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Background: Caregiver burden is a serious concern for family caregivers of dementia patients, but its nature is unclear in patients with semantic dementia (SD). This study aimed to clarify caregiver burden for right- (R > L) and left-sided (L > R) predominant SD versus behavioral-variant frontotemporal dementia (bvFTD) patients. Methods: Using the Japanese version of the Zarit Burden Interview (ZBI) and the Neuropsychiatric Inventory, we examined caregiver burden and behavioral and psychological symptoms of dementia (BPSD) in 43 first-visit outpatient/family caregiver dyads (bvFTD, 20 dyads; SD [L > R], 13 dyads; SD [R > L], 10 dyads). Results: We found a significant difference in ZBI score between the 3 diagnostic groups. Post hoc tests revealed a significantly higher ZBI score in the bvFTD than in the SD (L > R) group. The ZBI scores in the SD (L > R) and SD (R > L) groups were not significantly different, although the effect size was large. Caregiver burden was significantly correlated with BPSD scores in all groups and was correlated with activities of daily living and instrumental activities of daily living decline in the bvFTD and SD (R > L) groups. Conclusion: Caregiver burden was highest in the bvFTD group, comparatively high in the SD (R > L) group, and lowest in the SD (L > R) group. Adequate support and intervention for caregivers should be tailored to differences in caregiver burden between these patient groups. [ABSTRACT FROM AUTHOR]

Background/Aims: Based on Mini-Mental State Examination (MMSE) subitem scores, in dementia with Lewy bodies (DLB), we aimed to delineate features of cognitive impairment, identify cognitive domains improved by donepezil, and define a pretreatment cognitive profile likely to benefit from donepezil. Methods: Pooled data were used from two randomized controlled trials of donepezil in DLB (n = 235). Baseline MMSE subitem scores were calculated for all patients. Mean changes in subitem scores at week 12 were compared between the placebo and the active group. Finally, the subgroup identification based on differential effect search (SIDES) method was applied. Results: Baseline subitem scores were relatively low for serial 7's, delayed recall, and copying. Significant improvement by donepezil was found for orientation, serial 7's, repetition, 3-step command, and copying. The subgroup with pretreatment scores of serial 7's = 1, 2, or 3, delayed recall ⩾ 1, and copying = 0 were the best responders. MMSE change in subgroups increased as more of these three conditions were fulfilled. Conclusion: Cognitive domains characteristically impaired in DLB are particularly improved by donepezil. The number of fulfilled conditions for serial 7's = 1, 2, or 3, delayed recall ⩾ 1, and copying = 0 (likely to benefit score) may predict the response to donepezil in DLB patients. [ABSTRACT FROM AUTHOR]

Background/Aims: To evaluate the adequacy of using the consensus diagnostic criteria for dementia with Lewy bodies (DLB) to recruit patients with homogeneous characteristics in fu ture clinical trials, where multiple departments o f multinational centres are expected to participate with a long enrolment period, and additionally, to contribute to the possible future criteria revision. Methods: Using data from 2 trials o f donepezil for DLB, conducted 3 years apart, characteristics in patients with probable DLB were analysed and compared between studies and between psychiatric and neurological centres. Results: In 273 patients (phase II: 135, phase III: 138; psychiatric: 73, neurological: 184), clinical characteristics overall were very similar between studies, and between specialty centres, excluding distinctive parkinsonism in the neurological versus psychiatric centres: incidence o f parkinsonism (91.8 vs. 71.2%, p < 0.001), Hoehn and Yahr stage (III: 55.0 vs. 21.2%, p < 0.001), and concomitant anti-Parkinson medication (24.5 vs. 11.0%, p = 0.017). Rapid eye movement sleep behaviour disorder, depression, and delusion, suggestive or supportive features, were observed in 35-40%. A d d itio n ally, a high prevalence (55.3%) o f anxiety was observed. Conclusion: Employing the consensus criteria is adequate to enrol homogeneous DLB patients into future clinical trials regardless o f the specialty of centres and time. Further discussion could involve adding anxiety to future Criteria. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to clarify the effects of donepezil on extrapyramidal symptoms in patients with dementia with Lewy bodies (DLB). Methods: Using pooled datasets from phase 2 and 3, 12-week randomized, placebo-controlled trials (RCT, n = 281) and 52-week open-label long-term extension trials (OLE, n = 241) of donepezil in DLB, the effects of donepezil on the incidence of extrapyramidal adverse events (AEs) and on the Unified Parkinson's Disease Rating Scale (UPDRS) part III were assessed, and potential baseline factors affecting the AEs were explored. Results: The RCT analysis did not show significant differences between the placebo and active (3, 5, and 10 mg donepezil) groups in extrapyramidal AE incidence (3.8 and 6.5%, p = 0.569) and change in the UPDRS (mean ± SD: -0.2 ± 4.3 and -0.6 ± 6.5, p = 0.562). In the OLE analysis (5 and 10 mg donepezil), the incidence did not increase chronologically; all AEs leading to a dose reduction or discontinuation except one were relieved. The UPDRS was unchanged for 52 weeks. An exploratory multivariate logistic regression analysis of the RCTs revealed that donepezil treatment was not a significant factor affecting the AEs. Baseline severity of parkinsonism was a predisposing factor for worsening of parkinsonism without significant interactions between donepezil and baseline severity. Conclusion: DLB can safely be treated with donepezil without relevant worsening of extrapyramidal