27.6%) developed postoperative delirium. Age, use of psychotropic drugs, cognitive function (Mini-Cog

BackgroundVisual hallucinations (VH) are associated with visual prediction error in patients with dementia with Lewy bodies (DLB). Given this relationship, environmental adjustments have been suggested, but detailed contents for implementing such environmental adjustments and assessments are poorly documented. This case report preliminarily demonstrates methods for improving VH through our experience with two patients with DLB. We conducted familial interviews to assess the phenomenological features of VH and reviewed photographs of patients’ homes to identify the environmental triggers of VH, known as photo assessment of the living environment (PA-LE).Case descriptionPatient 1 was a 78-year-old woman with a Mini-Mental State Examination (MMSE) score of 11/30. She experienced seeing a stranger, children, and cats at home, which frightened her. VH frequently occurred in the living room and bedroom. The PA-LE showed that several environmental features, such as cushions on a sofa, the pattern on a carpet under a table, and clothing on hangers, were suggestive triggers of VH. Patient 2 was an 88-year-old woman with a MMSE score of 5/30. She had seen strangers, children, and animals at home, some of which were linked to a theft delusion. VH frequently occurred in the living room and bedroom. The PA-LE found that several environmental features, such as clothing on hangers and dolls, were suggestive of VH triggers. Non-pharmacological approaches were tailored to the patients’ environmental and psychological states using interviews and PA-LE. This included removing environmental triggers, reducing negative mood, and providing coping strategies for VH. This improved their VH and their caregivers’ knowledge of VH.ConclusionPhenomenological assessments using photographs of the patient’s home could identify the environmental triggers associated with VH in patients with DLB and assist in environmental adjustments.

Late-onset epilepsy, particularly focal impaired awareness seizures, often present without convulsions and can cause memory impairment. This can lead patients to initially seek consultation at memory clinics, potentially delaying referral to epilepsy specialists. We report on three patients, aged 40s to 70s, admitted for cognitive evaluation who were finally diagnosed with epileptic seizures as the underlying cause of their symptoms. Notably, all initially presented to local clinics with symptoms suggesting cognitive impairment. Despite initial diagnostic uncertainty, all patients exhibited epileptic activity on electroencephalography (EEG) and responded positively to antiepileptic drugs, suggesting epileptic mechanisms were involved in their symptoms. Both traditional clinical EEG systems and newly developed, one-minute portable EEG devices were used in their evaluations. The portable device, medically approved in Japan, successfully captured sharp-waves like activities with the same durations, amplitudes, and shapes as traditional devices. This highlights its potential to improve epilepsy diagnosis and future screening due to its portability and ease of use. Implementing portable EEG devices could promote timely and appropriate treatment, preventing misdiagnosis of neurological conditions.

Abstract Right temporal variant frontotemporal dementia, also called right-predominant semantic dementia, often has an unclear position within the framework of the updated diagnostic criteria for behavioral variant frontotemporal dementia or primary progressive aphasia. Recent studies have suggested that this population may be clinically, neuropathologically, and genetically distinct from those with behavioral variant frontotemporal dementia or left-predominant typical semantic variant primary progressive aphasia. Here we describe a Japanese case of right temporal variant frontotemporal dementia with novel heterozygous MAPT mutation Adenine to Thymidine in intervening sequence (IVS) 9 at position -7 from 3ʹ splicing site of intron 9/exon 10 boundary (MAPT IVS9-7A > T). Postmortem neuropathological analysis revealed a predominant accumulation of 4 repeat tau, especially in the temporal lobe, amygdala, and substantia nigra, but lacked astrocytic plaques or tufted astrocytes. Immunoelectron microscopy of the tau filaments extracted from the brain revealed a ribbon-like structure. Moreover, a cellular MAPT splicing assay confirmed that this novel variant promoted the inclusion of exon 10, resulting in the predominant production of 4 repeat tau. These data strongly suggest that the MAPT IVS9-7 A > T variant found in our case is a novel mutation that stimulates the inclusion of exon 10 through alternative splicing of MAPT transcript and causes predominant 4 repeat tauopathy which clinically presents as right temporal variant frontotemporal dementia.

The number of older adults living alone is rapidly increasing. Loneliness in older adults not only degrade their quality of life but also causes troubles such as heavy burden on the medical staff, especially when cognitive decline is present. Social robots could be used in several ways to reduce such problems. As a first step towards this goal, we introduced conversation robots into the homes of older adults with cognitive decline to evaluate the robot’s availability and acceptance during several months. The study involved two steps, one for evaluating the robustness of the proposed robotic system, and the second one to examine the long-term acceptance of social robots by older adults with cognitive decline living alone. Our data shows that after several weeks of human-robot interaction, the participants continued to use the robot and successfully integrated them into their lives. These results open the possibility of further research involving how sustained interaction can be achieved, as well as which factors contributed to the acceptance of the robot.

IntroductionPostoperative delirium (POD) is common and life-threatening, however, with intensive interventions, a potentially preventable clinical syndrome. Although electroencephalography (EEG) is a promising biomarker of delirium, standard 20-leads EEG holds difficulties for screening usage in clinical practice.ObjectiveWe aimed to develop an accurate algorithm to predict POD using EEG data obtained from portable device.MethodsWe recruited 128 patients who underwent scheduled cardiovascular surgery. Cognitive function assessments were conducted, and portable EEG recordings were obtained prior to surgery.ResultsAmong the patients, 47 (36.7%) patients with POD were identified and they did not significantly differ from patients without POD in sex ratio, age, cognitive function, or treatment duration of intensive care unit. However, significant differences were observed in the preoperative EEG power spectrum densities at various frequencies, especially gamma activity, between patients with and without POD. POD was successfully predicted using preoperative EEG data with a machine learning algorithm, yielding accuracy of 86% and area under the receiver operating characteristic curve of 0.93.DiscussionThis study provides new insights into the objective and biological vulnerability to delirium. The developed algorithm can be applied in general hospitals without advanced equipment and expertise, thereby enabling the reduction of POD occurrences with intensive interventions for high-risk patients.

