Greater than the Sum of Its Parts: δ can be Constructed from Item Level Data.

"δ", a latent variable constructed from cognitive performance and functional status measures, can accurately diagnose dementia. The minimal assessment needed is unknown. We have constructed a δ homolog, "dTEXAS", from Telephone Executive Assessment Scale (TEXAS) items, and validated it in a convenience sample of Japanese persons (n = 176). dTEXAS scores correlated strongly with both Instrumental Activities of Daily Living (IADL) (r = -0.86, p <  0.001) and Clinical Dementia Rating Scale (CDR) (r = 0.71, p <  0.001). Constructed independently of their diagnoses, dTEXAS scores accurately distinguished dementia versus controls (area under the receiver operating curve [(AUC; ROC) = 0.92], dementia versus mild cognitive impairment (MCI) (AUC = 0.80) and controls versus MCI (AUC = 0.74). These AUCs are higher than those of multiple observed executive measures, as reported recently by Matsuoka et al., 2014. A dTEXAS score of -0.58 best discriminated between dementia versus controls with 90.1% sensitivity and 80.0% specificity.

δ Scores are Exportable Across Cultural and Linguistic Boundaries.

The latent variable "δ", can accurately diagnose dementia. Its generalizability across populations is unknown. We constructed a δ homolog ("dT2J") in data collected by the Texas Alzheimer's Research and Care Consortium (TARCC). From this, we calculated a composite d-score "d". We then tested d's generalizability across random subsets of TARCC participants and to a convenience sample of elderly Japanese persons with normal cognition (NC), mild cognitive impairment (MCI), and dementia (AD) (n = 176). dT2J was indicated by Instrumental Activities of Daily Living and psychometric measures. Embedded in this battery were the Mini-Mental Status Examination (MMSE) and an executive clock-drawing task (CLOX). Only MMSE and CLOX were available in both TARCC and the Japanese cohort. Therefore, a second composite variable, "T2J", was constructed solely from the factor loadings of CLOX and MMSE on d. The diagnostic accuracy of T2J was estimated in the validation sample, the remainder of the TARCC cohort, and in the Japanese sample. The areas under the receiver operating curve (AUC; ROC) for T2J were compared in each sample, and against d in TARCC. The AUCs for T2J were statistically indiscriminable within TARCC, and in Japanese persons. In Japanese persons, AUCs for T2J were 0.97 for the discrimination between AD versus NC, 0.86 for AD versus MCI, and 0.79 for NC versus MCI. The AUCs for T2J in Japanese persons were higher than any individual psychometric measure in that sample. Valid d-score composites can be abstracted from a subset of δ's indicators. Moreover, those composites are exportable across cultural and linguistic boundaries.

Greater than the sum of its parts: δ Improves upon a battery's diagnostic performance.

OBJECTIVE: "δ", a latent variable constructed from batteries that contain both cognitive and functional status measures, can accurately diagnose dementia relative to expert clinicians. The minimal assessment needed is unknown. METHODS: We validated 2 δ homologs in a convenience sample of elderly Japanese persons with normal cognition (NC), mild cognitive impairment (MCI), and dementia (n = 176). The latent δ homolog "d" (for dementia) was constructed from Instrumental Activities of Daily Living (IADL) and Japanese translations of the Executive Clock-Drawing Task (CLOX), Frontal Assessment Battery (FAB), and Executive Interview (EXIT25). The latent delta homolog "d3" was constructed from a restricted set of d's factor loadings. RESULTS: d and d3 were highly intercorrelated (r = .97) and strongly related to both IADL and dementia severity, as rated blindly by the Clinical Dementia Rating Scale (CDR). d was more strongly related to IADL and CDR than any of its indicators. In multivariate regression, d explained more variance in CDR scores than all of its indicators combined. d's areas under the receiver operating characteristic curve (AUC) were 0.95 for the discrimination between Alzheimer's disease (AD) vs. NC, 0.84 for AD vs. MCI and 0.81 for NC vs. MCI. d3's AUC's were statistically indiscriminable. These AUC's are higher than any of d's indicators, as reported recently by Matsuoka et al. (2014), as well as the Mini-Mental State Examination (MMSE), which had been made available by Matsuoka et al. to the CDR raters. CONCLUSIONS: Latent variables can improve upon a battery's diagnostic performance and offer the potential for accurate dementia case-finding after a minimal bedside assessment.

