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Background: Few studies have investigated treatment options for patients with Alzheimer’s disease (AD) showing a poor response to oral cholinesterase inhibitors (ChEIs) in Japan. Objective: To investigate the efficacy and safety of switching from oral ChEIs to rivastigmine transdermal patch in patients with AD. Methods: In this multicenter, open-label, phase IV study in outpatient clinics in Japan, patients with mild-moderate AD who had a poor response to or experienced difficulty in continuing donepezil or galantamine were switched to rivastigmine transdermal patch (5 cm2; loaded dose 9 mg, delivery rate 4.6 mg/24 h) with a 1-step titration in week 4 (10 cm2; loaded dose 18 mg, delivery rate 9.5 mg/24 h), which was continued for 4 weeks in the titration period and 16 weeks in a maintenance period. The primary endpoint was the change in Mini-Mental State Examination (MMSE) total score from baseline to week 24. Results: A total of 118 patients were enrolled and switched to rivastigmine, of which 102 completed the 24-week study. The MMSE total score was essentially unchanged during the study, with a least-square mean change (SD) of −0.35 (2.64) at week 24 (p = 0.1750). Exploratory analysis with a mixed-effect model comparing changes in MMSE between the pre- and post-switch periods suggested that switching to rivastigmine prevented a worsening of MMSE. Application site skin reactions/irritations occurred in 30.5% of patients overall, in 22.0% in the 8-week titration period, and in 10.2% in the 16-week maintenance period. Conclusion: Within-class switching from an oral ChEI to rivastigmine transdermal patch might be an efficacious and tolerable option for AD patients showing a poor or limited response to a prior oral ChEI.

AIM Most patients with Alzheimer's disease (AD) experience poor food intake and/or loss of appetite, which accelerates cognitive impairment. Several reports have shown that rivastigmine improves appetite in AD patients. The present study investigated the efficacy of a rivastigmine transdermal patch for the treatment of low food intake in AD patients. METHODS AD patients, recruited through the Attitude Towards Food Consumption in Alzheimer's Disease Patients Revive with Rivastigmine Effects study, were recognized as experiencing either a loss of appetite or poor food intake. A rivastigmine transdermal patch was administered to study participants for 16 weeks. Patients' food intake, bodyweight, Mini-Mental State Examination scores and any adverse events were recorded. RESULTS A total of 38 patients with AD (age 86.2 ± 5.4 years) were examined. Their mean Mini-Mental State Examination score was 10.1 ± 7.0 at baseline. A significant increase in food intake amount (54.9 ± 98.0 g, P

Background: In this study, we examined the construct validity, concurrent validity concerning other standard scales, intrarater reliability, and changes in scores at 12 weeks of the previously developed ABC Dementia Scale (ABC-DS), a novel assessment tool for Alzheimer’s disease (AD). Methods: Data were obtained from 312 patients diagnosed with either AD or mild cognitive impairment. The scores on the ABC-DS and standard scales were compared. Results: The 13 items of the ABC-DS are grouped into three domains, and the domain-level scores were highly correlated with the corresponding conventional scales. Statistically significant changes in assessment scores after 12 weeks were observed for the total ABC-DS scores. Conclusion: Our results demonstrate the ABC-DS to have good validity and reliability, and its usefulness in busy clinical settings.

Various aging associated factors, such as functional decline, psychosocial problems, and cognitive dysfunction, are risk factors for somatoform disorders (SDs) in the elderly. The aim of the present study was to evaluate how cognition is correlated with the severity of late-life SDs from a neuropsychological viewpoint.Fifty-three patients over 60 years of age who had been diagnosed as having SDs were examined in this study. The severity of the somatic symptoms was assessed using the Hamilton Anxiety Rating Scales (HAMA). Cognitive functions were assessed using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), and the Japanese version of the Neurobehavioral Cognitive Examination (J-COGNISTAT).The J-COGNISTAT subtest score for attention was below the cutoff point (8 points) but was not correlated with the severity of the somatic symptoms in the patients with late-life SDs. The severity of anxiety as assessed using the HAMA was significantly correlated with the calculation scores (P0.005) among the J-COGNISTAT subtests, the FAB total (P0.05), and the FAB subtest scores (similarities and motor series) (P0.01). Other factors, including the benzodiazepine dosage, antidepressant dosage, the duration of illness, and the onset age, were not significantly correlated with the symptomatic severities.Patients with late-life SDs showed attention deficits, but no correlation was seen between the attention deficits and symptomatic severities. Attention deficits might be associated with the appearance of symptoms. Executive dysfunction and working memory might be associated with the severity of symptoms.

