Distinctive Association of the Functional Connectivity of the Posterior Cingulate Cortex on Memory Performances in Early and Late Amnestic Mild Cognitive Impairment Patients.

BACKGROUND: Attempts have been made to explore the biological basis of neurodegeneration in the amnestic mild cognitive impairment (MCI) stage, subdivided by memory performance. However, few studies have evaluated the differential impact of functional connectivity (FC) on memory performances in early- and late-MCI patients. OBJECTIVE: This study aims to explore the difference in FC of the posterior cingulate cortex (PCC) among healthy controls (HC) (n = 37), early-MCI patients (n = 30), and late-MCI patients (n = 35) and to evaluate a group-memory performance interaction against the FC of PCC. METHODS: The subjects underwent resting-state functional MRI scanning and a battery of neuropsychological tests. RESULTS: A significant difference among the three groups was found in FC between the PCC (seed region) and bilateral crus cerebellum, right superior medial frontal gyrus, superior temporal gyrus, and left middle cingulate gyrus (Monte Carlo simulation-corrected p < 0.01; cluster p < 0.05). Additionally, the early-MCI patients displayed higher FC values than the HC and late-MCI patients in the right superior medial frontal gyrus, cerebellum crus 1, and left cerebellum crus 2 (Bonferroni-corrected p < 0.05). Furthermore, there was a significant group-memory performance interaction (HC vs. early MCI vs. late MCI) for the FC between PCC and bilateral crus cerebellum, right superior medial frontal gyrus, superior temporal gyrus, and left middle cingulate gyrus (Bonferroni-corrected p < 0.05). CONCLUSION: These findings contribute to the biological implications of early- and late-MCI stages, categorized by evaluating the impairment of memory performance. Additionally, comprehensively analyzing the structural differences in the subdivided amnestic MCI (aMCI) stages could deepen our understanding of these biological meanings.

Late-life depression, subjective cognitive decline, and their additive risk in incidence of dementia: A nationwide longitudinal study.

OBJECTIVE: Late-life depression and subjective cognitive decline (SCD) are significant risk factors for dementia. However, studies with a large sample size are needed to clarify their independent and combined risks for subsequent dementia. METHODS: This nationwide population-based cohort study included all individuals aged 66 years who participated in the National Screening Program between 2009 and 2013 (N = 939,099). Subjects were followed from the day they underwent screening to the diagnosis of dementia, death, or the last follow-up day (December 31, 2017). RESULTS: Depressive symptom presentation, recent depressive disorder, and SCD independently increased dementia incidence with adjusted hazard ratio (aHR) of 1.286 (95% CI:1.255-1.318), 1.697 (95% CI:1.621-1.776), and 1.748 (95% CI: 689-1.808) respectively. Subjects having both SCD and depression had a higher risk (aHR = 2.466, 95% CI:2.383-2.551) of dementia than having depression (aHR = 1.402, 95% CI:1.364-1.441) or SCD (aHR = 1.748, 95% CI:1.689-1.808) alone. CONCLUSIONS: Depressive symptoms, depressive disorder, and SCD are independent risk factors for dementia. Co-occurring depression and SCD have an additive effect on the risk of dementia; thus, early intervention and close follow up are necessary for patients with co-occurring SCD and depression.

Association between Dementia and Clinical Outcome after COVID-19: A Nationwide Cohort Study with Propensity Score Matched Control in South Korea.

OBJECTIVE: Despite a high prevalence of dementia in older adults hospitalized with severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2), or so called COVID-19, research investigating association between preexisting diagnoses of dementia and prognosis of COVID-19 is scarce. We aimed to investigate treatment outcome of patients with dementia after COVID-19. METHODS: We explored a nationwide cohort with a total of 2,800 subjects older than 50 years who were diagnosed with COVID-19 between January and April 2020. Among them, 223 patients had underlying dementia (dementia group). We matched 1:1 for each dementia- non-dementia group pair yielding 223 patients without dementia (no dementia group) using propensity score matching. RESULTS: Mortality rate after COVID-19 was higher in dementia group than in no dementia group (33.6% vs. 20.2%, p=0.002). Dementia group had higher proportion of patients requiring invasive ventilatory support than no dementia group (34.1% vs. 22.0%, p=0.006). Multivariable analysis showed that dementia group had a higher risk of mortality than no dementia group (odds ratio=3.05, p<0.001). We also found that patients in dementia group had a higher risk of needing invasive ventilatory support than those in no dementia group. CONCLUSION: Our results suggest that system including strengthen quarantines are required for patients with dementia during the COVID- 19 pandemic.