symptoms, but treatment requires careful attention to symptom progression when administered to patients with relatively severe parkinsonism. © 2015 The Author(s) Published by S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate the safety and efficacy of long-term administration (52 weeks) of donepezil in patients with dementia with Lewy bodies (DLB). Methods: This was a 52-week, multicenter, open-label extension study. Up to 8 weeks after the completion of the preceding randomized, placebo-controlled trial (RCT), patients started treatment with 3 mg of donepezil daily for 2 weeks, followed by 5 mg daily for the remaining 50 weeks. Cognitive function, behavioral and psychiatric symptoms, cognitive fluctuations, and caregiver burden were assessed using the Mini-Mental State Examination, Neuropsychiatric Inventory, Cognitive Fluctuation Inventory, and the Zarit Caregiver Burden Interview, respectively. Safety parameters were monitored throughout. Results: In total, 108 patients were enrolled in the study. Cognitive function and dementia-related behavioral symptoms, including cognitive fluctuations, were improved after the start of donepezil treatment, and improvement was maintained for 52 weeks. Reduction in caregiver burden observed in the preceding RCT returned to the baseline level at 52 weeks. There was no significant imbalance in the incidence of adverse events (AEs) by onset time, and delayed AE onset induced by the long-term administration of donepezil was unlikely to appear. Conclusion: The long-term administration of donepezil at 5 mg/day was well tolerated in patients with DLB and is expected to exhibit lasting effects, improving impaired cognitive function and psychiatric symptoms up to 52 weeks. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study is to examine the clinical symptoms in a number of semantic dementia (SD) patients and to reveal the longitudinal progression and clinical course of these distinctive symptoms of SD. Methods: 19 consecutive SD patients were examined. Symptoms were classified into 23 distinct categories: behavioral symptoms, language and cognitive symptoms and symptoms concerning the impairment of activities of daily living (ADL). We divided patients into two subgroups, left- and right-dominant SD, and compared the onset of each symptom. Results: Language impairments occurred as the initial symptom in 16 cases. At the first examination, all cases showed both anomia and impairment of word comprehension. By around 3 years after onset, almost all language impairments were observed. Approximately 3–5 years after onset, prosopagnosia and behavioral symptoms appeared. Around the period when the loss of the language faculty and apathy became remarkable, impairment of ADL appeared. Patients spent all day in bed at this stage. Moreover, prosopagnosia appeared significantly earlier in right-dominant SD. Conclusion: Our findings clarify the progression of distinctive symptoms of SD patients. It is necessary to create a treatment strategy for SD patients with such a disease-specific course of SD. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aim: Some recent studies mentioned that late-onset frontotemporal dementia (FTD) is more common than previously assumed. Although much research has been done in the field, there are no systematic studies which have compared clinical characteristics of early- and late-onset FTD. The aim of this study was to compare cognitive function and psychiatric symptoms in patients with early- and late-onset FTD. Methods: Study participants were consecutive outpatients. There were 35 FTD patients; their mean age at onset was 63.0 years. We studied sex, education, duration from onset to consultation, Clinical Dementia Rating (CDR) scores, Mini-Mental State Examination (MMSE) scores, Raven’s Coloured Progressive Matrices (RCPM) scores, and Neuropsychiatric Inventory (NPI) scores at first consultation of early- and late-onset FTD patients. Results: There were no significant differences in sex ratio, education, CDR scores, and duration from onset to consultation. There were significant differences in the total MMSE scores, ‘three-word recall task’, ‘construction task’, and RCPM scores; late-onset groups scored significantly lower than early-onset groups. There were significant differences in the apathy domain of NPI and total NPI scores; late-onset groups scored significantly higher than early-onset groups. Conclusion: Late-onset FTD patients may have memory and visuospatial deficits in addition to their behavioural changes, even if they are clinically diagnosed according to consensus diagnostic criteria. They also present more apathy, and they may have a different histolopathological background. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: To investigate the frequency, rate of causes of dementia, and clinical characteristics of early-onset dementia in consecutive patients of a memory clinic. Methods: A total of 668 consecutive demented patients were involved in this study. We examined the distribution of patients’ diagnosis, differences in sex, education, dementia severity and cognitive function at the first visit, and the duration from onset to consultation. We also examined the changes in the proportion of subjects during the research period. Results: There were 185 early-onset patients, 28% of all demented patients. No significant differences were observed between the early-onset and late-onset dementia groups in Clinical Dementia Rating and Mini-Mental State Examination score at the first consultation, but the duration from onset to consultation was significantly longer in the early-onset group. In the early-onset group, the rates of patients with Alzheimer’s disease and dementia with Lewy bodies were relatively low and the rate of patients with frontotemporal lobar degeneration was relatively high. There were no significant differences in the proportion between either demented subjects and nondemented subjects or early-onset dementia patients and late-onset dementia patients during the research period. Conclusion: We conclude that early-onset dementia is not rare and its clinical characteristics and causes are different from late-onset dementia. