Characteristics of very late-onset schizophrenia-like psychosis classified with the biomarkers for Alzheimer's disease: a retrospective cross-sectional study.

OBJECTIVES: We aimed to investigate the association between very late-onset schizophrenia-like psychosis (VLOSLP), a schizophrenia spectrum disorder with an onset of ≥60 years, and Alzheimer's disease (AD) using biomarkers. DESIGN: Retrospective cross-sectional study. SETTING: Neuropsychology clinic of Osaka University Hospital in Japan. PARTICIPANTS: Thirty-three participants were classified into three groups: eight AD biomarker-negative VLOSLP (VLOSLP-AD), nine AD biomarker-positive VLOSLP (VLOSLP+AD), and sixteen amnestic mild cognitive impairment due to AD without psychosis (aMCI-P+AD) participants. MEASUREMENTS: Phosphorylated tau levels in the cerebrospinal fluid and 18F-Florbetapir positron emission tomography results were used as AD biomarkers. Several scales (e.g. the Mini-Mental State Examination (MMSE), Wechsler Memory Scale-Revised (WMS-R) Logical Memory (LM) I and II, and Neuropsychiatric Inventory (NPI)-plus) were conducted to assess clinical characteristics. RESULTS: Those in both VLOSLP-AD and +AD groups scored higher than those in aMCI-P+AD in WMS-R LM I. On the other hand, VLOSLP+AD participants scored in between the other two groups in the WMS-R LM II, with only VLOSLP-AD participants scoring significantly higher than aMCI-P+AD participants. There were no significant differences in sex distribution and MMSE scores among the three groups or in the subtype of psychotic symptoms between VLOSLP-AD and +AD participants. Four VLOSLP-AD and five VLOSLP+AD participants harbored partition delusions. Delusion of theft was shown in two VLOSLP-AD patients and five VLOSLP+AD patients. CONCLUSION: Some VLOSLP patients had AD pathology. Clinical characteristics were different between AD biomarker-positive and AD biomarker-negative VLOSLP, which may be helpful for detecting AD pathology in VLOSLP patients.

Validation of the Japanese version of the Social Functioning in Dementia scale and COVID-19 pandemic's impact on social function in mild cognitive impairment and mild dementia.

OBJECTIVES: We aimed to psychometrically evaluate and validate a Japanese version of the Social Functioning in Dementia scale (SF-DEM-J) and investigate changes in social function in people with dementia during the coronavirus disease-19 (COVID-19) pandemic. DESIGN: We interviewed people with mild cognitive impairment (MCI) and mild dementia and their caregivers during June 2020-March 2021 to validate patient- and caregiver-rated SF-DEM-J and compared their scores at baseline (April 2020 to May 2020) and at 6-8 months (January 2021 to March 2021) during a time of tighter COVID-19 restrictions. SETTING: The neuropsychology clinic in the Department of Psychiatry at Osaka University Hospital and outpatient clinic in the Department of Psychiatry and Neurology at Daini Osaka Police Hospital, Japan. PARTICIPANTS: 103 dyads of patients and caregivers. MEASUREMENTS: SF-DEM-J, Mini-Mental State Examination, Neuropsychiatric Inventory, UCLA Loneliness Scale, and Apathy Evaluation Scale. RESULTS: The scale's interrater reliability was excellent and test-retest reliability was substantial. Content validity was confirmed for the caregiver-rated SF-DEM-J, and convergent validity was moderate. Caregiver-rated SF-DEM-J was associated with apathy, irritability, loneliness, and cognitive impairment. The total score of caregiver-rated SF-DEM-J and the score of Section 2, "communication with others," significantly improved at 6-8 months of follow-up. CONCLUSIONS: The SF-DEM-J is acceptable as a measure of social function in MCI and mild dementia. Our results show that the social functioning of people with dementia, especially communicating with others, improved during the COVID-19 pandemic, probably as a result of adaptation to the restrictive life.

Precise Discrimination for Multiple Etiologies of Dementia Cases Based on Deep Learning with Electroencephalography.

