Relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetic patients (JDDM38).

AIMS/INTRODUCTION: We carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics. MATERIALS AND METHODS: We analyzed the CoDiC(®) database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug-naïve patients who were initiated with metformin, dipeptidyl peptidase-4 inhibitor (DPP-4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c). The patients were stratified according to their clinical features, and matched using a propensity score to adjust for baseline factors. RESULTS: HbA1c was reduced with all drugs, with the largest effect elicited by DPP-4i and the smallest by SU (P = 0.00). HbA1c increased with SU after 6 months in the patients stratified by an age-of-onset of <50 years (P = 0.00). BMI increased with SU in the patients stratified by a BMI of <25 (P = 0.00), and decreased with metformin in the patients with a BMI >25 (P = 0.00). The reduction in HbA1c was larger in patients with HbA1c of ≥8%, compared with that in patients with HbA1c of <8% (P = 0.00). HbA1c during the study period was higher in patients who were added to or swapped with other drug(s), than in patients continued on the original drug (P = 0.00). CONCLUSIONS: The effect on bodyweight and glycemic control differed among metformin, DPP-4i and SU, and the difference was associated with clinical features.

Predictors of prolonged hospital stay for the treatment of severe neuropsychiatric symptoms in patients with dementia: a cohort study in multiple hospitals.

BACKGROUND: Long hospitalization is often needed to treat severe behavioral and psychological symptoms of dementia (BPSD), which places heavy demands on hospital resources. Consequently, patients with severe BPSD usually wait for a long time to be admitted. There is a need to identify factors related to long hospitalization to better manage resources of a psychiatric hospital. METHODS: We surveyed 150 consecutive patients hospitalized in the neuropsychiatric units of three hospitals for treatment of BPSD from 11 May 2009 to 30 November 2010. Only patients with reliable relatives were included in the study. We evaluated data of the patients (demographics, cognitive impairment, activities of daily living, causal disease for dementia, dementia severity, and the amount of pension), their primary caregivers (demographics and care burden), and their doctors' years of experience in treating dementia. We followed up to 180 days and assessed the effect of these factors on the length of stay. RESULTS: Of the 150 patients, 104 were discharged within 180 days and 46 were hospitalized for more than 180 days. Average length of stay for patients was 110.4 ± 58.1 days. In both univariate and multivariate Cox proportional hazard analyses, length of stay was longer for patients with smaller pensions and patients whose doctors had fewer years of experience in treating dementia. Length of stay was not found to be associated with any of the other variables. CONCLUSIONS: Patients with smaller pensions and whose doctors had less experience in treating dementia tended to require longer hospitalization.

Reversibility of brain morphology after shunt operations and preoperative clinical symptoms in patients with idiopathic normal pressure hydrocephalus.

AIM: Brain deformations might prevent clinical symptoms from worsening in patients with idiopathic normal pressure hydrocephalus (iNPH). We investigated the relationship between reversibility of brain morphology after shunt operations and preoperative clinical symptoms in iNPH patients. METHODS: Using head magnetic resonance images with voxel-based morphometry, we measured the cerebrospinal fluid volume in the combined areas of the lateral and third ventricles and Sylvian fissure (the volume of the ventricles and Sylvian fissure (vVS)) and the volume of the subarachnoid space at high convexity and midline areas (vHCM) before and 1 year after lumboperitoneal shunt operations in 12 patients with shunt-responsive iNPH. We used the ratio of normalized vVS to normalized vHCM (nvVS/nvHCM) as an index of the severity of the brain deformation. The degree of reversibility of the brain morphology after the shunt operation was defined as the change ratio of the preoperative nvVS/nvHCM to the postoperative nvVS/nvHCM (CR-nvVS/nvHCM). Higher CR-nvVS/nvHCM values indicated more improvement in the brain deformation. In addition, we rated the severity of the white matter lesions on the preoperative magnetic resonance images based on the Fazekas scale. Dependency in activities of daily living, gait and cognition were evaluated before and 1 year after the shunt operations. RESULTS: After the shunt operations, the nvVS/nvHCM and nvVS decreased significantly, and nvHCM increased significantly. The CR-nvVS/nvHCM negatively correlated with the preoperative severity of dependency in activities of daily living, gait and cognitive impairments. The CR-nvVS/nvHCM negatively correlated with the Fazekas scale, but not with age, duration of the disease and cerebrospinal fluid pressure. CONCLUSIONS: Reversibility of brain morphology, which varied among iNPH patients, would prevent clinical symptoms from worsening in iNPH patients. The presence of white matter lesions reduced the degree of reversibility of the brain deformations in iNPH patients.

Association between milder brain deformation before a shunt operation and improvement in cognition and gait in idiopathic normal pressure hydrocephalus.

We investigated the association between the degree of deformation of the brain before shunt operation and improvement of gait and cognitive impairment after shunt operation in 16 patients with idiopathic normal pressure hydrocephalus (iNPH). We evaluated gait and cognitive impairment and measured the cerebrospinal fluid volume in the ventricles/sylvian fissure (vVS) and the subarachnoid space at high convexity/midline areas (vHCM) using MR images with voxel-based morphometry before and 3 months after shunt operation. We used the ratio of vVS to vHCM (vVS/vHCM) as an index of the severity of brain deformation. After shunt operation, improvements were observed in gait, as shown by the Timed Up and Go (TUG) test and 10-meter reciprocating walking test (WT), and in cognitive function, as shown by the Mini-Mental State Examination, Alzheimer Disease Assessment Scale, Frontal Assessment battery (FAB), and Trail Making test A (TMT-A). The vVS/vHCM ratio was negatively correlated with improvement of the FAB, TMT-A and TUG. Preoperative vVS/vHCM was not significantly correlated with preoperative clinical assessments. The rate of change of vVS/vHCM was positively correlated with improvement in the WT. The improvements of gait and cognitive function were larger in iNPH patients with milder deformation of the brain before shunt operation.