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Despite many studies about the association between caregiver burden and behavioral and psychological symptoms of dementia (BPSD), there have been no population-based studies to evaluate caregiver burden associated with each BPSD. Objective: To evaluate caregiver burden associated with the individual BPSD in elderly people living in the community. Methods: The subjects were 67 participants with dementia living with their caregivers (diagnosed in the third Nakayama study): 51 Alzheimer’s disease, 5 vascular dementia and 11 other. The Neuropsychiatric Inventory (NPI) and NPI Caregiver Distress Scale (NPI-D) were used to assess subjects’ BPSD and related caregiver distress, respectively. Results: In the subjects exhibiting BPSD, aberrant motor behavior had the highest mean NPI score, and depression/dysphoria had the lowest. Agitation/aggression had the highest mean NPI-D score, and euphoria/elation had the lowest. Delusion, agitation/aggression, apathy/indifference, irritability/lability and aberrant motor behavior showed a correlation between the NPI and NPI-D scores. Conclusion: The burden associated with BPSD is different for each symptom and does not always depend on frequency and severity of BPSD. These findings suggest that some symptoms, such as agitation/aggression and irritability/lability, may affect the caregivers significantly, although their frequency and severity are low. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Despite many reports about cognitive decline and behavioral changes in patients with frontotemporal lobar degeneration (FTLD), there have been very few systematic studies of initial symptoms of frontotemporal dementia (FTD) and semantic dementia (SD). Objective: It was the aim of this study to investigate FTD and SD and to establish whether they are characterized by different initial symptoms. Methods: Three groups of patients were studied: FTD (n = 36), SD (n = 17) and age-matched Alzheimer’s disease (AD) patients (n = 52). Information on initial symptoms was obtained from caregivers. Symptoms were classified into 22 distinct categories from the following domains, based on previous studies of symptoms of FTLD: (1) change in social behavior, affection, and daily activities, (2) cognitive decline, (3) language impairments, and (4) other abnormal symptoms. Results: Change in social behavior, affection, and daily activities was significantly more common in patients with FTD; on the other hand, language impairments were significantly more common in patients with SD as initial symptoms. Apathy and stereotypic behaviors were the most common initial symptoms among patients with FTD, while anomia, paraphasia, and impairment in word comprehension were the most common initial symptoms among patients with SD. Memory disturbance was the most common initial symptom among patients with AD. Conclusions: Behavioral and psychiatric symptoms are predominant initial symptoms in FTD, while language symptoms are predominant initial symptoms in SD. In addition to the assessment of current symptoms, the assessment of initial symptoms is useful for differential diagnosis in patients with FTD, SD and AD. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A few epidemiologic studies have dealt with the prevalence of frontotemporal lobar degeneration (FTLD), including Pick's disease. The aim of this study was to review the epidemiologic studies of FTLD in western countries and to compare them with those in Japan. A community-based study of early-onset dementia in London revealed that 12% of cases with frontotemporal dementia (FTD) fulfilled the Lund-Manchester criteria in contrast to 34% of cases with Alzheimer's disease (AD) in a sample of 185 cases. The Cambridge Group has recently examined the prevalence of early-onset dementia in a community-based study. Of 108 cases, 15.7% had FTLD and 25% had AD. FTLD included 13 FTD cases, and 2 each with semantic dementia (SD) and nonfluent progressive aphasia (PA). Almost one third of cases with FTLD (29%) had a positive family history. Of our consecutive 330 outpatients with dementia (hospital setting without age limitation), 42 (12.7%) had FTLD and 215 (65.1%) had AD. In our series of patients, 22 FTD, 15 SD and 5 PA cases were identified. There was no family history in all subtypes of FTLD. Epidemiologic studies, both community-based and hospital-based, demonstrate that FTLD is a more common cause of early-onset dementia than previously recognized. Regarding the subtypes of FTLD, in Japan, compared with the data from the UK, FTD is less common, SD may be more common and PA is equally common. The reason for this discrepancy is supposed to be mainly based on the role of heredity. [ABSTRACT FROM AUTHOR]

Patients with frontotemporal lobar degeneration (FTLD) present a profound personality change, social misconduct, overeating, and stereotyped behavior. We examined the hypothesis that many of the behavioral symptoms of FTLD will respond to selective serotonin reuptake inhibitors (SSRIs). Sixteen FTLD patients were treated with an SSRI (fluvoxamine maleate) in an open 12-week trial. Treatment responses for stereotyped behavior and other neurobehavioral symptoms were evaluated by the Stereotypy Rating Inventory and the Neuropsychiatric Inventory. The behavioral symptoms, especially stereotyped behaviors of FTLD, significantly improved after treatment. Randomized, placebo- and other SSRI-controlled trials may improve available treatments. [ABSTRACT FROM AUTHOR]