INTRODUCTION: It is critical to develop accurate and universally available biomarkers for dementia diseases to appropriately deal with the dementia problems under world-wide rapid increasing of patients with dementia. In this sense, electroencephalography (EEG) has been utilized as a promising examination to screen and assist in diagnosing dementia, with advantages of sensitiveness to neural functions, inexpensiveness, and high availability. Moreover, the algorithm-based deep learning can expand EEG applicability, yielding accurate and automatic classification easily applied even in general hospitals without any research specialist. METHODS: We utilized a novel deep neural network, with which high accuracy of discrimination was archived in neurological disorders in the previous study. Based on this network, we analyzed EEG data of healthy volunteers (HVs, N = 55), patients with Alzheimer's disease (AD, N = 101), dementia with Lewy bodies (DLB, N = 75), and idiopathic normal pressure hydrocephalus (iNPH, N = 60) to evaluate the discriminative accuracy of these diseases. RESULTS: High discriminative accuracies were archived between HV and patients with dementia, yielding 81.7% (vs. AD), 93.9% (vs. DLB), 93.1% (vs. iNPH), and 87.7% (vs. AD, DLB, and iNPH). CONCLUSION: This study revealed that the EEG data of patients with dementia were successfully discriminated from HVs based on a novel deep learning algorithm, which could be useful for automatic screening and assisting diagnosis of dementia diseases.

Cerebrospinal fluid amyloid beta and response of cognition to a tap test in idiopathic normal pressure hydrocephalus: a case-control study.

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 (Aß) 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 Aß1-42 to Aß1-40 (Aß42/40 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. Aß42/40 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 Aß42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aß42/40 ratio. The association between Aß42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline. CONCLUSIONS: A low CSF Aß42/40 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.

Apathy and right caudate perfusion in idiopathic normal pressure hydrocephalus: A case-control study.

OBJECTIVES: Apathy is prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH), a treatable disorder resulting from ventricular enlargement. We assessed the relationship between apathy and regional cerebral blood flow (rCBF) in patients with iNPH. METHODS: Before lumbo-peritoneal shunt surgery (LPS), 56 iNPH patients were evaluated on apathy and dysphoria subscales of the Neuropsychiatric inventory (NPI), and were divided into two groups according to NPI apathy score: 15 without apathy (iNPH-APA) and 41 with apathy (iNPH+APA). Among iNPH+APA, 29 patients were evaluated for apathy and dysphoria 3 months after LPS, and were divided into two groups on the basis of the change in NPI apathy score: 13 with improvement (iNPH+ImpAPA) and 16 without improvement in apathy (iNPH-ImpAPA). N-isopropyl-p-iodoamphetamine single photon emission computed tomography using the autoradiography method was performed before and after LPS, and rCBF was calculated in 22 regions of interest in the frontal cortex, basal ganglia, and limbic system. RESULTS: In iNPH+APA, rCBF in the right caudate nuclei before LPS was significantly lower than that in iNPH-APA (P = 0.004; two-sample t test). Between iNPH-ImpAPA and iNPH+ImpAPA, a significant group-by-shunt interaction was observed for rCBF in only the right caudate nuclei (F1, 28  = 11.75, P = 0.002; two-way repeated-measures analysis of variance), with increased rCBF in iNPH+ImpAPA but not in iNPH-ImpAPA. The significant group-by-shunt interaction persisted if change in NPI dysphoria scores was used as a covariate (F1, 27  = 8.33, P = 0.008). CONCLUSIONS: Our findings suggest that right caudate dysfunction might cause apathy in iNPH patients.

Cerebral blood flow and Alzheimer's disease-related biomarkers in cerebrospinal fluid in idiopathic normal pressure hydrocephalus.

