Yoshie Murata

Determinants of the Quality of Life in Alzheimer’s Disease Patients as Assessed by the Japanese Version of the Quality of Life – Alzheimer’s Disease Scale

Background: Although QOL is an important indicator to assess multiple facets of life, the QOL of Alzheimer’s disease (AD) subjects with impaired cognitive ability due to dementia has not yet been fully investigated. In this study, we developed the Japanese version of the Quality of Life – Alzheimer’s disease (QOL-AD) scale by means of back-translation, and ascertained its reliability and validity for evaluating the quality of life in AD subjects. We also hypothesized that the presence of neuropsychiatric symptoms may determine the characteristics and determinants of both the patients’ and the caregivers’ responses to the patients’ QOL questionnaire. Methods: We administered the QOL-AD questionnaire to subjects with mild or moderate AD (n = 140). The test-retest reliability was evaluated by the same interviewer after a month’s interval. Data from the following tests were also collected to ascertain the validity of the questionnaire: Short Memory Questionnaire (SMQ), Neuropsychiatry Inventory (NPI), Hyogo Activities of Daily Living Scale (HADL) and Mini-Mental State Examination (MMSE). Results: The Japanese version of the QOL-AD questionnaire demonstrated good internal reliability for both the patients’ (Cronbach’s α = 0.84) and the caregivers’ responses (Cronbach’s α = 0.82) and good test-retest reliability for both the patients’ (intraclass correlation coefficient = 0.84) and caregivers’ reports (intraclass correlation coefficient = 0.91). The concordance between the patients’ self-report and the caregivers’ observation was moderate (Pearson correlation coefficient = 0.60). The score for the ‘mood factor’ (apathy, depression/dysphoria) in NPI predicted the overall QOL score as determined from both the patients’ and the caregivers’ responses for subjects with mild (MMSE≧21, n = 88) and moderate (MMSE<21, n = 52) AD. The score for the ‘psychosis factor’ (delusions, hallucinations, anxiety, agitation, disinhibition, irritability, aberrant motor activity) in NPI predicted the total QOL score as determined by the patients and the caregivers among subjects with moderate AD only. Conclusions: As hypothesized, the presence of neuropsychiatric symptoms may be an important predictor of both the patients’ and caregivers’ responses to the patients’ QOL questionnaire. QOL-AD appears to be a promising measure of the QOL of subjects with mild to moderate AD in Japan.

Neuropsychiatric symptoms predict change in quality of life of Alzheimer disease patients: a two-year follow-up study.

Aim:  To examine the effect of neuropsychiatric symptoms on longitudinal changes in the quality of life (QOL) of patients with Alzheimer disease (AD).

Distinct neuropsychological profiles of three major symptom dimensions in obsessive-compulsive disorder.

Recent neuroimaging studies have suggested that different symptom dimensions are mediated by partially distinct neural systems in obsessive-compulsive disorder (OCD). However, the correlations between neuropsychological profiles and symptom dimensions in OCD are unknown. The aim of this study was to examine the extent to which OCD symptom dimensions were associated with episodic memory and attention and executive functions. The symptom dimensions of 63 patients with OCD were assessed using both the Padua Inventory and the Y-BOCS symptom checklist. Then, we administered the Logical Memory (LM) subset of the Wechsler Memory Scale-Revised (WMR-R) test and evaluated inhibition (Stroop test, Trail Making test) and cognitive flexibility (Digit Symbol test, Letter Fluency, and Category Fluency). While associations were observed between scores on the contamination/cleaning dimension and better performances on the LM and Trail Making tests, associations were also observed between scores on the aggressive/checking dimension and poorer performances on the Trail Making test. In addition, we found that scores on the symmetry/ordering dimension were associated with poorer performances on the LM and Trail Making tests. Our results support the hypothesis that different symptoms may represent distinct and partially overlapping neurocognitive networks in OCD patients.