Introduction: Although anxiety symptoms are often observed in Alzheimer's disease (AD), little attention has been paid to this symptom compared with other neuropsychiatric symptoms. Methods: Twenty-six patients with mild AD underwent both magnetic resonance imaging and single photon emission tomography with technetium-99m ethyl cysteinate dimer. Neuropsychiatric symptoms were evaluated using the Behavioral Pathology in Alzheimer's Disease Scale (Behave-AD). We investigated the relationship between anxiety and neuroimaging using Statistical Parametric Mapping 8 software. Results: The Behave-AD anxiety score was correlated with hyperperfusion in the bilateral anterior cingulate cortices and a reduction in the gray matter volume in the right precuneus and inferior parietal lobule. Conclusion: Our results suggest that anxiety in AD could overlap with the neural correlates of anxiety disorders, and that the specific degeneration associated with AD might be associated with anxiety.

Psychotic symptoms often occur as a complication in Parkinson's disease patients, and a set of criteria for Parkinson's disease with psychosis (PDPsy) has been established. Among these criteria, hallucinations are one of the specific symptoms, with visual hallucinations being the most common. While atypical antipsychotic agents are often used for the treatment of PDPsy, adverse effects, including extrapyramidal symptoms, often hinder its continuation or tolerance. There have been some reports and reviews indicating that antidepressants may be effective for PDPsy and other forms of dementia with psychosis. In this report, we present a patient with PDPsy who was treated with one of the new-generation antidepressants, mirtazapine. Mirtazapine improved the patient's refractory psychotic symptoms, especially her visual hallucinations, without worsening her motor symptoms.

Abnormal eating behaviours are specific to frontotemporal lobar degeneration and increase caregiver burden. Topiramate, an anticonvulsant, suppresses cravings for alcohol and other substances and is a potential treatment for binge eating. However, there are few reports on topiramate efficacy for abnormal eating behaviours in frontotemporal lobar degeneration patients. We present three Japanese frontotemporal lobar degeneration patients with abnormal eating behaviours. Topiramate was effective, especially for compulsive eating, in cases with distinct lobar atrophy, but not for all abnormal eating behaviours.

Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly and constitutes the second largest group of patients with degenerative dementia. To date, on the one hand, four cholinesterase inhibitors (ChEIs) have been approved for the treatment of Alzheimer’s disease (AD). On the other hand, there are no drug for approved for the treatment of DLB. However clinical benefits and good tolerability have recently been reported in several clinical trials of cholinesterase inhibitors (ChEIs), particularly donepezil. This review describes various aspects of donepezil, including basic pharmacology and pharmacokinetics, with the primary focus on the clinical work.

IntroductionIt has been said that nearly 30% of the patients with Alzheimer’ disease (AD) manifest loss of appetite, which might increase cognitive impairments and the incidence of neuropsychiatric symptoms, and malnutrition. As a result, a vicious cycle decreases functionality and quality of life in patients with AD. Cholinesterase inhibitors (ChEIs) is the first-line drugs in the treatment of AD. On the one hand, appetite or weight loss can be seen due to gastrointestinal side effects in the treatment of ChEIs. On the other hand, there are some reports in clinical-settings that patients with AD treated with rivastigmine transdermal patch showed the improvement of appetite loss.ObjectivesTo evaluate the efficacy of rivastigmine transdermal patch in AD patients with poor appetite.MethodsIn this 16-weeks, multicenter prospective study, patients with mild to moderate AD, who manifest loss of appetite and began to receive rivastigmine transdermal patch therapy, were enrolled. The amount of food, total time-eating, body weight, Mini Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI) were evaluated.ResultsThe amount of food eaten by treated patients significantly increased 10.5% at 8 weeks after the initiation of rivastigmine transdermal patch therapy.CommentsThis preliminary results might show favourable effects of rivastigmine transdermal patch therapy on AD patients with loss of appetite.Disclosure of interestStudy supported by Ono pharmaceutical co.

