[Show abstract][Hide abstract] ABSTRACT: The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial.
This 52-week study consisted of 16-week randomized placebo-controlled (RCT) and 36-week open-label extension phases. Of 142 DLB patients enrolled in the RCT phase (three arms: placebo, 5 mg, and 10 mg), 110 entered the extension phase. The placebo group of the RCT phase initiated active treatment at week 16, and the active groups maintained allocated treatment and dosages until week 24. After week 24, all patients received 10 mg. Dose reduction to 5 mg for safety concerns was allowed. Efficacy measures included Mini-Mental State Examination (MMSE) for cognitive function and Neuropsychiatric Inventory (NPI) for behavioral symptoms. Safety evaluations included adverse events (AEs) and the unified Parkinson disease rating scale.
In total, 100 subjects completed the study. Cognitive function improvement was sustained for 52 weeks (MMSE at week 52 in 10 mg: 2.8 ± 3.5 (mean ± standard deviation); P <0.001, Student paired t test)). Those who received placebo in the RCT phase showed an improvement after starting active treatment. NPI improved in all the groups throughout the study, including the placebo period. In the subgroup of the 5 mg group without remarkable cognitive or behavioral improvement at week 24, further improvement was observed after a dose increase to 10 mg. After week 24, 21 patients experienced dose reduction. The incidence of any AEs did not increase over time.
The long-term administration of donepezil at 10 mg/day improved cognitive function for up to 52 weeks in patients with DLB without increasing the risk of clinically significant safety events.
NCT01278407. Trial registration date: January 14, 2011.
Alzheimer's Research and Therapy 12/2015; 7(1):5. DOI:10.1186/s13195-014-0081-2 · 3.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Patients with Alzheimer's disease (AD) manifest various impairments in eating behavior. However, few previous studies have directly investigated the gustatory function of AD patients, and results have been inconsistent.
Thirty-two AD patients (Clinical Dementia Rating (CDR) 0.5/1/2, respectively 11/15/6 patients) and 22 normal control participants were examined to measure detection and recognition thresholds of the four elemental tastes (sweet, salty, sour, and bitter), and their ability to discriminate between tastes. Effects of demographic and clinical factors (age, sex, histories of alcohol and tobacco consumption, and CDR grade) on gustatory threshold were examined using ordinal logistic regression analysis. Performance was compared between AD and control groups.
Total threshold values (the sum of threshold grades for the four tastes) for detection and recognition of tastes were significantly higher in the AD group. Detection thresholds for sweet, salty, and bitter, and recognition thresholds for sweet and sour, were also significantly higher in the AD group. Ordinal logistic regression analysis revealed that CDR grade was the only factor that significantly affected both total threshold values. Regarding taste discrimination, there were no significant differences between the AD group and control group.
These findings suggest that progression of dementia severity accompanies gustatory decline. Although it seemingly paradoxical, weight loss and preference for sweet tastes are frequently, often simultaneously, observed in AD. Gustatory dysfunction may be partially involved in these symptoms. Thus, the nutritional care of patients with AD could be improved by making the taste of meals stronger, while controlling calorie and mineral intake.
International Psychogeriatrics 10/2015; DOI:10.1017/S1041610215001337 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Presenteeism refers to impaired performance attributed to attending work with health problems. There has been no study examining the state of presenteeism with objective measures. We compared cerebral hemodynamic changes, measured by near-infrared spectroscopy (NIRS), during neuropsychological tests conducted by university students with presenteeism and healthy controls. Twenty-two university students participated in the study; 11 of them with impaired performance caused by mental health problem were allocated to the presenteeism group and 11 without health problems to the control group. Presenteeism was assessed by the Presenteeism Scale for Students. To evoke hemodynamics changes, the participants completed a Word Fluency Test (WFT) and a Trail Making Test (TMT). The NIRS probes were located over the bilateral prefrontal area. Students with presenteeism had significantly higher incidences of depression than controls. However , there was no significant difference in behavioral performance examinations between the two groups. With regard to hemodynamics changes, the repeated measures analysis of covariance of the NIRS signals revealed significant interactions between group and task activation. Although we observed a significant increase in oxygenated hemoglobin concentration during the WFT among controls (simple main effect; left channel, F(1, 19) = 27.34, P < 0.001; right channel, F(1, 19) = 22.05, P < 0.001), no changes were found in students with presenteeism during either the WFT (simple main effect; left channel, F(1, 19) = 0.12, P < 0.732; right channel, F(1, 19) = 0.08, P < 0.778) or TMT tasks (left channel, t = −0.94, P with Bonferroni correction = 0.745; right channel, t = −2.19, P with Bon-ferroni correction < 0.113). This is the first study to reveal differences in activity in the cerebral cortex associated with presenteeism. The fact that students with presenteeism have prefrontal dysfunction might reinforce the concept of presenteeism.
