Cognitive Effect of Transcranial Direct Current Stimulation on Left Dorsolateral Prefrontal Cortex in Mild Alzheimer's Disease: A Randomized, Double-Blind, Cross-Over Small-Scale Exploratory Study.

Background: Transcranial direct current stimulation (tDCS) is considered a potential therapeutic instrument for Alzheimer's disease (AD) because it affects long-term synaptic plasticity through the processes of long-term potentiation and long-term depression, thereby improving cognitive ability. Nevertheless, the efficacy of tDCS in treating AD is still debated. Dorsal lateral prefrontal cortex is the main role in executive functions. Objective: We investigate the cognitive effects of tDCS on AD patients. Methods: Thirty mild AD patients aged 66-86 years (mean = 75.6) were included in a double-blind, randomized, sham-controlled crossover study. They were randomly assigned to receive 10 consecutive daily sessions of active tDCS (2 mA for 30 min) or a sham intervention and switched conditions 3 months later. The anodal and cathodal electrodes were placed on the left dorsal lateral prefrontal cortex and the right supraorbital area, respectively. Subjects underwent various neuropsychological assessments before and after the interventions. Results: The results showed that tDCS significantly improved Cognitive Abilities Screening Instrument scores, especially on the items of "concentration and calculation", "orientation", "language ability", and "categorical verbal fluency". Mini-Mental State Examination and Wisconsin Card Sorting Test scores in all domains of "concept formation", "abstract thinking", "cognitive flexibility", and "accuracy" also improved significantly after tDCS. For the sham condition, no difference was found between the baseline scores and the after-intervention scores on any of the neuropsychological tests. Conclusion: >: Using tDCS improves the cognition of AD patients. Further large size clinical trials are necessary to validate the data.

The Lift Effects of Chordwise Wing Deformation and Body Angle on Low-Speed Flying Butterflies.

This work investigates the effects of body angle and wing deformation on the lift of free-flying butterflies. The flight kinematics were recorded using three high-speed cameras, and particle-image velocimetry (PIV) was used to analyze the transient flow field around the butterfly. Parametric studies via numerical simulations were also conducted to examine the force generation of the wing by fixing different body angles and amplifying the chordwise deformation. The results show that appropriately amplifying chordwise deformation enhances wing performance due to an increase in the strength of the vortex and a more stabilized attached vortex. The wing undergoes a significant chordwise deformation, which can generate a larger lift coefficient than that with a higher body angle, resulting in a 14% increase compared to a lower chordwise deformation and body angle. This effect is due to the leading-edge vortex attached to the curved wing, which alters the force from horizontal to vertical. It, therefore, produces more efficient lift during flight. These findings reveal that the chordwise deformation of the wing and the body angle could increase the lift of the butterfly. This work was inspired by real butterfly flight, and the results could provide valuable knowledge about lift generation for designing microaerial vehicles.

The Effect of Agomelatine in Behavioral and Psychological Symptoms of Dementia.

Objective: Moderate and severe behavioral and psychological symptoms of dementia (BPSD) often need medical treatment to improve symptoms. Agomelatine is a selective melatonergic (MT1/MT2) agonist that has normalizing effects on disturbed circadian rhythms and disrupted sleep-wake cycles. Its activity of 5HT-2C receptor antagonism is associated with lessening depression and anxiety and increasing slow-wave sleep. Based on past clinical records and current findings it suggests that agomelatine can improve BPSD for patients. This retrospective cohort study was designed to compare the BPSD before and after using agomelatine. Methods: Records of dementia cases who had ever received agomelatine treatment for BPSD in a general hospital setting during the past 2.5 years were identified and reviewed. Scores from before and after 3 months of treatment with agomelatine were collected for Neuropsychiatric Inventory (NPI), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) to compare and analyze the difference of psychological and behavioral symptoms pre- and post-agomelatine used. Results: Records of 144 cases of dementia with BPSD who had ever used agomelatine from January 2015 to June 2017 were collected. All of the 112 cases had BPRS and CGI scores, of which 75 cases had additional NPI scores. Among these 112 cases, the BPRS and CGI scores were significantly improved in all types of dementia. NPI scores indicated that the use of agomelatine alleviated obvious symptoms and decreased overall distress, especially in the depression/poor mood, anxiety, and sleep/night behavior. Conclusion: It is consistent with an effective result of agomelatine in improving BPSD.

