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Background: Behavioral and psychological symptoms of dementia (BPSD) cause a heavy burden for both patient and caregivers. These symptoms are diverse, and their mechanism is still unclear. Agitation is the most common and difficult to treat among BPSD. In recent years, while changes in DNA methylation levels have been receiving attention as a biomarker of aging and dementia, associations with BPSD have not been examined. Objective: Focusing on agitation, the objective of the present study was to identify a region where changes in DNA methylation levels are associated with agitation. Methods: Using genome-wide DNA methylation analysis data for 7 dementia subjects with agitation, 5 dementia subjects without agitation, and 4 normal elderly controls, we determined a signaling pathway in the WNT5A gene promoter region to be associated with agitation. Based on this result, we measured DNA methylation levels in this region for 26 dementia subjects with agitation and 82 dementia subjects without agitation by means of methylation-sensitive high-resolution melting (MS-HRM) analysis. Results: The WNT5A DNA methylation level in dementia subjects with agitation was significantly lower than in those without agitation (p = 0.001). Changes in WNT5A DNA methylation levels were not influenced by age, sex, body mass index, APOE ɛ4, medication, or inflammatory cytokines. Conclusion: Our results suggested an association of agitation with Wnt signaling, in particular with changes in WNT5A DNA methylation levels, which could be a potentially useful biomarker for predicting the appearance of agitation. It may contribute to the elucidation of the mechanism of BPSD.

Neuropsychiatric symptoms (NPS) inevitably occur during the course of Alzheimer's disease (AD) including psychosis, aggression, and depression. The effectiveness of pharmacological treatments for NPS has been limited because of their lack of efficacy, discontinuation due to undesirable adverse events, or poor adherence. In recent consensus guidelines, non-pharmacological treatments for NPS have been prioritized as first-line management strategies. Pharmacological treatments for severe NPS should be administrated as a second-line approach, and have been suggested to be started at a lower dosage followed by titration to a minimum effective dosage and for a limited time period. However, recent studies have shown that some patients receiving pharmacological treatments do not exhibit treatment efficacy in comparison with placebo. The concurrence of several sub-symptoms in NPS makes it difficult to target one symptom exclusively. Therefore, the current review focuses on a strategy for such refractory NPS in patients with AD. Recent randomized controlled trials have shown that the severity of NPS gradually reduces in a time-dependent manner regardless of active treatments. Therefore, clinicians should consider potential causes of NPS sub-symptoms from multifactorial aspects and select alternative treatments (e.g. neuromodulation or relocation into specialized care units) during the long-term disease course.

Objectives: We examined the clinicodemographic and psychosocial factors that relate to the presentation and severity of delusions of theft among female patients with amnestic mild cognitive impairment (a-MCI) and Alzheimer's disease (AD).Methods: We enrolled a total of 177 female patients with a-MCI or AD, of whom 40 presented with delusions of theft. We compared the differences in clinicodemographic and psychosocial factors of the 40 patients (delusions of theft group) with 50 age- and Mini-Mental State Examination (MMSE)-matched controls without delusions (control group). Furthermore, we identified the factors associated with the presentation of delusions of theft using a general linear model (GLM). The severity of delusions of theft was calculated using the Neuropsychiatric Inventory Questionnaire, and correlations between the clinicodemographic and psychosocial factors were examined.Results: Between the two groups, the delusions of theft group had lower scores on the Physical Self-Maintenance Scale and instrumental activities of daily living (IADL) and higher scores on the Japanese version of the Zarit Caregiver Burden Interview (ZBI-J) than the control group. GLM analysis revealed that the IADL score was related to the presentation of delusions of theft. The severity of delusions of theft correlated with the MMSE and the ZBI-J scores in the delusions of theft group.Conclusions: The two groups had several differences regarding clinicodemographic and psychosocial factors. Furthermore, lower IADL scores were related to symptom presentation. Symptom severity correlated with cognitive functioning and caregiver burden.Clinical Implications: In the determination of treatment or care, differences in these factors should be considered.

Alzheimer's disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) appear during the progressive course of the disease. A lack of self-awareness (anosognosia) of cognitive and functional impairments is often seen in patients with AD, and associations between anosognosia and other NPSs have been previously reported. To account for anosognosia pathogenesis neurocognitively, the cognitive awareness model (CAM) has been helpful for explaining the stream of events from sensory input to behavioural/affective and metacognitive outputs. According to CAM, there are three types of anosognosia: (i) primary anosognosia, (ii) executive anosognosia, and (iii) mnemonic anosognosia. These types of anosognosia are generated from different neurocognitive modulations leading to metacognitive outputs or behavioural/affective regulations. Primary anosognosia is considered to be caused by deficits in the metacognitive awareness system (MAS). While preserved MAS function is associated with milder depression and anxiety in AD, a severer depressive mood in patients with mild AD can inversely cause self-underestimation. The modulation of executive anosognosia is thought to be associated with dangerous/disinhibition behaviours and apathy among NPS sub-symptoms, via impairments of comparator mechanism (Cm) within the central executive system. Other neurobehavioral reactions linked to self-awareness include 'denying' and 'confabulation', and each of these reactions is thought to be affected by the MAS and a Cm. Denial of one's own memory impairments appears as a defensive reaction to protect against dysphoric feelings, and the confabulatory comment is instantly reaction constructed by fabrications according to misinterpretations of memory information about oneself. Similarly, the innovative development of a theoretical model (CAM) has contributed to explaining the mechanism of anosognosia and some neurobehavioral outputs from a neurocognitive perspective.

