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Background There is limited evidence regarding the relationship between Diabetes mellitus (DM) in middle age and mild cognitive impairment after a follow-up. Therefore, we investigated the relationship between fasting blood glucose (FBG) levels in middle age and cognitive function (assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) in later life, following over 15 years of follow-up in the Aichi Workers' Cohort Study in Japan. Methods Participants were 253 former local government employees aged 60-79 years in 2018 who participated in a baseline survey conducted in 2002. Using baseline FBG levels and self-reported history, participants were classified into the normal, impaired fasting glucose (IFG) and, and DM groups. Total MoCA-J score ranges from 0 to 30, and cognitive impairment was defined as MoCA-J score ≤25 in this study. A general linear model was used to estimate the mean MoCA-J scores in the FBG groups, adjusted for age, sex, educational year, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, total cholesterol, and estimated glomerular filtration rate. Results The mean MoCA-J score in the total population was 25.0, and the prevalence of MoCA-J score ≤25 was 49.0%. Multivariable-adjusted total MoCA-J scores were 25.2, 24.8, and 23.4 in the normal, IFG, and DM groups, respectively. The odds ratio of MoCA-J score ≤25 in the DM group was 3.29. Conclusions FBG level in middle age was negatively associated with total MoCA-J scores assessed later in life, independent of confounding variables.

Discrepancies in efficacy between single-dose and repeated administration of oxytocin for autism spectrum disorder have led researchers to hypothesize that time-course changes in efficacy are induced by repeated administrations of the peptide hormone. However, repeatable, objective, and quantitative measurement of autism spectrum disorder’s core symptoms are lacking, making it difficult to examine potential time-course changes in efficacy. We tested this hypothesis using repeatable, objective, and quantitative measurement of the core symptoms of autism spectrum disorder. We examined videos recorded during semi-structured social interaction administered as the primary outcome in single-site exploratory (n = 18, crossover within-subjects design) and multisite confirmatory (n = 106, parallel-group design), double-blind, placebo-controlled 6-week trials of repeated intranasal administrations of oxytocin (48 IU/day) in adult males with autism spectrum disorder. The main outcomes were statistical representative values of objectively quantified facial expression intensity in a repeatable part of the Autism Diagnostic Observation Schedule: the maximum probability (i.e. mode) and the natural logarithm of mode on the probability density function of neutral facial expression and the natural logarithm of mode on the probability density function of happy expression. Our recent study revealed that increases in these indices characterize autistic facial expression, compared with neurotypical individuals. The current results revealed that oxytocin consistently and significantly decreased the increased natural logarithm of mode on the probability density function of neutral facial expression compared with placebo in exploratory (effect-size, −0.57; 95% CI, −1.27 to 0.13; P = 0.023) and confirmatory trials (−0.41; −0.62 to −0.20; P < 0.001). A significant interaction between time-course (at baseline, 2, 4, 6, and 8 weeks) and the efficacy of oxytocin on the natural logarithm of mode on the probability density function of neutral facial expression was found in confirmatory trial (P < 0.001). Post hoc analyses revealed maximum efficacy at 2 weeks (P < 0.001, Cohen’s d = −0.78; 95% CI, −1.21 to −0.35) and deterioration of efficacy at 4 weeks (P = 0.042, Cohen’s d = −0.46; 95% CI, −0.90 to −0.01) and 6 weeks (P = 0.10, Cohen’s d = −0.35; 95% CI, −0.77 to 0.08), while efficacy was preserved at 2 weeks post-treatment (i.e. 8 weeks) (P < 0.001, Cohen’s d = −1.24; 95% CI, −1.71 to −0.78). Quantitative facial expression analyses successfully verified the positive effects of repeated oxytocin on autistic individuals’ facial expressions and demonstrated a time-course change in efficacy. The current findings support further development of an optimized regimen of oxytocin treatment.

