Mamoru Hashimoto

Neuropsychiatric Symptoms in Patients with Idiopathic Normal Pressure Hydrocephalus

Objective: To clarify the characteristics of neuropsychiatric symptoms in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods: Neuropsychiatric symptoms of 64 iNPH patients with mild triad symptoms from three kinds of hospitals were evaluated with the Neuropsychiatric Inventory (NPI) and compared with 126 patients with Alzheimer’s disease (AD). Results: The most frequently observed neuropsychiatric symptom in the iNPH patients was apathy followed by anxiety and aggression. No symptom was more prevalent or more severe in iNPH than in AD. The severity of cognitive impairment was correlated with both aberrant motor activity and apathy. Conclusions: Neuropsychiatric symptoms were mild in patients with iNPH and apathy was the most prevalent symptom. The correlation between neuropsychiatric symptoms and cognitive impairment in iNPH appears to arise from a common pathology in the frontal lobe.

Long-term safety and efficacy of donepezil in patients with dementia with Lewy bodies: results from a 52-week, open-label, multicenter extension study.

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.

Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan, a traditional Japanese medicine.

Background:u2002 This multicentre open‐label trial examined the efficacy and safety of the traditional Japanese medicine, or Kampo medicine, yokukansan (YKS), for behavioural and psychological symptoms of dementia (BPSD) in patients with dementia with Lewy bodies.

Neuroanatomy of a neurobehavioral disturbance in the left anterior thalamic infarction

Background and purpose Cognitive and behavioural symptoms represent primary clinical manifestations of anterior thalamic infarcts (ATIs) in the tuberothalamic artery territory. The aim of the study is to understand the pathomechanism of cognitive and behavioural disturbances in left ATI (LATI). Methods 6 patients with isolated LATIs were investigated using neuropsychological assessments, MRI stereotactic lesion localisation and positron emission tomography. Results The patients were characterised clinically by verbal memory impairment, language disturbances dominated by anomia and word-finding difficulty and apathy. The ventral anterior nucleus (VA) proper, magnocellular VA (VAmc), ventral lateral anterior nucleus (VLa), ventral lateral posterior nucleus (VLp) and mammillothalamic tract were involved in all patients. Compared with healthy controls, the regional cerebral blood flow was lower in the thalamus, the dorsolateral, medial and orbital frontal lobes, the anterior temporal lobe, the inferior parietal lobule and the occipital lobe of the left hemisphere. Conclusions The authors propose that the Papez circuit disruption at the mammillothalamic tract and possibly thalamomedial temporal disconnection at the VA region is responsible for memory impairment and that the thalamo-anterior temporal disconnection is associated with language disturbance in LATI, respectively.

Prevalence and Topography of Small Hypointense Foci Suggesting Microbleeds on 3T Susceptibility-Weighted Imaging in Various Types of Dementia

BACKGROUND AND PURPOSE: The prevalence and topography of small hypointense foci suggesting microbleeds on 3T SWI in various types of dementia have not been systematically investigated. The purpose of this study was to determine the prevalence and topography of SHF on 3T SWI in patients with different dementia subtypes. MATERIALS AND METHODS: We included 347 consecutive patients (217 women, 130 men; age range, 42–93 years; mean age, 74 years) who attended our memory clinic and underwent 3T SWI. They were divided into 6 groups: subjective complaints, MCI, AD, DLB, VaD, and FTLD. Two neuroradiologists evaluated the number and location of SHF on SWIs. Statistical analyses were performed to evaluate inter- and intragroup differences. RESULTS: Of the 347 patients, 160 (46.1%) exhibited at least 1 small hypointense focus. This was true in 86% with VaD, 54% with DLB, 48% with AD, 41% with MCI, 27% with FTLD, and 22% with subjective complaints. With the subjective complaints group as a reference, the odds ratio adjusted by age, sex, and arterial hypertension was 9.2 (95% CI, 2.0–43.6) for VaD; 5.4 (95% CI, 1.2–24.3) for AD; 3.1 for DLB (95% CI, 1.1–8.8); 2.0 for MCI (95% CI, 0.5–8.1); and 1.5 for FTLD (95% CI, 0.4–5.4). There was a significant lobar predilection for AD, DLB, and FTLD groups (P < .05). CONCLUSIONS: On 3T SWI, patients with VaD, AD, and DLB manifested a high SHF prevalence. In patients with AD, DLB, and FTLD, the SHF exhibited a lobar predilection.

Relationship between Eating Disturbance and Dementia Severity in Patients with Alzheimer’s Disease

Background Eating is one of the most important daily activities in managing patients with dementia. Although various eating disturbance occur as dementia progresses, to our knowledge, most of the studies focused on a part of eating disturbance such as swallowing and appetite. There have been few comprehensive studies including eating habits and food preference in patients with Alzheimer’s disease (AD). The aims of this study were to investigate almost all eating disturbance and to examine the relationship of eating disturbance to dementia stage in AD. Methods A total of 220 patients with AD and 30 normal elderly (NE) subjects were recruited. Eating disturbance was assessed by a comprehensive questionnaire that had been previously validated. Potential relationships between the characteristics of eating disturbance and dementia stage as classified by the Clinical Dementia Rating (CDR) were assessed. Results Overall, 81.4% of patients with AD showed some eating and swallowing disturbance, whereas only 26.7% of the NE subjects had such a disturbance. Even in an early stage, patients with AD had many types of eating disturbance; “Appetite change” was shown in nearly half of the mild AD patients (49.5%). In the moderate stage, the scores of “change of eating habits and food preference” were highest, and in the severe stage “swallowing disturbance” became critical. Conclusion In AD, the relationship of dementia stage to eating disturbance differs according to the type of eating disturbance. The relationships between various eating disturbance and the severity of dementia should be considered.