A 16-year-old male with language disorders, such as motor aphasia or mutism, was hospitalized on day 4 after the onset of fever. Magnetic resonance imaging (MRI) on admission revealed lesions of the corpus callosum and brain white matter. Brain single photon emission computed tomography (99mTc-ethyl cysteinate dimer) on day 7 shows hypoperfusion (with right dominance) of bilateral upper parietal region. His condition improved gradually with symptomatic treatments alone, and he was discharged on day 13. The lesions on the MRI disappeared by day 15. Although this case might have suffered from leukoencephalopathy, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) type II was suspected from the reversible splenial lesion. Except for the elevation (640 times) of mycoplasma pneumonia antibody titer (particle agglutination) in the serum, the blood tests and cerebrospinal fluid findings showed no significant abnormalities. We then considered this encephalopathy was related to mycoplasma pneumonia infection. Since no symptoms of mycoplasma infection except for neurologic symptoms were observed, indirect mechanism, such as immune-mediated reactions, is suggested to cause encephalopathy in this case.

The present study aimed to analyze the association between preoperative nutritional assessment and poor postoperative outcomes in geriatric patients with colorectal cancer. This retrospective study included 138 patients aged ≥80 years with colorectal cancer who underwent surgery from January 2013 to December 2018. Patients were classified into two groups according to outcomes, poor group and normal group. Clinicopathological factors were compared between the groups, and the relationships of several nutritional indices were examined. There was no significant difference in sex, age, or preoperative comorbidities. There were significant differences in volume of blood loss and proportion of laparoscopic surgery. The group with poor outcomes had significantly higher neutrophil/lymphocyte ratio (NLR) and modified Glasgow prognostic score (mGPS) than the group with normal outcomes. Multivariate analysis revealed that open approach, high NLR, and category D mGPS were independent risk factors of poor postoperative outcomes in elderly patients with colorectal cancer. Our findings indicate that mGPS and NLR could be useful nutritional indicators of short-term outcomes of surgical treatment in geriatric patients with colorectal cancer. They can be evaluated based on albumin and C-reactive protein levels and blood count, which are inexpensive and beneficial to use in routine clinical practice.

Background Polysplenia refers to the presence of two or more equal-sized spleens. Very rarely, one of the multiple spleens may develop torsion and infarction. Case presentation A 21-year-old woman presented with left upper quadrant pain, the cause of which could not be diagnosed. She returned to our hospital, 2 days later, without any pain improvement. Enhanced computed tomography showed splenic infarction and polysplenia. Initially, we could not identify the cause of the infarction and started conservative therapy, which did not result in any improvement. Hence, we performed a splenectomy, after securing informed consent. Because the patient was a young woman, we opted for a laparoscopic approach. During surgery, we identified the cause of the infarction as spleen pedicle torsion; the infarcted spleen was excised using an automated suturing device. We completed the laparoscopic surgery without converting it to an open laparotomy, and the patient was discharged 4 days later. This was a rare case of polysplenia with splenic torsion. Conclusion Laparoscopic splenectomy is minimally invasive and has cosmetic advantages. Thus, this approach may be considered as a treatment option for this condition.

Early diagnosis of dementia including Alzheimer’s disease (AD) is an urgent medical and welfare issue. However, to date, no simple biometrics have been available. We reported that blood DNA methylation levels of the COASY gene, which encodes coenzyme A synthase, were increased in individuals with AD and amnestic mild cognitive impairment (aMCI). The present study sought to replicate these findings with larger numbers of samples. Another objective was to clarify whether COASY methylation is associated with neurodegeneration through a comparison of AD, AD with cardiovascular disease (CVD), and vascular dementia (VaD). We measured blood COASY methylation levels in normal controls (NCs) (n = 200), and individuals with aMCI (n = 22), AD (n = 151), and VaD (n = 21). Compared with NCs, they were significantly higher in individuals with aMCI and AD. Further, they were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them. These findings suggest that COASY methylation levels may be related to neurodegeneration in AD.

Background Anosognosia in Alzheimer's disease (AD) is a complicated, non-unitary phenomenon. In a clinical setting, patients with mild AD often preserve their awareness partially. We hypothesized that compensation, as well as neural dysfunction, could be correlated with anosognosia in mild AD. Methods The severity of anosognosia was evaluated using the Anosognosia Questionnaire for Dementia in 37 subjects with mild AD or mild cognitive impairment due to AD. The subjects also underwent single-photon emission computed tomography with N-isopropyl-p-[123 I]iodoamphetamine. Correlation between the severity of anosognosia and perfusion was assessed, and anosognosia (+) and (-) groups were compared. Results The severity of anosognosia was relatively mild; the mean Anosognosia Questionnaire for Dementia score was 6.76 ± 14.16. Subjects were divided into two groups: anosognosia (+) (n = 11) and anosognosia (-) (n = 26). In the single-photon emission computed tomography data analysis, the severity of anosognosia was correlated with both lower regional cerebral blood flows of the right prefrontal cortex and higher regional cerebral blood flows of the parietal cortex, especially the left temporo-parietal junction. Conclusions Our results suggest that anosognosia in mild AD could be correlated with compensation as well as neural dysfunction. We speculate that this compensation may be related to the retrieval of outdated autobiographical memory.