Objective : To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. Methods : A total of 36 patients with mediastinal cystic lesions were enrolled. The patients were separated into two groups based on pathological findings : those with mediastinal cysts (n=23) and those with mediastinal tumors (n=13). The cystic components were measured using imaging parameters including mean computed tomography (CT) value, apparent diffusion coefficient (ADC), T1 signal intensity ratio (T1SI-ratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Both groups were statistically compared. Results : Comparative parameters between the cysts and tumors revealed the following ratios : CT value, 40.9±21.2 versus (vs) 24.8±12.9 (p = 0.019) ; SUVmax, 1.18±0.50 vs 4.32±3.52 (p = 0.003) ; ADC, 3.46±0.96 vs 2.68±0.74 (p = 0.022) ; T1SI-ratio, 1.06±0.60 vs 1.35±0.92 (p = 0.648) ; T2SI-ratio, 5.40±1.80 vs 4.33±1.58 (p = 0.194). However, there was no correlation between FDG uptake and ADC value. Conclusions : SUVmax from 18F-FDG PET/CT and ADC derived from MRI were effective in facilitating preoperative diagnosis to differentiate mediastinal cysts from tumors. However, these examinations may be complementary to one another, not dominant.

Summary: Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese population and confirmed an increased burden of rare exonic CNVs in both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to both disorders, were found in about 8% of ASD and SCZ cases, which was significantly higher than in controls. Phenotypic analysis revealed an association between clinically significant CNVs and intellectual disability. Gene set analysis showed significant overlap of biological pathways in both disorders including oxidative stress response, lipid metabolism/modification, and genomic integrity. Finally, based on bioinformatics analysis, we identified multiple disease-relevant genes in eight well-known ASD/SCZ-associated CNV loci (e.g., 22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and provide biological insights into these disorders. : Kushima et al. perform comparative analyses of CNVs in ASD and SCZ in a Japanese population. They identify pathogenic CNVs and biological pathways in each disorder with significant overlap. Patients with pathogenic CNVs have a higher prevalence of intellectual disability. Disease-relevant genes are detected in eight well-known ASD/SCZ-associated CNV loci. Keywords: autism spectrum disorder, schizophrenia, copy-number variation, array comparative genomic hybridization, genetic overlap, Japanese population, oxidative stress response, genome integrity, lipid metabolism, gene ontology

Resting-state (rs) functional magnetic resonance imaging (fMRI) studies have revealed dysfunctional thalamocortical functional connectivity (FC) in schizophrenia. However, the relationship between thalamocortical FC and cognitive impairment has not been thoroughly investigated. We hypothesized that aberrant thalamocortical FC is related to attention deficits in schizophrenia. Thirty-eight patients with schizophrenia and 38 matched healthy controls underwent rs-fMRI and task fMRI while performing a Flanker task. We observed decreased left thalamic activation in patients with schizophrenia using task fMRI to determine the thalamic seed. A seed-based analysis using this seed was performed in the whole brain to assess differences in thalamocortical FC between the groups. Significantly worse performance was observed in the patient group. The rs-fMRI analysis revealed significantly increased FC between the left thalamus seed and the occipital cortices/postcentral gyri in patients when compared to controls. In the patient group, significant positive correlations were observed between the degree of FC from the left thalamus to the bilateral occipital gyri, which correspond to the visual cortex, and the Flanker effect. No significant correlation was detected in the control group. These results indicate that aberrant FC between the left thalamus and the visual cortex is related to attention deficits in schizophrenia.

Although automobile driving is necessary for many people, including patients with mental disorders, the influence of psychotropic drugs on driving performance remains unclear and requires scientific verification. Therefore, the objective of this study was to conduct a review of the literature in order to aid the development of a valid evaluation method regarding the influence of medication on driving performance. We conducted a literature search using two sets of terms on PubMed. One set was related to psychotropic drugs, and the other to driving tests. We excluded reviews and case studies and added literature found on other sites. A total of 121 relevant reports were found. The experiments were roughly divided into on-the-road tests (ORT) and driving simulators (DS). Although highway driving tests in ORT are most often used to evaluate driving performance, DS are becoming increasingly common because of their safety and low cost. The validity of evaluation methods for alcohol should be verified; however, we found that there were few validated tests, especially for DS. The scenarios and measurement indices of each DS were different, which makes it difficult to compare the results of DS studies directly. No evaluation indices, except for SD of lateral position, were sufficiently validated. Although highway ORT are the gold standard, DS were shown to have an increasing role in evaluating driving performance. The reliability of DS needs to be established, as does their validation with alcohol in order to accumulate more high-quality evidence.

