Yosuke Ichimiya

Clinical effects of high oral dose of donepezil for patients with Alzheimer's disease in Japan

Background:  Donepezil 10 mg/day gained approval in Japan in August 2007 for the treatment of cognitive dysfunction in advanced Alzheimers disease.

A juvenile case of frontotemporal dementia: Neurochemical and neuropathological investigations

1. An autopsy case of frontotemporal dementia with onset at the early age of 28 years is reported. 2. The neuropathological features consisted of limited, knife-like frontotemporal atrophy with severe neuronal loss, spongiform change and gliosis, which is compatible with the frontotemporal dementia. 3. Biochemical determinations disclosed that biogenic amines and their metabolites, predominant in the dopaminergic markers, were depleted in the damaged regions. 4. Since biochemical data in frontotemporal dementia are few in previous studies, it will be determined whether these biochemical changes are characteristic for the juvenile type of frontotemporal dementia or not.

Clinical evaluation of percutaneous endoscopic gastrostomy tube feeding in Japanese patients with dementia

Aim:  The aim of this study was to clinically evaluate percutaneous endoscopic gastrostomy (PEG) tube feeding of elderly Japanese patients with dementia.

Risk factors for delusion of theft in patients with Alzheimer's disease showing mild Dementia in Japan

The mechanism underlying delusion in Alzheimers disease patients has not been fully clarified; however, the occurrence of delusion is a critical issue for dementia patients and their caregivers. In Japan, delusion of theft is the most frequent delusion in AD patients. We examined the risk factors for delusion of theft in AD patients showing mild dementia. Fifty-six AD patients were administered HDS-R, MMSE and COGNISTAT, including the ‘speech sample’, to assess their neuropsychological and social cognitive functions. The age, years of education, presence of cohabiting family members and premorbid personality traits were obtained from family members. About 25.0% of AD patients showed delusion of theft (D-group), and 75% did not (non-D-group). About 33.3% of female patients and 5.9% of male patients were included in the D-group (p < 0.05). About 13.6% of patients who were cohabiting with family members and 66.7% of patients who were living alone were included in the D-group (p < 0.05). About 35.1% of patients who had a neurotic personality and 5.3% of patients who did not were included in the D-group (p < 0.05). There were no significant differences in scores on HDS-R, MMSE and COGNISTAT sub-scales, except for ‘speech sample’, between the two groups. In the ‘speech sample’, 38.7% of patients who understood a relationship between two boys and 12.0% of patients who did not were included in the D-group (p < 0.05). These results indicated that delusion of theft in AD patients was related to female gender, absence of cohabiting family members, neurotic personality and retained social cognitive function.

Effect of Rikkunshi-to on appetite loss found in elderly dementia patients: a preliminary study.

Background:  Functional gastrointestinal symptoms are frequently found in elderly dementia patients. In such a case, we attempt treatment by the administration of antidepressants or second‐generation antipsychotics. However, these medications have a risk of side‐effects. In the present study, we carried out oral administration of Rikkunshi‐to to elderly dementia patients with appetite loss, and examined its effects on food intake.

(123)I-FP-CIT SPECT findings and its clinical relevance in prodromal dementia with Lewy bodies.

PurposeEvidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the 123I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance.MethodsWe enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer’s disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in 18F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of 123I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups.ResultsMean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB.Conclusion123I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway.

Long-term effect of donepezil for Alzheimer's disease: Retrospective clinical evaluation of drug efficacy in Japanese patients

Background:  Alzheimers disease (AD) is common in the Japanese population. In 1999, donepezil was authorized in Japan for the treatment of AD. However, because the time since donepezil was authorized is relatively short, there are few reports regarding the long‐term effects of donepezil in Japanese AD patients.

Serum insulin-like growth factor-I and amyloid beta protein in Alzheimer's disease: relationship with cognitive function

Previous studies have suggested that insulin‐like growth factor‐I (IGF‐I) deficiency may lead to cognitive deficits in neurodegenerative diseases such as Alzheimers disease. The present study aimed to investigate the possible relationship between cognitive function and concentration of IGF‐I or amyloid beta protein (Aβ) in serum in Alzheimers patients.

Safety and pharmacokinetics of bapineuzumab in a single ascending-dose study in Japanese patients with mild to moderate Alzheimer's disease.

To evaluate the safety, tolerability and pharmacokinetic profile of bapineuzumab after a single intravenous injection in Japanese patients with mild to moderate Alzheimers disease.

Manic episode induced by steroid (fluorometholone) eye drops in an elderly patient

DYSAUTONOMIA AND DEPRESSION often antedate the onset of dementia with Lewy bodies (DLB) by years or even decades. Previous studies revealed that many DLB patients have an initial clinical diagnosis of depression before core features of DLB appear. It is challenging to clinically diagnose DLB in elderly depressed patients because of the differences in prognosis and management. With the development of I-metaiodobenzylguanidine (MIBG) scintigraphy, increasing clinical attention has been focused on cardiac sympathetic denervation in DLB patients. Although pathological studies revealed that cardiac sympathetic denervation begins early in the Lewy body disease (LBD) process, there is limited information regarding MIBG scintigraphy images of prodromal DLB. Thus, it is clinically important to determine if the cardiac MIBG scintigraphy is useful for the detection of the prodromal DLB state in elderly depressed patients. Yokoyama et al. reported that milnacipran, a serotoninnorepinephrine reuptake inhibitor, influences the cardiac MIBG scintigraphy indices in elderly depressed patients who were suspected to have underlying LBD. They demonstrated that cardiac MIBG reuptake is significantly lower in depressed patients and controls who are taking milnacipran compared to those who are not. This finding helps us to interpret the cardiac MIBG scintigraphy results in elderly depressed patients, but the effects of depressed conditions were not considered in their study. Although the depressed patients may have episodes of emotional or psychological stress at their initial examinations, subsequent MIBG scintigraphy was performed in the remission state. Takotsubo cardiomyopathy (TTC) is characterized by transient systolic dysfunction without obstructive coronary artery disease after an intensive emotional stressor. TTC is probably related to a high adrenergic state and shows transient reduced cardiac MIBG reuptake. Given that depression was associated with increased odds of developing TTC, the emotional and psychological stress in depressed patients may contribute to the onset of TTC. Even if there are no overt cardiac symptoms, stressful episodes, which can cause a high adrenergic state in depressed patients, may influence the cardiac MIBG scintigraphy index. Although the sample size was small (six depressed patients and two controls) in Yokoyama’s study, the washout rate was significantly lower in depressed patients than in controls when both groups were taking milnacipran (P = 0.02 by t-test). In contrast, there was no difference between the two groups when the patients were not taking the drug (P = 0.28 by Mann–Whitney rank sum test). These differences suggest that depressed conditions influence MIBG scintigraphy results because an increased washout rate indicates sympathetic hyperactivity. The influence of possible multiple factors on the index of MIBG scintigraphy should be considered in elderly depressed patients to determine whether underlying LBD is present. Noguchi and Yamaga reported a patient with major depression and TTC preceding the onset of DLB. In this case, dysautonomia at prodromal DLB state and depressed episode may contribute to concomitant TTC. Sympathetic abnormality detected by cardiac MIBG scintigraphy may be one of the key clinical features, forming the link between depression and subsequent onset of DLB. Further longitudinal follow-up studies are warranted to elucidate the time course of cardiac MIBG reuptake in elderly depressed patients who develop DLB.