Aim In patients with Alzheimer's disease (AD), cognitive impairments cause a progressive reduction in Activities of Daily Living (ADL). Neuropsychiatric symptoms (NPS) also appear in most patients; however, the association between NPS and reductions in ADL remains unclear. The present study evaluated whether NPS influence such reductions using two different ADL measures in patients with AD. Methods Among 546 consecutive outpatients who visited the memory clinic at the Jikei University Kashiwa Hospital, we recruited 208 patients with AD and investigated the correlations between either the Physical Self-Maintenance Scale (PSMS) score or the Instrumental ADL (IADL) level, and each of the Behavioral Pathology in AD (Behave-AD) subscales. To clarify the causal relationships of these correlations, we then verified the associations between statistically significant demographic variables and the Behave-AD subscales as well as the two ADL scales (PSMS score and IADL percentage) using a general linear model. Results Neither the PSMS nor the IADL results were significantly influenced by the aberrant motor behaviors score. However, the IADL was significantly influenced by the Mini-Mental State Exam (MMSE) score. Furthermore, diurnal rhythm disturbances and the interaction between diurnal rhythm disturbances score and the MMSE score significantly influenced the PSMS results. Conclusion Basic ADL reductions may be influenced by diurnal rhythm disturbances, in addition to cognitive impairments in patients with AD. Furthermore, the interaction between the diurnal rhythm disturbances score and cognitive function may also influence basic ADL. Geriatr Gerontol Int 2020; ••: ••-••.

INTRODUCTION Several studies have reported the treatment of pediatric appendicitis with single-incision laparoscopy-assisted appendectomy using a muscle hook without pneumoperitoneum to lift the abdominal wall. However, very few studies have investigated the advantages of this procedure. We examined the utility of this procedure in our department. METHODS This study included 33 children with appendicitis who underwent single-incision laparoscopy-assisted appendectomy at our hospital from April 2011 to March 2018. Patients were divided into two groups depending on whether they underwent the procedure with pneumoperitoneum: the no pneumoperitoneum group (n = 12) and the pneumoperitoneum group (n = 21). The clinicopathological factors and surgical costs were compared between the two groups. RESULTS In the pneumoperitoneum group, the procedure was initiated in four patients by lifting the abdominal wall but was changed to include a pneumoperitoneum because of difficulty. There were no significant differences between the two groups with regard to age, sex, or pathological severity. CT revealed a significant difference in the distance from the appendicular root to the umbilicus between the groups. There was a significant difference in the operative duration, but not in estimated blood loss or length of postoperative hospital stay. Complications were observed in one patient in each group. There was a significant difference in cost between the two groups. CONCLUSIONS Single-incision laparoscopy-assisted appendectomy without pneumoperitoneum is less expensive because certain supplies and CO2 are not required. Because there were no differences in the length of postoperative hospital stay or complications, this procedure may be safe in cases that are expected to be mild.

BACKGROUND/AIM Chemotherapy dose adjustments in colorectal cancer are usually based on body surface area (BSA). The goal of this study was to investigate patients with nutritional disorder who developed early peripheral neuropathy due to inappropriate dose adjustment of oxaliplatin. PATIENTS AND METHODS The study subjects were 88 patients with advanced or recurrent colorectal cancer who underwent chemotherapy with oxaliplatin. The psoas muscle area (PMA) was used as a nutritional index. Mild (grades 0-1, MN group) and severe (grades 2-3, SN group) peripheral neuropathy was defined using neurotoxicity criteria of Debiopharm. RESULTS Severe peripheral neuropathy developed in 29 patients (33.0%). The total oxaliplatin dose/PMA was significantly higher for the SN group (107.6±8.5 mg/cm2) and compared with the MN group (53.8±6.0 mg/cm2) in univariate (p

BACKGROUND Nutritional status influences cancer prognosis. Measurement of the area of the psoas muscle on computed tomography is useful for evaluation of skeletal muscle mass and prediction of prognosis. PATIENTS AND METHODS The psoas muscle index (PMI) was determined in 42 patients undergoing surgery for stage 4 colorectal cancer. Patients were classified into high and low PMI groups using a cutoff of 5.5×10-4 cm2 m-2 Relationships of PMI with prognosis, chemotherapy period, and postoperative complications were examined. RESULTS The 3-year overall survival rate was 24.0%. PMI was significantly associated with 3-year OS in univariate (high vs. low PMI: 43.0% vs. 12.9%, p=0.0415) and multivariate (p=0.0146) analyses. A low PMI was associated with a shorter period of chemotherapy. A reduction in PMI was a predictor of a poor prognosis. CONCLUSION PMI status is related to the period of chemotherapy and is an independent prognostic factor in patients with stage 4 colorectal cancer.

Objective This study sought to determine psychosocial and clinico-demographic factors related to each symptomatic cluster (i.e., aggressiveness, psychosis, apathy/eating problems, and emotion/disinhibition) of neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD) needing interventional treatment against their agitation or psychotic symptoms. These clusters were classified from 12 Neuropsychiatric Inventory (NPI) subscores in our previous study using the Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer's Disease (CATIE-AD) dataset. Methods Based on clinical data from 421 AD outpatients with agitation or psychotic symptoms needed interventional treatment enrolled in the CATIE-AD, we conducted logistic regression analyses to examine the relationships between each symptomatic cluster and three psychosocial (marital status, residence, and caregivers' burden) and nine clinico-demographic (age, gender, education year, general cognition, activity of daily living [ADL], general medical health, race, and intake of anti-dementia drugs or psychotropics) factors. Results While no factor contributed to aggressiveness, psychosis was associated with several clinico-demographic factors: female gender, non-Caucasian race, and lower cognitive function. Apathy/eating problems was associated with more severe caregiver burden, living in one's own home, lower ADL level, and male gender, while emotion/disinhibition was predicted by more severe caregiver burden, lower education level, not-married status, and younger age. Conclusions Among the four NPS clusters, apathy/eating problems and emotion/disinhibition were associated with psychosocial as well as clinico-demographic factors in AD patients with psychotic symptoms or agitation needed interventional treatment.