Although small-scale studies have described the effects of oxytocin on social deficits in autism spectrum disorder (ASD), no large-scale study has been conducted. In this randomized, parallel-group, multicenter, placebo-controlled, double-blind trial in Japan, 106 ASD individuals (18–48 y.o.) were enrolled between Jan 2015 and March 2016. Participants were randomly assigned to a 6-week intranasal oxytocin (48IU/day, n = 53) or placebo (n = 53) group. One-hundred-three participants were analyzed. Since oxytocin reduced the primary endpoint, Autism Diagnostic Observation Schedule (ADOS) reciprocity, (from 8.5 to 7.7; P

AIM Although the effects of psychotropics on driving ability have received much attention, little research is available on driving performance of stable outpatients with depression undergoing real-world treatment. This observational study investigated driving performance, cognitive functions, and depressive symptomatology of partly remitted outpatients with depression under daily-practice psychopharmacologic treatment. METHODS Seventy stable outpatients with depression and 67 healthy volunteers were enrolled. Patients' prescriptions were not controlled in order to capture the real-world treatment environment. Participants underwent three driving tasks - road-tracking, car-following, and harsh-braking - using a driving simulator, and three cognitive tasks - Continuous Performance Test, Wisconsin Card Sorting Test, and Trail-Making Test. The Symptom Assessment Scale - Structured Interview Guide for the Hamilton Depression Rating Scale, Beck Depression Inventory-II, Social Adaptation Self-Evaluation Scale, and Stanford Sleepiness Scale were also completed. RESULTS Although many patients received various pharmacologic treatments, there were no significant differences in the three driving tasks between outpatients with depression and healthy controls. Difficulty of maintaining set in the Wisconsin Card Sorting Test was significantly increased in patients with depression. Results on the Social Adaptation Self-Evaluation Scale were significantly associated with road-tracking and car-following performance, in contrast to results on the Hamilton Depression Rating Scale and the Beck Depression Inventory-II. CONCLUSION We conclude that partly remitted depressive patients under steady-state pharmacologic treatment do not differ from healthy controls with respect to driving performance, which seems to be more affected by psychosocial functioning than by pharmacologic agents. This, however, should be investigated systematically in an off/on study.

Aim Studies have reported that cognitive decline occurs after the onset of schizophrenia despite heterogeneity in cognitive function among patients. The aim of this study was to investigate the degree of estimated cognitive decline in patients with schizophrenia by comparing estimated premorbid intellectual functioning and current intellectual functioning. Methods A total of 446 patients with schizophrenia (228 male, 218 female), consisting of three sample sets obtained from 11 psychiatric facilities, and 686 healthy controls participated in this study. The Wechsler Adult Intelligence Scale-III (WAIS-III) was used to measure the participants’ current full-scale IQ (FSIQ). The premorbid IQ was estimated using the Japanese Adult Reading Test-25. Estimated cognitive decline (difference score) was defined as the difference between the estimated premorbid IQ and the current FSIQ. Results Patients with schizophrenia showed greater estimated cognitive decline, a lower FSIQ, and a lower premorbid IQ compared with the healthy controls. The mean difference score, FSIQ, and estimated premorbid IQ were −16.3, 84.2, and 100.5, respectively, in patients with schizophrenia. Furthermore, 39.7% of the patients had a difference score of 20 points or greater decline. A discriminant analysis showed that the difference score accurately predicted 81.6% of the patients and healthy controls. Conclusion These results show the distribution of difference score in patients with schizophrenia. These findings may contribute to assessing the severity of estimated cognitive decline and identifying patients with schizophrenia who suffer from cognitive decline.

Aim Short sleep duration is a risk factor for cardiovascular diseases. Cerebral blood flow and its regulation are affected by pathological conditions commonly observed in the elderly population, such as dementia, atherosclerosis, diabetes mellitus (DM), stroke, and hypertension. The purpose of this study was to examine the influence of sleep duration on cortical oxygenated hemoglobin (OxyHb) using near-infrared spectroscopy (NIRS). Methods Seventy-three individuals (age, 70.1 ± 3.9 years, 51 men and 22 women) participated in this study. Cortical OxyHb levels were measured with NIRS. We evaluated age, body mass index (BMI), smoking status, alcohol intake, sleep duration, hypertension, DM, and hyperlipidemia using a questionnaire. Blood pressure was measured using plethysmography. Results Peak OxyHb and area under the NIRS curve significantly decreased in participants with sleep duration