Sex differences in the diagnosis of autism spectrum disorder and effects of comorbid mental retardation and attention-deficit hyperactivity disorder.

BACKGROUND/PURPOSE: The association between sex and diagnostic behavior of autism spectrum disorder (ASD), and the effects of comorbid mental retardation (MR) and attention-deficit hyperactivity disorder (ADHD), were explored. METHODS: Based on the Taiwan Longitudinal Health Insurance Database (LHID)-2000 and data from 1996 through 2008, the cumulative incidence of ASD over time was compared between the sexes (both cohorts n = 38,117) using the log-rank test. The effects of comorbid MR and ADHD on the incidence of ASD were evaluated using Cox proportional hazard regression analysis. The age at first diagnosis of ASD in the two sexes was compared using the independent-sample t-test. RESULTS: The incidence was higher in males than in females (0.0007 vs. 0.0002) across ages. Comorbid MR or ADHD increased the incidence of ASD in both sexes; comorbid MR or ADHD also decreased the male to female hazard ratio of ASD, with no significant differences in the incidence density of ASD between sexes. ADHD delayed diagnosis in both sexes (males: 6.61 vs 5.10, p < 0.0001; females: 6.83 vs 4.69, p = 0.0037). CONCLUSION: The general concept of a higher incidence of ASD among males was noted in this study of a Taiwanese population, but disappeared in those with comorbid MR or ADHD, indicating unique vulnerabilities to MR/ADHD or under-identification of high-functioning females with ASD in childhood. Increasing the diagnostic sensitivity of ASD in those with comorbid ADHD is important due to a delayed diagnostic age in this group.

Association between Anti-Psychotic Drugs Use and Hip Fractures in Patients with Dementia: A Nationwide Population-Based Study.

BACKGROUND: People with dementia are a high-risk group for hip fractures. Although the increased risk of hip fractures associated with antipsychotic drugs (APD) is found in older populations, little is known about the risk for people with dementia living in Asia. We aimed to investigate the association between hip fractures and the characteristics of APD use in patients with dementia. METHODS: A nested case-control analysis was conducted on a nationwide cohort in Taiwan. People with diagnoses of dementia during 2003-2012 were identified. Conditional logistic regression analysis was performed, and adjusted odds ratios (aORs) were calculated with a 95% confidence interval (CI) to estimate the risk of hip fractures. RESULTS: APD use was associated with an increased risk of hip fractures in patients with dementia; current use or combined use of first and second generations of APDs had even higher risks. Regarding the duration of APD use, a U-shape curve of hip fracture risk was noted, and the risk peaked during 0-15 days and >215 days of exposure (aOR = 1.46, 95% CI 1.37-1.57; aOR = 1.47, 95% CI 1.37-1.58; respectively). Considering the doses of APDs, the hip fracture risk was significantly increased with all four levels of the cumulative doses and average daily doses and peaked in the group with the highest average daily dose. CONCLUSIONS: The findings suggest that caution must be taken when initiating APD use in patients with dementia, even in a small dose, and mixed types of APD prescriptions should be administered with care. Furthermore, frequent evaluation of the possibility of tapering or withdrawal of the medication is necessary, as the risk does not attenuate after long-term use.

Maternal breastfeeding and autism spectrum disorder in children: A systematic review and meta-analysis.

OBJECTIVES: Autism spectrum disorder (ASD) refers to a group of conditions variably affecting communicative and social interactive abilities presenting alongside behaviors with various restricted and repetitive patterns. In addition to genetic factors that influence the onset of the symptoms, there is growing interest in the potential involvement of non-genetic environmental factors. Some aspects of breastfeeding practices, including rates, timing, or optimality, have been put forward as environmental risk factors for autism. However, previous studies showed a controversial relationship between ASD and breastfeeding. METHODS: A meta-analysis on the association between maternal breastfeeding and ASD in children was conducted. We also explored potential moderating factors which might influence this association. Articles reporting the association between breastfeeding and a diagnosis of ASD were included. RESULTS: Seven articles were included in the meta-analysis. Cumulatively, children with ASD (n = 1463), either in the form of clinical diagnosis or self-report, were significantly less likely to have been breastfed than children without ASD (n = 1180) (OR = 0.61, 95% CI = 0.45-0.83, P = 0.002). Subgroup analyses revealed that results remained significant for children who were breastfed with additional supplementation. DISCUSSION: This meta-analysis provides evidence that breastfeeding (exclusively or including additional supplements) may protect against ASD. Prospective longitudinal research is required to disentangle the complex relationships and to explore potential pathophysiological mechanisms.