Background/Aims Interaction of receptor for advanced glycation end products (RAGE) with amyloid-β increases amplification of oxidative stress and plays pathological roles in Alzheimer's disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs. Methods Four single nucleotide polymorphisms (SNPs)—rs1800624, rs1800625, rs184003, and rs2070600—of the gene were analyzed using a case–control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls. Results Linkage disequilibrium (LD) examination showed strong LD from rs1800624 to rs2070600 on the gene (1.1 kb) in our cases in Japan. Rs184003 was associated with an increased risk of AD. Although there were no statistical associations for the other three SNPs, haplotypic analyses detected genetic associations between AD and the RAGE gene. Although relatively few cases were studied, results from the SNPs showed that they did not modify the risk of developing LBDs in the Japanese population. Conclusion Our findings suggested that polymorphisms in the RAGE gene are involved in genetic susceptibility to AD. Copyright © 2016 John Wiley & Sons, Ltd.

Several studies have noted an effect of DNA methylation on the pathogenesis of Alzheimer's disease (AD). We have already reported that DNA methylation levels in the NCAPH2/LMF2 promoter region can be a useful biomarker for the diagnosis of AD and amnesic mild cognitive impairment (aMCI). However, there is still uncertainty about the mechanism by which NCAPH2/LMF2 methylation affects the pathogenesis of AD and aMCI. In this study, we investigated relationships between NCAPH2/LMF2 methylation and other factors. AD (n=30) and aMCI (n=28) subjects were included in this study. NCAPH2/LMF2 methylation levels were measured by pyrosequencing. Correlations between methylation levels and other factors including age at onset, sex, duration of disease, education, mini-mental state examination (MMSE) and frontal assessment battery (FAB) scores, APOE genotype, degree of hippocampal atrophy, and total brain atrophy were measured. Degrees of hippocampal atrophy and total brain atrophy were measured by VSRAD (Voxel-Based Specific Regional Analysis System for Alzheimer's Disease). Regression analysis revealed that only hippocampal atrophy according to VSRAD is a significant dependent variable correlated with NCAPH2/LMF2 methylation levels. Our results suggest that DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy through apoptosis.

Background Late-life somatoform disorders (SDs) are characterized by various aging-associated factors. Recently, cognitive decline, including executive dysfunction, has been reported as an etiological factor of late-life SDs. The response to treatment for late-life SDs varies from one patient to another. Treatment strategies for late-life SDs require these etiological factors to be considered. We hypothesized that the treatment response in patients with late-life SDs was associated with executive dysfunction. Objective The aim of the present study was to confirm the changes in disease severity over a 2-year follow-up period and to determine which etiological factors are related to the treatment response in patients with late-life SDs. Methods We examined 55 patients with late-life SDs who were treated with pharmacotherapy and supportive psychotherapy at baseline. The changes in the disease severity and cognitive profiles over a 2-year follow-up period were evaluated. Additionally, we investigated which etiological factors at baseline were related to treatment resistance. Results Of the 55 patients who were enrolled in the present study, 31 completed the 2-year follow-up period. Overall, the disease severity improved significantly in patients with late-life SDs. On the contrary, executive function decreased throughout the research period. Moreover, we found that executive dysfunction and the presence of hyperlipidemia at baseline were related to treatment resistance. Conclusions These results suggest that aging-associated etiological factors be considered for the treatment of late-life SDs.

Background/Aims: Mutations in the presenilin 2 (PSEN2) gene cause familial Alzheimer's disease (AD). Common polymorphisms affect gene activity and increase the risk of AD. Nonsynonymous polymorphisms in the PSEN2 gene showed Lewy body dementia (LBD) phenotypes clinically. Therefore, we aimed to investigate whether PSEN2 gene polymorphisms were associated with AD or LBD. Methods: Seven single nucleotide polymorphisms (SNPs) of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBD patients, and 105 age-matched controls. Results: Linkage disequilibrium (LD) examination showed strong LD from rs1295645 to rs8383 on the gene in our cases from Japan. There were no associations between the SNPs studied here and AD onset, and haplotypic analyses did not detect genetic associations between AD and the PSEN2 gene. Although the number of the cases was small, the SNPs studied did not modify the risk of developing LBD in a Japanese population. Conclusion: The common SNPs of the PSEN2 gene did not affect the risk of AD or LBD in a Japanese population. Because genetic variability of the PSEN2 gene is associated with behavioral and psychological symptoms of dementia (BPSD) in AD and LBD, further detailed analyses considering BPSD of both diseases would be required.