Journal of Behavioral and Brain Science 08/2015; 5(09):339-347. DOI:10.4236/jbbs.2015.59034
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
PLoS ONE 08/2015; 10(8):e0133666. DOI:10.1371/journal.pone.0133666 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Behavioral and psychological symptoms of dementia (BPSD) are common in the clinical manifestation of dementia. Although most patients with dementia exhibit some BPSD during the course of the illness, the association of BPSD with the stage of dementia remains unclear. It was the aim of this study to evaluate the impact of severity of dementia on the expression of BPSD in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
Ninety-seven patients with DLB and 393 patients with AD were recruited from 8 dementia clinics across Japan. BPSD were assessed by the Neuropsychiatric Inventory (NPI). A relationship between BPSD and dementia stage classified by the Clinical Dementia Rating (CDR) in each type of dementia was assessed.
No significant difference was seen in NPI total score across CDR staging in the DLB group. On the other hand, the NPI total score significantly increased with dementia stage in the AD group.
The relationship of dementia stage with the expression of BPSD was different according to the type of dementia. BPSD and dementia stage were correlated in AD subjects, in whom psychiatric symptoms increase as the disease progresses, but not in DLB subjects.
[Show abstract][Hide abstract] ABSTRACT: Cerebral small vessel disease (SVD), including subcortical lacunar infarcts (lacunes) and white matter hyperintensities (WMH), is commonly observed on MRI of elderly individuals with and without dementia. SVD is frequently observed in patients with Alzheimer's disease (AD). However, the association between SVD and clinical symptoms exhibited by patients with AD remains unclear. Our recent studies suggest that cerebral SVD observed on CT/MRI of patients with AD is associated with delusions and delirium as well as depression. Mechanisms underlying these psychiatric symptoms in patients with AD remain unclear.
Brain and nerve = Shinkei kenkyū no shinpo 04/2015; 67(4):427-32. DOI:10.11477/mf.1416200158
[Show abstract][Hide abstract] ABSTRACT: Purpose: This study was conducted to clarify the utility of patient-held records as an integrated care approach for patients with dementia in the community. Method: We analyzed the family-held/patient-held records of patients with dementia in the community. The inclusion criteria in the study were as follows: 1) patient-held/family member-held records of patients with dementia in the community; 2) patient-held records designed to share information across different professionals, direct-care staff members, and local government staff; and 3) the continuous participation of psychiatrists in the development and use of the patient-held records. Results: We identified eight sets of family-held/patient-held records in Japanese communities of various sizes, all of which were aimed at integrating information from various services, including information provided by medical and psychiatric professionals to the family and patient. Innovative tools have been available in the areas of the hopes and preferences of the patient, medication and monitoring, sharing information, and the use of information technology. Conclusion and Discussion: Family-held/patient-held records have potential as a tool to enhance the integrated care of people with dementia in the community.
Open Journal of Psychiatry 03/2015; 5(2):129-136. DOI:10.4236/ojpsych.2015.52014
[Show abstract][Hide abstract] ABSTRACT: Abstract Hirotaka Tanabe was a Japanese neuropsychiatrist engaged in neuropsychological research on cerebrovascular disease and dementia. He contributed widely to the symptomatology of dementia, especially in the field of frontotemporal dementia (FTD). He focused on clarifying the clinical features of a language disturbance, termed Gogi-aphasia by Imura (1943), in 7 patients with anterior temporal circumscribed atrophy. He attributed the nature of Gogi-aphasia to a selective impairment of semantic memory for words and proposed that the pathological process of lobar atrophy with temporal predominance might affect the semantic memory system. In addition, he described in detail the behavioral symptoms of FTD. In his later years, he adovocated a neuropsychological approach to psychiatry.
Brain and nerve = Shinkei kenkyū no shinpo 11/2014; 66(11):1355-62. DOI:10.11477/mf.1416200040
[Show abstract][Hide abstract] ABSTRACT: Background:
Sense of coherence (SOC) is associated with a reduced risk of various health problems and is thought to be a major factor related to the ability to cope with stress. In the present study, we examined the association between caregiver burden and SOC among caregivers to persons with dementia.
Participants included 274 caregivers or family members of community-dwelling elderly dementia patients. To assess the cognitive function of patients, neuropsychological tests (e.g. Mini-Mental State Examination, Clinical Dementia Rating) were conducted by a clinical psychologist who was well trained in interviewing participants; the tests used a semi-structured interview protocol. Senior neurologists and psychiatrists also independently evaluated the dementia status of patients. To assess the SOC and caregiver burden, a social welfare counsellor asked questions from a 13-item version of the SOC scale and the short, eight-item Japanese version of the Zarit Caregiver Burden Interview (ZBI).