Abstract Alzheimer’s disease (AD) is a progressive neuropsychiatric disease affecting many elderly people and is characterized by progressive cognitive impairment of memory, visuospatial, and executive functions. As the elderly population is growing, the number of AD patients is increasing considerably. There is currently growing interest in determining AD’s cognitive dysfunction markers. We used exact low-resolution-brain-electromagnetic-tomography independent-component-analysis (eLORETA-ICA) to assess activities of five electroencephalography resting-state-networks (EEG-RSNs) in 90 drug-free AD patients and 11 drug-free patients with mild-cognitive-impairment due to AD (ADMCI). Compared to 147 healthy subjects, the AD/ADMCI patients showed significantly decreased activities in the memory network and occipital alpha activity, where the age difference between the AD/ADMCI and healthy groups was corrected by linear regression analysis. Furthermore, the age-corrected EEG-RSN activities showed correlations with cognitive function test scores in AD/ADMCI. In particular, decreased memory network activity showed correlations with worse total cognitive scores for both Mini-Mental-State-Examination (MMSE) and Alzheimer’s Disease-Assessment-Scale-cognitive-component-Japanese version (ADAS-J cog) including worse sub-scores for orientation, registration, repetition, word recognition and ideational praxis. Our results indicate that AD affects specific EEG-RSNs and deteriorated network activity causes symptoms. Overall, eLORETA-ICA is a useful, non-invasive tool for assessing EEG-functional-network activities and provides better understanding of the neurophysiological mechanisms underlying the disease.

Abnormal expansions of GGGGCC repeat sequence in the noncoding region of the C9orf72 gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded repeat sequence is translated into dipeptide repeat proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles in the pathogenesis of C9-ALS/FTD, we here investigate the regulatory mechanisms of RAN translation, focusing on the effects of RNA-binding proteins (RBPs) targeting GGGGCC repeat RNAs. Using C9-ALS/FTD model flies, we demonstrated that the ALS/FTD-linked RBP FUS suppresses RAN translation and neurodegeneration in an RNA-binding activity-dependent manner. Moreover, we found that FUS directly binds to and modulates the G-quadruplex structure of GGGGCC repeat RNA as an RNA chaperone, resulting in the suppression of RAN translation in vitro. These results reveal a previously unrecognized regulatory mechanism of RAN translation by G-quadruplex-targeting RBPs, providing therapeutic insights for C9-ALS/FTD and other repeat expansion diseases.

Abstract Background Understanding the treatment needs of patients with dementia with Lewy bodies (DLB) is essential to develop treatment strategies. We examined the treatment needs of patients with DLB and their caregivers and the extent to which the attending physicians understand these treatment needs. Methods This was a cross-sectional, observational study conducted using questionnaires for patients, caregivers, and physicians. The study participants included patients, their caregivers, and their attending physicians who were experts in DLB. Fifty-two symptoms that are frequent and clinically important in DLB were pre-selected and classified into seven symptom domains. Treatment needs of patients and caregivers were defined as “symptom that causes them most distress,” and the frequency of each answer was tabulated. To assess the physician’s understanding of the treatment needs of patients and caregivers, patient–physician and caregiver–physician concordance rates for each answer regarding treatment needs were calculated according to symptom domains. Results In total, 263 pairs of patients–caregivers and 38 physicians were surveyed. The mean age of patients was 79.3 years, and their mean total score on the Mini-Mental State Examination was 20.9. Thirty-five and 38 symptoms were selected as symptoms causing patients and caregivers most distress, respectively. Memory impairment was most frequently selected for the treatment needs of patients, followed by constipation and bradykinesia. Memory impairment was also most frequently selected by caregivers, followed by visual hallucinations. For the symptom domain that causes patients or caregivers most distress, only about half of the patient–physician pairs (46.9%) and caregiver–physician pairs (50.8%) were matched. Logistic regression analysis identified that concordance rates for treatment needs between patient–physician and caregiver–physician were lower when autonomic dysfunction and sleep-related disorders were selected as the symptom domains that cause most distress. Conclusion There was considerable variability in the treatment needs of patients with DLB and their caregivers. Attending physicians had difficulty understanding the top treatment needs of their patients and caregivers, despite their expertise in DLB, because of various clinical manifestations. Attending physicians should pay more attention to autonomic dysfunction and sleep-related disorders in the treatment of DLB. Trial registration UMIN Clinical Trials Registry, UMIN000041844. Registered on 23 September 2020

Abstract Background Impaired cerebrospinal fluid (CSF) dynamics may contribute to the pathophysiology of neurodegenerative diseases, and play a crucial role in brain health in older people; nonetheless, such age-related changes have not been well elucidated. Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a neuroimaging phenotype of idiopathic normal-pressure hydrocephalus, originating from impaired CSF dynamics, and closely associated with aging. This study aimed to investigate the pathophysiology of DESH and determine age-related changes in CSF dynamics. Methods Using magnetic resonance imaging, we investigated the pathophysiology of DESH by quantitatively evaluating the volumes of DESH-related regions (ventricles [VS], Sylvian fissure [SF], and subarachnoid spaces at high convexity and midline [SHM]) and brain parenchyma in community-dwelling individuals aged ≥ 65 years. DESH-related regions were assessed using a visual rating scale, and volumes measured using voxel-based morphometry. Brain parenchyma volumes were measured using FreeSurfer software. Results Data from 1,356 individuals were analyzed, and 25 (1.8%) individuals had DESH. Regarding the relationships between the volume of each CSF space and age, VS and SF volumes increased with age, whereas SHM volume did not increase. VS and SF volumes increased as the whole brain volume decreased, whereas SHM volume did not increase even if the whole brain volume decreased; that is, SHM did not expand even if brain atrophy progressed. Moreover, lower Mini-Mental State Examination scores were significantly associated with lower SHM volume and higher VS volume. These associations remained significant even when individuals with DESH were excluded. Conclusions This study showed that the volume of high-convexity and medial subarachnoid spaces did not expand and tended to decrease with age; the human brain continuously progresses toward a “DESH-like” morphology with aging in community-dwelling older persons (i.e., DESH might be an “accelerated aging stage” rather than an “age-related disorder”). Our results indicated that brain atrophy may be associated with the development of “DESH-like” morphology. In addition, this morphological change, as well as brain atrophy, is an important condition associated with cognitive decline in older adults. Our findings highlight the importance of investigating the aging process of CSF dynamics in the human brain to preserve brain health in older people.