Greater Impairment of Ability in the Divided Attention Task Is Seen in Alzheimer’s Disease Patients with Depression than in Those without Depression

Background: Recent studies have emphasized specific deficits of attention and executive functions, such as those of cognitive flexibility, divided attention, in geriatric patients with depression. In Alzheimer’s disease (AD), depressive symptoms are known to occur even from an early stage of the disease. However, the nature of the impairment of executive functions in depression associated with AD remains unclear, because of the frequent occurrence of the apathy syndrome as a major confounding factor. Method: In this study, we conducted a comprehensive comparative neuropsychological assessment in AD patients with (n = 21) and without (n = 21) depression. The diagnosis of depression was based on provisional criteria proposed by Olin’s group. Results: In terms of apathy symptoms, both groups had a similar degree of deficits, which were mild as assessed according to Neuropsychiatric Inventory criteria. While no significant differences were observed in regard to the scores in general intellectual functioning, episodic memory and some attention and executive tasks between the two groups, AD patients with depression showed significantly lower scores in several attention and executive function tasks, such as the dual-task performance task administered to assess the capacity for divided attention, and the cognitive flexibility (Trail Making Test; Part B), than AD patients without depression. Conclusions: Our results suggest that depressive symptoms in AD patients increase the deficits of cognitive flexibility and divided attention. This is the first study to report a correlation between depressions, diagnosed based on the provisional criteria for depression in AD by Olin’s group, and an impaired capacity for divided attention in AD patients.

Impairment of Decision-making Cognition in a Case of Frontotemporal Lobar Degeneration (ftld) Presenting With Pathologic Gambling and Hoarding as the Initial Symptoms

ObjectiveThe aim of this study was to use the Iowa Gambling Task (IGT) to examine decision-making cognition in a patient with mild frontal variant of frontotemporal dementia (fv-FTD). BackgroundAlthough fv-FTD may present with bizarre and dramatic behavioral changes, traditional executive tasks are sometimes preserved in patients with mild fv-FTD. Some evidence suggests that tasks assessing decision-making cognition, such as the IGT, may be sensitive to detect cognitive dysfunction in patients with mild fv-FTD. Here, we report a patient with fv-FTD who presented with bizarre behavior including hoarding, pathologic gambling, and abnormal sexual behavior. MethodsA 54-year-old man who had been diagnosed as having fv-FTD was examined using a behavioral assessment, a wide range of neuropsychologic tasks, and the IGT. Brain magnetic resonance imaging and brain 99mTc-ethylcysteinate dimer single-photon emission computed tomography examinations were also performed. ResultsAlthough the patients cognitive abilities were almost fully preserved for a number of traditional neuropsychologic tasks (memory, executive function), the IGT suggested that his decision-making cognition was impaired. The 99mTc-ethylcysteinate dimer single-photon emission computed tomography examination revealed hypometabolism in bilateral medial frontal and orbitofrontal regions of the cerebral cortex, and also in the cingulate gyri. ConclusionsOur findings suggest that the IGT may be a sensitive tool for assessing patients with mild fv-FTD before the development of severe dementia. We speculate that the deficit in decision-making cognition observed in the present case was associated with hypometabolism in the neural networks of the frontal lobe and involving both the bilateral medial frontal and orbitofrontal regions of the cerebral cortex.

Reliability and validity of the Japanese version of the Frontal Assessment Battery in patients with the frontal variant of frontotemporal dementia

