[Cotard's Syndrome in Three Patients with Schizophrenia--Pathology of Involutional and Senile-onset Endogenous Psychosis].

A large number of case studies on Cotard's syndrome have reported that this syndrome develops after repeated episodes of depression in the presenile stage of life. Therefore, it has been defined as a severe type of affective spectrum disorder. This report describes three patients who exhibited symptoms characteristic of Cotard's syndrome, such as negative thoughts and delusions of immortality, in the presenile and senile stages of their lives. They also had a history of long-term treatment for schizophrenia based on a diagnosis in early adulthood. Our review of reports on Cotard's syndrome revealed that the syndrome is more prevalent among presenile and senile female patients, who initially visit psychiatrists in their involutional and presenile stages of life with symptoms of an affective spectrum disorder, and later exhibit the symptoms of Cotard's syndrome. The results of the three case studies suggest that biological factors related to aging and sex differences may be associated with the development of Cotard's syndrome, regardless of the primary disorder. The pathology of "involutional and senile-onset endogenous psychosis," including Cotard's syndrome, is also discussed.

Neuropsychosocial features of very mild Alzheimer's disease (CDR 0.5) and progression to dementia in a community: the Tajiri project.

The borderline condition between normal aging and dementia should be detected to predict further deterioration. The authors cross-sectionally analyzed neuropsychological data, memory complaints, and social activities for community-dwelling older adults. The rate of decline from Clinical Dementia Rating (CDR) 0.5 to dementia during a 3-year interval was also analyzed. Short-term memory rather than long-term memory was found to be sensitive in distinguishing those with CDR 0 from those with CDR 0.5. Relatives' observations of memory decline rather than subjective memory complaints were significantly different. Participants with CDR 0.5 reported fewer problems with social activities than did their relatives. Ten of the 29 CDR 0.5 participants (34.5%) showed cognitive decline, the decliners showing lower scores on short-term memory and orientation at the baseline condition. The neuropsychological data showed CDR 0.5 to be similar to very mild Alzheimer's disease. It would be better if subjective complaints were excluded from the criteria of the borderline condition.

[The Japanese version of RBANS (Repeatable Battery for the Assessment of Neuropsychological Status)].

In Japan, neuropsychological assessment of dementing illnesses has been done mainly using Mini-Mental State Examination (MMSE) and a revised version of Hasegawa Dementia Scale (HDS-R). However, because of a lack of appropriately designed test domains, early detection of senile dementia and/or cognitive impairment is hardly possible, even if using these batteries. This paper is to introduce a Japanese Version of RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) which was originally developed by Randolph and revised by us. The entire battery of Japanese Version RBANS took less than 30 minutes to administer, and yielded scaled scores for five cognitive domains such as immediate memory, visuospatial/constructional ability, language, attention, and delayed memory. On RBANS, abnormal cognitive decline in the older adult was much easily detected, being compared to MMSE and HDS-R: 52 normal volunteer subjects ranging from 24 to 80 years old showed a significant (p < 0.05 on t test) impairment of delayed and immediate memories due to ageing. The aged (60-79) subjects with average scores of MMSE and HDS-R being over 25, significantly showed impairment of both immediate memory (list and story learnings) and delayed memory (list, story and figure recalls). The present data suggest that the Japanese Version RBANS is useful for both detecting and characterizing early dementia, and should be widely utilized for a neuropsychological screening battery in the clinical practice throughout Japan.

[Nursing home directors' attitude toward medical decision-making and medical care for elderly people with dementia].

Medical decision-making involving elderly people with dementia often troubles care providers in Japan. Meanwhile, little attention has been paid to the routine medical care of nondementia illnesses in such patients. To understand the current situation surrounding the issue, we conducted a postal survey with nursing home directors across the nation. A self-administered questionnaire was sent to 1,117 randomly selected nursing homes, one third of all such facilities in Japan, and 502 (44.9%) responded. Of the respondents, 291 (58.0%) said more than a half of their residents have difficulties in daily life because of dementia. Less than 20% of the facilities said that they routinely confirm residents' preferences in writing when they are admitted concerning each of the following items; terminal care, medical information disclosure, leaving a will, funerals and application for the guardian system. 206 (41.0%) facilities have difficulties in finding a hospital for the elderly with dementia when necessary. The Mann-Whitney U test showed no significant relation between facilities' characteristics and their difficulties in finding a hospital that would admit demented patients. At present, a number of nursing homes confirm their residents' preferences only some time after they are admitted. However, the way of confirming seems inappropriate under the circumstances in which more than a majority of residents have difficulties in daily life due to dementia. Though more than a half of nursing homes have difficulties in finding a hospital that would admit dementia patients, no significant relation was found between the difficulties and the facility-hospital relation. The problem seems to lie in the acceptance mechanism of hospitals.

Differentiation of first-episode schizophrenia patients from healthy controls using ROI-based multiple structural brain variables.

