Prediction of remission in pharmacotherapy of untreated major depression: development and validation of multivariable prediction models.

BACKGROUND: Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals. METHODS: The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 2011). Using the first half of the cohort as the derivation set, we applied multiply-imputed stepwise logistic regression with backward selection to build a prediction model to predict remission, defined as scoring 4 or less on the Patient Health Quetionnaire-9 at week 9. We used three successively richer sets of predictors at baseline only, up to week 1, and up to week 3. We examined the external validity of the derived prediction models with the second half of the cohort. RESULTS: In total, 37.0% (95% confidence interval 34.8-39.1%) were in remission at week 9. Only the models using data up to week 1 or 3 showed reasonable performance. Age, education, length of episode and depression severity remained in the multivariable prediction models. In the validation set, the discrimination of the prediction model was satisfactory with the area under the curve of 0.73 (0.70-0.77) and 0.82 (0.79-0.85), while the calibration was excellent with non-significant goodness-of-fit χ2 values (p = 0.41 and p = 0.29), respectively. CONCLUSIONS: Patients and clinicians can use these prediction models to estimate their predicted probability of achieving remission after acute antidepressant therapy.

Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial.

BACKGROUND: For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished. METHODS: This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates. RESULTS: Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), - 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects. CONCLUSIONS: In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01109693 . Registered on 23 April 2010.

Cognitive and Behavioral Skills Exercises Completed by Patients with Major Depression During Smartphone Cognitive Behavioral Therapy: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: A strong and growing body of evidence has demonstrated the effectiveness of cognitive behavioral therapy (CBT), either face-to-face, in person, or as self-help via the Internet, for depression. However, CBT is a complex intervention consisting of several putatively effective components, and how each component may or may not contribute to the overall effectiveness of CBT is poorly understood. OBJECTIVE: The aim of this study was to investigate how the users of smartphone CBT use and benefit from various components of the program. METHODS: This is a secondary analysis from a 9-week, single-blind, randomized controlled trial that has demonstrated the effectiveness of adjunctive use of smartphone CBT (Kokoro-App) over antidepressant pharmacotherapy alone among patients with drug-resistant major depressive disorder (total n=164, standardized mean difference in depression severity at week 9=0.40, J Med Internet Res). Kokoro-App consists of three cognitive behavioral skills of self-monitoring, behavioral activation, and cognitive restructuring, with corresponding worksheets to fill in. All activities of the participants learning each session of the program and completing each worksheet were uploaded onto Kokoro-Web, which each patient could use for self-check. We examined what use characteristics differentiated the more successful users of the CBT app from the less successful ones, split at the median of change in depression severity. RESULTS: A total of 81 patients with major depression were allocated to the smartphone CBT. On average, they completed 7.0 (standard deviation [SD] 1.4) out of 8 sessions of the program; it took them 10.8 (SD 4.2) days to complete one session, during which they spent 62 min (SD 96) on the app. There were no statistically significant differences in the number of sessions completed, time spent for the program, or the number of completed self-monitoring worksheets between the beneficiaries and the nonbeneficiaries. However, the former completed more behavioral activation tasks, engaged in different types of activities, and also filled in more cognitive restructuring worksheets than the latter. Activities such as "test-drive a new car," "go to a coffee shop after lunch," or "call up an old friend" were found to be particularly rewarding. All cognitive restructuring strategies were found to significantly decrease the distress level, with "What would be your advice to a friend who has a similar problem?" found more helpful than some other strategies. CONCLUSIONS: The CBT program offered via smartphone and connected to the remote server is not only effective in alleviating depression but also opens a new avenue in gathering information of what and how each participant may utilize the program. The activities and strategies found useful in this analysis will provide valuable information in brush-ups of the program itself and of mobile health (mHealth) in general. TRIAL REGISTRATION: Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik).