Abstract Background This study aimed to identify cases of potential prodromal DLB in very late-onset schizophrenia-like psychosis (VLOSLP), using indicative biomarkers of dementia with Lewy bodies (DLB), and to evaluate the characteristics of psychosis as prodromal DLB. Methods Data of patients with VLOSLP without dementia and Parkinsonism, who underwent testing for at least one indicative biomarker of DLB, were retrospectively collected from the database of the psychiatry clinic at the Osaka University Hospital. Patients were divided into two groups based on the positive (VLOSLP+LB) and negative (VLOSLP–LB) results of the indicative biomarkers of DLB. Age, gender, cognitive battery scores, prevalence of each type of delusions and hallucinations, cerebral volume, and cerebral perfusion were compared between the two groups. Results Eleven VLOSLP+LB and 23 VLOSLP–LB participants were enrolled. There were no significant differences in age, proportion of females, and MMSE scores between the two groups. The standardized score of the digit symbol substitution test was significantly lower in the VLOSLP+LB than in VLOSLP–LB group (6.9 [3.1] vs. 10.0 [2.7], p = 0.005). The prevalence of visual hallucinations was significantly higher in the VLOSLP+LB group than in the VLOSLP-LB group (81.8% vs. 26.1%, p = 0.003). Auditory hallucinations were prevalent in both groups (43.5% in VLOSLP–LB, and 45.5% in VLOSLP+LB). Among patients with auditory hallucinations, auditory hallucinations without coexistent visual hallucinations tended to be more prevalent in VLOSLP–LB (7 out of 10) than in VLOSLP+LB patients (1 out of 5). Although cerebral volume was not different in any region, cerebral perfusion in the posterior region, including the occipital lobe, was significantly lower in the VLOSLP+LB group. Conclusions Psychomotor slowing, visual hallucinations, and reduced perfusion in the occipital lobe may be suggestive of prodromal DLB in VLOSLP patients, even though the clinical manifestations were similar in many respects between VLOSLP+LB and VLOSLP–LB. Although auditory hallucinations were prevalent in both groups, most patients in VLOSLP+LB complained of auditory hallucinations along with visual hallucinations. Future studies with a larger number of patients without selection bias are desirable.

IntroductionDeveloping approaches for early detection of possible risk clusters for mental health problems among undergraduate university students is warranted to reduce the duration of untreated illness (DUI). However, little is known about indicators of need for care by others. Herein, we aimed to clarify the specific value of study engagement and lifestyle habit variables in predicting potentially high-risk cluster of mental health problems among undergraduate university students.MethodsThis cross-sectional study used a web-based demographic questionnaire [the Utrecht Work Engagement Scale for Students (UWES-S-J)] as study engagement scale. Moreover, information regarding life habits such as sleep duration and meal frequency, along with mental health problems such as depression and fatigue were also collected. Students with both mental health problems were classified as high risk. Characteristics of students in the two groups were compared. Univariate logistic regression was performed to identify predictors of membership. Receiver Operating Characteristic (ROC) curve was used to clarify the specific values that differentiated the groups in terms of significant predictors in univariate logistic analysis. Cut-off point was calculated using Youden index. Statistical significance was set at p

IntroductionThis study aimed to determine the characteristics of aphasic mild cognitive impairment (aphasic MCI), which is characterized by a progressive and relatively prominent language impairment compared with other cognitive impairments, in the prodromal phase of dementia with Lewy bodies (DLB).MethodsOf the 26 consecutive patients with aphasic MCI who had been prospectively recruited at our hospital, 8 patients were diagnosed with prodromal DLB and underwent language, neurological, neuropsychological, and neuroimaging (N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography; IMP-SPECT) testing. Three of these patients also underwent cholinesterase inhibitor therapy with donepezil.ResultsIn our aphasic MCI cohort, the clinical diagnosis of probable prodromal DLB accounted for more than 30% of cases; therefore, the presence of language impairment in prodromal DLB was not very uncommon. Five patients were diagnosed with progressive anomic aphasia and three with logopenic progressive aphasia. Anomic aphasia was characterized by apparent anomia but relatively preserved repetition and comprehension ability and logopenic progressive aphasia by anomia, phonemic paraphasia, and impaired repetition. IMP-SPECT revealed hypoperfusion of the temporal and parietal lobes in the left hemisphere in all but one patient. All patients who underwent cholinesterase inhibitor therapy with donepezil showed improvement in general cognitive function, including language function.DiscussionThe clinical and imaging features of aphasic MCI in prodromal DLB are similar to those observed in Alzheimer's disease. Progressive fluent aphasia, such as progressive anomic aphasia and logopenic progressive aphasia, is one of the clinical presentations in prodromal state of DLB. Our findings provide further insight into the clinical spectrum of prodromal DLB and may contribute to the development of medication for progressive aphasia caused by cholinergic insufficiency.

Abstract Cognitive frailty (CF) is a clinical condition defined by the presence of both mild cognitive impairment (MCI) and physical frailty (PF). Elderly with CF are at greater risk of dementia than those with MCI or PF alone, but there are few known clinical or neuroimaging features to reliably distinguish CF from PF or MCI. We therefore conducted a population-based cross-sectional study of community elderly combining physical, cognitive, neuropsychiatric, and multisequence magnetic resonance imaging (MRI) evaluations. The MRI evaluation parameters included white matter (WM) lesion volumes, perivascular and deep subcortical WM lesion grades, lacunar infarct prevalence, microbleed number, and regional medial temporal lobe (MTL) volumes. Participants were divided into 4 groups according to the presence or absence of MCI and PF—(1) no MCI, PF (n = 27); (2) no PF, MCI (n = 119); (3) CF (MCI + PF) (n = 21), (4) normal controls (n = 716). Unique features of CF included shorter one-leg standing time; severe depressive symptoms; and MRI signs of significantly more WM lesions, lacunar infarcts, small-vessel disease lesions, microbleeds, and reduced MTL volumes. These unique deficits suggest that interventions for CF prevention and treatment should focus on motor skills, depressive symptoms, and vascular disease risk factor control.

Rationale & Objective: Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese. Study Design: Population-based cross-sectional study. Setting & Participants: A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018. Exposures: UACR and eGFR levels. Outcomes: The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV). Analytical Approach: The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance. Results: Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (P for trend = 0.009 and

Robotic assistive technology for frail older adults has drawn attention, along with raising ethical concerns. The ethical implications of a robot's usage have been characterized in the literature as detrimental, such as emotional deception, unhealthy attachment, and reduced human contact from a deontological perspective. These concerns require practical investigations, although the long-term effect of robot usage on older adults remains uncertain. Our longitudinal study aimed to investigate how older adults with cognitive decline could be affected by using a robot for communication in their homes and how this situation could be reflected in possible emotional attachment to the robot i.e., emotional distress from the robot being taken away once they had become attached to it. We selected 13 older adults living alone and set up a humanoid robot in their homes with whom they could interact at any time for a period of 1–4 months. Questionnaire results indicated participants had a close attachment to the robots even after they were taken away. Interviews revealed that participants became distressed without the robots; however, despite the distress caused by feeling lonely, participants reported that their relationships with the robots were meaningful and that they were satisfied with the memories of having had the robot as a companion. The results raised new questions for further investigation into issues that should be addressed and potential factors affecting the user's adaptation processes. Regarding the consequences of the use of a companion robot, it is important to evaluate the positive aspects of the robot's usage including the emotional support lasting after it was no longer available and other effects on the users. Accordingly, we emphasize the significance of real-world exploration into the effects on the users as well as theoretical reflection on appropriate robot usage.

