Reliability and validity of the Japanese version of the Agitated Behaviour in Dementia Scale in Alzheimer's disease: three dimensions of agitated behaviour in dementia.

BACKGROUND: Agitation in dementia seriously affects not only patients' quality of life (QOL), but also caregivers' QOL. Thus, an appropriate assessment of agitated behaviour in dementia is needed for clinical management. We developed the Japanese version of the Agitated Behaviour in Dementia scale (ABID), examined its reliability and validity, and carried out its factor analysis to elucidate its factor structure. METHODS: The Japanese version of the ABID was given caregivers of 149 Japanese patients with Alzheimer's disease (AD). The internal-consistency, test-retest reliability and concurrent validity of the Japanese version of the ABID were then examined. A factor analysis was used to examine the agitated behavioural dimensions underlying ABID. RESULTS: The Japanese version of the ABID showed an excellent internal reliability for both frequency ratings (Cronbach's α= 0.89) and reaction ratings (Cronbach's α= 0.92), and an excellent test-retest reliability for both frequency ratings and reaction ratings. The total score for the frequency ratings of the ABID was significantly associated with the Cohen-Mansfield Agitation Inventory (CMAI), and the total score for the reaction ratings of the ABID was significantly associated with the Zarit Burden Interview. The factor analysis showed three subtypes: physically agitated behaviour, verbally agitated behaviour and psychosis symptoms. CONCLUSIONS: The Japanese version of the ABID promises to be useful for assessing agitated behaviour in patients with AD. Importantly, understanding these subtypes of agitated behaviour might have implications for individualized treatment plans.

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.

Neural correlates of memory in depression measured by brain perfusion SPECT at rest.

AIM: Brain metabolism activated studies have indicated associations between memory and the anterior cingulate cortex and hippocampus in patients with depression. The aim of the present study was therefore to investigate memory function, measured as performance on the Wechsler Memory Scale-Revised (WMS-R), and its relationship to brain perfusion using single-photon emission computed tomography (SPECT) at rest in patients with depression. METHODS: The Hamilton Rating Scale for Depression (HAMD) and WMS-R were measured for 17 patients with depression by an independent clinical evaluation team. Voxel-based correlation analyses were performed with statistical parametric mapping at an extent threshold of 200 voxels. Associations were controlled for state and trait factors. RESULTS: WMS-R measurements of verbal, visual, and general memory were inversely correlated with brain perfusion in the right anterior cingulate cortex, left premotor cortices, and both regions, respectively. The HAMD directly correlated with brain perfusion in the right anterior cingulate cortex. CONCLUSION: Brain perfusion SPECT measurements of the anterior cingulate cortex at rest were associated with the severity of depression and immediate memory scores measured with the WMS-R.

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). METHODS: First, we investigated whether neuropsychiatric symptoms at baseline predict changes in the QOL of AD patients over time. Then we examined the associations between changes in neuropsychiatric symptoms and changes in QOL. QOL was assessed using the Japanese version of the Quality of Life-Alzheimer Disease (QOL-AD) scale and other clinical instruments [the Mini-Mental State Examination, The Neuropsychiatry Inventory (NPI)] at baseline and again two years later in 96 AD patients among 140 AD patients at baseline. We performed a multiple regression analysis of the baseline QOL-AD score, NPI score (mood, psychosis, and euphoria factor), Mini-Mental State Examination score, and other clinical instrument variables (e.g. Activities-of-Daily-Living scores) to determine their contribution to the change in QOL-AD score. RESULTS: While the total QOL-AD score based on the patients' responses did not change significantly, the total QOL-AD score derived from the caregivers' responses declined. Both the Activities-of-Daily-Living score and the mood factor of the NPI score predicted the change in the QOL-AD score as assessed by the caregivers' responses. In addition, there was a significant correlation between the changes in two factors of the NPI, i.e. the mood and psychosis factor, and the changes in the QOL-AD score based on the caregivers' responses. CONCLUSIONS: The presence of specific neuropsychiatric symptoms (mood and psychosis symptoms) was associated with changes in the QOL of AD patients during the follow-up period.

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.

Impact of depression on insight into memory capacity in patients with Alzheimer disease.

BACKGROUND: The influence of depressive symptoms on awareness of memory disturbances in patients with Alzheimer disease (AD) and metamemory is unknown. OBJECTIVE: We compared the level of awareness of memory disturbances in AD patients with and without depression using 2 measures: a questionnaire comparing discrepancies in patients/caregivers' assessments and the patients' predictions of their own performances on a memory task. METHODS: AD patients with depression (n=21) or without depression (n=21) were asked to complete an assessment of self-reported memory dysfunction (Short Memory Questionnaire; SMQ) and memory task performance prediction (10-words-recall Questionnaire). In addition, the caregivers' evaluations of the memory deficits in the study patients were assessed using the SMQ. RESULTS: We observed a greater discrepancy in the SMQ scores given by the caregivers' and the patients' among AD patients without depression, compared with those with depression. A greater discrepancy was also observed in the ratio score (patient's predicted performance/actual performance) for the 10-words-recall Questionnaire in AD patients without depression than in those with depression. CONCLUSIONS: AD patients with depression may estimate their memory ability either more accurately or more negatively than AD patients without depression, as shown using the above 2 methods.

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 Alzheimer's 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.

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).