Defensive function of persecutory delusion and discrepancy between explicit and implicit self-esteem in schizophrenia: study using the Brief Implicit Association Test.

BACKGROUND: If delusions serve as a defense mechanism in schizophrenia patients with paranoia, then they should show normal or high explicit self-esteem and low implicit self-esteem. However, the results of previous studies are inconsistent. One possible explanation for this inconsistency is that there are two types of paranoia, "bad me" (self-blaming) paranoia and "poor me" (non-self-blaming) paranoia. We thus examined implicit and explicit self-esteem and self-blaming tendency in patients with schizophrenia and schizoaffective disorder. We hypothesized that patients with paranoia would show lower implicit self-esteem and only those with non-self-blaming paranoia would experience a discrepancy between explicit and implicit self-esteem. METHODS: Participants consisted of patients with schizophrenia and schizoaffective disorder recruited from a day hospital (N=71). Participants were assessed for psychotic symptoms, using the Brief Psychiatric Rating Scale (BPRS), and self-blaming tendency, using the brief COPE. We also assessed explicit self-esteem, using the Rosenberg Self-Esteem Scale (RSES), implicit self-esteem, using Brief Implicit Association Test (BIAT), and discrepancy between explicit and implicit self-esteem. RESULTS: Contrary to our hypothesis, implicit self-esteem in paranoia and nonparanoia showed no statistical difference. As expected, only patients with non-self-blaming paranoia experienced a discrepancy between explicit and implicit self-esteem; other groups showed no such discrepancy. CONCLUSION: These results suggest that persecutory delusion plays a defensive role in non-self-blaming paranoia.

Japanese versions of the executive interview (J-EXIT25) and the executive clock drawing task (J-CLOX) for older people.

BACKGROUND: The aim of the study was to develop the Japanese versions of Executive Interview (J-EXIT25) and Executive Clock Drawing Task (J-CLOX) and to evaluate the aspects of executive function that these two tests will be examining. METHODS: The concurrent validity and reliability of J-EXIT25 and J-CLOX were first examined in all participants (n = 201). Next, the relationship between the two tests was examined using receiver operating characteristic (ROC), correlation, and regression analyses in healthy participants (n = 45) and participants with mild cognitive impairment (n = 36) and dementia (n = 95). RESULTS: Satisfactory concurrent validity and reliability of J-EXIT25 and J-CLOX were shown. ROC analysis indicated that J-EXIT25 and J-CLOX1 were superior to the Frontal Assessment Battery, but inferior to the Mini-Mental State Examination (MMSE), in discriminating between non-dementia and dementia. J-EXIT25, J-CLOX1, and J-CLOX2 scores were significantly correlated with age, scores on the MMSE, Instrumental Activities of Daily Living (IADL) and Physical Self-Maintenance Scale (PSMS), and care level. In stepwise regression analyses of IADL scores, MMSE and J-EXIT25 were significantly independent predictors in men, and MMSE, age, and J-CLOX1 were significantly independent predictors in women. J-EXIT25, MMSE, and J-CLOX1 were significantly independent predictors in stepwise regression analysis of PSMS scores, and J-EXIT25 was the only significantly independent predictor in stepwise regression analysis of care level. CONCLUSIONS: J-EXIT25 and J-CLOX are valid and reliable instruments for assessment of executive function in older people. The present results suggest that these tests have common and distinct psychometric properties in the assessment of executive function.

Diagnostic performance of a combination of Mini-Mental State Examination and Clock Drawing Test in detecting Alzheimer's disease.

OBJECTIVE: Because of the growing need for quick cognitive screening tests to distinguish Alzheimer's disease (AD) from mild cognitive impairment (MCI), we compare the diagnostic performance of a combination of the Mini-Mental State Examination (MMSE) and a Clock Drawing Test (CDT) to the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-J cog) in differentiating between patients with AD, patients with MCI, and healthy controls (HC). METHODS: Data from 146 subjects with AD and 60 subjects with MCI, as well as 49 HC, was retrospectively analyzed. We used logistic regression analysis with diagnosis as dependent variables and scores of the MMSE, the CDT-command, and the CDT-copy as independent variables, and receiver operating characteristic analysis to distinguish patients with AD from patients with MCI or HC. RESULTS: When patients with AD were compared to HC, the independent predictors of AD were scores on the MMSE and the CDT-command. This combination was more sensitive than the MMSE alone and has nearly the same sensitivity and specificity as the ADAS-J cog. When patients with AD were compared to patients with MCI, the independent predictors were the MMSE and the CDT-copy. This combination was more sensitive and specific than the MMSE alone and was almost as sensitive and specific as the ADAS-J cog. CONCLUSION: The combination of the MMSE and the CDT could be a powerful screening tool for differentiating between patients with AD, patients with MCI, and HC. Its sensitivity and specificity are comparable to ADAS-J cog, which takes more time.

