Teruyuki Matsuoka

Anterior insular volume is larger in patients with obsessive-compulsive disorder.

There has been increasing evidence indicating gray matter abnormalities in patients with obsessive-compulsive disorder (OCD). Several voxel-based morphometry (VBM) studies have reported volume changes in the insular cortex. Although there are distinct differences in the connectivity and functions in the anterior and posterior insular cortices, these two regions have never been distinguished in previous VBM studies. In this study, we adopted a region of interest (ROI) method to measure insular volume separately. We investigated insular volume in 32 drug-free patients with OCD and in 34 healthy controls using magnetic resonance imaging (MRI). Repeated measures multivariate analysis of covariance (MANCOVA) was conducted to examine the difference between the patients and the controls. Compared with the healthy controls, the patients had a significantly larger gray matter volume in the anterior insular cortex bilaterally (post hoc test, p=0.036; left, p=0.047; right). This is the first volumetric MRI study to separately investigate the anterior and posterior insular cortex volumes in non-medicated patients with OCD. The results suggest that the anterior insular cortex may be related to the pathophysiology of OCD.

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.

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 Alzheimers 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.

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 Alzheimers 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.

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 Alzheimers 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.

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.

Challenging behavior of patients with frontal dysfunction managed successfully with behavioral intervention

Herein, we report on two clinical cases in which behavioral disturbances occurred due to frontal dysfunction. Both patients were treated successfully with behavioral intervention. In the first case, the patients challenging behavior of repeatedly entering his wifes workplace and interrupting her work was reduced after the patients wife changed her response to the behavior and her schedule prior to work to ensure that she spent time with him in the morning. In the second case, the patients challenging behavior of urinating in the street was reduced by changing his walking route. The successful outcome in both cases suggests that behavioral intervention based on Antecedents, Behavior, and Consequences (ABC) analysis is useful in the management of behavioral disturbance due to frontal dysfunction.

Brain regions associated with anosognosia for memory disturbance in Alzheimer’s disease: a magnetic resonance imaging study

Background and objective Patients with Alzheimer’s disease (AD) are frequently unaware of their cognitive symptoms and medical diagnosis. The term “anosognosia” is used to indicate a general lack of awareness of one’s disease or disorder. The neural substrate underlying anosognosia in AD is unclear. Since anosognosia for memory disturbance might be an initial sign of AD, it is important to determine the neural correlates. This study was designed to investigate the characteristics and neural correlates of anosognosia for memory disturbance in patients with mild AD. Methods The subjects were 49 patients with mild AD who participated in a retrospective cross-sectional study. None of the patients had been treated with cholinesterase inhibitors, memantine, or psychotropic drugs. All patients underwent magnetic resonance imaging (MRI). Anosognosia for memory disturbance was assessed based on the discrepancy between questionnaire scores of patients and their caregivers. Structural MRI data were analyzed to explore the association between anosognosia and brain atrophy, using a voxel-based approach. Statistical parametric mapping software was used to explore neural correlations. In image analysis, multiple regression analysis was performed to examine the relationship between anosognosia score and regional gray matter volume. Age, years of education, and total intracranial volume were entered as covariates. Results The anosognosia score for memory disturbance was significantly negatively correlated with gray matter volume in the left superior frontal gyrus. Conclusion The left superior frontal gyrus was involved in anosognosia for memory disturbance, while the medial temporal lobe, which is usually damaged in mild AD, was not associated with anosognosia. The left superior frontal gyrus might be an important region for anosognosia in mild AD.

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.

Reduced Pineal Volume in Alzheimer Disease: A Retrospective Cross-sectional MR Imaging Study

Purpose To evaluate pineal volume in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and healthy control subjects and to correlate the findings with results of cognitive testing and brain parenchymal volumes. Materials and Methods The ethics committee approved this retrospective study. The participants included 63 patients with AD, 33 patients with MCI, and 24 healthy control subjects. There were 36 men and 84 women, with a mean age (±standard deviation) of 76.7 years ± 7.6. The pineal gland volume and pineal parenchymal volume were measured by using three-dimensional volumetric magnetic resonance imaging (T1-weighted magnetization-prepared rapid gradient-echo sequence; spatial resolution, 0.9 × 0.98 × 0.98 mm). With age and total intracranial volume as covariates, analysis of covariance with the Bonferroni post hoc test was performed to compare the pineal volume among the AD, MCI, and control groups. Multiple regression analyses were used to identify predictor variables associated with pineal volume. Results The mean pineal gland volume in patients with AD (72.3 mm3 ± 5.4; 95% confidence interval [CI]: 61.5 mm3, 83.1 mm3) was significantly smaller than that in control subjects (102.1 mm3 ± 9.0; 95% CI: 84.4 mm3, 119.9 mm3) (P = .019). The mean pineal parenchymal volume in patients with AD (63.8 mm3 ± 4.2; 95% CI: 55.4 mm3, 72.1 mm3) was significantly smaller than that in patients with MCI (81.7 mm3 ± 5.8; 95% CI: 70.3 mm3, 93.1 mm3; P = .044) and control subjects (89.1 mm3 ± 6.9; 95% CI: 75.4 mm3, 102.9 mm3; P = .009). Multiple regression analyses demonstrated that the Mini-Mental State Examination score and total intracranial volume were significant independent predictors of both pineal gland volume and pineal parenchymal volume (P < .001). Conclusion Pineal volume reduction showed correlation with cognitive decline and thus might be useful to predict cognitive decline in patients with AD.