AIM: Alzheimer's disease (AD) pathology is highly prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH), and the presence of AD pathology may involve regional cerebral blood flow (rCBF). In this study, we examined the relationship between rCBF and AD-related biomarkers in the cerebrospinal fluid of iNPH patients. METHODS: Patients with iNPH (n = 39) were classified into groups with (iNPH/AD+) (n=15) and without (iNPH/AD-) (n=24) high biomarker probability of AD (i.e. combined low amyloid ß 42 and high total tau in the cerebrospinal fluid). rCBF was quantified in 17 regions of interest by N-isopropyl-p-[123 I]iodoamphetamine single-photon emission computed tomography with the autoradiography method. We compared rCBF between the iNPH/AD- and iNPH/AD+ groups at baseline using a t-test and then compared changes in rCBF after shunt surgery between the groups using a paired t-test and two-way repeated measures ANOVA. RESULTS: At baseline, there were no significant differences in rCBF between the groups in most regions apart from the putamen. After shunt surgery, a significant increase in rCBF in the putamen, amygdala, hippocampus, and parahippocampal gyrus was observed in iNPH/AD- patients. In iNPH/AD+ patients, no significant improvement in rCBF was observed in any region. In repeated measures analysis of variance, a significant group × shunt interaction was observed in the parietal lobe, frontal lobe, posterior cingulate cortex, precuneus, lateral temporal lobe, amygdala, hippocampus, parahippocampal gyrus, and putamen. CONCLUSIONS: Improvement in rCBF after shunt surgery in iNPH/AD+ patients may be poorer than that in iNPH AD- patients.

Changes in brain morphology in patients in the preclinical stage of idiopathic normal pressure hydrocephalus.

BACKGROUND: Specific ventriculomegaly features, including tight high-convexity and medial subarachnoid spaces, are found on magnetic resonance images in patients with idiopathic normal pressure hydrocephalus (iNPH). However, some healthy elderly individuals with no typical triad symptoms of iNPH also exhibit specific magnetic resonance image features of iNPH. Therefore, this study quantitatively clarified the brain morphology of suspected iNPH patients with no objective triad symptoms (iNPH-NOS). METHODS: We recruited patients with suspected iNPH and divided them into two groups based on their iNPH grading scale scores: the iNPH-NOS group and the iNPH with apparent objective triad symptoms (iNPH-AOS) group. Data for normal controls (NC) were taken from the database used in our previous study. We compared the relative volumes of ventricle systems (VS), Sylvian fissures (SF), and sulci at high convexity and the midline (SHM), adjusted by the intracranial volume, of the iNPH-NOS, iNPH-AOS, and NC groups. Additionally, we compared the relative volumes of VS, SF, and SHM in iNPH-NOS patients between their first visit and follow-up 1 year later. RESULTS: Fifteen iNPH-NOS patients and 45 iNPH-AOS patients were recruited, and 24 NCs were found in the database. The relative volumes of VS and SF were significantly smaller than in NCs than in the iNPH-NOS and iNPH-AOS groups, and the relative volume of SHM was significantly larger in NCs. The relative volume of SHM was significantly larger in the iNPH-NOS group than in the iNPH-AOS group, but there were no significant differences in the relative volumes of VS and SF between these groups. In the iNPH-NOS group, the relative volumes of VS and SF were significantly smaller at the first visit than 1 year later, whereas the relative volume of SHM was significantly larger. In 6 of 15 iNPH-NOS patients, objective symptoms appeared during the observation period. CONCLUSIONS: Our results indicate that iNPH-NOS patients were in the transitional stage between normal and iNPH-AOS, both morphologically and clinically.

Advantages of different care services for reducing neuropsychiatric symptoms in dementia patients.

BACKGROUND: It is assumed that care services effectively reduce behavioural and psychological symptoms of dementia (BPSD). However, it is unclear which care services are effective for reducing specific BPSD. The aim of this study was to clarify which care services were recognized by care specialists as being effective for reducing each of 11 BPSD. METHODS: We sent unsigned questionnaires to care specialists in Japan. The questionnaires asked specialists to choose from 12 kinds of care services the most, second-most, and third-most effective service for reducing each of 11 BPSD. The most effective service was scored as 3 points, the second-most was 2 points, and the third-most was 1 point. Specialists were also asked to describe why they chose each service. The 12 kinds of care services were categorized into four categories: (i) home-visit; (ii) outpatient; (iii) short-stay; and (iv) facility. Total scores for each category were analyzed using a two-way anova. The reasons care specialists chose each service were analyzed using morphological analysis, and representative reasons were extracted. RESULTS: A total of 103 questionnaires were returned. Of the four service categories, outpatient services yielded the highest score for reducing apathy (P < 0.001) due to the effectiveness of participating in recreation and receiving stimulation. Facility services yielded the highest score for reducing aberrant motor behaviour (P < 0.001). Short-stay services yielded the lowest score for reducing depression (P < 0.001). For eight other kinds of BPSD, there were no significant differences between home-visit and facility services or between outpatient and facility services. CONCLUSIONS: Care specialists reported that effective care services for reducing BPSD differed among types of BPSD. In-home care services might be effective at reducing many BPSD except for aberrant motor behaviour, suggesting that greater use of in-home care services might enable people with BPSD to live in their homes for longer.

