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.

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.

Thalamic pulvinar metabolism, sleep disturbances, and hallucinations in dementia with Lewy bodies: Positron emission tomography and actigraphy study.

OBJECTIVES: Although sleep disturbances are prevalent among patients with dementia with Lewy bodies (DLB), their neural substrates remain unclear. We aimed to clarify the neural substrates of sleep disturbances in patients with DLB. METHODS: We evaluated sleep disturbances, neuropsychiatric symptoms, and brain glucose metabolism in 22 patients with probable DLB using actigraphy, the Neuropsychiatric Inventory (NPI), and 18 F-fluorodeoxyglucose (FDG) positron emission tomography, respectively. Total sleep time (TST) and average activity count per minute (AAC) during sleep were calculated for seven consecutive days via actigraphy. We investigated associations between FDG uptake and the actigraphy parameters using Statistical Parametric Mapping version 12b. Spearman's rank correlation coefficients were used to investigate associations among TST, AAC, and clinical symptoms. The level of statistical significance was set at P < .05. P values were adjusted using the Benjamini-Hochberg method for multiple comparisons. This study was registered with ClinicalTrials.gov (NCT00776347). RESULTS: TST exhibited a significant positive association with FDG uptake in the bilateral orbitofrontal cortex and left thalamus, while AAC exhibited a significant negative association with FDG uptake in the left thalamus and the left parieto-occipital region. FDG uptake in the left pulvinar was associated with both TST and AAC. In addition, TST exhibited a significant negative association with the NPI hallucinations score (r = -0.66, P = .001), while AAC exhibited significant positive associations with the NPI delusions (r = 0.70, P < .001) and hallucinations (r = 0.63, P = .002) scores. CONCLUSIONS: TST and bodily activity during sleep are associated with dysfunction of the left pulvinar and the severity of hallucinations in patients with DLB.

Association between milder brain deformation before a shunt operation and improvement in cognition and gait in idiopathic normal pressure hydrocephalus.

We investigated the association between the degree of deformation of the brain before shunt operation and improvement of gait and cognitive impairment after shunt operation in 16 patients with idiopathic normal pressure hydrocephalus (iNPH). We evaluated gait and cognitive impairment and measured the cerebrospinal fluid volume in the ventricles/sylvian fissure (vVS) and the subarachnoid space at high convexity/midline areas (vHCM) using MR images with voxel-based morphometry before and 3 months after shunt operation. We used the ratio of vVS to vHCM (vVS/vHCM) as an index of the severity of brain deformation. After shunt operation, improvements were observed in gait, as shown by the Timed Up and Go (TUG) test and 10-meter reciprocating walking test (WT), and in cognitive function, as shown by the Mini-Mental State Examination, Alzheimer Disease Assessment Scale, Frontal Assessment battery (FAB), and Trail Making test A (TMT-A). The vVS/vHCM ratio was negatively correlated with improvement of the FAB, TMT-A and TUG. Preoperative vVS/vHCM was not significantly correlated with preoperative clinical assessments. The rate of change of vVS/vHCM was positively correlated with improvement in the WT. The improvements of gait and cognitive function were larger in iNPH patients with milder deformation of the brain before shunt operation.

Predictors of prolonged hospital stay for the treatment of severe neuropsychiatric symptoms in patients with dementia: a cohort study in multiple hospitals.

BACKGROUND: Long hospitalization is often needed to treat severe behavioral and psychological symptoms of dementia (BPSD), which places heavy demands on hospital resources. Consequently, patients with severe BPSD usually wait for a long time to be admitted. There is a need to identify factors related to long hospitalization to better manage resources of a psychiatric hospital. METHODS: We surveyed 150 consecutive patients hospitalized in the neuropsychiatric units of three hospitals for treatment of BPSD from 11 May 2009 to 30 November 2010. Only patients with reliable relatives were included in the study. We evaluated data of the patients (demographics, cognitive impairment, activities of daily living, causal disease for dementia, dementia severity, and the amount of pension), their primary caregivers (demographics and care burden), and their doctors' years of experience in treating dementia. We followed up to 180 days and assessed the effect of these factors on the length of stay. RESULTS: Of the 150 patients, 104 were discharged within 180 days and 46 were hospitalized for more than 180 days. Average length of stay for patients was 110.4 ± 58.1 days. In both univariate and multivariate Cox proportional hazard analyses, length of stay was longer for patients with smaller pensions and patients whose doctors had fewer years of experience in treating dementia. Length of stay was not found to be associated with any of the other variables. CONCLUSIONS: Patients with smaller pensions and whose doctors had less experience in treating dementia tended to require longer hospitalization.