Maternal breastfeeding and attention-deficit/hyperactivity disorder in children: a meta-analysis.

Previous studies have suggested environmental factors may contribute to the risk of attention-deficit/hyperactivity disorder (ADHD). The current meta-analysis examined (1) the difference in the duration of maternal breastfeeding between children with and without ADHD, and (2) the association between maternal breastfeeding and ADHD in children. The data of individual studies were synthesized with a random-effects model. Eleven articles were included in this meta-analysis. Children with ADHD had significantly less breastfeeding duration than controls (Hedges' g = - 0.36, 95% confidence intervals (CIs) = - 0.61 to - 0.11, p = 0.005; difference in means: - 2.44 months, 95% CIs = - 3.17 to - 1.71, p < 0.001). In addition, the rates of non-exclusive breastfeeding in children with ADHD is significantly higher in "under 3 months" (odds ratio (OR) = 1.90, 95% CIs = 1.45 to 2.48, p < 0.001) but lower in "6 to 12 months" (OR = 0.69, 95% CIs = 0.49 to 0.98, p = 0.039) and "over 12 months" (OR = 0.58, 95% CIs = 0.35 to 0.97, p = 0.038) than controls. Children with ADHD received significantly higher rate of exclusive breastfeeding duration "under 3 months" (OR = 1.51, 95% CIs = 1.20 to 1.89, p < 0.001) but lower in "over 3 months" (OR = 0.52, 95% CIs = 0.29 to 0.95, p = 0.033) than controls. Furthermore, an association was found between non-breastfeeding and ADHD children (adjusted OR = 3.71, 95% CI = 1.94 to 7.11, p < 0.001). Our results suggest maternal breastfeeding is associated with a lower risk of ADHD in children. Future longitudinal research is required to confirm/refute these findings and to explore possible mechanisms underlying this association.

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer's disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27th, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787-0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576-0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556-0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620-1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818-0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383-1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449-0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475-1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD.

Peripheral iron levels in children with autism spectrum disorders vs controls: a systematic review and meta-analysis.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, and nutritional deficiency may play a role in the development of ASD. A relationship between ASD and iron levels/iron deficiency (ID) has been reported; however, the results have been inconsistent. Therefore, we conducted this meta-analysis to examine the relationship between ASD and ID following the Meta-Analysis of Observational Studies in Epidemiology guidelines. We performed a systematic search of PubMed, ScienceDirect, Embase, ProQuest, ClinicalTrials.gov, and Cochrane CENTRAL databases up to September 22, 2017. Studies providing data on peripheral iron levels and/or the prevalence of ID in children with ASD vs those without ASD (non-ASD) were included. Primary outcomes included the difference in peripheral iron levels in children with ASD compared with those without ASD, and the odds ratio of ASD in children with ID compared with those without ID. Twenty-five articles met the inclusion criteria. We found that peripheral iron levels were not significantly different between the ASD and non-ASD groups, including serum ferritin (k = 4, Hedges g = 0.016, 95% confidence interval [CI] = -0.482 to 0.515, P = .949) or hair iron (k = 12; Hedges g = -0.219, 95% CI = -0.551 to 0.113, P = .196). There was no significant difference in the amount of iron in food content between the ASD and non-ASD groups (k = 6; Hedges g = -0.458, 95% CI = -1.246 to 0.330, P = .254). However, the reciprocal comorbidity of ASD and ID was significantly higher than in the children without these disorders. Our analysis showed that the available evidence is inconsistent with regard to whether children with ASD have lower iron levels. Future longitudinal studies are required to confirm or refute these associations and elucidate potential mechanisms.

Peripheral iron levels in children with attention-deficit hyperactivity disorder: a systematic review and meta-analysis.