Abstract To characterize Parkinson’s disease, abnormal phase-amplitude coupling is assessed in the cortico-basal circuit using invasive recordings. It is unknown whether the same phenomenon might be found in regions other than the cortico-basal ganglia circuit. We hypothesized that using magnetoencephalography to assess phase-amplitude coupling in the whole brain can characterize Parkinson’s disease. We recorded resting-state magnetoencephalographic signals in patients with Parkinson’s disease and in healthy age- and sex-matched participants. We compared whole-brain signals from the two groups, evaluating the power spectra of 3 frequency bands (alpha, 8–12 Hz; beta, 13–25 Hz; gamma, 50–100 Hz) and the coupling between gamma amplitude and alpha or beta phases. Patients with Parkinson’s disease showed significant beta–gamma phase-amplitude coupling that was widely distributed in the sensorimotor, occipital, and temporal cortices; healthy participants showed such coupling only in parts of the somatosensory and temporal cortices. Moreover, beta- and gamma-band power differed significantly between participants in the two groups (P

Abstract Background This study aimed to clarify the neuropsychiatric symptoms of right-sided predominant semantic dementia (SD-R) by comparing them with those of behavioral variant frontotemporal dementia (bvFTD), left-sided predominant SD (SD-L), and Alzheimer’s disease (AD). This study also aimed to identify clinical factors related to caregiver burden for bvFTD, SD-R, and SD-L. Methods The neuropsychiatric symptoms of 28 patients with bvFTD, 14 patients with SD-R, 24 patients with SD-L, and 43 patients with AD were evaluated using the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Dementia severity was assessed using the Clinical Dementia Rating. Activities of daily living were assessed using the Lawton Instrument Activities of Daily Living (IADL) scale and the Physical Self-Maintenance Scale. We compared the NPI and SRI scores among the four groups using the Kruskal-Wallis test. In addition, clinical factors related to caregiver burden, represented by the Japanese version of the Zarit Burden Interview (J-ZBI), were analyzed using multiple regression analysis in the bvFTD, SD-R, and SD-L groups. Results The NPI total score and the NPI subscale scores of apathy and disinhibition were significantly higher in the bvFTD group than in the SD-L and AD groups. The SD-R group scores were closer to those of the bvFTD group than the SD-L group. The SRI total score and SRI subscale scores for eating and cooking and speaking were significantly higher in the bvFTD, SD-R, and SD-L groups than in the AD group. The NPI total score was significantly associated with the J-ZBI score in the bvFTD group. The NPI total score and Lawton IADL scale score were independently associated with the J-ZBI score in the SD-R group. Furthermore, the NPI total score and MMSE score were independently associated with the J-ZBI score in the SD-L group. Conclusions SD-R seemed to be a similar condition to bvFTD rather than SD-L regarding behavioral symptoms. Our results suggest that each frontotemporal dementia subgroup requires different approaches to reduce the caregiver burden.

Abstract The precise neural underpinnings of face pareidolia in patients with Parkinson’s disease (PD) remain unclear. We aimed to clarify face recognition network abnormalities associated with face pareidolia in such patients. Eighty-three patients with PD and 40 healthy controls were recruited in this study. Patients with PD were classified into pareidolia and nonpareidolia groups. Volumetric analyses revealed no significant differences between the pareidolia (n = 39) and nonpareidolia (n = 44) patient groups. We further observed decreased functional connectivity among regions of interest in the bilateral frontotemporal lobes in patients with pareidolia. Seed-based analysis using bilateral temporal fusiform cortices as seeds revealed significantly decreased connectivity with the bilateral inferior medial prefrontal cortices in the pareidolia group. Post hoc regression analysis further demonstrated that the severity of face pareidolia was negatively correlated with functional connectivity between the bilateral temporal fusiform and medial prefrontal cortices. Our findings suggest that top-down modulation of the face recognition network is impaired in patients with PD experiencing face pareidolia.

Brain aging causes loss of synaptic spines, neuronal apoptosis, and a reduction in neurotransmitter levels. These aging phenomena disturb cortical electrical activity and its synchronization with connected regions. Previous electroencephalography (EEG) studies reported an age-related decrease in electrical activity in the alpha frequency band at occipital, parietal, and temporal areas as well as a decrease in occipital delta activity. However, there is an ongoing debate about whether there is an increase or decrease of the activity in other frequency bands with aging due to inconsistent study findings. In this study, we aimed to detect age-related changes of cortical electrical activities in all five frequency bands (delta, theta, alpha, beta, and gamma) in a large sample of healthy subjects for the first time. Using eLORETA (exact low-resolution brain electromagnetic tomography) analysis, we applied an eLORETA source estimation method to resting-state EEG data in 147 healthy subjects (median age 55, IQR 26.5–67.0) to obtain cortical electrical activity and assessed age-related changes in this activity using correlation analysis with multiple comparison correction. The combination of the eLORETA source estimation method and correlation analysis implemented in eLORETA software detected age-related changes in specific cortical regions for each frequency band: (1) delta and theta cortical electrical activities decreased at the occipital area with age, (2) alpha cortical electrical activity decreased at the occipitoparietotemporal areas with age, (3) beta cortical electrical activity increased at the insula, sensorimotor area, supplementary motor area, premotor area, and right temporal areas with age (most significant correlation at the right insula), (4) gamma cortical electrical activity increased at the frontoparietal and left temporal areas with age. These findings extend previous EEG study findings and provide valuable information related to mechanisms of healthy aging. Overall, our findings revealed that even healthy aging greatly affects cortical electrical activities in a region-specific way.