Among 78 caregivers of elderly subjects with cognitive impairment due to dementia, the ZBI score was significantly associated with SOC (r = -0.38, P = 0.001). Multiple regression analyses revealed that SOC scores (β = -0.42, P < 0.001) and Mini-Mental State Examination scores (β = -0.28, P = 0.009) were significantly associated with ZBI scores (F(2, 76) = 10.51, P < 0.001). SOC was closely associated with personal strain in the ZBI (β = -0.41, P < 0.001; F(3, 75) = 8.53, P < 0.001).
Caregivers with a strong SOC may be less prone to experiencing personal strain from their burden. These results suggest that reinforcement of SOC would contribute to reducing the personal strain.
[Show abstract][Hide abstract] ABSTRACT: Background
In responses to self-reported depression screening questionnaires, item non-response, which refers to the absence of answers to specific questions, is problematic. The objective of this study were (1) to clarify the features of respondents with item non-response on a self-reported elderly depression screening questionnaire (15-item geriatric depression scale; GDS-15) as compared to respondents with full responses, and (2) to compare positive depression screening rates calculated using two methods: excluding respondents with item non-response (complete case analysis; CCA) and estimating by multiplying mean scores from valid responses by the total number of GDS-15 items for respondents with item non-response.
This was a cross-sectional study conducted from 2010 to 2012. Of 4794 elderly subjects (65 years and older) living in one town in Japan 2836 community-dwelling elderly people (59.2%) were included in the analysis.
Item non-response was observed in 25.0% of respondents. Respondents with item non-response had a higher rate of depression and mental and physical problems. Respondents with depression (estimated GDS-15 score ≥6) and suicidal ideation both had a 1.6-times higher risk of item non-response on the GDS-15. The positive depression screening rate on GDS-15 by CCA was 16.5%, compared with 18.9% when calculated by the estimated GDS-15 score.
Our survey was conducted in one rural area and targeted only elderly people.
The incidence of item non-response among community-dwelling elderly people was associated with depression of the respondent. Excluding subjects with item non-response when calculating positive depression screening rates in elderly individuals causes the rate to be underestimated.
[Show abstract][Hide abstract] ABSTRACT: Purposes
The Japanese word “ronin-sei” refers to a student who has failed their university entrance examination and is preparing to re-take the examination in the following year. We aimed to determine how sleep duration is associated with daytime sleepiness or depression in ronin-sei because impaired daytime performance is known to result from sleep deprivation.
The participants in this cross-sectional study were 1075 ronin-sei and 285 university students. Sleepiness and depressive symptoms were assessed using the Epworth Sleepiness Scale (ESS) and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively.
Ronin-sei had significantly shorter sleep duration and earlier bed- and rise-times than university students. There was no significant difference in CES-D between the groups; however, the ESS score of university students was significantly higher than of ronin-sei. Ronin-sei who slept for 5 to less than 6 hours had higher ESS scores than those who slept for 6 to less than 7 hours. The mean CES-D score in ronin-sei who slept less than 5 hours was significantly higher than in those who slept for 5 to less than 6 hours, from 6 to less than 7 hours, and from 7 to less than 8 hours. Ronin-sei who slept for more than 8 hours also had higher depression scores.
Sleep deprivation appears to be common among ronin-sei. Furthermore, a U-shaped relationship was found between sleep duration and depressive symptoms, revealing that ronin-sei who had too little or too much sleep were more likely to exhibit an increase in depressive symptoms.
Asian Journal of Psychiatry 06/2014; 9. DOI:10.1016/j.ajp.2014.01.006
[Show abstract][Hide abstract] ABSTRACT: Background:
Previous studies in western countries have shown that about 30%-50% of patients with frontotemporal lobar degeneration (FTLD) have a positive family history, whereas the few epidemiological studies on FTLD done in Asia reported much lower frequencies. It is not clear the reason why the frequencies of FTLD with positive family history were lower in Asia. Furthermore, these findings were not from studies focused on family history. Therefore, it is necessary to conduct further studies on the family history of FTLD in Asia. This international multi-center research aims to investigate the family histories in patients with FTLD and related neurodegenerative diseases such as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and motor neuron diseases in a larger Asian cohort.
Participants were collected from five countries: India, Indonesia, Japan, Taiwan, and Philippines. All patients were diagnosed with behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive non-fluent aphasia (PA), frontotemporal dementia with motor neuron disease (FTD/MND), PSP, and corticobasal degeneration (CBD) according to international consensus criteria. Family histories of FTLD and related neurodegenerative diseases were investigated in each patient.
Ninety-one patients were included in this study. Forty-two patients were diagnosed to have bvFTD, two patients had FTD/MND, 22 had SD, 15 had PA, one had PA/CBS, five had CBS and four patients had PSP. Family history of any FTLD spectrum disorder was reported in 9.5% in bvFTD patients but in none of the SD or PA.
In contrast to patients of the western countries, few Asian FTLD patients have positive family histories of dementia.
International Psychogeriatrics 04/2014; 26(12):1-5. DOI:10.1017/S1041610214000635 · 1.93 Impact Factor