Reversibility of brain morphology after shunt operations and preoperative clinical symptoms in patients with idiopathic normal pressure hydrocephalus.

AIM: Brain deformations might prevent clinical symptoms from worsening in patients with idiopathic normal pressure hydrocephalus (iNPH). We investigated the relationship between reversibility of brain morphology after shunt operations and preoperative clinical symptoms in iNPH patients. METHODS: Using head magnetic resonance images with voxel-based morphometry, we measured the cerebrospinal fluid volume in the combined areas of the lateral and third ventricles and Sylvian fissure (the volume of the ventricles and Sylvian fissure (vVS)) and the volume of the subarachnoid space at high convexity and midline areas (vHCM) before and 1 year after lumboperitoneal shunt operations in 12 patients with shunt-responsive iNPH. We used the ratio of normalized vVS to normalized vHCM (nvVS/nvHCM) as an index of the severity of the brain deformation. The degree of reversibility of the brain morphology after the shunt operation was defined as the change ratio of the preoperative nvVS/nvHCM to the postoperative nvVS/nvHCM (CR-nvVS/nvHCM). Higher CR-nvVS/nvHCM values indicated more improvement in the brain deformation. In addition, we rated the severity of the white matter lesions on the preoperative magnetic resonance images based on the Fazekas scale. Dependency in activities of daily living, gait and cognition were evaluated before and 1 year after the shunt operations. RESULTS: After the shunt operations, the nvVS/nvHCM and nvVS decreased significantly, and nvHCM increased significantly. The CR-nvVS/nvHCM negatively correlated with the preoperative severity of dependency in activities of daily living, gait and cognitive impairments. The CR-nvVS/nvHCM negatively correlated with the Fazekas scale, but not with age, duration of the disease and cerebrospinal fluid pressure. CONCLUSIONS: Reversibility of brain morphology, which varied among iNPH patients, would prevent clinical symptoms from worsening in iNPH patients. The presence of white matter lesions reduced the degree of reversibility of the brain deformations in iNPH patients.

Predicting postoperative delirium after cardiovascular surgeries from preoperative portable electroencephalography oscillations.

Introduction: Postoperative 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. Objective: We aimed to develop an accurate algorithm to predict POD using EEG data obtained from portable device. Methods: We recruited 128 patients who underwent scheduled cardiovascular surgery. Cognitive function assessments were conducted, and portable EEG recordings were obtained prior to surgery. Results: Among 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. Discussion: This 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.

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.

Development of postoperative delirium prediction models in patients undergoing cardiovascular surgery using machine learning algorithms.

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 < 4), index of activities of daily living (Barthel Index < 100), history of stroke or cerebral hemorrhage, and eGFR (estimated glomerular filtration rate) < 60 were selected to develop delirium prediction models. The Extra-trees model had the best area under the receiver operating characteristic curve (0.76 [standard deviation 0.11]; sensitivity: 0.63; specificity: 0.78). XGBoost showed the highest sensitivity (AUROC, 0.75 [0.07]; sensitivity: 0.67; specificity: 0.79). Machine learning algorithms could predict post-cardiovascular delirium using preoperative data.Trial registration: UMIN-CTR (ID; UMIN000049390).

Classification of delusions in Alzheimer's disease and their neural correlates.

BACKGROUND: Previous findings on neural correlates of delusion in Alzheimer's disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single-photon emission computed tomography data. METHODS: We selected AD patients with delusions from our consecutive outpatients from 2004 to 2010. In this study, eight types of delusions were evaluated with Neuropsychiatric Inventory and classified by factor analysis. Twenty-five of the patients also had single-photon emission computed tomography data, which we used to assess the relationships between cerebral regions of hypoperfusion and hyperperfusion and each classified delusion. The relations were assessed using Statistical Parametric Mapping with normalization to the white matter cerebral blood flow. RESULTS: The delusions were classified into three factors. Factor 1 consisted of a belief that his/her house is not his/her home, phantom boarder symptom, delusion of abandonment, and belief that one's spouse or others are not who they claim to be. Factor 1 was related to hypoperfusion in the right temporal pole and hyperperfusion in the medial frontal and precentral regions. Factor 2 consisted of delusion relating to the television and delusion of persecution. Factor 2 was related to hypoperfusion in the precuneus and hyperperfusion in the insula and thalamus. Factor 3 consisted of delusion of abandonment and delusional jealousy. Factor 3 was related to hypoperfusion in the right inferior temporal and frontal regions and hyperperfusion in the middle frontal gyrus, insula and posterior cingulate gyrus. Delusion of theft was not included in any factors, and it was related to hypoperfusion in the bilateral thalami and left posterior cingulate gyrus and hyperperfusion in the left inferior frontal regions and anterior cingulate gyrus. CONCLUSIONS: Delusions in AD were classifiable, and each classified delusion was related to different neural networks.