BackgroundDelusional infestation is characterized by delusions of being infested with parasites, vermin, or small insects and is frequently accompanied by tactile and visual hallucinations. Herein, we report two cases of dementia with Lewy bodies (DLB) with delusional infestation.Case presentationCase 1 was an 83-year-old man. At the age of 75, he began to show symptoms of rapid eye movement sleep behavior disorder. At the age of 83, he began to complain of visual hallucinations of people and delusional infestation with tactile and visual hallucinations of insects, resulting in the use of insecticides for non-existent insects. He also complained of mild amnesia and was admitted to our psychiatric ward for evaluation and treatment. After admission, the delusional infestation disappeared without any new medication. Based on our examinations, he was diagnosed with probable DLB with delusional infestation. He was treated with 5 mg/day of donepezil hydrochloride; his visual and tactile hallucinations disappeared, and the delusional infestation had not recurred at the 1-year follow-up. Case 2 was a 69-year-old woman. At the age of 60, she underwent clipping for subarachnoid hemorrhage (SAH). At the age of 65, she began to have visual hallucinations of people. At the age of 67, she began to complain of visual illusions in which she mistook lint for insects. At the age of 69, she developed delusional infestation and mild amnesia. She took various actions to get rid of these non-existent insects, including insecticide use, consulting an exterminator, and visiting several dermatologists. She eventually burnt her leg in an attempt to kill the non-existent insects. Based on our examinations, she was diagnosed with prodromal DLB in addition to SAH sequelae. We determined that her delusional infestation was caused by DLB rather than SAH sequelae based on the course of her symptoms. She was treated with a combination of 3 mg/day of donepezil hydrochloride and 12.5 mg/day of quetiapine. Thereafter, the delusional infestation partially improved, and she took no further action against non-existent insects.ConclusionDelusional infestation may be caused by DLB. Acetylcholinesterase inhibitors (AChEI) may be effective for delusional infestation in DLB, although antipsychotics may also be needed in severe cases.

Background The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population.Methods We stratified 177 individuals who participated in the Japanese Alzheimer’s Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)tau and AT(N)NfL). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles.Results We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer’s disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)tau and AT(N)NfL classifications. When we used t-tau as the N marker (AT(N)tau), those who had T− were more frequently assigned to (N)−, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)NfL). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)tau and AT(N)NfL classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)tau classification, but not in the AT(N)NfL classification.Conclusions AT(N)tau and AT(N)NfL in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.

This retrospective cohort study investigates the association between the incidence of sleep problems and changes in digital media use among university students during the COVID-19 pandemic. It used data from annual health check-ups performed at a Japanese university in 2019 and 2020. Students undergoing these check-ups were identified to respond to questions about sleep problems, digital media use, breakfast and exercise habits, and stress. In total, 3,869 students were included in the analysis. The association between the incidence of sleep problems in 2020 and the changes in digital media use between 2019 and 2020 was assessed using logistic regression models. The rate of long digital media use (≥ 2 hours) in 2019 was 42.6%, while in 2020 it was 53.6%. Incidence of sleep problems was observed in 244 students (6.3%) in 2020. There were 786 students (20.3%) who used digital media for ≤ 2 h in 2019 and ≥ 2 h in 2020. From the sample, 66 students (8.4%) reported incidence of sleep problems in 2020. Additionally, those respondents who specifically reported increased digital media use between 2019 and 2020 (increased use) where at greater risk (OR: 1.76; 95% CI: 1.21, 2.55) of reporting sleep problems in 2020, even after controlling for other study variables. Thus, this study provides evidence that the incidence of sleep problems has had a significant association with an increase in digital media use among university students throughout the COVID-19 pandemic. These findings highlight the importance of ensuring appropriate digital media use among students for improved quality of sleep.

Abstract Aim As an emergency measure during the coronavirus disease pandemic, the monitoring interval for clozapine use was temporarily extended beyond the regulatory requirement in Japan, which is the safest monitoring interval worldwide. In this study, we aimed to explore the effect of this measure on patients undergoing clozapine treatment. Methods This retrospective chart review study included patients with treatment‐resistant schizophrenia (TRS) who were undergoing clozapine treatment at four psychiatric institutions in Japan. Demographic characteristics and clinical information of these patients were collected on April 27, 2020, when Japanese psychiatrists were virtually allowed to prescribe clozapine beyond the regulatory requirement. Furthermore, information of adverse events related to the emergency measure was collected and analyzed. Results Of the 41 patients with TRS included in this study, 19 patients underwent extended hematological monitoring during clozapine treatment. No psychiatric or hematological adverse events were observed in the patients during the extended monitoring interval. Conclusion This study suggested that there were few adverse events of clozapine‐treated patients related to emergency measures in Japan. However, hematological monitoring intervals during clozapine treatment have been emergently extended worldwide; hence, it is necessary to verify the results of these measures.

Abstract Background Catatonia is a psychomotor syndrome that presents various symptoms ranging from stupor to agitation, with prominent disturbances of volition. Its pathogenesis is poorly understood. Benzodiazepines and electroconvulsive therapy (ECT) are safe and effective standard treatments for catatonia; however, alternative treatment strategies have not been established in cases where these treatments are either ineffective or unavailable. Here, we report a case of catatonia associated with late-life psychosis, which was successfully treated with lithium. Case presentation A 66-year-old single man with hearing impairment developed hallucination and delusions and presented with catatonic stupor after a fall. He initially responded to benzodiazepine therapy; however, his psychotic symptoms became clinically evident and benzodiazepine provided limited efficacy. Blonanserin was ineffective, and ECT was unavailable. His catatonic and psychotic symptoms were finally relieved by lithium monotherapy. Conclusions Catatonic symptoms are common in patients with mood disorders, suggesting that lithium may be effective in these cases. Moreover, lithium may be effective for both catatonic and psychotic symptoms, as it normalizes imbalances of excitatory and inhibitory systems in the brain, which underlies major psychosis. Cumulative evidence from further cases is needed to validate our findings.

Abstract Neurofilament light chain (NfL) is a novel biomarker of neurodegenerative diseases. It is detectable in the peripheral blood, allowing low-invasive assessment of early signs of neurodegeneration. The level of NfL gradually increases with age; however, what other factors affect it remains unclear. The present study examined the association between blood NfL level and renal function among healthy participants undergoing a health check (n = 43, serum NfL) and patients with diabetes mellitus (n = 188, plasma NfL). All participants were 60 years of age or older; none were diagnosed with dementia. In each group, levels of blood NfL and serum creatinine significantly correlated (coefficient r = 0.50, 0.56). These associations remained statistically significant even after adjustment for age, sex, and body mass index. These findings indicate that blood NfL level might be partially affected by renal function. We recommend measuring renal function for a more precise evaluation of neuroaxonal damage, in particular, among older adults.