Aim: The aim of this study was to develop a simple diagnostic procedure for subjects at high risk of developing dementia using the Clinical Dementia Rating (CDR), which is applicable to community-based activities. Methods: This study divided 252 community-dwelling elderly with a CDR score of 0.5 into two groups based on the presence or absence of cognitive decline within the previous one year of the baseline, as assessed by a semi-structured interview. One hundred subjects were in the ‘previously progressive group’ (PP group) and 152 subjects were in the ‘previously stable group’ (PS group). After 6 years of observation, a total of 111 subjects were assessed in the follow-up investigation. Results: Among the 39 subjects from the PP group (82.9 ± 6.8 years old, 11 male, 28 female), 34 developed dementia (87%). Among the 72 subjects from the PS group (84.4 ± 6.0 years old, 22 male, 50 female), 44 developed dementia (61%). The relative risk of developing dementia for the PP group versus the PS group was 1.43. The rate of conversion to dementia was 12.9% per 100 person-years in the PP group, and 9.8% in the PS group. In the PP group, the Mini-Mental State Examination score was significantly lower and the CDR score was significantly higher than in the PS group. Conclusion: Although there have been many attempts to identify subjects with high risk of dementia, this preliminary study suggests that information about temporal changes in cognitive function is useful when performing community-based surveys.

Depression and dementia, in particular Alzheimer's disease (AD), are critically important issues in the mental health of old age. Both conditions apparently reduce quality of life and increase the impairment of activities of daily living for elderly persons. AD usually shows poor prognosis owing to progressive neuronal degeneration, while depression is basically reversible. However, depressive symptoms are common in AD and occur in approximately 20-30% of patients with AD. Epidemiological studies have shown a possible pathological association between depression and AD. Some longitudinal studies have reported that depression is a prodromal sign or might be both a prodromal symptom of AD and a risk factor. Other studies have suggested that depressive symptoms appear to coincide with or follow the onset of AD rather than precede it. However, it still remains controversial whether depressive symptoms represent a risk factor for AD, whether they are an early symptom of neurodegeneration, or whether they are a reaction to early cognitive deficits. A better understanding of the link between AD and depression might have important clinical and research implications. This review provides an overview of current knowledge regarding a relation between depression and AD and also proposes a research and clinical perspective on depression in AD.

In Asia, the past two decades have seen rapid demographic changes, including a shift in the population age structure, while increases in urbanization, educational attainment, and nonagricultural employment are affecting the social and economic landscape. All family systems in Asia traditionally faced the problems of generational succession, economic support of the non-active elderly and physical care of the frail elderly, but the structures that provided solutions to these problems were by no means uniform. An example of health service and social welfare for the elderly is the long-term care insurance, which was started in Japan from 2000. Asian societies are starting from an inherently different cultural, social, structural and economic base than the developed countries of the West. The strongly ingrained cultural basis of family responsibility for support and care of the elderly will lead to a transformation quite different from that characterizing the elderly in the Western countries.