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 Behavioral and Psychological Symptoms on Caregiver Burden in Patients With Dementia With Lewy Bodies.

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.

KIBRA genetic polymorphism influences episodic memory in Alzheimer's disease, but does not show association with disease in a Japanese cohort.

BACKGROUND/AIMS: A single-nucleotide polymorphism (SNP) in the KIBRA gene, rs17070145, was reported to be significantly associated with episodic memory in cognitively normal cohorts. This observation has expanded genetic studies on KIBRA to Alzheimer's disease (AD). Importantly, the association between KIBRA and episodic memory in AD has never been addressed. In this study, we investigated whether the KIBRA rs17070145 SNP influences AD episodic memory and the disease in a Japanese cohort. METHODS: Blood samples from 346 AD patients and 375 normal cognitive controls were collected and genotyped for rs17070145. Episodic memory was measured in 32 AD patients, diagnosed for the first time, by use of the Rivermead Behavioral Memory Test (RBMT). RESULTS: We found that KIBRA C allele carriers scored significantly lower than KIBRA non-C carriers on both RBMT total profile score (p = 0.042, effect size = 0.84) and RBMT total screening score (p < 0.001, effect size = 1.42). The KIBRA gene did not show association with AD in our Japanese cohort. CONCLUSION: Our results evidence a strong association between the KIBRA gene and episodic memory impairment in AD, but show no influence on AD in our Japanese cohort. We propose that KIBRA might have an effect similar to cognitive reserve.

Normalized power variance of eLORETA at high-convexity area predicts shunt response in idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric disease characterized by gait disturbance, cognitive deterioration and urinary incontinence associated with excessive accumulation of cerebrospinal fluid (CSF) in the brain ventricles. These symptoms, in particular gait disturbance, can be potentially improved by shunt operation in the early stage of the disease, and the intervention associates with a worse outcome when performed late during the course of the disease. Despite the variable outcome of shunt operation, noninvasive presurgical prediction methods of shunt response have not been established yet. In the present study, we used normalized power variance (NPV), a sensitive measure of the instability of cortical electrical activity, to analyze cortical electrical activity derived from EEG data using exact-low-resolution-electromagnetic-tomography (eLORETA) in 15 shunt responders and 19 non-responders. We found that shunt responders showed significantly higher NPV values at high-convexity areas in beta frequency band than non-responders. In addition, using this difference, we could discriminate shunt responders from non-responders with leave-one-subject-out cross-validation accuracy of 67.6% (23/34) [positive predictive value of 61.1% (11/18) and negative predictive value of 75.0% (12/16)]. Our findings indicate that eLORETA-NPV can be a useful tool for noninvasive prediction of clinical response to shunt operation in patients with iNPH.

Effects of donepezil on sleep disturbances in patients with dementia with Lewy bodies: An open-label study with actigraphy.

We investigated whether donepezil, a cholinesterase inhibitor, can be used to treat sleep disturbances in patients with dementia with Lewy bodies (DLB). Sleep disturbances were evaluated with the sleep disturbances item of the Neuropsychiatric inventory (NPI) and an actigraph in 16 DLB patients and 24 normal elderly control (NC) subjects. The presence/absence of nine kinds of sleep symptoms, such as dream enactment, were also evaluated in the DLB patients. The DLB patients were then given 5mg/day donepezil for 14 weeks and evaluated again. Eight of the 16 DLB patients had some sleep disturbances before taking donepezil. The actigraphy data indicated that average activity count per minute in sleep (AAC), which reflects body activity at night, was significantly higher and total sleep time was significantly longer in DLB patients than in NC subjects. The NPI sleep disturbances score significantly improved and the number of DLB patients who had sleep disturbances decreased after taking donepezil. The actigraphy results indicate that the sum of all wake epochs within the sleep period, which reflects the degree of fragmented sleep, and the AAC decreased in the DLB patients after donepezil treatment. These results indicate that donepezil treatment reduced sleep disturbances in DLB patients.