Introduction: Response inhibition in eating disorders (ED) has been studied using methods such as Go/No-go tasks and cognitive conflict tasks, but the results have been inconsistent with regard to the presence or absence of impaired response inhibition in ED. This may be due to variation across the studies in the characteristics of the tasks and in the degree of underweight of ED participants. Method: We investigated the presence or absence of impaired response inhibition in an ED patient group, including many severe cases (body mass index

Reelin protein (RELN), an extracellular matrix protein, plays multiple roles that range from embryonic neuronal migration to spine formation in the adult brain. Results from genetic studies have suggested that RELN is associated with the risk of psychiatric disorders, including schizophrenia (SCZ). We previously identified a novel exonic deletion of RELN in a patient with SCZ. High-resolution copy number variation analysis revealed that this deletion included exons 52 to 58, which truncated the RELN in a similar manner to the Reln Orleans mutation (Relnrl-Orl). We examined the clinical features of this patient and confirmed a decreased serum level of RELN. To elucidate the pathophysiological role of the exonic deletion of RELN in SCZ, we conducted behavioral and neurochemical analyses using heterozygous Relnrl-Orl/+ mice. These mice exhibited abnormalities in anxiety, social behavior, and motor learning; the deficits in motor learning were ameliorated by antipsychotics. Methamphetamine-induced hyperactivity and dopamine release were significantly reduced in the Relnrl-Orl/+ mice. In addition, the levels of GABAergic markers were decreased in the brain of these mice. Taken together, our results suggest that the exonic deletion of RELN plays a pathological role, implicating functional changes in the dopaminergic and GABAergic systems, in the pathophysiology of SCZ.

Objective To assess the effects of hypnotics on prefrontal cortex activity in healthy subjects using near-infrared spectroscopy (NIRS) in a double-blind, placebo-controlled crossover trial. Methods Eighteen healthy males received acute doses of ramelteon (8 mg), triazolam (0.125 mg), or placebo in a predetermined randomization schedule, with a washout period of more than 1 week. All subjects performed a verbal fluency task during NIRS assessments at baseline and at 1 and 4 hr post-dose. The number of words correctly generated during the task (behavioral performance) and scores on the Stanford Sleepiness Scale (SSS) were also recorded at each test time. Results Compared with the placebo, triazolam (0.125 mg) significantly decreased oxyhemoglobin (oxy-Hb) concentration change in NIRS during the posttask period and significantly increased behavioral performance, whereas triazolam (0.125 mg) and ramelteon (8 mg) significantly increased SSS scores. Conclusions The differential effects of two types of hypnotics on oxy-Hb change measured by NIRS were observed in acute dosing, suggesting that when assessing brain activity of patients with psychiatric disorders, researchers should consider how certain types of hypnotics can influence brain function. This would also provide useful information to clinicians when prescribing hypnotics suitable for their patients' conditions.

Chronic sleep restriction adversely effects cognitive performance and mood, resulting in accidents and economic loss. We examined the effects of three nights of sleep restriction on cortical oxygenation, cognitive performance and mood. We studied 14 young adults. All subjects spent ≥8 h/night in bed prior to the study day (sufficient sleep), followed by

The impact of cognitive decline on driving safety and mobility in drivers with mild cognitive impairment (MCI) remains unclear. Therefore a cross-sectional study was carried out, to clarify the risk of elderly drivers with MCI compared to controls and to clarify whether MCI affects personal mobility on elderly drivers. 133 community-dwelling elderly drivers applied to baseline survey, 8 were excluded following exclusion criteria: (1) general cognitive impairment (MMSE < 21: n=1), and (2) driving cessation at baseline (n=7). And 125 participants were divided into control group (n=93) or MCI group (n=32). At baseline, participants were assessed individually cognitive and psychiatric state, driving-related risks based on performances of driving simulator (DS) and self-reported driving event (crashes, traffic citations, and unrecorded mistakes), driving behavior, and mobility. The frequency of traffic citation is larger in the control group compared to the MCI group, whereas there were no statistically significant differences between groups in a frequency of crashes and unrecorded driving mistakes. Both the number of miles driven/week and travel distance/week showed no different between groups, but the area of driving and travelling were reduced slightly in elderly drivers with MCI. Moreover, there were no statistically significant differences of DS performance between groups. These results support the finding from other studies showing that cognitive decline is associated with scale-down of personal mobility in elderly people. The current study could not demonstrate pronounced decline of driving ability in drivers with MCI. Prospective studies will need to clear driving-related risks in elderly drivers with MCI.