Multiple thalamo-cortical disconnections in anterior thalamic infarction: Implications for thalamic mechanisms of memory and language

Amnesia and linguistic deficits that are associated with thalamic damage have attracted the attention of researchers interested in identifying the neural networks involved in memory and language. The Papez circuit, which is composed of the hippocampus, mammillary body and anterior thalamic nuclei, was first proposed to be critical for memory. However, subsequently, the roles of the neural circuit consisting of the rhinal/parahippocampal cortices and the mediodorsal thalamic nuclei became evident. The ventral lateral nuclei or its adjacent structures have been found to be involved in semantic processing, but the specific neural circuits dedicated to language functions have not been identified. Anterior thalamic infarcts, which affect very circumscribed regions of the ventral anterior portion of the thalamus, often cause paradoxically prominent memory and language deficits. We conducted tractography analyses in 6 patients with left anterior thalamic infarcts to identify neural connections or circuits in which disruptions are associated with memory and language deficits in this condition. The current study demonstrated that the mammillothalamic tract, which connects the mammillary body with the anterior thalamic nuclei, and the anterior and inferior thalamic peduncles, which contain neural fibers that extend from several thalamic nuclei to the anterior temporal, medial temporal and frontal cortices, are disrupted in anterior thalamic infarction. These extensive thalamo-cortical disconnections appear to be due to the dissection of the neural fibers that penetrate the ventral anterior nucleus of the thalamus. Our results suggest the following: (1) amnesia that is associated with anterior thalamic infarction is best interpreted in the context of dual/multiple-system theories of memory/amnesia that posit that multiple neural circuits connecting the anterior and mediodorsal thalamic nuclei with the hippocampus and rhinal/parahippocampal cortices work in concert to support memory function; and (2) the semantic deficits observed in this syndrome may be associated with thalamo-anterior temporal and thalamo-lateral frontal disconnections.

Neuropsychiatric symptoms of progressive supranuclear palsy in a dementia clinic.

Background:u2002 Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by supranuclear gaze palsy, postural instability, akinesia and other parkinsonism. Recently, the relationship between PSP and frontotemporal dementia (FTD) has been recognized, which includes clinical, pathological, biochemical and genetic features. However, there have been few studies that directly compared neuropsychiatric symptoms between PSP and FTD. The aim of the present study was to investigate comprehensive psychiatric and behavioural symptoms in PSP and compared them with those in FTD.

The relationship between post-stroke depression and physical recovery

BACKGROUNDnPost-stroke depression (PSD) is a serious and common complication of stroke. In this prospective study on the relationship between clinical PSD and physical recovery, we focused on (1) distinguishing between depression and apathy, (2) issues in assessment of PSD, and (3) timing of assessment.nnnMETHODSnJapanese stroke patients (n=117) were studied. We used self-rating scales [Zung Self-Rating Depression Scale (SDS) for depression; Apathy Scale (AS) for apathy] and observer-rating scales [Montgomery-Åsberg Depression Rating Scale (MADRS) for depression; Neuropsychiatric Inventory-Nursing Home (NPI-NH) for apathy] to assess psychological state. We assessed physical disability using the Functional Independence Measurement (FIM). Two-way analysis of covariance was used to determine effects of depression and apathy on functional outcome. We evaluated PSD twice, within 10 days after hospitalization and four weeks later.nnnRESULTSnObjective scales gave higher prevalence than subjective scales for both depression and apathy. A significant effect of apathy on FIM recovery was seen with objective scale assessment during hospitalization; there was a marginal effect of depression at the same time.nnnLIMITATIONSnWe did not consider the stroke size and location. In addition, we excluded patients with severe comprehension deficits or with a history of stroke.nnnCONCLUSIONSnOur findings indicate that depression and apathy could occur independently after stroke and could individually influence functional recovery. We obtained more accurate estimates of functional recovery using objective measures. Furthermore, our findings suggest that depression and apathy should be assessed not only at admission but also during hospitalization to estimate and enhance the functional recovery of stroke patients.

Impact of donepezil hydrochloride on the care burden of family caregivers of patients with Alzheimer's disease

Background:u2002 To evaluate the impact of donepezil hydrochloride on the care burden on family members of patients with Alzheimers disease (AD). At present, donepezil is the only drug approved for the treatment of AD in Japan. Although the care burden on primary caregivers of AD patients comprises both physical and psychological burdens and donepezil is recognized to improve cognitive dysfunction and associated symptoms, there are few data on the effects of the drug on the care burden.