BACKGROUND: Brain morphometric measures from magnetic resonance imaging (MRI) have not been used to discriminate between first-episode patients with schizophrenia and healthy subjects. METHODS: Magnetic resonance images were acquired from 34 (17 males, 17 females) first-episode schizophrenia patients and 48 (24 males, 24 females) age- and parental socio-economic status-matched healthy subjects. Twenty-nine regions of interest (ROI) were measured on 1-mm-thick coronal slices from the prefrontal and central parts of the brain. Linear discriminant function analysis was conducted using standardized z scores of the volumes of each ROI. RESULTS: Discriminant function analysis with cross-validation procedures revealed that brain anatomical variables correctly classified 75.6% of male subjects and 82.9% of female subjects, respectively. The results of the volumetric comparisons of each ROI between patients and controls were generally consistent with those of the previous literature. CONCLUSIONS: To our knowledge, this study provides the first evidence of MRI-based successful classification between first-episode patients with schizophrenia and healthy controls. The potential of these methods for early detection of schizophrenia should be further explored.

Enhanced carbonyl stress in a subpopulation of schizophrenia.

CONTEXT: Various factors are involved in the pathogenesis of schizophrenia. Accumulation of advanced glycation end products, including pentosidine, results from carbonyl stress, a state featuring an increase in reactive carbonyl compounds (RCOs) and their attendant protein modifications. Vitamin B(6) is known to detoxify RCOs, including advanced glycation end products. Glyoxalase I (GLO1) is one of the enzymes required for the cellular detoxification of RCOs. OBJECTIVES: To examine whether plasma levels of pentosidine and serum vitamin B(6) are altered in patients with schizophrenia and to evaluate the functionality of GLO1 variations linked to concomitant carbonyl stress. DESIGN: An observational biochemical and genetic analysis study. SETTING: Multiple centers in Japan. PARTICIPANTS: One hundred six individuals (45 schizophrenic patients and 61 control subjects) were recruited for biochemical measurements. Deep resequencing of GLO1 derived from peripheral blood or postmortem brain tissue was performed in 1761 patients with schizophrenia and 1921 control subjects. MAIN OUTCOME MEASURES: Pentosidine and vitamin B(6) concentrations were determined by high-performance liquid chromatographic assay. Protein expression and enzymatic activity were quantified in red blood cells and lymphoblastoid cells using Western blot and spectrophotometric techniques. RESULTS: We found that a subpopulation of individuals with schizophrenia exhibit high plasma pentosidine and low serum pyridoxal (vitamin B(6)) levels. We also detected genetic and functional alterations in GLO1. Marked reductions in enzymatic activity were associated with pentosidine accumulation and vitamin B(6) depletion, except in some healthy subjects. Most patients with schizophrenia who carried the genetic defects exhibited high pentosidine and low vitamin B(6) levels in contrast with control subjects with the genetic defects, suggesting the existence of compensatory mechanisms. CONCLUSIONS: Our findings suggest that GLO1 deficits and carbonyl stress are linked to the development of a certain subtype of schizophrenia. Elevated plasma pentosidine and concomitant low vitamin B(6) levels could be the most cogent and easily measurable biomarkers in schizophrenia and should be helpful for classifying heterogeneous types of schizophrenia on the basis of their biological causes.

Alcoholic cerebellar degeneration: a clinicopathological study of six Japanese autopsy cases and proposed potential progression pattern in the cerebellar lesion.

Alcoholic cerebellar degeneration (ACD) is one of the most common neurological complications in alcoholics. As far as we know, however, only four Japanese autopsy cases of ACD have been reported, and only limited clinicopathological data on this disease are now available in Japan. The aims of this study were: (i) to examine the clinicopathological correlation of six Japanese autopsy cases of ACD, including three asymptomatic cases; and (ii) to elucidate the pattern of progression of the cerebellar lesion in ACD. All six alcoholics were histopathologically diagnosed as having "pure" ACD without Wernicke's encephalopathy. The characteristics of the topographical distribution of the cerebellar lesion were as follows. Symptomatic cases (cases 1-3) showed more severe and widespread change than asymptomatic cases (cases 4-6). Even in case 6, which had the mildest lesion, the anterior vermis developed a moderate change (Purkinje cell loss and narrowing of the molecular layer). In cases 4 and 5 with more severe and widespread lesions, the superior and posterior vermis and the adjacent regions of the superior hemisphere, including the anterior lobe and simple lobule, were involved. In all symptomatic cases, the anterior superior hemisphere had severe lesions involving the granular cell layer. In contrast to asymptomatic cases, all symptomatic cases also had severe to moderate lesions in the anterior inferior hemisphere. In cases 1 and 2 with the most severe lesions, the moderate to severe changes were distributed in the posterior and inferior portions of both the vermis and hemisphere. These findings suggest that in ACD, severe lesions successively develop: (i) in the anterior superior vermis; (ii) anterior superior hemisphere; (iii) anterior inferior hemisphere; and (iv) anterior inferior vermis. In addition, cerebellar symptoms may frequently occur if the anterior superior hemisphere and anterior inferior hemisphere, in addition to the anterior superior vermis, are involved.