Anorexia nervosa (AN) is a psychiatric disorder, in which the prognosis for some patients is poor. The etiology and effective treatments for AN have not been established. We examined morphometric changes in the brain of AN and clarified how the changes were associated with symptoms and pathophysiology. We enrolled 52 participants: 7 with the restrictive type of AN, 13 with the binge-eating/purging type, 3 with eating disorder not otherwise specified, and 29 healthy controls. Participants underwent T1-weighted MRI. Group differences between patients and controls in gray matter volume (GMV) were analyzed using voxel-based morphometry. Age and body mass index (BMI) were considered covariates. Correlations between regional GMVs and drive for thinness and body dissatisfaction were examined. Patients had decreased GMV in the superior/middle temporal gyrus (STG/MTG), pulvinar, and superior frontal gyrus after correction for age and BMI, and in the STG/MTG, middle frontal gyrus, and cingulate after correction for age. A correlational group difference was detected for body dissatisfaction and GMV in the STG. Our findings suggest that decreased GMV in the STG is related to body dissatisfaction that could come from impaired visuospatial perception, together with GMV decreases in several regions, which may be involved in development of AN.

Aims Type 2 diabetes mellitus (T2DM) is a risk for cognitive decline in older adults. The current study was carried out to determine the factors associated with cognitive decline. Methods The older T2DM patients (aged ≥65 years, mean age 79.2 ± 5.1 years) were observed for 6 years, and the mean values in clinical indicators of participants with and without cognitive decline over a 6-year period were compared. Then, multiple logistic analysis was carried out to determine the factors associated with cognitive decline. Separate analyses were also carried out for each of five cognitive assessments (Mini-Mental State Examination, word immediate and delayed recall, Stroop test, digit symbol substitution). Results In the composite of several cognitive assessments, higher age and a lower level of high-density lipoprotein cholesterol were associated with cognitive decline in older T2DM patients. Lower systolic blood pressure was associated with a decline in delayed word list recall. Higher plasma insulin level was associated with a decline in the Stroop test performance. Conclusion Lower high-density lipoprotein cholesterol was significantly associated with general cognitive decline in older T2DM patients during our 6-year observation. Several other factors were also associated with cognitive assessments of various cognitive domains. Geriatr Gerontol Int 2015; 15: 302–310.

Summary Background:Schizophrenia is a relatively common disorder, with a lifetime prevalence of about 1%. Family history is the most important risk factor for schizophrenia, consistent with a genetic contribution to its etiology. Recent human genetic studies reported that some common variants located within BCL9 are associated with schizophrenia in the Chinese population, but not associated with bipolar disorder in the Caucasian population. Methods: Single nucleotide variant (SNP) prioritization sample was comprised of 575 patients with schizophrenia and 564 healthy controls with no personal or family history of psychiatric illness. For SNP association analysis, we used an independent Japanese sample set (replication sample) comprising 1464 cases and 1171 controls. For the analysis of cognitive performance, we investigated 115 cases and 87 controls using Continuous Performance Test (CPT-IP) and the Wisconsin Card Sorting Test Keio version (WCST). Meta-selectanalysis was performed using a combined Japanese total sample (N=3735) and a Chinese sample from a previous study. Results: In the replication sample set, we did not detect any association in 2 SNPs (rs672607 and rs10494252) and schizophrenia. Meta-analysis of rs672607 showed significant association (p-value 0.012, odds ratio 0.855). There was a significant (p Conclusions: We were able to detect evidence for an association between rs672607 in BCL9 and schizophrenia in the meta-analysis of Japanese and Chinese populations. Additionally, this common variant may affect cognitive performance, as measured by the CPT-IP in schizophrenia patients.