Neural correlates of the components of the clock drawing test.

BACKGROUND: The aim of this study was to identify the neural correlates of each component of the clock drawing test (CDT) in drug-naïve patients with Alzheimer's disease (AD) using single photon emission computed tomography. METHODS: The participants were 95 drug-naïve patients with AD. The Rouleau CDT was used to score the clock drawings. The score for the Rouleau CDT (R total) is separated into three components: the scores for the clock face (R1), the numbers (R2), and the hands (R3). A multiple regression analysis was performed to examine the relationship of each score (i.e. R total, R1, R2, and R3) with regional cerebral blood flow (rCBF). Age, gender, and education were included as covariates. The statistical threshold was set to a family-wise error (FWE)-corrected p value of 0.05 at the voxel level. RESULTS: The R total score was positively correlated with rCBF in the bilateral parietal and posterior temporal lobes and the right middle frontal gyrus. R1 was not significantly positively correlated with rCBF, R2 was significantly positively correlated with rCBF in the right posterior temporal lobe and the left posterior middle temporal lobe, and R3 was significantly positively correlated with rCBF in the bilateral parietal lobes, the right posterior temporal lobe, the right middle frontal gyrus, and the right occipital lobe. CONCLUSIONS: Various brain regions were associated with each component of the CDT. These results suggest that an assessment of these components is useful for the detection of localization of brain damage.

Treatment in a ward for elderly patients with dementia in Japan.

BACKGROUND: Japan has become the world's most aged country. The percentage of elderly people in Japan is estimated to reach 25.2% in 2013, and the number of patients with dementia is estimated to reach 2.5 million in 2015. In addition to its deterioration of physical function and activities of daily living (ADL), behavioral and psychological symptoms of dementia (BPSD) often become major clinical problems, greatly annoying patients and their caregivers. In Japan, we utilize wards for elderly patients with dementia (WEDs) for BPSD treatment. However, there are few studies investigating the effectiveness of treatment in a WED. In such treatment, physical complications are a challenge physicians must overcome while treating BPSD and safely returning patients home or to the institutions in which they live. Therefore, we investigated the effectiveness of treatment in a WED, focusing on physical complications. METHODS: The subjects were 88 patients who were admitted to and discharged from a WED. Severity of dementia, basic ADL, and BPSD were investigated using the Clinical Dementia Rating, Physical Self-Maintenance Scale (PSMS), and Neuropsychiatric Inventory. Differences in characteristics between patients discharged from the WED because of physical complications and all other patients were also examined. RESULTS: We found significant improvements in the PSMS score and decreases in delusions and sleep disturbances in all patients. Patients discharged from the WED because of physical complications had significantly greater severity of dementia at discharge compared to all other patients. CONCLUSION: Treatment in a WED seems to be effective for BPSD and ADL, but care should be taken regarding physical complications, especially in patients with advanced dementia.

Relationship between patients' quality of life and coercion in psychiatric acute wards.

The influence of coercion on quality of life (QoL) was investigated in 202 patients in acute psychiatric wards. There was no correlation between either subjective or objective coercion and QoL. Global Assessment of Functioning scores on improvement and insight were correlated with QoL.

Effect of toki-shakuyaku-san on regional cerebral blood flow in patients with mild cognitive impairment and Alzheimer's disease.

The aim of this study was to examine the effect of toki-shakuyaku-san (TSS) on mild cognitive impairment (MCI) and Alzheimer's disease (AD) using single-photon emission computed tomography (SPECT). All subjects were administered TSS (7.5 g/day) for eight weeks. SPECT and evaluations using the Mini Mental State Examination (MMSE), Neuropsychiatric Inventory, and Physical Self-Maintenance Scale were performed before and after treatment with TSS. Three patients with MCI and five patients with AD completed the study. No adverse events occurred during the study period. After treatment with TSS, regional cerebral blood flow (rCBF) in the posterior cingulate was significantly higher than that before treatment. No brain region showed a significant decrease in rCBF. TSS treatment also tended to improve the score for orientation to place on the MMSE. These results suggest that TSS could be useful for treatment of MCI and AD.