Noninvasive prediction of shunt operation outcome in idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, cognitive deterioration and urinary incontinence in elderly individuals. These symptoms can be improved by shunt operation in some but not all patients. Therefore, discovering predictive factors for the surgical outcome is of great clinical importance. We used normalized power variance (NPV) of electroencephalography (EEG) waves, a sensitive measure of the instability of cortical electrical activity, and found significantly higher NPV in beta frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2) in shunt responders compared to non-responders. By utilizing these differences, we were able to correctly identify responders and non-responders to shunt operation with a positive predictive value of 80% and a negative predictive value of 88%. Our findings indicate that NPV can be useful in noninvasively predicting the clinical outcome of shunt operation in patients with iNPH.

EEG and Neuronal Activity Topography analysis can predict effectiveness of shunt operation in idiopathic normal pressure hydrocephalus patients.

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by gait disturbance, cognitive impairment and urinary incontinence that affect elderly individuals. These symptoms can potentially be reversed by cerebrospinal fluid (CSF) drainage or shunt operation. Prior to shunt operation, drainage of a small amount of CSF or "CSF tapping" is usually performed to ascertain the effect of the operation. Unfortunately, conventional neuroimaging methods such as single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), as well as electroencephalogram (EEG) power analysis seem to have failed to detect the effect of CSF tapping on brain function. In this work, we propose the use of Neuronal Activity Topography (NAT) analysis, which calculates normalized power variance (NPV) of EEG waves, to detect cortical functional changes induced by CSF tapping in iNPH. Based on clinical improvement by CSF tapping and shunt operation, we classified 24 iNPH patients into responders (N = 11) and nonresponders (N = 13), and performed both EEG power analysis and NAT analysis. We also assessed correlations between changes in NPV and changes in functional scores on gait and cognition scales before and after CSF tapping. NAT analysis showed that after CSF tapping there was a significant decrease in alpha NPV at the medial frontal cortex (FC) (Fz) in responders, while nonresponders exhibited an increase in alpha NPV at the right dorsolateral prefrontal cortex (DLPFC) (F8). Furthermore, we found correlations between cortical functional changes and clinical symptoms. In particular, delta and alpha NPV changes in the left-dorsal FC (F3) correlated with changes in gait status, while alpha and beta NPV changes in the right anterior prefrontal cortex (PFC) (Fp2) and left DLPFC (F7) as well as alpha NPV changes in the medial FC (Fz) correlated with changes in gait velocity. In addition, alpha NPV changes in the right DLPFC (F8) correlated with changes in WMS-R Mental Control scores in iNPH patients. An additional analysis combining the changes in values of alpha NPV over the left-dorsal FC (∆alpha-F3-NPV) and the medial FC (∆alpha-Fz-NPV) induced by CSF tapping (cut-off value of ∆alpha-F3-NPV + ∆alpha-Fz-NPV = 0), could correctly identified "shunt responders" and "shunt nonresponders" with a positive predictive value of 100% (10/10) and a negative predictive value of 66% (2/3). In contrast, EEG power spectral analysis showed no function related changes in cortical activity at the frontal cortex before and after CSF tapping. These results indicate that the clinical changes in gait and response suppression induced by CSF tapping in iNPH patients manifest as NPV changes, particularly in the alpha band, rather than as EEG power changes. Our findings suggest that NAT analysis can detect CSF tapping-induced functional changes in cortical activity, in a way that no other neuroimaging methods have been able to do so far, and can predict clinical response to shunt operation in patients with iNPH.

Different characteristics of cognitive impairment in elderly schizophrenia and Alzheimer's disease in the mild cognitive impairment stage.

We compared indices of the revised version of the Wechsler Memory Scale (WMS-R) and scaled scores of the five subtests of the revised version of the Wechsler Adult Intelligence Scale (WAIS-R) in 30 elderly schizophrenia (ES) patients and 25 Alzheimer's disease (AD) patients in the amnestic mild cognitive impairment (aMCI) stage (AD-aMCI). In the WMS-R, attention/concentration was rated lower and delayed recall was rated higher in ES than in AD-aMCI, although general memory was comparable in the two groups. In WAIS-R, digit symbol substitution, similarity, picture completion, and block design scores were significantly lower in ES than in AD-aMCI, but the information scores were comparable between the two groups. Delayed recall and forgetfulness were less impaired, and attention, working memory and executive function were more impaired in ES than in AD-aMCI. These results should help clinicians to distinguish ES combined with AD-aMCI from ES alone.