Classification of delusions in Alzheimer's disease and their neural correlates.

BACKGROUND: Previous findings on neural correlates of delusion in Alzheimer's disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single-photon emission computed tomography data. METHODS: We selected AD patients with delusions from our consecutive outpatients from 2004 to 2010. In this study, eight types of delusions were evaluated with Neuropsychiatric Inventory and classified by factor analysis. Twenty-five of the patients also had single-photon emission computed tomography data, which we used to assess the relationships between cerebral regions of hypoperfusion and hyperperfusion and each classified delusion. The relations were assessed using Statistical Parametric Mapping with normalization to the white matter cerebral blood flow. RESULTS: The delusions were classified into three factors. Factor 1 consisted of a belief that his/her house is not his/her home, phantom boarder symptom, delusion of abandonment, and belief that one's spouse or others are not who they claim to be. Factor 1 was related to hypoperfusion in the right temporal pole and hyperperfusion in the medial frontal and precentral regions. Factor 2 consisted of delusion relating to the television and delusion of persecution. Factor 2 was related to hypoperfusion in the precuneus and hyperperfusion in the insula and thalamus. Factor 3 consisted of delusion of abandonment and delusional jealousy. Factor 3 was related to hypoperfusion in the right inferior temporal and frontal regions and hyperperfusion in the middle frontal gyrus, insula and posterior cingulate gyrus. Delusion of theft was not included in any factors, and it was related to hypoperfusion in the bilateral thalami and left posterior cingulate gyrus and hyperperfusion in the left inferior frontal regions and anterior cingulate gyrus. CONCLUSIONS: Delusions in AD were classifiable, and each classified delusion was related to different neural networks.

Different characteristics of cognitive impairment in elderly schizophrenia and Alzheimer's disease in the mild cognitive impairment stage.

We compared indices of the revised version of the Wechsler Memory Scale (WMS-R) and scaled scores of the five subtests of the revised version of the Wechsler Adult Intelligence Scale (WAIS-R) in 30 elderly schizophrenia (ES) patients and 25 Alzheimer's disease (AD) patients in the amnestic mild cognitive impairment (aMCI) stage (AD-aMCI). In the WMS-R, attention/concentration was rated lower and delayed recall was rated higher in ES than in AD-aMCI, although general memory was comparable in the two groups. In WAIS-R, digit symbol substitution, similarity, picture completion, and block design scores were significantly lower in ES than in AD-aMCI, but the information scores were comparable between the two groups. Delayed recall and forgetfulness were less impaired, and attention, working memory and executive function were more impaired in ES than in AD-aMCI. These results should help clinicians to distinguish ES combined with AD-aMCI from ES alone.

KIBRA genetic polymorphism influences episodic memory in Alzheimer's disease, but does not show association with disease in a Japanese cohort.

BACKGROUND/AIMS: A single-nucleotide polymorphism (SNP) in the KIBRA gene, rs17070145, was reported to be significantly associated with episodic memory in cognitively normal cohorts. This observation has expanded genetic studies on KIBRA to Alzheimer's disease (AD). Importantly, the association between KIBRA and episodic memory in AD has never been addressed. In this study, we investigated whether the KIBRA rs17070145 SNP influences AD episodic memory and the disease in a Japanese cohort. METHODS: Blood samples from 346 AD patients and 375 normal cognitive controls were collected and genotyped for rs17070145. Episodic memory was measured in 32 AD patients, diagnosed for the first time, by use of the Rivermead Behavioral Memory Test (RBMT). RESULTS: We found that KIBRA C allele carriers scored significantly lower than KIBRA non-C carriers on both RBMT total profile score (p = 0.042, effect size = 0.84) and RBMT total screening score (p < 0.001, effect size = 1.42). The KIBRA gene did not show association with AD in our Japanese cohort. CONCLUSION: Our results evidence a strong association between the KIBRA gene and episodic memory impairment in AD, but show no influence on AD in our Japanese cohort. We propose that KIBRA might have an effect similar to cognitive reserve.

[A case of meningeal carcinomatosis presenting with bilateral hearing loss].

We report the case of a 63-year-old male who developed rapidly progressive bilateral deafness. Two months later he became stuporous, and was transferred to our hospital. The patient's MRI demonstrated bilateral hypertrophic VII-VIII cranial nerve roots that were well enhanced. Gradually, the patient's condition worsened, and he died on the 12th day after admission. Autopsy revealed meningeal carcinomatosis with poorly differentiated gastric adenocarcinoma. White firm masses of the bilateral seventh and eighth bilateral cranial nerve roots were found at autopsy, which were found to be metastases of the gastric cancer cells as well. Metastatic tumors can be take into consideration as a differential diagnosis for bilateral-enhanced eighth cranial nerve root masses.