Frequency and clinicopathological characteristics of alcoholic cerebellar degeneration in Japan: a cross-sectional study of 1,509 postmortems.

Alcoholic cerebellar degeneration (ACD) is a pivotal neurological complication in alcoholics. However, although there are a few autopsy reports and some data on its frequency, it is considered very rare in Japan. The aims of this study were (1) to estimate the frequency of the disease in Japanese autopsy cases, and (2) to examine the clinicopathological features of symptomatic and asymptomatic cases of ACD. We reviewed the records of 1,509 Japanese autopsies obtained from three autopsy series in Japan, and selected all 55 cases (3.6%) with alcoholism. On neuropathological reexamination, ACD was confirmed in six male alcoholics [0.4% of all subjects; 10.9% of all alcoholics; mean age at death 59.3+/-13.4 years (+/- SD)], including three asymptomatic cases. These frequencies were much lower than some previous Western findings, but more common than that has been expected in Japan. The frequencies of memory impairment and ataxia in ACD cases were significantly higher than those in alcoholics without any alcohol-related pathologies. In ACD cases, loss of Purkinje cells, narrowing of the width of the molecular layer, and tissue rarefaction in the granular layer were observed in the anterior and superior portions of the vermis of the cerebellum. In adjacent regions, the Purkinje cell and molecular layers were more mildly affected. The distribution of severely affected regions was more restricted in the asymptomatic cases than in the symptomatic cases. This study confirmed the frequency of asymptomatic cerebellar degeneration in alcoholics, suggesting that early intervention in alcoholism in the subclinical phase is important to prevent the development of cerebellar symptoms.

Distribution of cerebral cortical lesions in diffuse neurofibrillary tangles with calcification: a clinicopathological study of four autopsy cases showing prominent parietal lobe involvement.

We investigated clinicopathologically four Japanese autopsy cases of diffuse neurofibrillary tangles with calcification (DNTC), which has been believed to be characterized by temporal or temporofrontal circumscribed lobar atrophy, and examined the distribution of their cerebral cortical lesions using hemisphere specimens. The lesions were classified into three categories (slight, moderate, and severe). Severe lesions were present in the temporal lobes and insular gyri of all four cases, consistent with the studies reported to date. In contrast, severe lesions were encountered in the parietal lobe of case 1 and moderate lesions were found in the parietal lobes of cases 2-4. Furthermore, moderate lesions of the precentral gyrus were present in cases 2-4, and moderate lesions of the postcentral gyrus were encountered in all four cases. We postulate that the distribution of cerebral cortical lesions in DNTC is more widespread than previously assumed. Our data also indicate that the unusual clinical signs of DNTC reported by several Japanese researchers, including parietal signs such as apraxia and agnosia, are roughly consistent with the topographic distribution of cerebral cortical lesions in DNTC elucidated in this study.

Identification of a male schizophrenic patient carrying a de novo balanced translocation, t(4; 13)(p16.1; q21.31).

Herein is reported the case of a male patient with schizophrenia who displayed a de novo balanced translocation between the short arm of chromosome 4 and the long arm of chromosome 13, t(4; 13)(p16.1; q21.31). The 4p16.1 region is where the causative gene (WFS1) for Wolfram syndrome has been mapped. In Wolfram syndrome, approximately 60% of patients suffer from major mental illness. The other breakpoint, chromosome 13q21.31, is another region where previous linkage studies have repeatedly detected linkage to schizophrenia. The documentation of the present case could therefore provide a valuable resource for identifying disease susceptibility genes by localizing the breakpoints.

Parkinson's disease mimicking senile dementia of the Alzheimer type: a clinicopathological study of four autopsy cases.

This report concerns four Japanese autopsy cases of Parkinson's disease (PD) mimicking senile dementia of the Alzheimer type. Three patients with a clinical diagnosis of senile dementia of the Alzheimer type developed memory disturbance as the initial sign, and a patient with a clinical diagnosis of atypical senile dementia presented with hallucination and delusion as the initial sign. Dementia was evident in all four patients, and slight parkinsonism appeared in the middle to late stages of the disease in two patients. Macroscopical examination of the brain disclosed slight depigmentation of the substantia nigra and prominent depigmentation of the locus ceruleus in all four cases. Histological examination of the four patients showed neuronal loss with astrocytosis and the appearance of Lewy bodies in the substantia nigra, locus ceruleus, and dorsal vagal nucleus. The nucleus basalis of Meynert was involved in three cases, in which this structure was examined. The total Lewy body scores of the four cases were 1 in three cases and 0 in the other, compatible with PD. Massive appearance of senile plaques, consistent with Braak stage C, was found in one case, and the slight appearance of senile plaques, consistent with Braak stage A, was evident in two cases. One case had no evidence of senile plaques. In all four cases, slight neurofibrillary changes were present in the limbic areas, compatible with Braak stages II to III. Based on these clinicopathological findings and a review of the literature, we concluded that PD simulating Alzheimer's disease without overt parkinsonism rarely exists. Furthermore, we postulate that the clinical features of PD are more widespread than previously believed.