Abstract  Patients with the frontal variant of frontotemporal dementia (fv‐FTD) exhibit deficits of executive functions. However, no single executive function task that might be used to detect the executive function deficits in fv‐FTD patients has been established as yet. The frontal assessment battery (FAB) devised by Dubois et al. (2000) has been reported to be a quick and simple bedside screening test that is sensitive for differentiating between FTD and Alzheimer’s disease (AD). The present study was conducted with the aim of ascertaining the reliability and validity of the Japanese version of the FAB among Japanese patients with fv‐FTD. The Japanese version of FAB was given to patients with mild fv‐FTD (n = 18) and those with AD (n = 18). The test–retest reliability was evaluated after a 3‐week interval by the same interviewer. Data from the Wisconsin Card Sorting Test (Keio version: KWCST) were also collected to ascertain the validity of the FAB. The Japanese version of the FAB exhibited good internal reliability (Cronbach’s α: 0.70, 95% confidence interval [CI] = 0.50–0.84) and good test–retest reliability (intraclass correlation coefficient: 0.89, 95%CI = 0.77–0.95). Significant correlations were observed between the total FAB score and the category achieved (r = 0.454, P < 0.05) and number of perseveration errors (number of errors that were perseverations; r = 0.719, P < 0.01) in the KWCST. A cut‐off of 10 for the total FAB score yielded the highest sensitivity (85%) and specificity (92%) for discriminating between patients with fv‐FTD and AD with the highest positive likelihood (12.0, 95%CI = 2.6–55.4). The Japanese version of the FAB offers promise as an easy and quick bedside screening test to distinguish fv‐FTD from AD.

Association between apathy/depression and executive function in patients with Alzheimer's disease

BACKGROUND Apathy and depression may be strongly associated with executive dysfunction in Alzheimers disease (AD). The Frontal Assessment Battery (FAB) is an instrument for assessing executive function. The dual task paradigm is also useful for assessing divided attention. However, the association between apathy/depression and these tasks is unclear. METHODS Both the FAB and the dual task were used to evaluate AD patients. A two-way analysis of variance was then conducted between the FAB and dual task results and the absence versus the presence of depression or the absence versus the presence of apathy. RESULTS Of 88 patients with AD, 26 had both apathy and depression, 26 had depression only, 18 had apathy only, and 18 had neither. Total FAB scores and dual task scores differed significantly between the AD patients with depression and those without depression; the scores were also different between those with apathy and those without apathy. Also, a significant interaction between depression and apathy was noted for the total FAB and dual task scores. CONCLUSIONS The deficits in the total FAB and dual task scores were larger in AD patients with both apathy and depression compared with patients with either apathy or depression alone. AD patients with both symptoms may have greater deficits in frontal lobe function relative to AD patients with either apathy or depression alone.

SPECT-Identified Neuroanatomical Predictor of the Cognitive Effects of Donepezil Treatment in Patients with Alzheimer’s Disease

Background/Objective: We attempted to determine whether the pretreatment regional cerebral blood flow (rCBF) might predict cognitive changes in response to donepezil treatment, as assessed in terms of the Alzheimer Disease Assessment Scale cognitive subscale (ADAS-cog), and in relation to the severity of subcortical hyperintensities (SH). Method: Forty-one patients with Alzheimer’s disease (AD) were treated with donepezil at baseline. All the patients underwent a single photon emission computed tomography examination before donepezil therapy. They also completed the ADAS-cog at baseline and after 24 weeks of donepezil therapy. SH were assessed semiquantitatively using a recently developed visual rating scale. We analyzed the correlation between the baseline rCBF and changes in the ADAS-cog score using statistical parametric mapping, including the severity of the SH as a covariate. Results: Lower pretreatment rCBF levels in the right orbitofrontal cortex (OFC) predicted a better improvement in the ADAS-cog score in response to donepezil therapy. The severity of SH did not appear to influence this correlation. Conclusions: This effect may reflect the choline acetyltransferase activity associated with the OFC. The presence of SH did not appear to influence the effect of donepezil therapy on the cognitive function as assessed by ADAS-cog.