Background The Neuropsychiatric Inventory (NPI) comprises 12 items, which were conventionally determined by psychopathological symptoms of patients with dementia. The clinical rating scales with structured questionnaires have been useful to evaluate neuropsychiatric symptoms (NPSs) of patients with dementia over the past twenty year. Objective The aim of this study was to classify the conventional NPSs in patients with Alzheimer's disease (AD) requiring antipsychotic treatment for their NPSs into distinct clusters to simplify assessment of these numerous symptoms. Methods Twelve items scores (product of severity and frequency of each symptom) in the NPI taken from the baseline visit were classified into subgroups by principle component analysis using data from 421 outpatients with AD enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Phase 1. Chi square tests were conducted to examine the co-occurrence of the subgroups. Results We found four distinct clusters: aggressiveness (agitation and irritabilities), apathy and eating problems (apathy and appetite/eating disturbance), psychosis (delusions and hallucinations), and emotion and disinhibition (depression, euphoria, and disinhibition). Anxiety, aberrant motor behavior, and sleep disturbance were not included by these clusters. Apathy and eating problems, and emotion and disinhibition co-occurred (p = 0.002), whereas aggressiveness and psychosis occurred independent of the other clusters. Conclusions Four distinct category clusters were identified from NPSs in patients with AD requiring antipsychotic treatment. Future studies should investigate psychosocial backgrounds or risk factors of each distinct cluster, in addition to their longitudinal course over treatment intervention.

AIM: The recommended treatment for acute cholecystitis is early laparoscopic cholecystectomy (LC) within 72 hours after onset of symptoms. However, palliative treatment using percutaneous transhepatic gallbladder drainage (PTGBD) is often chosen for clinical and logistical reasons, including difficulty performing early surgery due to manpower constraints. The goal of this study was to investigate the clinical significance of PTGBD on the outcome of patients with cholecystitis in our hospital. MATERIALS AND METHODS: Relationships between preoperative drainage status (treatment with or without PTGBD) and clinicopathologic factors were examined in 190 patients with cholecystitis who underwent LC. The short-term impact of preoperative drainage on prognosis was evaluated by univariate and multivariate analysis. RESULTS: Preoperative PTGBD was performed in 24 patients (12.6%). The average period between PTGBD and LC was 21.0 days. Preoperative PTGBD had a significant correlation with operation time and length of stay (LOS) after surgery (p

Background Late-life somatic symptom disorder (SSD) is characterized by various aging-associated factors, such as a functional decline, psychosocial problems, and cognitive dysfunction. However, the details of the cognitive dysfunction that occur in late-life SSD are still unknown. Objective The aims of this study were to reveal the cognitive profile of patients with late-life SSD and to evaluate how cognitive dysfunction affects disease severity. Methods We compared the cognitive profiles of patients with late-life SSD ( n = 40) with those of normal control subjects ( n = 21). In addition, we divided the patients with late-life SSD into mild-to-moderate ( n = 24) and severe ( n = 16) groups and compared the cognitive profiles of the 3 groups. Results Patients with late-life SSD exhibited a lower Mini-Mental State Examination total score and attention decline. In the 3-group comparison, the severe group had a lower Mini-Mental State Examination score and Frontal Assessment Battery score than the normal control group, whereas no significant difference was seen between the mild-to-moderate and the normal control groups. Conclusions Our data suggest that different cognitive patterns may exist depending on disease severity, possibly indicating differences in pathogenesis.

Background There is a high morbidity rate after digestive surgery in patients with nutritional disorders such as high body mass index and depletion of skeletal muscle. Materials and methods The ratio of psoas muscle area to trunk area was defined as the Psoas and All trunk Ratio (PandA Ratio) and used as an index of the balance between muscle and adipose tissue. This ratio was determined in 77 patients undergoing laparoscopy-assisted gastrectomy (LAG) for gastric cancer. Patients were classified into groups with and without postoperative complications. Clinicopathological factors were compared between the groups, and relationships of PandA Ratio with other nutritional indices were examined. PandA Ratios were also analyzed in males and females in each Clavien-Dindo grade. Results Complications developed in 22 patients (28.6%) after LAG. The PandA Ratio was significantly lower in patients with complications in univariate (2.76 ± 0.22% versus 3.66 ± 0.14%, P = 0.0009) and multivariate ( P = 0.0064) analyses. A low PandA Ratio was also associated with more severe complications in males. Conclusions Measurement of the areas of the psoas muscle and trunk on CT is useful for evaluation of the balance between skeletal and adipose tissue. The PandA Ratio derived from these measurements is a predictor of the clinical course after LAG in males.

Psychotic symptoms often occur as a complication in Parkinson's disease patients, and a set of criteria for Parkinson's disease with psychosis (PDPsy) has been established. Among these criteria, hallucinations are one of the specific symptoms, with visual hallucinations being the most common. While atypical antipsychotic agents are often used for the treatment of PDPsy, adverse effects, including extrapyramidal symptoms, often hinder its continuation or tolerance. There have been some reports and reviews indicating that antidepressants may be effective for PDPsy and other forms of dementia with psychosis. In this report, we present a patient with PDPsy who was treated with one of the new-generation antidepressants, mirtazapine. Mirtazapine improved the patient's refractory psychotic symptoms, especially her visual hallucinations, without worsening her motor symptoms.

Aims: In the present study, we investigated whether apolipoprotein E (APOE) polymorphisms influenced the cognitive function of Japanese patients with Alzheimer's disease (AD) at certain ages. Methods: Among 200 outpatients with dementia and amnestic mild cognitive impairment, 133 Japanese patients with AD were recruited and divided into two genotypic groups: APOE ε4 carriers and noncarriers. Then, we compared several neuropsychological test scores between the two genotypic groups for two different generations: 70s (70-79 years) and 80s (80-89 years). Results: The total Mini-Mental State Examination score (p < 0.05) and one of its subtest scores, the 3-stage command score (p < 0.01), were significantly lower for the ε4 carriers than for the noncarriers among patients in their 80s, but not among those in their 70s. The duration of illness differed significantly between the ε4 carriers and the noncarriers among subjects in their 80s but was not correlated with cognitive function. Conclusion: The present results suggest that APOE may significantly influence comparatively simple memory processing in certain generations of Japanese patients with AD.