Abstract Background The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. Methods The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. Results The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer’s disease. Conclusions The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.

BackgroundThe occurrence of behavioral and psychological symptoms of dementia is affected by individualized context. However, details regarding delusion of theft have been poorly documented. This report describes a useful assessment to understand the environmental context of delusion through two cases of Alzheimer's disease (AD).Familial interview was conducted to assess the phenomenological features. Photos of patients' homes were used to increase the assessment accuracy and check the individualized environmental contexts; this is known as Photo Assessment of Living Environment (PA-LE).Case DescriptionCase 1 was of an 88-year-old woman whose Mini-Mental State Examination (MMSE) score was 23/30. She believed that one neighbor stole her wallet and stored it on a shelf in the living room. She sometimes placed it in other places, such as under the bed as safekeeping. The delusion often occurred when getting ready to go shopping. PA-LE confirmed that the room and shelf were not cluttered, although the incorrect storage place seemed to be hard-to-find.Case 2 was of a 78-year-old woman. The MMSE score was 20/30. She believed that some neighbors stole her garden items. The delusion was limited to her garden, yet the items were varied. Auditory hallucinations exacerbated her belief that the neighbors intruded the garden. PA-LE confirmed that the garden was cluttered with several duplicated items. Moreover, the patient inaccurately remembered the condition of the garden.Non-pharmacological approaches were tailored to the patients' environmental and psychological states, referring to the interview and PA-LE. This included environmental adjustment or increasing self-esteem. Antipsychotics were also prescribed. Environmental and psychological triggers of delusion were improved by the interventions, and the patients had uneventful courses without active delusions.ConclusionEvaluating patients' homes using photos could detect the environmental context of delusion of theft among patients with AD and assist in the management.

Background and purposeAn early and accurate diagnosis of Dementia with Lewy bodies (DLB) is critical because treatments and prognosis of DLB are different from Alzheimer's disease (AD). This study was carried out in Japan to validate an Electroencephalography (EEG)-derived machine learning algorithm for discriminating DLB from AD which developed based on a database of EEG records from two different European countries.MethodsIn a prospective multicenter study, patients with probable DLB or with probable AD were enrolled in a 1:1 ratio. A continuous EEG segment of 150 seconds was recorded, and the EEG data was processed using MC-004, the EEG-based machine learning algorithm, with all clinical information blinded except for age and gender.ResultsEighteen patients with probable DLB and 21 patients with probable AD were the included for the analysis. The performance of MC-004 differentiating probable DLB from probable AD was 72.2% (95% CI 46.5-90.3%) for sensitivity, 85.7% (63.7-97.0%) for specificity, and 79.5% (63.5-90.7%) for accuracy. When limiting to subjects taking ≤5 mg donepezil, the sensitivity was 83.3% (95% CI 51.6-97.9), the specificity 89.5% (66.9-98.7), and the accuracy 87.1% (70.2-96.4).ConclusionsMC-004, the EEG-based machine learning algorithm, was able to discriminate between DLB and AD with fairly high accuracy. MC-004 is a promising biomarker for DLB, and has the potential to improve the detection of DLB in a diagnostic process.

Abstract Aim Matrix metalloproteinase‐9 (MMP‐9) has been shown to modulate synaptic plasticity and may contribute to the pathophysiology of schizophrenia. This study investigated the peripheral levels of MMP‐9 and its association with cognitive functions in patients with schizophrenia to see the possible involvement of MMP‐9 in pathophysiology of schizophrenia, especially in cognitive decline. Methods We measured the plasma levels of MMP‐9 in 257 healthy controls and 249 patients with schizophrenia, including antipsychotic drug–free patients. We also explored the possible association between plasma MMP‐9 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition (WAIS‐ III), the Wechsler Memory Scale‐Revised (WMS‐R), and the Rey Auditory Verbal Learning Test (AVLT). Results We found that the plasma levels of MMP‐9 were significantly higher in patients with schizophrenia, including antipsychotic drug–free patients, than in healthy controls. We found a significant negative association between plasma MMP‐9 levels and cognitive performance in controls and patients with schizophrenia. Conclusion Together, these convergent data suggest a possible biological mechanism for schizophrenia, whereby increased MMP‐9 levels are associated with cognitive impairment.

Abstract Aim Eye movement abnormalities are often associated with psychiatric illness. Subjects with either schizophrenia or autism spectrum disorder (ASD) have been reported to show eye movement abnormalities. However, it is still unclear whether eye movement abnormalities in schizophrenia and in ASD have common features. This study aimed to understand the similarities/differences in eye movement abnormalities of subjects with schizophrenia and those with ASD. Methods We analyzed 75 eye movement characteristics of 83 subjects with schizophrenia, 17 subjects with ASD and 255 healthy controls that were collected during fixation, smooth pursuit and free viewing tasks using analysis of covariance with the covariates age and sex. Results We found significant effects across groups on 21 eye movement characteristics, of which 4 characteristics had large effect sizes. Post hoc multiple comparisons indicated significant differences between the subjects with schizophrenia and healthy controls across all 21 characteristics. On the other hand, no significant difference between the ASD group and healthy control group was found. Instead, the subjects with ASD showed significant differences from the subjects with schizophrenia in 5 eye movement characteristics during the free viewing and smooth pursuit eye movements. Conclusions The present results suggest that eye movement abnormalities in the subjects with ASD are different from those with schizophrenia and that the tasks in this study are suitable to detect eye movement abnormality in schizophrenia. Thus, the eye movement examinations used here may distinguish subjects with schizophrenia from those with ASD.

Background/Aims: Age-related changes in impairments in activities of daily living (ADL) in older adults with very mild Alzheimer’s disease (vmAD) have been scarcely explored. We clarified the characteristics of ADL impairment and examined how ADL impairments differed by age in such patients compared with community-dwelling cognitively normal older adults. Methods: The participants were 107 older adults with vmAD (Mini-Mental State Examination [MMSE] score ≥24), all of whom were first-visit outpatients at the Dementia Clinic of the Department of Neuropsychiatry, Kumamoto University Hospital. The controls were 682 community-dwelling older adults who participated in the 3rd Nakayama Study with MMSE score ≥24. We examined the association of instrumental and basic ADL (IADL and BADL, respectively) independence with the odds of vmAD using multiple logistic regression analysis and determined differences in ADL impairment by age using age- and sex-matched analysis. Results: Impairments in handling finances (OR 57.08), managing medication (OR 5.13), and dressing (OR 3.35; BADL) were associated with greater odds of vmAD. Among those aged 65 years and above, there were fewer patients with vmAD than healthy controls who could independently handle finances and medication. Among patients with vmAD, the percentages of those who could independently manage shopping, food preparation, and housekeeping only decreased after age 74. Age-related decreases in independence were observed in few BADL items; these, however, were temporary. Conclusions: Patients with vmAD show significantly decreased IADL independence from early old age.