Background: The aim of the present study was to estimate prevalence rates of dementia and its subtypes in the population aged 65 years or more in a rural area of Japan. Methods: A survey was conducted in Itoigawa, a city with 33 120 inhabitants in Niigata Prefecture, Japan. There were 7847 persons aged 65 years or older, and they comprised 23.4% of the total population. The first phase survey included questions on medical history, activities of daily living, psychiatric and behavioral symptoms and MMSE. When the responses were examined 6394 valid replies were received (81.5%) and 914 subjects were identified who were suspected of having dementia. In addition, 200 samples were selected randomly as controls from the 5480 people who were not suspected of dementia. The second phase survey was applied to a total of 1114 subjects. Pairs of psychiatrists and nurses made house-to-house visits and examined the subjects in detail. Clinical diagnoses of the subtypes of dementia were based on the criteria set out by the Consortium to Establish a Registry for Alzheimer's Disease and DSM IV. Results: The prevalence rate of dementia was estimated at 6.2% (men 4.5%, women 7.4%), which is higher than that found by previous reports in Japan. Alzheimer type dementia was the most frequent diagnosis, accounting for 4.0%, followed by vascular dementia (1.2%), other type of dementia (0.3%) and unknown dementia (0.8%). ‘Questionable dementia’, as defined by the Clinical Dementia Rating 0.5, was found in 4.4% of respondents (men 6.3%, women 3.0%). Conclusions: The prevalence of dementia in a rural area was higher than that of previous Japanese reports, and the prevalence rate of Alzheimer type dementia was much higher than that of vascular dementia.

In order to elucidate brain mechanisms that contribute to the increased tendency for vigilance dysregulation in the elderly, we examined the spatial organization of brain electric activity [electroencephalogram (EEG)] during decreasing vigilance from alertness to onset of sleep stage 2, comparing 7 old and 10 younger, healthy subjects (60-79 and 18-41 years old, respectively). Two features were analyzed: (1) change of location of the brain electric source gravity centers of the EEG frequency bands, and (2) magnitude of fluctuation of these locations over time. Multichannel EEG was analyzed into source gravity center localizations for seven EEG frequency bands, using fast Fourier transform (FFT) Dipole Approximation (first principal component-single source modeling in the frequency domain). Multivariate analysis of covariance (MANCOVA) showed: source localizations were more anterior in old than younger subjects for beta-1 and more superior for all three beta bands; from alertness to sleep, delta and theta EEG sources (inhibitory activity) changed to more posterior and superior areas, and alpha-1 and -2 (routine activity) and beta-1 and -2 sources (excitatory activity) towards anterior and superior areas. Fluctuations of the source locations of delta and beta-2 were larger on the superior--inferior axis, and of beta-2 smaller on the left-right axis in the old than younger subjects. The results suggest functional specifications (inhibitory, routine, excitatory) of cortical positron emission tomography (PET) changes reported in sleep. In sum, aging exhibits changes in spatial organization of EEG-generating neuronal assemblies; during the transition wakefulness-to-sleep, aging affects the spatial-temporal dynamics of this organization. The latter is suggested to contribute to the increased risk for consciousness disturbances in the elderly.

Background. A new public long-term care (LTC) insurance was launched in 2000 in Japan. However, there have been few studies involving factors that increase LTC costs of demented subjects; no follow-up studies involving the Government-Certified Index (GCI) and requisite costs related to the causes of dementia.Method. An epidemiological survey was conducted in a rural area in Japan in 1999, and 271 subjects were diagnosed as dementia patients. Age, sex, mini-mental state examination, clinical dementia rating, activity of daily living, causes of dementia, and coexisting physical disease were confirmed. After the LTC insurance has been launched, we tracked the GCI stages and payment amounts every month for 8 years.Result. 209 subjects were certified to be eligible for LTC insurance; however, 13 did not receive any payment. Only 49 out of 209 were alive after the follow-up period. The most common cause of dementia was Alzheimer’s disease (AD), followed by vascular dementia (VaD). There was no significant difference between the mortality rates of the two groups. VaD subjects required higher costs than AD subjects in the total certified period and in GCI stage 5.Conclusion. Our results indicate that causes of dementia can have an impact on the requisite costs for the LTC insurance.