The first 100 patients in the SUN(

BACKGROUND: Initial glitches and unexpected inconsistencies are unavoidable in the early stage of a large, multi-centre trial. Adaptive modifications of the trial's protocol and operational procedures to ensure its smooth running are therefore imperative. We started a large pragmatic, multi-centre, assessor-blinded, 25-week trial to investigate the optimal first- and second-line treatments for untreated episodes of nonpsychotic major depression in 2010 [Strategic Use of New generation antidepressants for Depression, abbreviated SUN(^_^)D] and would like to herein report an examination of the trial's feasibility and adherence among the first 100 participants. METHODS: We examined the participants' characteristics, the treatments that were allocated and received during each step of the trial, and the quality of the outcome assessments among the first 100 patients enrolled in the SUN(^_^)D trial. RESULTS: Of the 2,743 first-visit patients who visited the two collaborating centres between December 2010 and July 2011, 382 were judged as potentially eligible, and 100 of these patients provided written informed consent. These patients represented the whole spectrum of mild to very severe depression. Of the 93 patients who had reached Week 3 of the study by the end of July 2011, one withdrew consent for both the treatment and the assessment, and eight withdrew consent for the treatment only. Altogether, the primary outcomes were successfully assessed in 90 (96.8%) of the patients at Week 3. Of the 72 patients who had reached Week 9, three withdrew consent for the treatment, but 70 were successfully interviewed (97.2%). Of the 32 patients who had reached Week 25, 29 (90.5%) were successfully followed up. The inter-rater reliability of the assessments of the primary outcomes was nearly perfect and their successful blinding was confirmed. Minor modifications and clarifications to the protocol were deemed necessary. DISCUSSION: Given the satisfactory feasibility and adherence to the study protocol and the minor modifications that were necessary, we conclude that the data obtained from the first 100 patients can be safely included in the main study. We now intend to accelerate the study by recruiting more collaborating centres and clinics/hospitals. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01109693.

Ictal physiological characteristics of remitters during bilateral electroconvulsive therapy.

Ictal heart rate (HR) and postictal suppression in ictal EEG are believed to be predictive of the therapeutic efficacy of eletroconvulsive therapy (ECT) for depression. However, regarding ictal peak HR, previous studies investigated ictal HR on only one or two occasions during the course of ECT. We prospectively examined whether two physiological parameters, ictal peak HR and postictal suppression in ictal EEG, during every session, including those with abortive seizure, predicted ECT efficacy. Ictal peak HR and postictal suppression index were analyzed in 53 consecutive inpatients with depression using generalized estimating equations analysis, which corrects for the repeated nature of the observations. The peak HR and postictal suppression index were associated with therapeutic efficacy in remitters during sessions with adequate seizure. The physiological characteristics of the remitters included lower peak HR, lower stimulus energy, and higher postictal suppression index. However, these results could not be generalized, and are limited to non-atropine conditions and bilateral ECT.

A case with Hodgkin lymphoma and fronto-temporal lobular degeneration (FTLD)-like dementia facilitated by chemotherapy.

We report a case of a 39-year-old man with Hodgkin lymphoma who developed depressive symptoms after starting adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy and later exhibited sexual disinhibition in addition to cognitive dysfunction (mainly executive dysfunction). Seven months after the start of adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy, he was finally diagnosed as having fronto-temporal lobular degeneration-like dementia facilitated by adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy. At the time of writing, the patient's condition has persisted for more than 6 months after the discontinuation of adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy, and the changes in brain function brought on by the adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy may now be irreversible. This case points to the importance of being attentive to the appearance of neuropsychiatric symptoms and evaluating brain functions properly when performing anti-cancer chemotherapy.

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.

Changes after behavior therapy among responsive and nonresponsive patients with obsessive-compulsive disorder.

Neuroimaging studies have suggested that behavior therapy (BT) might change abnormal activity in the frontal-subcortical circuits of the brain in patients with obsessive-compulsive disorder (OCD). However, the results of these studies have been rather inconsistent. The aim of the present study was to use statistical parametric mapping (SPM) analysis to explore the effects of successful BT on regional cerebral blood flow (rCBF) in patients with OCD. Forty-five OCD patients who were treatment-resistant to a single serotonin reuptake inhibitor (SRI) trial were examined. Single photon emission computed tomography (SPECT) using 99mTc-ECD was performed before and after the completion of 12 weeks of BT. Although no significant differences in pre-treatment rCBF were observed between responders and nonresponders to BT, the post-treatment rCBF values in the left medial prefrontal cortex (Brodmann area 10) and bilateral middle frontal gyri (Brodmann area 10) were significantly lower in the responders than in the nonresponders. Furthermore, the baseline rCBF in the bilateral orbitofrontal cortex (OFC) was significantly correlated with the change in the Y-BOCS score among the responders. Our results support the hypothesis that while the OFC may be associated with the BT response, BT may result in changes in rCBF in the medial and middle frontal cortex.

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.

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.

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 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.

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.

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.