Neuropsychological and functional correlates of clock-drawing test in elderly institutionalized patients with schizophrenia.

BACKGROUND: There has been a growing need for a cognitive assessment tool that can be used for older adults with schizophrenia in clinical settings. The clock-drawing test (CDT) is a brief cognitive test that covers a wide range of cognitive function. Although it is widely used to assess patients with dementia, limited data are available on its usefulness in older patients with schizophrenia. Thus, we investigated the psychometric properties of the CDT and their relationship with life functions to examine the test's usefulness for assessing cognitive function in older adults with schizophrenia. METHODS: Seventy-three older adults with chronic schizophrenia who had been hospitalized for over 1 year participated in the study. We adopted the executive clock-drawing task for administration and scoring of the CDT, which consists of free-drawn and copy conditions. The Mini-Mental State Examination and the Brief Assessment of Cognition in Schizophrenia were administered. Symptom severity and life functions were assessed with the Positive and Negative Syndrome Scale and the Life Skills Profile, respectively. RESULTS: Both free-drawn and copy scores significantly correlated with the Mini-Mental State Examination score and the Brief Assessment of Cognition in Schizophrenia composite score. These scores also significantly correlated with symptom severity and length of current hospitalization. Stepwise regression analysis showed that only the copy score, together with symptom severity, predicted the Life Skills Profile score. CONCLUSIONS: The CDT can assess cognitive function in older adults with schizophrenia. Moreover, CDT performance is associated with life functions independent from other clinical variables. These results suggest that the CDT is a useful cognitive assessment tool for this population.

Neural correlates of performance on the different scoring systems of the clock drawing test.

The aim of this study was to identify brain regions associated with performance on various measures of the clock drawing test (CDT) using magnetic resonance imaging (MRI).We recruited 48 participants (four healthy, eight with mild cognitive impairment and 36 with Alzheimer's disease). Multiple regression analyses identified relationships between each CDT scoring system (Shulman CDT, Rouleau CDT and CLOX1) and regional gray matter (GM) volume.CDT scores were positively correlated with regional GM volume in the right parietal lobe for all three CDT scoring systems. In addition, CDT scores were positively correlated with regional GM volume in the bilateral posterior temporal lobes for the Shulman CDT, in the right posterior inferior temporal lobe for the Rouleau CDT and in the right posterior superior temporal lobe for the CLOX1.Although the scoring systems share commonalities, each CDT scoring system may reflect different areas of brain damage.

Insight and quality of life in long-term hospitalized Japanese patients with chronic schizophrenia.

AIM: The aim of the study was to investigate the relationship between insight and quality of life (QOL) and the respective predictive factors in long-term hospitalized patients with chronic schizophrenia. METHODS: The present subjects were 47 Japanese patients with chronic schizophrenia who were hospitalized for >1 year (mean hospitalization period, 9.8 years). Assessments were made using the Scale of Unawareness of Mental Disorder (SUMD) and the EuroQoL-5 Dimensions (EQ-5D) scale. Sociodemographic details and illness-related variables were also evaluated, including use of the Positive and Negative Syndrome Scale. RESULTS: There was no association between SUMD and EQ-5D scores. Hallucinatory behavior was a predictor of good insight. Poor rapport was a predictor of bad insight. Poor attention was a predictor of bad QOL. CONCLUSION: The relationship between insight and QOL and the respective predictive factors might be different between acute and chronic stages. Further studies are needed to investigate how these changes occur.

Insular hypoperfusion correlates with the severity of delusions in individuals with Alzheimer's disease.

BACKGROUND: The aim of this study was to identify the brain regions associated with the severity of delusions in individuals with Alzheimer's disease (AD) using single-photon emission computed tomography. METHODS: Thirty-five AD patients participated in this study. Multiple regression analysis was performed to identify a linear correlation between the delusion subscale score of the Neuropsychiatric Inventory (NPI) and regional cerebral blood flow (rCBF) in AD patients with delusions (n = 14). In addition, rCBF in patients with (n = 14) and without delusions (n = 21) was compared using a 2-sample t test. RESULTS: The delusion subscale score of the NPI was negatively correlated with rCBF in the right anterior insula (uncorrected p < 0.01 at the voxel level and corrected p < 0.05 at the cluster level). Compared to patients without delusions, however, rCBF in the right anterior insula was not significantly decreased in patients with delusions. CONCLUSION: We suggest that right anterior insular dysfunction may exacerbate delusions, although it is not responsible for the onset of delusions.