Abstract Background Neologisms are commonly encountered in patients with acute cerebrovascular diseases, particularly in those with Wernicke’s aphasia. However, few studies have investigated primary progressive aphasia with neologisms in neurodegenerative disease. Case presentation We describe the case of a 74-year-old, right-handed man who developed logopenic progressive aphasia (LPA) with neologisms. He was assessed with neuropsychological tests, magnetic resonance imaging, and single-photon emission computed tomography. Neologisms accounted for a relatively large portion of the paraphasic errors in the naming tests performed during the neuropsychological assessment. He had all the diagnostic features of LPA. Notably, the unique feature of this patient was the presentation of neologisms, which are seldom observed in typical LPA. Conclusions Neologisms are considered rare symptoms in patients with early-stage LPA. Our findings in this case report provide new insights into the spectrum of clinical features in LPA.

Background/Objective: Behavioral and psychological symptoms of dementia (BPSD) have been reported to affect caregiver burden in patients with dementia with Lewy bodies (DLB). However, the factor structure of BPSD and the factors that affect caregiver burden in DLB remain unknown. This study sought to classify BPSD and to reveal what type of BPSD affects caregiver burden in patients with DLB.Methods: We collected data on neuropsychiatric inventory-plus (NPI-plus), Zarit Burden Interview (ZBI), Mini-Mental State Examination (MMSE), Lawton's Instrumental Activities of Daily Living and Physical Self-Maintenance Scale (IADL/PSMS), age, and sex of 102 patients with probable DLB. An exploratory factor analysis of 13 items of the NPI-plus was carried out to classify BPSD. Multivariate regression analyses were conducted to extract the clinical variables related to caregiver burden, including factors resulting from the aforementioned factor analysis.Results: The mean age and MMSE score were 78.6 (5.6) and 20.2 (5.2), respectively. Factor analysis revealed four factors of “psychosis,” “affection,” “wakefulness,” and “hyperactivity.” “Psychosis” and “affection” factors as well as MMSE, IADL, and PSMS were significantly associated with ZBI. Multivariate regression analyses revealed that the total score of ZBI was associated with “psychosis,” “affection,” and IADL, that the personal strain score of ZBI was associated with “affection” and IADL, and that the role strain score of ZBI was associated with “wakefulness” and IADL.Conclusions: BPSD in DLB consists of three factors common to Alzheimer's disease and a specific “wakefulness” factor. In addition to IADL, each BPSD factor would affect caregiver burden in different ways in DLB.

This study aimed to clarify the adaptation features of University students exposed to fully online education during the novel coronavirus disease 2019 (COVID-19) pandemic and to identify accompanying mental health problems and predictors of school adaptation. The pandemic has forced many universities to transition rapidly to delivering online education. However, little is known about the impact of this drastic change on students' school adaptation. This cross-sectional study used an online questionnaire, including assessments of impressions of online education, study engagement, mental health, and lifestyle habits. In total, 1,259 students were assessed. The characteristics of school adaptation were analyzed by a two-step cluster analysis. The proportion of mental health problems was compared among different groups based on a cluster analysis. A logistic regression analysis was used to identify predictors of cluster membership. P-values < 0.05 were considered statistically significant. The two-step cluster analysis determined three clusters: school adaptation group, school maladaptation group, and school over-adaptation group. The last group significantly exhibited the most mental health problems. Membership of this group was significantly associated with being female (OR = 1.42; 95% CI 1.06–1.91), being older (OR = 1.21; 95% CI 1.01–1.44), those who considered online education to be less beneficial (OR = 2.17; 95% CI 1.64–2.88), shorter sleep time on weekdays (OR = 0.826; 95% CI 0.683–.998), longer sleep time on holidays (OR = 1.21; 95% CI 1.03–1.43), and worse restorative sleep (OR = 2.27; 95% CI 1.81–2.86). The results suggest that academic staff should understand distinctive features of school adaptation owing to the rapid transition of the educational system and should develop support systems to improve students' mental health. They should consider ways to incorporate online classes with their lectures to improve students' perceived benefits of online education. Additionally, educational guidance on lifestyle, such as sleep hygiene, may be necessary.

The association between primary psychotic disorders emerging in later life and neurodegenerative diseases, including Alzheimer's disease (AD), is controversial. We present two female non-demented cases of psychosis with onset above the age of 60 years. Cases 1 and 2 were aged was 68 and 81 years, respectively. They suffered from persecutory delusions and scored 28 on the Mini-Mental State Examination (MMSE) at the first examination. Although detailed neuropsychological tests detected amnesia, they had preserved daily life function. Brain magnetic resonance imaging, N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) single-photon emission computed tomography, and cardiac [123I]-metaiodobenzylguanidine (123I-MIBG) scintigraphy showed no specific abnormalities in either case. We diagnosed them with very-late-onset schizophrenia-like psychosis (VLOSLP) because there was no evidence that their psychoses were derived from organic diseases or affective disorders. Upon close inspection, the AD biomarkers, cerebrospinal fluid (CSF) testing and Florbetapir F 18 positron emission tomography (PET), were positive in Case 1 and negative in Case 2. Case 1 scored 25 1 year later and 23 2 years later on the MMSE and was finally diagnosed as AD dementia. These two cases suggest that some clinically diagnosed VLOSLPs may be a prodromal AD. Although VLOSLP is a disease entity supposed to be a primary psychotic disorder, some are probably secondary psychosis with insidious neurodegeneration. Advanced biomarkers such as amyloid PET and CSF may contribute to the detection of secondary psychosis from clinically diagnosed VLOSLP.