Alpha event-related synchronization after eye closing differs in Alzheimer's disease and dementia with Lewy bodies: a magnetoencephalography study.

BACKGROUND: The electroencephalography (EEG) abnormalities found in patients with dementia with Lewy bodies (DLB) are conflicting. In this study, we used magnetoencephalography, which has higher spatial resolution than electroencephalography, to explore neurophysiological features of DLB that may aid in the differential diagnosis. METHODS: Six patients with DLB, 11 patients with Alzheimer's disease, and 11 age-matched normal subjects were recruited. We investigated alterations in the ratio of event-related synchronization (ERS) in the alpha band after eye-closing. RESULTS: Although the averaged ratio change of alpha ERS after eye-closing appeared predominantly in the posterior brain regions in all study groups, DLB patients had the weakest ratio change of alpha ERS. In particular, DLB patients exhibited a significantly reduced ratio change of alpha ERS in the bilateral inferior temporal gyrus, right occipital pole, and left parieto-occipital cortex compared to Alzheimer's disease patients or normal controls. CONCLUSION: Our findings indicated that a reduced ratio change of alpha ERS in the posterior brain regions elicited by eye-closing is a brain electromagnetic feature of DLB.

Utilizing portable electroencephalography to screen for pathology of Alzheimer's disease: a methodological advancement in diagnosis of neurodegenerative diseases.

Background: The 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. Methods: This 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. Results: The 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. Conclusions: Our 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.

A deep learning model for the detection of various dementia and MCI pathologies based on resting-state electroencephalography data: A retrospective multicentre study.

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.

Normalized Power Variance: A new Field Orthogonal to Power in EEG Analysis.

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.

Characteristics of very late-onset schizophrenia-like psychosis as prodromal dementia with Lewy bodies: a cross-sectional study.

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.

Impact of age on the cerebrospinal fluid spaces: high-convexity and medial subarachnoid spaces decrease with age.

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.

Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease: a multicenter study.

OBJECTIVE: Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also aimed to determine the cutoffs for amyloid positivity for quantitative measures by investigating the agreement between quantitative and visual assessments. METHODS: Ninety-nine patients suspected of having AD underwent 18F-florbetapir PET at five institutions. Site-specialized physicians provided a diagnosis of AD or non-AD with a percentage estimate of their confidence and their plan for patient management in terms of medication, prescription dosage, additional diagnostic tests, and care planning both before and after receiving the amyloid imaging results. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by four board-certified nuclear medicine physicians. The PET images were also quantitatively analyzed using the standardized uptake value ratio (SUVR) and Centiloid (CL) scale. RESULTS: Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ2 = 5.334, p = 0.0209). Amyloid PET results also resulted in at least one change to the patient management plan in 42 patients (42%), mainly medication (20 patients, 20%) and care planning (25 patients, 25%). Receiver-operating characteristic analysis determined the best agreement of the quantitative assessments and visual interpretation of PET scans to have an area under the curve of 0.993 at an SUVR of 1.19 and CL of 25.9. CONCLUSION: Amyloid PET using 18F-florbetapir PET had a substantial clinical impact on AD and non-AD diagnosis and on patient management by enhancing diagnostic confidence. In addition, the quantitative measures may improve the visual interpretation of amyloid positivity.

Case Report: De Clerambault's Syndrome in Dementia With Lewy Bodies.

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.

Characteristics of behavioral symptoms in right-sided predominant semantic dementia and their impact on caregiver burden: a cross-sectional study.

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.

Repurposing bromocriptine for Aß metabolism in Alzheimer's disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer's disease with presenilin 1 (PSEN1) mutations.

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.