Surface modification of porous scaffolds with nanothick collagen layer by centrifugation and freeze-drying.

Three-dimensional (3D) porous scaffolds constructed from biodegradable synthetic polymers are frequently used in tissue engineering. Their surfaces are hydrophobic and require treatment to be changed to hydrophilic before use in cell culture. We developed a novel surface modification for 3D porous scaffolds made of synthetic polymers by coating the surfaces of the pores with a nanothick collagen layer. First, a collagen aqueous solution was introduced under reduced pressure to fully fill the pores of the PLGA sponges. The collagen-containing sponges were then centrifuged to remove any excess collagen solution. Finally, the sponges were freeze-dried to form a thin collagen layer. Scanning electron microscopy observation and water absorption tests demonstrated that the excess collagen was removed; the effect of modification was evident when the collagen-containing sponges were centrifuged at high centrifugal acceleration. Scanning probe microscopy analysis demonstrated the formation of a nanometer-thick collagen layer on the PLGA surface. The collagen-coated PLGA sponges facilitated cell seeding and spatial distribution. The method will be useful for the surface modification of 3D porous scaffolds.

Effective cell separation utilizing poly(N-isopropylacrylamide)-grafted polypropylene membrane containing adsorbed antibody.

We previously developed a cell separation method using a poly(N-isopropylacrylamide)-grafted polypropylene (PNIPAAm-g-PP) membrane containing an adsorbed monoclonal antibody (mAb). The purpose of this study is to elucidate the cell separation mechanism in detail and to design an optimal method. As the grafting yield of PNIPAAm increased, the level of the adsorption of IgG(1) and cell adhesion to the membrane decreased. After BSA was adsorbed to a PNIPAAm-g-PP membrane at 6 degrees C, where PNIPAAm was hydrophilic, a small amount of IgG(1) was adsorbed to the membrane at 37 degrees C, where PNIPAAm was hydrophobic. The desorption of the adsorbed IgG(1) was not enhanced even though temperature was reduced to 10 degrees C, where PNIPAAm was hydrophilic. These results indicate that the antibody adsorbed to the intact PP surface of the membrane predominantly contributes to the capture of target cells through the antigen-antibody reaction and that a thermoresponsive transition of PNIPAAm contributes to the detachment of the captured cells. The total number of cells recovered from a PNIPAAm-g-PP membrane containing the adsorbed mAb decreased as the grafting yield increased. A PNIPAAm-g-PP membrane with a 1.7% grafting yield containing adsorbed anti-human CD34 mAb enriched CD34-positive KG-1a cells to 85% from a 1:1 cell suspension of KG-1a cells and CD34-negative Jurkat cells.

Poly(N-isopropylacrylamide)-graft-polypropylene membranes containing adsorbed antibody for cell separation.

We developed a novel selective cell-separation method based on using a poly(N-isopropylacrylamide)-graft-polypropylene (PNIPAAm-g-PP) membrane containing adsorbed monoclonal antibody specific to the target cell. This membrane was prepared by plasma-induced polymerization and soaking in an antibody solution at 37 degrees C. Poly(N-isopropylacrylamide) has a thermoresponsive phase transition: at 32 degrees C water-insoluble (hydrophobic) and water-soluble (hydrophilic) states interconvert. Adsorption of antibody onto PNIPAAm-g-PP membrane at 37 degrees C and its desorption at 4 degrees C was verified by fluorescence-microscopy of the PNIPAAm-g-PP membrane after soaking it in fluorescein-conjugated goat anti-mouse IgG in phosphate-buffered saline. PNIPAAm-g-PP membranes containing adsorbed anti-mouse CD80 monoclonal antibody preferentially captured mouse-CD80 transfected cells at 37 degrees C compared with membranes lacking antibody or containing anti-mouse CD86 monoclonal antibody. Detachment of captured cells from PNIPAAm-g-PP membranes was facilitated by washing at 4 degrees C because of the thermoresponsive phase transition of PNIPAAm. With this method, mouse CD80- or mouse CD86-transfected cells were enriched from a 1:1 cell suspension to 72% or 66%, simply and with high yield.