From the standpoint of early interventions for dementia, a convenient method of diagnosis using biomarkers is required for Alzheimer’s disease (AD) in the early stage as well as amnesic mild cognitive impairment (aMCI). Focusing on differences in DNA methylation due to AD and aMCI, in the present study, we first conducted genome-wide screening, measuring blood DNA methylation levels by the Illumina Infinium HD Methylation Assay in 3 small age-and gender-matched groups consisting of 4 subjects each: normal controls (NC), aMCI and AD. The genome-wide analysis produced 11 DNA methylation loci that distinguished the 3 groups. For confirmation, we increased group sizes and examined samples by pyrosequencing which revealed that DNA methylation in the NCAPH2/LMF2 promoter region was significantly decreased in the AD (n = 30) and aMCI (n = 28) groups as compared to the NC group (n = 30) (P < 0.0001, ANCOVA). No association was found between methylation levels and APOE genotype. NCAPH2/LMF2 methylation levels were considered to potentially be a convenient and useful biomarker for diagnosis of AD and aMCI.

We investigated whether neurotrophin (NT)-3 polymorphisms influenced the executive function of patients with 2 separate disease stages with similar dementia conditions: amnestic mild cognitive impairment (A-MCI) or mild Alzheimer disease (AD).Among 215 outpatients with dementia and MCI, 155 with mild AD (n = 108) or A-MCI (n = 47) were recruited and divided into three genotypic groups based on the representative NT-3 functional polymorphisms rs6332 and rs6489630. Next, we compared the frontal assessment battery (FAB) total and subtest scores between the three genotypic groups.The total FAB score was not significantly associated with the rs6332 and rs6489630 genotypes; however, the conflicting instructions score among the 6 subtests was significantly associated with the rs6332 genotype (p0.05). Moreover, in patients with mild AD, the conflicting instructions score differed significantly among the three genotypic groups of rs6332 (p0.05) (G/GA/A: p = 0.042 and G/AA/A: p = 0.041). No significant differences in any other demographic variables were observed among the three genotypes of rs6332 and rs6489630.These results suggested that an NT-3 polymorphism, rs6332, may significantly influence executive function, reflecting interference performances among patients with mild-stage AD.

Background: Previous research has described the executive dysfunction that occurs in patients with amnestic-mild cognitive impairments (A-MCI) and early-stage Alzheimer's disease (EAD), which are comparatively similar stages of dementia. The aim of the present cross-sectional study is to evaluate executive dysfunction using the Frontal Assessment Battery (FAB) screening test in two groups and to investigate the interaction with other cognitive impairments. Methods: Among 170 consecutive patients with Alzheimer's disease or A-MCI, we recruited 48 subjects who were under 75 years of age and had been diagnosed as having either A-MCI or EAD. We then compared the total and the subtest scores of the mini-mental state examination (MMSE) and the FAB between the two groups. Moreover, we investigated the statistical interactive associations of the FAB subtest scores with the influential MMSE subtest scores or the diagnosis (A-MCI or EAD). Results: No significant differences in the age, sex ratio, duration of illness, and education years were observed between the two groups. However, significant differences in the FAB total and subtest scores (conflicting instructions and go/no-go) were found between the two groups. Furthermore, significant differences in the MMSE total and subtest scores (orientation, memory delayed recall, and attention and calculation) were also noted between the two groups. In a generalized linear model analysis, only two FAB subtest scores (conflicting instructions and go/no-go) were significantly influenced by the diagnosis (A-MCI or EAD) in a manner that was independent of the interaction with the orientation or memory delayed recall. Conclusion: The present findings suggest that the FAB total score and subtest scores reflecting interference performances (conflicting instructions and go/no-go) significantly declined in patients with EAD, independent of the disorientation and memory disorder. Such characteristics of neuropsychological screening test scores may be useful to clinicians for differentiating EAD and A-MCI at bedside.

Background Complete resection with negative surgical margins has been a long-held surgical philosophy based on the concept that even minimal remaining cancer cells will develop recurrences. Objectives This study investigated the clinical significance of microscopic positive margin on the outcome of patients with gastric cancers. Methods The relationships between the margin status and other clinicopathologic factors were examined in gastric cancer patients undergoing gastrectomy, and then the prognostic impact of the margin status was evaluated by univariate and multivariate analysis. Results The microscopic positive margin was identified in 23 patients (2.8%) by standard H&E staining. The positive margin showed a strong correlation significantly with tumor size (P

Background: To address the functional roles of genetic polymorphisms of brain-derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) from a neuropsychological aspect, we used a cross-sectional study design to investigate the association between novel single nucleotide polymorphisms (SNPs) of the BDNF gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score, which reflects executive function as a non-memory cognitive impairment. Methods: One hundred and sixty-nine outpatients with AD or amnestic mild cognitive impairment (A-MCI) were recruited to the study and divided into three genotypic groups for each representative BDNF functional polymorphism as follows: (i) Val66Met (G196A): G/G (n= 45), G/A (n= 104), and A/A (n= 20); and (ii) C270T: C/C (n= 160), C/T (n= 9), and T/T (n= 0). Then, age, sex ratio, duration of illness (months), education years, Mini-Mental State Examination (MMSE) score, behavioral pathology in Alzheimer disease (Behave-AD) score, Clinical Dementia Rating (CDR) ratio, and total and subtest FAB scores were compared between the genotypic groups for each SNP. Results: Significant differences were found in the total (P < 0.01) and subtest (conflicting instructions and prehension behavior; P < 0.01) FAB scores between the C270T polymorphism groups (C/C and C/T), but not among the G196A polymorphism groups. However, no significant differences in age, sex ratio, duration of illness (months), education years, Behave-AD score, CDR ratio, or MMSE score (reflecting attention and memory function) were found between the individual polymorphism genotypes (G196A and C270T). Conclusion: Of the known BDNF polymorphisms, the C270T SNP may influence executive dysfunction as a non-memory cognitive impairment in Japanese patients with AD.

