Clinical and brain structural effects of the Illness Management and Recovery program in middle-aged and older patients with schizophrenia.

AIMS: In this study, we implemented the Illness Management and Recovery (IMR) program for middle-aged and older patients with schizophrenia hospitalized for long periods and assessed the effect of the IMR program on psychiatric symptoms and psychosocial function. The effects of the IMR program on brain structure were also evaluated. METHODS: The IMR program was implemented for 19 patients with schizophrenia; 17 patients with schizophrenia receiving treatment as usual (TAU) were also recruited as controls. In all patients, mean age was 61.4 years (range, 50-77 years) and mean hospitalization duration was 13.1 years (range, 1-31 years) at enrollment. Structural magnetic resonance images and Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores as clinical variables were obtained at the beginning and end of the IMR program. Longitudinal analyses were performed to compare the effects of the IMR program on clinical symptoms and cortical thickness in the superior temporal gyrus (STG) between the IMR and TAU groups. RESULTS: Significant improvements in GAF scores and the total, Insight and Judgment, and Positive components of the PANSS were found in the IMR group compared with the TAU group. Cortical thickness in the left STG was preserved in the IMR group compared with the TAU group. CONCLUSIONS: This is the first report demonstrating the effectiveness of the IMR program for improving psychotic symptoms and psychosocial function and protecting brain structure in middle-aged and older inpatients with schizophrenia hospitalized for long periods.

Anti-epileptic drugs improved serial 7s scores on the Mini-Mental State Examination in elderly with cognitive impairment and epileptiform discharge on electroencephalography.

AIM: As the population ages, epilepsy among elderly people is increasing. Epileptic seizures in the elderly are mostly complex partial seizures without convulsions, so more caution is needed in the diagnosis of epilepsy. If epileptic seizures in the context of memory impairment are overlooked, epilepsy may be misdiagnosed as dementia. However, in older patients with epilepsy, there is a possibility that cognitive function may be impaired in the interictal phase. This study aims to investigate the efficacy of anti-epileptic drug (AED) treatment for patients with cognitive impairment and interictal epileptiform discharge (IED) on electroencephalography. METHODS: The outcome of AED administration in 50 patients who exhibited IED was retrospectively investigated. Their cognitive functions were assessed by the Mini-Mental State Examination (MMSE) at both baseline and after AED administration. RESULTS: In all patients who underwent electroencephalography, IED were temporal spikes, and re-examination of the 50 patients revealed that the frequency of temporal spikes had decreased or else disappeared in 41 patients (82%) after AED administration. In these 41 patients, the mean MMSE score significantly increased from 23.4 ± 3.7 at baseline to 24.7 ± 4.8 after AED treatment (P <0.01). Similarly, the mean serial 7s score (MMSE subscale) also improved significantly from 2.5 ± 1.8 to 3.6 ± 1.6 (P <0.01). The MMSE score was significantly improved only in the 41 patients with recovery of IED. CONCLUSION: AED treatment for elderly amnestic patients with temporal spikes was effective in improving cognitive decline and related electroencephalographic abnormalities. A more thorough search of IED is necessary in elderly amnesic patients because there is a possibility that IED modifies cognitive function.

Association of the five-factor personality model with prefrontal activation during frontal lobe task performance using two-channel near-infrared spectroscopy.

AIM: The aim of this study was to investigate the biological background of the five-factor model using near-infrared spectroscopy and cognitive tasks. METHODS: Twenty right-handed healthy volunteers participated in this study. Their personality traits were assessed using the NEO Five-Factor Inventory, and changes in oxyhemoglobin concentration ([oxy-Hb]) were measured during cognitive tasks using a wireless near-infrared spectroscopy. RESULTS: The average [oxy-Hb] in the right prefrontal area had a significant positive correlation with the agreeableness score during the Stroop test at incongruent stimulus block. For the verbal fluency task, there were no significant correlations of bilateral [oxy-Hb] changes with any items. CONCLUSION: Higher agreeableness scores may involve less suppression to the default mode network related to resting state brain function. Keeping selective attention during the Stroop test may require more power of concentration than retrieving words during the verbal fluency task.

Prefrontal dysfunction in remitted depression at work reinstatement using near-infrared spectroscopy.