Background/Aims: In recent years, the relationship between chronic kidney disease (CKD) and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD) is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years) were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2). SVD was evaluated by the presence and severity of silent brain infarcts (SBIs) and white matter lesions (WMLs) on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017) and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026) after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

To elucidate the effectiveness of steroid administration and transcorneal electrical stimulation (TES) on anatomic changes and visual function in a rodent model of nonarteritic ischemic optic neuropathy (rNAION).Methylprednisolone (20 mg/kg) was injected through a central venous catheter twice a day for 3 days. TES was delivered with biphasic square pulses of 1 ms/phase, 100 μA of current, and 20 Hz of frequency for 60 min 3 h after induction on the 1st, 4th, 7th, 14th, and 28th days.Intravenous infusion of methylprednisolone significantly decreased the degree of acute disc edema but did not preserve the inner retinal thinning, decreasing the amplitude of scotopic threshold responses (STR) and decreasing retinal ganglion cell (RGC) numbers in rNAION. TES preserved the decreasing STR amplitude and the decreasing RGC numbers in rNAION.Steroids are effective for reducing disc edema in the acute stage in rNAION. TES is effective for preserving decreasing RGC numbers and function in the chronic stage of rNAION.

OBJECTIVE: This study aimed to evaluate the effects of repeated treatments with the sedative antidepressants mirtazapine and trazodone on driving performance and cognitive function. METHODS: Nineteen healthy men received continuous nocturnal doses of 15-mg mirtazapine , 25-mg trazodone, or placebo for 8 days in a double-blinded, three-way crossover trial. Subjects were asked to perform three driving tasks (road tracking, car following, and harsh braking) using a driving simulator and cognitive tasks (the Wisconsin Card Sorting Test, Continuous Performance Test, and N-back Test) at baseline and on Days 2 and 9. Stanford Sleepiness Scale scores were also assessed. RESULTS: Mirtazapine significantly increased the standard deviation of lateral position in the road-tracking task as compared with trazodone on Day 2. Mirtazapine significantly increased Stanford Sleepiness Scale scores as compared with trazodone and placebo. For the remaining tasks, no significant effects of treatment were observed. CONCLUSIONS: Acute treatment of mirtazapine impaired road-tracking performance and increased sleepiness, but sedative effects disappeared under repeated administrations. Trazodone did not affect driving performance or cognitive function under acute or repeated administrations. Both initial sedative effects and pharmacological profiles should be taken into consideration when using sedative antidepressants. Copyright © 2013 John Wiley & Sons, Ltd. Language: en

Summary The prevalence of insomnia increases with age. Short sleep duration is associated with deficits in cognitive performance. We hypothesized that short sleep duration and sleep quality influence cognitive performance in older adults. The study included 78 adults aged 60 years and over (72.2 ± 5.9 years). Total sleep time and sleep efficiency (total sleep time/time in bed × 100) were calculated using actigraphy. We evaluated cognitive performance with the continuous performance test-identical pairs and the number-back test. Sleep apnea was evaluated overnight with a portable home monitoring system. The accuracy of the 0-back test significantly decreased in participants with total sleep time less than 5 h compared with those with total sleep time greater than 7 h, but there was no significant difference in continuous performance test-identical pairs between the two groups. Participants with sleep efficiency

Aim Episodic memory is vulnerable to deterioration in people suffering from Alzheimer's disease. Currently, the Logical Memory (LM) subtest of the Wechsler Memory Scale-Revised (WMS-R) is used internationally as an operational definition to identify people with mild cognitive impairment (MCI). However, the Japanese version of the LM has not been adequately normalized for old-old people. Therefore, norms of the LM for people aged 75 years and over are required, and the effects of sex, age and education on performance were evaluated. Methods A total of 50 (27 female and 23 male) participants without a history of dementia and symptomatic stroke events recruited from the community and hospital populations were investigated using the Mini-Mental State Examination, the LM and some interference tasks. Results The mean scores (standard deviations) of the sample were 15.5 (5.4) on LM-I and 9.9 (6.6) on LM-II. The distributions of the LM-I and -II scores satisfied the normality assumption. The LM-I and LM-II scores correlated with age and the LM-I score correlated with educational background. Conclusions For the Japanese version of the LM, the means, standard deviations and distribution features of the old-old sample are presented. Although the normal sample was chosen to closely match the demographic profile of the Japanese population, the present sample might have had a higher educational background than the age-matched population, especially the males. Further study is required to standardize the Japanese version of the LM subtest for each 5-year interval for latter-stage elderly people. Geriatr Gerontol Int 2013; 13: 726–730.

Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD) in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR), albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.