A 48-year-old woman with Parkinson disease (PD) suffered from auditory hallucinations (AH). We had treated her with a reduction in antiparkinsonian agents and the use of atypical antipsychotic agents. However, her symptoms did not improve, and her extrapyramidal symptoms (EPS) worsened. To lessen her depressive symptoms, treatment with a new-generation antidepressant, mirtazapine (MRZ), was commenced. The patient's AH gradually decreased with no worsening of EPS, and the AH disappeared 4 weeks after the commencement of treatment with MRZ. The present case suggests the effectiveness of MRZ for the treatment of refractory AHs in patients with PD.

Schizotypal personality disorder (SPD) has rarely been reported as an eating disorder-related personality trait. A 23-year-old woman was diagnosed as having anorexia nervosa binge eating/purging type. At the age of 53 years, she was admitted to Jikei University Hospital because of excessive bodyweight loss. She was diagnosed as having SPD based on bizarre behavior, ideation and a tendency to seek isolation. She was treated with low-dose antipsychotics, and her impulsive behavior improved. The patient's SPD was considered to have had a psychopathological contribution to her chronic episodes of anorexia nervosa.

In order to conduct early therapeutic interventions for Alzheimer's disease (AD), convenient, early diagnosis markers are required. We previously reported that changes in DNA methylation levels were associated with amnestic mild cognitive impairment (aMCI) and AD. As the results suggested changes in DNA methylation levels in the COASY and SPINT1 gene promoter regions, in the present study we examined DNA methylation in these regions in normal controls (NCs, n = 30), aMCI subjects (n = 28) and AD subjects (n = 30) using methylation-sensitive high resolution melting (MS-HRM) analysis. The results indicated that DNA methylation in the two regions was significantly increased in AD and aMCI as compared to NCs (P < 0.0001, P < 0.0001, ANOVA). Further analysis suggested that DNA methylation in the COASY gene promoter region in particular could be a high sensitivity, high specificity diagnosis biomarker (COASY: sensitivity 96.6%, specificity 96.7%; SPINT1: sensitivity 63.8%, specificity 83.3%). DNA methylation in the COASY promoter region was associated with CDR Scale Sum of Boxes (CDR-SB), an indicator of dementia severity. In the SPINT1 promoter region, DNA methylation was negatively associated with age in NCs and elevated in aMCI and AD subjects positive for antibodies to Herpes simplex virus type 1 (HSV-1). These findings suggested that changes in DNA methylation in the COASY and SPINT1 promoter regions are influenced by various factors. In conclusion, DNA methylation levels in the COASY and SPINT1 promoter regions were considered to potentially be a convenient and useful biomarker for diagnosis of AD and aMCI.

After infection with herpes simplex virus type 1 (HSV-1), latent infection persists for life in the trigeminal ganglion and reactivation results in an outbreak of cold sores around the mouth. Many previous studies have reported HSV-1 reactivation to be a risk factor for Alzheimer's disease (AD). This study enrolled subjects with AD (n=85), subjects with amnestic mild cognitive impairment (aMCI; a prodromal stage of AD) (n=34), and healthy controls (n=28). The avidity index of anti-HSV-1 IgG antibodies--a known indicator of HSV-1 reactivation--was measured in order to clarify the relationship between HSV-1 reactivation and symptoms of cognitive function in AD. Cognitive function in AD and aMCI were evaluated using scores from the mini-mental state examination (MMSE) and frontal assessment battery (FAB). The results showed that the subjects with aMCI, for which cerebral function is better preserved than subjects with AD, had a higher anti-HSV-1 IgG antibody avidity index than the AD subjects or healthy controls. Furthermore, the anti-HSV-1 IgG antibody avidity index was even higher in the subjects with high MMSE scores on orientation to time and three-step command subscores. We observed a negative correlation between the anti-HSV-1 IgG antibody avidity index and plasma BDNF concentration, which is an indicator of encephalitis. This suggests that HSV-1 reactivation, as observed through an increase in the anti-HSV-1 IgG avidity index, does not progress to encephalitis. These results suggest that HSV-1 reactivation occurs from the stage of aMCI, which is prodromal to AD, and can affect AD symptoms without an intermediary stage of severe encephalitis. The study demonstrates that the anti-HSV-1 IgG antibody avidity index could be a useful biomarker for the early diagnosis of aMCI as well as AD, and suggests that antiviral medication to treat HSV-1 could play a role in preventing the onset of AD.