Background: Erotomania, also known as de Clerambault's syndrome, is characterized by the delusion that a person has fallen in love with the patient. It occasionally appears secondary to psychiatric disorders and organic brain diseases. However, there have been no reports on cases secondary to dementia with Lewy bodies (DLB).Case Presentation: The patient was an 83-year-old woman who lived alone. Mild cognitive impairment appeared at the age of 82 years. Soon after, she had the delusional conviction that her family doctor was in love with her. Her symptoms, such as gradually progressive cognitive impairment, cognitive fluctuations, and parkinsonism, indicated DLB. She was treated with a small dose of antipsychotic agents.Conclusions: This case report suggests the possibility of de Clerambault's syndrome during the early stages of DLB. Further investigations are required to clarify the mechanism and treatment of de Clerambault's syndrome in patients with DLB.

Introduction Alzheimer’s disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for patients with AD bearing PSEN1 mutation (PSEN1-AD) are limited to symptomatic therapies and no established radical treatments are available. Induced pluripotent stem cell (iPSC)-based drug repurposing identified bromocriptine as a therapeutic candidate for PSEN1-AD. In this study, we used an enrichment strategy with iPSCs to select the study population, and we will investigate the safety and efficacy of an orally administered dose of bromocriptine in patients with PSEN1-AD.Methods and analysis This is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted.Ethics and dissemination The proposed trial is conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board (K070). The study results are expected to be disseminated at international or national conferences and published in international journals following the peer-review process.Trial registration number jRCT2041200008, NCT04413344.

Objective: Neurophysiological changes related to meditation have recently attracted scientific attention. We aimed to detect changes in electroencephalography (EEG) parameters induced by a meditative intervention in subjects with post-traumatic residual disability (PTRD), which has been confirmed for effectiveness and safety in a previous study. This will allow us to estimate the objective effect of this intervention at the neurophysiological level. Methods: Ten subjects with PTRD were recruited and underwent psychological assessment and EEG recordings before and after the meditative intervention. Furthermore, 10 additional subjects were recruited as normal controls. Source current density as an EEG parameter was estimated by exact Low Resolution Electromagnetic Tomography (eLORETA). Comparisons of source current density in PTRD subjects after the meditative intervention with normal controls were investigated. Additionally, we compared source current density in PTRD subjects between before and after meditative intervention. Correlations between psychological assessments and source current density were also explored. Results: After meditative intervention, PTRD subjects exhibited increased gamma activity in the left inferior parietal lobule relative to normal controls. In addition, changes of delta activity in the right precuneus correlated with changes in the psychological score on role physical item, one of the quality of life scales reflecting the work or daily difficulty due to physical problems. Conclusions: These results show that the meditative intervention used in this study produces neurophysiological changes, in particular the modulation of oscillatory activity of the brain. Significance: Our meditative interventions might induce the neurophysiological changes associated with the improvement of psychological symptoms in the PTRD subjects. Keywords: EEG, Meditation, eLORETA, PTRD, Gamma band, Delta band

Abstract Aim To explore the characteristics of psychiatric morbidity in chronic pain patients who present with or without fibromyalgia. Methods Patients are referred to our chronic pain clinic from primary medical institutions, as we are a secondary medical institution. Although some patients have chronic pain, they have no clear organic disorder such as rheumatoid arthritis to account for the pain. Among the 367 new patients seen during the period from March 2009 to August 2012, 347 patients underwent psychiatric evaluation in face‐to‐face interviews with mental health specialists before a physical examination. Results Of the 347 patients examined, at least one psychiatric diagnosis was made for 94.6%. The average number of DSM‐IV‐TR diagnoses was 1.46 in the 330 chronic pain patients who had at least one psychiatric diagnosis. The breakdown of the number of psychodiagnoses was one in 60.8%, two in 27.1%, three in 4.9%, and more than three in 2.3% chronic pain patients with or without fibromyalgia. In fibromyalgia patients, the highest relative frequencies were found for somatoform disorders (76%), followed by dysthymic disorder (17%) and major depressive disorder (15%). In patients without fibromyalgia, the highest relative frequencies were found for somatoform disorders (64%), followed by major depressive disorder (15%) and dysthymic disorder (14%). Psychiatric disorders were found in 96.9% of fibromyalgia patients, and in 93.5% of chronic pain patients without fibromyalgia in Japan (no significant difference using chi‐square test). Conclusion Results show that chronic pain patients with or without fibromyalgia are extremely likely to be diagnosed with a psychiatric disorder.

ObjectiveTo investigate the behavioral characteristics of semantic dementia (SD) using an instrument originally developed for patients with autism spectrum disorder.MethodsThe behavioral symptoms of 20 patients with SD and 20 patients with Alzheimer's disease (AD) in both the preclinical state and the dementia state were evaluated using the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS).ResultsThe SD group showed high prevalence in four behaviors related to stereotypy and social impairment: eating very few food items, selfishness, difficulty in recognizing others' feeling and thoughts, and interpreting language literally. Scores on the PARS short version, which is sensitive for diagnosis of autism spectrum disorder, were significantly higher in the dementia state than in the preclinical state in both the SD (11.5 ± 6.0 and 1.7 ± 2.5, respectively; t (19) = 6.7, p < 0.001) and AD (6.9 ± 4.6 and 1.7 ± 2.0, respectively; t (19) = 5.1, p < 0.001) groups. PARS short version scores after dementia onset increased in both the SD and AD groups, although the increase was significantly larger in the SD group (F = 5.6, p = 0.023). Additionally, a significantly higher rate of patients exceeded the cutoff score for autism diagnosis in the dementia state in the SD group (75%) than in the AD group (40%; χ2 = 5.0, p = 0.025). PARS scores in the dementia state were significantly correlated with illness duration (r = 0.46, p = 0.04) and Mini-Mental State Examination scores (r = -0.75, p < 0.001) in the SD group only.ConclusionsAlthough SD and autism spectrum disorder are etiologically distinct diseases, patients with semantic dementia behave like those with autism spectrum disorder. Our findings suggest the symptomatic similarity of the two disorders.

Abstract Dementia with Lewy bodies (DLB) research has seen a significant growth in international collaboration over the last three decades. However, researchers face a challenge in identifying large and diverse samples capable of powering longitudinal studies and clinical trials. The DLB research community has begun to focus efforts on supporting the development and harmonization of consortia, while also continuing to forge networks within which data and findings can be shared. This article describes the current state of DLB research collaborations on each continent. We discuss several established DLB cohorts, many of whom have adopted a common framework, and identify emerging collaborative initiatives that hold the potential to expand DLB networks and diversify research cohorts. Our findings identify geographical areas into which the global DLB networks should seek to expand, and we propose strategies, such as the creation of data‐sharing platforms and the harmonization of protocols, which may further potentiate international collaboration.