A long-term and/or recurrent sickness absence from work due to depression has been an important health problem in industrial countries. In addition, previous sick leave is a risk factor of recurrence. However, many characteristics, especially biological aspects, have not been investigated in remitted depressive patients who were ready to return to work from sickness absence. Therefore, the purpose of this study is to clarify the pathophysiological characteristics of patients who were at risk for recurrence of sickness absence. We recruited 21 patients and 16 healthy control subjects. All patients were ready to return to work within one month from long-term sickness absence. All subjects were examined for prefrontal function represented by oxyHb changes during the verbal fluency task (VFT) and the Stroop task using near-infrared spectroscopy. Suppressed prefrontal reaction during the VFT and increased prefrontal reaction during the Stroop task were observed in the patient group compared with the control group. Significantly lengthened reaction time was observed in the incongruent condition in the patient group during the Stroop task. Depressive patients showed impaired executive function measured by the Stroop task and had prefrontal dysfunction despite clinical remission. Residual prefrontal dysfunction may be one biological reason for repetitive sickness absence.

Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein.

We previously reported on a monoclonal antibody (mAb) that targeted amyloid beta (Aß) protein. Repeated injection of that mAb reduced the accumulation of Aß protein in the brain of human Aß transgenic mice (Tg2576). In the present study, cDNA encoding the heavy and light chains of this mAb were subcloned into an adeno-associated virus type 1 (AAV) vector with a 2A/furin adapter. A single intramuscular injection of 3.0×10(10) viral genome of these AAV vectors into C57BL/6 mice generated serum anti-Aß Ab levels up to 0.3 mg/ml. Anti-Aß Ab levels in excess of 0.1 mg/ml were maintained for up to 64 weeks. The effect of AAV administration on Aß levels in vivo was examined. A significant decrease in Aß levels in the brain of Tg2576 mice treated at 5 months (prophylactic) or 10 months (therapeutic) of age was observed. These results support the use of AAV vector encoding anti-Aß Ab for the prevention and treatment of Alzheimer's disease.

Administration of zonisamide in three cases of dementia with Lewy bodies.

Zonisamide (ZNS) add-on administration was used to treat parkinsonian symptoms in three cases of dementia with Lewy bodies (DLB). ZNS was added after doses of the anti-Parkinson's disease drugs were fixed for at least 4 weeks. A total of 25 mg of ZNS produced mild-moderate improvement of parkinsonian symptoms in two cases, but it did not affect the cognitive functions and behavioral or psychological symptoms. Caregiver burdens were decreased in two cases. Although dizziness and drowsiness were detected, these were improved by decreasing the dose. ZNS may be useful for the treatment of motor symptoms in DLB patients.

A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia.

The effectiveness and safety of yokukansan (TJ-54), a traditional Japanese medicine (kampo) for the treatment of the behavioural and psychological symptoms of dementia (BPSD), were evaluated in 106 patients diagnosed as having Alzheimer's disease (AD) (including mixed-type dementia) or dementia with Lewy bodies. Patients were randomly assigned to group A (TJ-54 treatment in period I and no treatment in period II; each period lasting 4 wk) or group B (no treatment in period I and TJ-54 treatment in period II). BPSD and cognitive functions were evaluated using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE), respectively. Activities of daily living (ADL) were evaluated using Instrumental Activities of Daily Living (IADL) in outpatients and the Barthel Index in in-patients. For the safety evaluation, adverse events were investigated. Significant improvements in mean total NPI score associated with TJ-54 treatment were observed in both periods (Wilcoxon test, p=0.040 in period I and p=0.048 in period II). The mean NPI scores significantly improved during TJ-54 treatment in groups A and B (p=0.002 and p=0.007, respectively) but not during periods of no treatment. Among the NPI subscales, significant improvements were observed in delusions, hallucinations, agitation/aggression, depression, anxiety, and irritability/lability. The effects of TJ-54 persisted for 1 month without any psychological withdrawal symptoms in group A. TJ-54 did not show any effect on either cognitive function or ADL. No serious adverse reactions were observed. The present study suggests that TJ-54 is an effective and well-tolerated treatment for patients with BPSD.

Total Mini-Mental State Examination score and regional cerebral blood flow using Z score imaging and automated ROI analysis software in subjects with memory impairment.