There is growing recognition that the risk of attention-deficit hyperactivity disorder (ADHD) in children may be influenced by micronutrient deficiencies, including iron. We conducted this meta-analysis to examine the association between ADHD and iron levels/iron deficiency (ID). We searched for the databases of the PubMed, ScienceDirect, Cochrane CENTRAL, and ClinicalTrials.gov up to August 9th, 2017. Primary outcomes were differences in peripheral iron levels in children with ADHD versus healthy controls (HCs) and the severity of ADHD symptoms in children with/without ID (Hedges' g) and the pooled adjusted odds ratio (OR) of the association between ADHD and ID. Overall, seventeen articles met the inclusion criteria. Peripheral serum ferritin levels were significantly lower in ADHD children (children with ADHD = 1560, HCs = 4691, Hedges' g = -0.246, p = 0.013), but no significant difference in serum iron or transferrin levels. In addition, the severity of ADHD was significantly higher in the children with ID than those without ID (with ID = 79, without ID = 76, Hedges' g = 0.888, p = 0.002), and there was a significant association between ADHD and ID (OR = 1.636, p = 0.031). Our results suggest that ADHD is associated with lower serum ferritin levels and ID. Future longitudinal studies are required to confirm these associations and to elucidate potential mechanisms.

The effectiveness of adjunct mindfulness-based intervention in treatment of bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Mindfulness-based interventions (MBIs) have been increasingly used as an adjunctive treatment to pharmacotherapy for a few psychiatric disorders. However, few studies have investigated the efficacy of MBIs in bipolar disorder (BD). METHODS: We performed a systematic review and meta-analysis to evaluate the efficacy of MBIs as an adjunctive treatment in BD. Major electronic databases were independently searched by two authors for controlled and uncontrolled studies which examined the effects of MBIs on psychiatric symptoms in subjects with BD. Data from original studies were synthesized by using a random effects model. RESULTS: Twelve trials were eligible for inclusion into current meta-analysis, including three controlled studies (n=132) and nine uncontrolled studies (n=142). In within-group analysis, MBIs significantly reduced depressive (7 studies, n=100, Hedges' g=0.58, p<0.001) and anxiety (4 studies, n=68, Hedges' g=0.34, p=0.043) symptoms, but not manic symptoms (6 studies, n=89, Hedges' g=0.09, p=0.488) and cognition (3 studies, n=43, Hedges' g=0.35, p=0.171), compared to baseline. In between-group analysis (intervention group versus waiting list group, all patients with BD), MBIs did not reduce depressive (3 studies, n=132, Hedges' g=0.46, p=0.315) or anxiety (3 studies, n=132, Hedges' g=0.33, p=0.578) symptoms. LIMITATIONS: Only three controlled trials compared MBIs to control conditions. CONCLUSIONS: Our meta-analysis showed significantly beneficial effects on depressive and anxiety symptoms of BD patients in within-group analysis. However, this significance was not observed in comparison with the control groups. Further clinical trials are warranted to investigate the differences in the benefits of MBIs between treatment and control subjects.

Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis.

Add-on ketamine anesthesia in electroconvulsive therapy (ECT) has been studied in depressive patients in several clinical trials with inconclusive findings. Two most recent meta-analyses reported insignificant findings with regards to the treatment effect of add-on ketamine anesthesia in ECT in depressive patients. The aim of this study is to update the current evidence and investigate the role of add-on ketamine anesthesia in ECT in depressive patients via a systematic review and meta-analysis. We performed a thorough literature search of the PubMed and ScienceDirect databases, and extracted all relevant clinical variables to compare the antidepressive outcomes between add-on ketamine anesthesia and other anesthetics in ECT. Total 16 articles with 346 patients receiving add-on ketamine anesthesia in ECT and 329 controls were recruited. We found that the antidepressive treatment effect of add-on ketamine anesthesia in ECT in depressive patients was significantly higher than that of other anesthetics (p<0.001). This significance persisted in both short-term (1-2 weeks) and moderate-term (3-4 weeks) treatment courses (all p<0.05). However, the side effect profiles and recovery time profiles were significantly worse in add-on ketamine anesthesia group than in control group. Our meta-analysis highlights the significantly higher antidepressive treatment effect of add-on ketamine in depressive patients receiving ECT compared to other anesthetics. However, clinicians need to take undesirable side effects into consideration when using add-on ketamine anesthesia in ECT in depressive patients.