Studies have reported that cognitive decline occurs after the onset of schizophrenia despite heterogeneity in cognitive function among patients. The aim of this study was to investigate the degree of estimated cognitive decline in patients with schizophrenia by comparing estimated premorbid intellectual functioning and current intellectual functioning.A total of 446 patients with schizophrenia (228 male, 218 female), consisting of three sample sets obtained from 11 psychiatric facilities, and 686 healthy controls participated in this study. The Wechsler Adult Intelligence Scale-III (WAIS-III) was used to measure the participants' current full-scale IQ (FSIQ). The premorbid IQ was estimated using the Japanese Adult Reading Test-25. Estimated cognitive decline (difference score) was defined as the difference between the estimated premorbid IQ and the current FSIQ.Patients with schizophrenia showed greater estimated cognitive decline, a lower FSIQ, and a lower premorbid IQ compared with the healthy controls. The mean difference score, FSIQ, and estimated premorbid IQ were -16.3, 84.2, and 100.5, respectively, in patients with schizophrenia. Furthermore, 39.7% of the patients had a difference score of 20 points or greater decline. A discriminant analysis showed that the difference score accurately predicted 81.6% of the patients and healthy controls.These results show the distribution of difference score in patients with schizophrenia. These findings may contribute to assessing the severity of estimated cognitive decline and identifying patients with schizophrenia who suffer from cognitive decline.

Short sleep duration is a risk factor for cardiovascular diseases. Cerebral blood flow and its regulation are affected by pathological conditions commonly observed in the elderly population, such as dementia, atherosclerosis, diabetes mellitus (DM), stroke, and hypertension. The purpose of this study was to examine the influence of sleep duration on cortical oxygenated hemoglobin (OxyHb) using near-infrared spectroscopy (NIRS).Seventy-three individuals (age, 70.1 ± 3.9 years, 51 men and 22 women) participated in this study. Cortical OxyHb levels were measured with NIRS. We evaluated age, body mass index (BMI), smoking status, alcohol intake, sleep duration, hypertension, DM, and hyperlipidemia using a questionnaire. Blood pressure was measured using plethysmography.Peak OxyHb and area under the NIRS curve significantly decreased in participants with sleep duration7 h compared with those with sleep duration ≥7 h (0.136 ± 0.212 mM·mm vs 0.378 ± 0.342 mM·mm, P = 0.001; 112.0 ± 243.6 vs 331.7 ± 428.7, P = 0.012, respectively). Sleep duration was significantly correlated with peak OxyHb level and area under the NIRS curve (r = 0.378, P = 0.001; r = 0.285, P = 0.015, respectively). Multiple regression analysis, including age, BMI, sex, smoking status, alcohol intake, sleep duration, hypertension, DM, and hyperlipidemia revealed that sleep duration was the only significant independent factor associated with peak OxyHb and area under the NIRS curve (β = 0.343, P = 0.004; β = 0.244, P = 0.049, respectively), and smoking status was independently correlated with time to the peak OxyHb (β = -0.319, P = 0.009).Sleep duration may be an important factor that influences cortical oxygenation in the elderly population.

Japanese researchers have recently conducted studies using near-infrared spectroscopy (NIRS) to help diagnose psychiatric disorders based on changes in brain activity. However, the influence of psychotropic drugs on NIRS measurements has not been clarified. To assess the effects of sedative antidepressants on prefrontal cortex activity in healthy subjects using NIRS in a double-blinded, placebo-controlled, crossover trial. Nineteen healthy males received nocturnal doses of mirtazapine 15 mg, trazodone 25 mg, or placebo for eight consecutive days in rotation, with a washout period of more than 1 week between each rotation. Subjects performed a verbal fluency task during NIRS on a total of seven occasions during the study period: more than a week prior to receiving the first dose of the first medication; and on days 2 and 9 of each rotation. The number of words correctly generated during the task (behavioral performance) was also recorded. Stanford Sleepiness Scale (SSS) scores were determined each day. Mirtazapine 15 mg significantly increased oxyhemoglobin (oxy-Hb) concentration change in NIRS on day 9, compared to trazodone 25 mg and placebo. Mirtazapine 15 mg significantly increased SSS on day 2, compared to the other conditions. No significant differences in behavioral performance were observed. Administration of mirtazapine for eight consecutive days affected oxy-Hb changes on NIRS. This result indicates that researchers should consider how certain types of antidepressant could influence brain function when the brain activity of patients with psychiatric disorders is assessed.