Although a number of studies have examined anosognosia of cognitive deficits in patients with Alzheimer's 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.

Ictal electroencephalographic correlates of posttreatment neuropsychological changes in electroconvulsive therapy: a hypothesis-generation study.

OBJECTIVES: Electroconvulsive therapy (ECT) has been associated with memory and neuropsychological changes, but which features of ECT are associated with those changes have not been well investigated. The aim of this hypothesis-generation study was to examine correlations between ictal electroencephalographic (EEG) characteristics and cognitive side effects after ECT. METHODS: Eight patients with major depressive disorder were examined with the Wechsler Memory Scale-Revised (WMS-R), the Stroop test, the Trail Making Test, and verbal fluency before and after ECT treatment. Seven ictal EEG measurements (eg, slow-wave phase amplitude, postictal suppression) were manually rated by 3 independent psychiatrists. The correlations between ictal EEG measurements, changes in WMS-R subset scores, and non-memory-related neuropsychological assessments were examined with Spearman rank correlation. RESULTS: Verbal memory, general memory, attention/concentration, delayed memory of WMS-R subset scores, and the Stroop test scores improved significantly after ECT treatment. Postictal suppression and slow-wave amplitude correlated positively with delayed memory and visual/verbal discrepancy score. Slow-wave amplitude correlated negatively with letter fluency. The longer the polyspike wave duration, the higher the attention/concentration test results. CONCLUSIONS: Certain ictal EEG measurements were associated with changes in several neuropsychological test results that had improved 2 weeks after the final ECT treatment. A hypothesis-testing study with a larger sample is needed to verify the relationships between EEG measurements and neuropsychological test performance.

Impairment of decision-making cognition in a case of frontotemporal lobar degeneration (FTLD) presenting with pathologic gambling and hoarding as the initial symptoms.

OBJECTIVE: The 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). BACKGROUND: Although 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. METHODS: A 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. RESULTS: Although the patient's 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. CONCLUSIONS: Our 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 Dysexecutive Questionnaire (DEX) in Alzheimer's disease: validation of a behavioral rating scale to assess dysexecutive symptoms in Japanese patients with Alzheimer's disease.

BACKGROUND: Both executive cognitive dysfunction and behavioral problems contribute to dysexecutive symptoms in daily life. The aim of the present study was to develop a behavior rating scale for assessing dysexecutive symptoms in Japanese patients with AD. METHOD: The Dysexecutive Questionnaire (DEX), devised by Burgess et al. (1998), was used to evaluate 122 Japanese patients with AD. The factor structure, internal consistency, test-retest reliability, and construct validity of the Japanese version of the DEX were then examined. RESULTS: The Japanese version of the DEX demonstrated a good internal reliability and a good test-retest reliability. Factor analysis revealed three factors that were named 'apathy', 'hyperactivity' and 'planning and monitoring process of the purposive action'. The 'apathy' factor of the DEX was significantly correlated with the 'apathy' score of the Neuropsychiatric Inventory (NPI), while 'planning and monitoring process' factor of the DEX was significantly correlated with the total score of the Frontal Assessment Battery (FAB) and the 'hyperactivity' factor of the DEX was significantly correlated with the 'aggression', 'euphoria' and 'disinhibition' scores of the NPI. CONCLUSIONS: The Japanese DEX is a reliable and valid instrument for assessing executive dysfunction conveniently in real life situations of AD patients. While two factors, 'apathy' and 'hyperactivity', were associated with emotional and behavioral changes, the 'planning and monitoring process' was associated with the cognitive executive function in the patients with AD. These findings suggest that both a neuropsychiatric syndrome and cognitive function contribute to the dysexecutive symptoms experienced by AD patients in daily life.

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.

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

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 alpha: 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.

The differential impact of executive attention dysfunction on episodic memory in obsessive-compulsive disorder patients with checking symptoms vs. those with washing symptoms.

Neuropsychological studies of obsessive-compulsive disorder (OCD) have pointed to memory and attention deficits among its sufferers, but these reports have largely ignored the possibility that cognitive disturbances may vary across OCD clinical subtypes, or that their interactions may differ between subtypes. The purpose of the present study was to determine whether "checkers" and "washers" demonstrate differences in their memory and executive attention function. Fifty-three outpatients with primary DSM-IV diagnosis of OCD with typical checking (n=27) or washing (n=26) rituals participated in the study. Patients were administered the Wechsler Memory Scale-Revised and a comprehensive neuropsychological battery to assess executive attention function. Various neuropsychological tests were then subjected to factor analysis. Neuropsychological test results and obtained factor scores were compared between "washers" and "checkers". Effects of these factor scores on memory by OCD subtypes were examined. No significant difference in terms of demographic and clinical variables was found between the two groups. Checkers displayed performance deficits on Stroop test, Trail Making Test, GO/NO GO test (commission errors) and category fluency. Three factors, inhibition, cognitive flexibility, and multi-tasking, were obtained. Statistically significant differences were observed between the two groups on the inhibition and the cognitive flexibility scores, but not on the general memory or the multi-tasking score. There was a statistically significant interaction between groups and the inhibition score. Only among "checkers", a significant correlation was noted between the inhibition factor and the general memory, while no such correlation was observed among "washers". Among "checkers", poor general memory was related to inhibition deficits.

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 alpha = 0.84) and the caregivers' responses (Cronbach's alpha = 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>or=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.