Two dimensions of anosognosia in patients with Alzheimer's disease : Reliability and validity of the Japanese version of the Anosognosia Questionnaire for Dementia (AQ-D)

Abstract  Although a number of studies have examined anosognosia of cognitive deficits in patients with Alzheimers disease (AD), not much is known about the anosognosia of behavioral symptoms in AD. The aims of the present study were to establish a Japanese version of the Anosognosia Questionnaire–Dementia (AQ‐D) and to examine its factor structure, reliability and validity, and to identify the effects of various variables on the AQ‐D. Factor structure, internal consistency, test–retest reliability and concurrent validity of the Japanese version of the AQ‐D were analyzed. Multiple regression was then done using the results of the AQ‐D as dependent variables and entering all relevant predictor variables. Both the internal consistency and the test–retest reliability of the AQ‐D were excellent. Factor analysis indicated four factors: anosognosia of basic and instrumental activities of daily living; that of episodic memory and orientation; that of disinhibited behaviors; and that of apathy and depression. The first two factors were regarded as anosognosia of cognitive deficits and were associated with Mini‐Mental State Examination scores, while the latter two factors were regarded as anosognosia of behavioral symptoms and were associated with the Neuropsychiatric Inventory (NPI) score. A dissociation between the two domains of anosognosia was confirmed, namely of cognitive deficits and of behavioral symptoms using the Japanese version of the AQ‐D. The knowledge that various factors may have different effects on different domains of anosognosia in patients with AD may serve as useful information for clinicians assessing anosognosia in AD.

Efficacy of olanzapine augmentation of paroxetine therapy in patients with severe body dysmorphic disorder

ALTHOUGH SEROTONIN-REUPTAKE INHIBITOR (SRI) augmentation with antipsychotics for the treatment of body dysmorphic disorder (BDD) has recently received attention, the benefits of such augmentation remain unclear. Here, we report a case that exhibited a dramatic improvement in BDD symptoms following the addition of olanzapine to SRI therapy. The patient was a 26-year-old woman with a 10-year history of BDD. At the age of 16, she became obsessed with the idea that she must always keep her body’s skin clean. She became preoccupied with the appearance of her skin and spent many hours a day grooming her body hair. At the age of 20, she experienced a relationship breakup. Thereafter, she became preoccupied with the shape of nose, believing it to be ugly. She frequently checked her nose in the mirror and asked her family for reassurance regarding her nose. Her preoccupation with her appearance resulted in her work being impaired. At the age of 24, she was first admitted to our hospital because of severe weight loss and insomnia because she wasted almost her entire day looking in mirrors and grooming her body hair. Based on the DSM-IV criteria, she was diagnosed as having BDD. In the past, she had been treated with selective serotonin reuptake inhibitors (SSRIs) and an atypical antipsychotic. Neither fluvoxamine (300 mg/day) nor risperidone augmentation of the fluvoxamine treatment diminished her BDD symptoms. Her symptoms also did not improve following the administration of paroxetine (40 mg/day). Her symptoms did not change. Therefore, at the age of 26 years, the paroxetine (40 mg/day) treatment that she was receiving was augmented with 2.5 mg/day of olanzapine. This dose was increased to 5 mg/day after a partial response was observed at 4 weeks. At 6 weeks, her preoccupation with her physical appearance began to subside. Both the amount of time and the frequency with which she checked mirrors and groomed her body hair and toes improved dramatically. This was the first remission of her symptoms since onset at the age of 20 years. Her Yale Brown Obsessive-Compulsive Scale score decreased from 39 to 20. Although she complained of undesired weight gain, at a 1-year follow-up examination, her symptoms were still in remission. Studies that previously examined the effect of the augmentation of SRI therapy with antipsychotics in patients with BDD failed to show any improvement in symptoms. To the best of our knowledge, this is the first BDD case to be successfully treated with olanzapine augmentation of paroxetine therapy. With regard to OCD patients, several studies have reported that olanzapine augmentation of ongoing SRI treatment resulted in an improvement of OCD symptoms. The present case report may support the speculation that BDD has features in common with OCD disorders. Although the neurochemical mechanism underlying BDD is unclear, the serotonin and dopamine system may interact in the mediation of BDD symptoms. Further larger placebo-controlled, double-blinded studies are required to ascertain the effect of olanzapine augmentation of SRI therapy.