In the present study, we examined whether brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) influenced the changeable executive dysfunction of patients with two separate disease stages: amnestic mild cognitive impairment (A-MCI) or mild Alzheimer disease (AD), which are comparatively similar demented conditions.Among 200 outpatients with dementia and MCI, 146 outpatients with mild AD or A-MCI were recruited and divided into two genotypic groups, valine homozygosity (Val/Val) and methionine (Met) carriers, based on the representative BDNF functional polymorphism Val66Met. Next, we compared the Frontal Assessment Battery (FAB) total and subtest scores between the two genotypic groups according to each of two different disease stages: A-MCI (n = 42) and mild AD (n = 104).Among patients with only a mild stage of AD, the FAB total and go/no-go scores were significantly lower (p0.05) among the subjects with the Val/Val genotype than among the Met carriers. However, no significant differences in any other demographic variables were observed between the genotypes according to each of different disease stages. A significant interaction between Val66Met and age was not observed for the FAB scores.These results suggested that the BDNF gene may significantly influence executive dysfunction, including inhibition tasks, among patients with mild-stage AD.

Background/Aims: To address the clinical neurocognitive roles of nerve growth factor (NGF) genetic polymorphism in early-stage Alzheimer’s disease (AD) and amnestic mild cognitive impairment (A-MCI), we investigated the association between this single-nucleotide polymorphism (SNP) and executive dysfunction as a nonmemory cognitive impairment. Methods: Among 200 outpatients with dementia and MCI whose NGF SNP rs6330 genotype was identified, those with A-MCI (n = 35) and early-stage AD (n = 67) were recruited and divided into three groups according to genotype (C/C: n = 58, C/T: n = 39, T/T: n = 5). Then, the Frontal Assessment Battery (FAB) scores were compared among the three (C/C, C/T, T/T) or two (C/C, T carrier) genotype groups. Results: Among the subtests, a significant difference was only noted for the go/no-go scores (p < 0.01) between C/C and T carriers. However, no significant differences in the demographic variables and other neuropsychological subtest scores reflecting attentional and memory function were observed among the genotypes. Conclusion: Regarding the functional roles of neurotrophin polymorphisms as they relate to executive dysfunction, the NGF gene rs6330 might influence the inhibition task in Japanese patients with early-stage AD or A-MCI.

Background: Some previous research has hypothesized that executive dysfunction in patients with early Alzheimer's disease (AD) occurs as a result of a disconnection between different cerebral areas. The aim of the present study was to evaluate how the hippocampal volume influences executive function as a non-memory cognitive function.Methods: From 157 consecutive patients with AD or amnestic mild cognitive impairment (A-MCI), we recruited 107 subjects who had a global Clinical Dementia Rating (CDR) of 0.5 or 1.0 and whose degree of hippocampal atrophy had been measured using magnetic resonance imaging (MRI); the severity of atrophy was assessed using the voxel-based specific regional analysis for Alzheimer's disease (VSRAD) system. We divided the subjects into three groups: mild atrophy, 0 < Z-score < 1.0 (N = 21); moderate atrophy, 1.0 ≤ Z-score < 2.0 (N = 46); or severe atrophy, 2.0 ≤ Z-score < 4.0 (N = 40) according to the Z-score and compared the Frontal Assessment Battery (FAB) and its subtest scores between each atrophy group.Results: The results demonstrated that age, sex ratio, duration of illness, education years, MMSE score, Behave-AD score, and proportion of atrophy area in total brain (%) were not significantly different among the three groups. Only the go/no-go score among the six subtests was significantly lower for increasing atrophy severity (P < 0.05). Furthermore, hippocampal atrophy significantly influenced the go/no-go score independently of interactions from whether the diagnosis was early AD or A-MCI (P < 0.05).Conclusion: These results support a significant association between hippocampal atrophy and executive dysfunction as a non-memory cognitive impairment in patients with early AD and A-MCI.

Background: In order to address the neuropsychological pathogenesis of aberrant motor behaviors in Alzheimer's disease (AD), we used a cross-sectional study design to investigate the association between frontal lobe function, including executive function, and activity disturbances (wandering, purposeless activities and inappropriate activities).Methods: Among 75 consecutive outpatients with AD, 50 subjects with a Clinical Dementia Rating (CDR) score of 1 or 2 were selected and divided into two groups based on data obtained from interviews with their caregivers: an aberrant motor behaviors (AMB) group (n = 22), and a non-aberrant motor behaviors (NAMB) group (n = 28). Aberrant motor behavior was defined according to whether the “activity disturbance” score (ranging from 0 to 9) of the Behavioral Pathology in Alzheimer Disease (Behave-AD) scale was 0 or ≥1. The total and subtest scores of the Frontal Assessment Battery (FAB) were then compared between the two groups.Results: Significant differences were found between the FAB total (P < 0.05) and the subtest scores (lexical fluency, conflicting instructions; P < 0.05) in the two groups. The FAB score was significantly associated with the activity disturbance score (r = −0.49; PP < 0.001).Conclusions: This finding suggested that in addition to episodic memory disturbance, frontal lobe dysfunctions might lead patients with AD to develop aberrant motor behavior.

Aims: The purpose of the present study was to investigate the relationship between delusional thoughts (delusional ideation or misidentification) and frontal lobe function using the Japanese version of the Frontal Assessment Battery (FAB) bedside screening neuropsychological test in early stage Alzheimer's disease (AD) patients. Methods: Forty-eight probable AD patients with Mini-Mental State Examination score ≧18 points and a clinical dementia rating score of either 0.5 or 1.0 were divided into two groups based on data obtained from interviews with their caregivers: a delusional thought group (n = 19) and a non-delusional thought group (n = 29). The FAB total and subtest scores were then compared for the two groups. Results: Significant differences were found between the FAB total (P