Psychotic symptoms often occur as a complication in Parkinson's disease patients, and a set of criteria for Parkinson's disease with psychosis (PDPsy) has been established. Among these criteria, hallucinations are one of the specific symptoms, with visual hallucinations being the most common. While atypical antipsychotic agents are often used for the treatment of PDPsy, adverse effects, including extrapyramidal symptoms, often hinder its continuation or tolerance. There have been some reports and reviews indicating that antidepressants may be effective for PDPsy and other forms of dementia with psychosis. In this report, we present a patient with PDPsy who was treated with one of the new-generation antidepressants, mirtazapine. Mirtazapine improved the patient's refractory psychotic symptoms, especially her visual hallucinations, without worsening her motor symptoms.

Alzheimer's disease (AD) is the most common cause of dementia and is characterized by an insidious onset and slow deterioration in cognition, activities of daily living (ADL), mood stability and social functioning. The cholinesterase inhibitors (ChEIs), developed based on the cholinergic hypothesis, are currently considered to be the best established treatment for AD, although the significant advances in the symptomatic pharmacotherapy of AD may be followed by disease-modification treatments. Donepezil is a mixed competitive and noncompetitive acetylcholinesterase inhibitor that shows a relative selectivity for acetylcholinesterase inhibitor compared with butyrylcholinesterase. In many clinical trials of donepezil, beneficial effects on standard measures of cognitive function, ADL and behavior have been shown in patients with mild, moderate or severe AD. Although the pharmacological and phamacokinetic profiles of the currently available ChEIs have notable differences that may affect efficacy, the clinical significance of these differences remains hypothetical in the absence of large, randomized trials that compare the ChEIs with each other.

Background Of all the psychiatric disorders associated with insomnia, depression is the most common. It has been estimated that 90% of patients with depression complain about sleep quality. Since the first reports of short rapid eye movement (REM) latency in depressed patients and of the effect of sleep deprivation on depression in the 1970s, numerous sleep studies have provided extensive observations and theoretical hypotheses concerning the etiology and pathophysiology of depression. The aim of this review is to summarize knowledge regarding the relationships between sleep and depression. Data sources and selection MEDLINE and PsycINFO searches of the literature published in English or French between 1964 and 2005 that examined the relationships between sleep disturbance and depression were conducted. Search terms used were depression, depressive disorder, affective disorder, mood disorders, seasonal affective disorder, sleep, sleep disorders, insomnia, REM, polysomnography, sleep deprivation, electroencephalography, PET, SPECT, and fMRI. Data synthesis Two hundred five papers were identified and selected and then integrated into the following categories: sleep architecture, antidepressive therapies, age- and gender-associated differences, functional imaging results, and sleep-related hypotheses explaining the pathophysiology of depression. Conclusion Numerous studies provide findings indicating the remarkable relationship between sleep alterations and depression. Although the existing hypotheses are not likely to explain all aspects of the sleep alterations in depression, each may be worth being maintained for refinements of pathophysiologic models of depression as new data accumulate. Further research taking into account the heterogeneity of depressive disorder and linking the different areas of research is needed to develop more comprehensive theoretical models and new therapies for depression.

Even though both electro-oculography (EOG) and EEG have been widely used for assessing alertness, the relationship between these two measures has not yet been clarified at various alertness levels. We estimated the frequencies of eye movements faster than 15°/s (NoEM 15 ) and EEG power at every 0.5 Hz step frequency point, quantitatively as well as continuously from alert to very light sleep (Stage 1) in 14 healthy adults. We devised a new EOG derivation for a computerized analysis, because conventional EOG recordings suffer from EEG contamination and have been analyzed manually. EOG electrodes were attached to the left orbitale in this study. The eye movements were detected as peaks in differentiated EOG signals. Significant correlations were found between NoEM 15 and EEG powers at several frequency points, mainly in the alpha and beta bands. Though fluctuating EEG components in close correspondence to the frequency of the eye movements varied depending on the individual, EEG power at the peak frequency of the awake state was most closely associated with the eye movements. A broad band power that centers at the peak frequency may be a better measure for alertness assessment than powers in fixed bands.