Background and aims: Methods of assessing driving abilities in the elderly are urgently needed. Although the driving simulator (DS) appears to be a safe and cost-effective method of objectively evaluating driving performance, it may pose adaptation problems for elderly adults. In this study, we examined age-related adaptation deficits on the DS. Methods: Healthy young adults (n=15) and healthy elderly persons (n=17) completed some neuropsychological tests, and then performed a road-tracking task with the DS, which was repeated four times (Trials 1–4). Results: After simulated driving in DS, simulator sickness (SS) was observed in 18.8% of participants. The frequency of SS was 29.4% in elderly adults and 6.7% in young adults, and 17.6% of the elderly participants dropped out of the experiment. Performance on the Necker cube copying task was significantly correlated with the onset of SS. Driving performance also showed a significant interaction between group and trial, for both driving accuracy and vehicle speed. In addition, the performance of elderly adults significantly improved between trials 1 and 4, reaching a plateau in trial 4, whereas that of young adults did not change across trials. Conclusion: This study provides preliminary evidence of slower adaptation to a DS-based driving task by older adults, which was associated with cognitive aging. Age affected driving accuracy and velocity when a road-tracking task was simply repeated. It is concluded that the capacity of elderly people to adapt to DS environments should be taken into consideration when evaluating their performance on DS tasks.

Objectives Serum brain-derived neurotrophic factor (BDNF) levels are reduced in depressed patients, and successful antidepressant treatment leads to increases in BDNF levels. However, little is known about how psychotropic drugs affect the mechanism of the human response to mental stress. We investigated the influence of psychotropic drugs on plasma BDNF levels under mental stress using a driving simulator (DS) task. Methods Fourteen healthy male volunteers received one of four drugs, diazepam (5mg), tandospirone (20mg), paroxetine (10mg), and matched placebo, in a double-blind, crossover manner. Subjects were asked to perform the DS task 4h post-dosing. Plasma BDNF levels were measured before and after the DS task. Results Plasma BDNF levels under the placebo, diazepam, and tandospirone conditions significantly decreased after the DS task compared with before the task. Conversely, no significant differences in plasma BDNF levels were detected under the paroxetine condition. Conclusion As these three psychotropic drugs have differential effects on plasma BDNF levels under mental stress after 4h post-dosing, antidepressants, unlike anxiolytics, might have a prompt positive effect on the mentalstress response.Copyright © 2012John Wiley & Sons, Ltd. key words—antidepressant; anxiolytic drug; brain-derived neurotrophic factor; mental stress

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【目的】本研究では便秘傾向の女子大学生を対象とし，Bifidobacterium breveヤクルト株，Streptococcus thermophilus，Lactococcus lactis，ガラクトオリゴ糖およびポリデキストロースを含む発酵乳の摂取による排便への影響について，ストレスレベル別に調べることを目的とした。【試験デザイン】プラセボを用いた無作為化二重盲検平行群間比較試験とした。【対象者】排便回数が週5回以下を基本とした92名の女子大学生で行った。【試験スケジュールおよび内容】観察期4週間（非摂取期間），飲用期4週間（摂取期間）の合計8週間とした被験者は，排便状況，食事の有無・主食の摂取頻度，起床時刻，就寝時刻および排便に影響を及ぼす可能性がある特記事項について毎日日誌に記録した。食物摂取頻度調査ならびCornell Medical Index-health questionnaire（CMI）を期間中約1ヶ月おきに実施した。【結果】試験飲料4週間の飲用は，観察期との比較で試験飲料群の排便頻度を有意に増加させたが，プラセボ群と群間差はなかった。解析対象者をCMI判別基準に基づくストレスレベル別に分類したところ，領域I（心理的正常）の試験飲料群では，同プラセボ飲料群と比較し排便頻度の有意な増加や，尿中フェノールの有意な減少が見られた。しかし領域Iよりストレスレベルが高い領域の群では，試験飲料の摂取によるそれらの現象は見られなかった。【結論】ストレスは，排便に対する発酵乳の飲用効果に，負の影響を与える可能性が示唆された。

In line with the recent initiative to establish a standard measure of cognitive decline in bipolar disorder1,2), the present study tested the criterion-related validity and test-retest reliability of the California Verbal Learning Test (CVLT)-II3) Japanese version.4)