OBJECTIVE: The Mini-Mental State Examination (MMSE) is considered a useful supplementary method to diagnose dementia and evaluate the severity of cognitive disturbance. However, the region of the cerebrum that correlates with the MMSE score is not clear. Recently, a new method was developed to analyze regional cerebral blood flow (rCBF) using a Z score imaging system (eZIS). This system shows changes of rCBF when compared with a normal database. In addition, a three-dimensional stereotaxic region of interest (ROI) template (3DSRT), fully automated ROI analysis software was developed. The objective of this study was to investigate the correlation between rCBF changes and total MMSE score using these new methods. METHODS: The association between total MMSE score and rCBF changes was investigated in 24 patients (mean age +/- SD 71.5 +/- 9.2 years; 6 men and 18 women) with memory impairment using eZIS and 3DSRT. Step-wise multiple regression analysis was used for multivariate analysis, with the total MMSE score as the dependent variable and rCBF change in 24 areas as the independent variable. RESULTS: Total MMSE score was significantly correlated only with the reduction of left hippocampal perfusion but not with right (P < 0.01). CONCLUSIONS: Total MMSE score is an important indicator of left hippocampal function.

Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidoses.

A number of the lysosomal storage diseases that have now been characterized are associated with intra-lysosomal accumulation of lipids, caused by defective lysosomal enzymes. We have previously reported neuronal accumulation of both alpha- and beta-synucleins in brain tissue of a GM2 gangliosidosis mouse model. Although alpha-synuclein has been implicated in several neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, its functions remain largely unclear. In our present study, we have examined a cohort of human lipidosis cases, including Sandhoff disease, Tay-Sachs disease, metachromatic leukodystrophy, beta-galactosialidosis and adrenoleukodystrophy, for the expression of alpha- and beta-synucleins and the associated lipid storage levels. The accumulation of alpha-synuclein was found in brain tissue in not only cases of lysosomal storage diseases, but also in instances of adrenoleukodystrophy, which is a peroxisomal disease. alpha-synuclein was detected in both neurons and glial cells of patients with these two disorders, although its distribution was found to be disease-dependent. In addition, alpha-synuclein-positive neurons were also found to be NeuN-positive, whereas NeuN-negative neurons did not show any accumulation of this protein. By comparison, the accumulation of beta-synuclein was detectable only in the pons of Sandhoff disease cases. This differential accumulation of alpha- and beta-synucleins in human lipidoses may be related to functional differences between these two proteins. In addition, the accumulation of alpha-synuclein may also be a condition that is common to lysosomal storage diseases and adrenoleukodystrophies that show an enhanced expression of this protein upon the elevation of stored lipids.

Perospirone in treatment of Huntington's disease: a first case report.

Huntington's disease (HD) is a hereditary disorder clinically characterized by involuntary movements, cognitive decline and psychiatric symptoms. We report on a patient with HD, whose involuntary movements and psychiatric symptoms were clinically improved with perospirone, a second-generation antipsychotic agent with antagonistic effects on serotonin 5-HT(2A) and dopamine D(2) (D(2)) receptors, as well as a unique agonistic effect on serotonin 5-HT(1A) (5-HT(1A)) receptors. The fact that perospirone antagonizes D(2) receptors could explain its effects on the hyperkinetic syndrome, while its agonistic effects on 5-HT(1A) receptors may explain the amelioration of psychiatric symptoms (fear and anxiety) in this patient. Future studies would be valuable to elucidate the utility of perospirone for the treatment of involuntary movements and psychiatric symptoms in HD.

Decrease in GTP-sensitive high affinity agonist binding of muscarinic acetylcholine receptors in autopsied brains of dementia with Lewy bodies and Alzheimer's disease.

To determine changes in signal transduction from the muscarinic acetylcholine receptor (mAChR) to G protein in brain tissue of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we investigated GTP-sensitive agonist high affinity binding, which is considered an index of the formation of the mAChR-G protein complex. Brain tissue was obtained at necropsy from eight patients with DLB, nine patients with Alzheimer's disease and seven patients as controls. Membrane fractions were prepared from frontal and temporal cerebral tissues. Displacement curves of [(3)H]l-quinuclidinyl benzilate (QNB) binding by carbamylcholine were analyzed by the nonlinear least-squares methods. The proportion of and affinity for the agonist in GTP-sensitive agonist high affinity binding were estimated. The percentages GTP-sensitive agonist high affinity bindings were significantly decreased in DLB (P<0.01) and Alzheimer's disease (P<0.05) only in the frontal lobe. There were no significant differences in the temporal lobe. The ratio of agonist affinity (Kd value of low affinity component/Kd value of high affinity component) did not significantly differ among groups in either the frontal lobe or temporal lobe. The concentration of mAChR-G protein complex is considered reduced in the frontal lobe of brains with DLB and Alzheimer's disease. Therefore, signal transduction from mAChR to G protein was disturbed in the frontal lobe in these diseases.