Impact of Transcranial Direct Current Stimulation on Cognitive Function, Brain Functional Segregation, and Integration in Patients with Mild Cognitive Impairment According to Amyloid-Beta Deposition and APOE ε4-Allele: A Pilot Study.

Anodal transcranial direct current stimulation (anodal-tDCS) is known to improve cognition and normalize abnormal network configuration during resting-state functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI). We aimed to evaluate the impact of sequential anodal-tDCS on cognitive functions, functional segregation, and integration parameters in patients with MCI, according to high-risk factors for Alzheimer's disease (AD): amyloid-beta (Aß) deposition and APOE ε4-allele status. In 32 patients with MCI ([18 F] flutemetamol-: n = 10, [18 F] flutemetamol+: n = 22; APOE ε4-: n = 13, APOE ε4+: n = 19), we delivered anodal-tDCS (2 mA/day, five times/week, for 2 weeks) over the left dorsolateral prefrontal cortex and assessed the neuropsychological test battery and resting-state fMRI measurements before and after 2 weeks stimulation. We observed a non-significant impact of an anodal-tDCS on changes in neuropsychological battery scores between MCI patients with and without high-risk factors of AD, Aß retention and APOE ε4-allele. However, there was a significant difference in brain functional segregation and integration parameters between MCI patients with and without AD high-risk factors. We also found a significant effect of tDCS-by-APOE ε4-allele interaction on changes in the functional segregation parameter of the temporal pole. In addition, baseline Aß deposition significantly associated negatively with change in global functional integrity of hippocampal formation. Anodal-tDCS might help to enhance restorative and compensatory intrinsic functional changes in MCI patients, modulated by the presence of Aß retention and the APOE ε4-allele.

A Comparative Study on the Predictive Value of Different Resting-State Functional Magnetic Resonance Imaging Parameters in Preclinical Alzheimer's Disease.

Objective: Diverse resting-state functional magnetic resonance imaging (rs-fMRI) studies showed that rs-fMRI might be able to reflect the earliest detrimental effect of cerebral beta-amyloid (Aß) pathology. However, no previous studies specifically compared the predictive value of different rs-fMRI parameters in preclinical AD. Methods: A total of 106 cognitively normal adults (Aß+ group = 66 and Aß- group = 40) were included. Three different rs-fMRI parameter maps including functional connectivity (FC), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Receiver operating characteristic (ROC) curve analyses were utilized to compare classification performance of the three rs-fMRI parameters. Results: FC maps showed the best classifying performance in ROC curve analysis (AUC, 0.915, p < 0.001). Good but weaker performance was achieved by using ReHo maps (AUC, 0.836, p < 0.001) and fALFF maps (AUC, 0.804, p < 0.001). The brain regions showing the greatest discriminative power included the left angular gyrus for FC, left anterior cingulate for ReHo, and left middle frontal gyrus for fALFF. However, among the three measurements, ROI-based FC was the only measure showing group difference in voxel-wise analysis. Conclusion: Our results strengthen the idea that rs-fMRI might be sensitive to earlier changes in spontaneous brain activity and FC in response to cerebral Aß retention. However, further longitudinal studies with larger sample sizes are needed to confirm their utility in predicting the risk of AD.

Default mode network dissociation linking cerebral beta amyloid retention and depression in cognitively normal older adults.

Cerebral beta amyloid (Aß) deposition and late-life depression (LLD) are known to be associated with the trajectory of Alzheimer's disease (AD). However, their neurobiological link is not clear. Previous studies showed aberrant functional connectivity (FC) changes in the default mode network (DMN) in early Aß deposition and LLD, but its mediating role has not been elucidated. This study was performed to investigate the distinctive association pattern of DMN FC linking LLD and Aß retention in cognitively normal older adults. A total of 235 cognitively normal older adults with (n = 118) and without depression (n = 117) underwent resting-state functional magnetic resonance imaging and 18F-flutemetamol positron emission tomography to investigate the associations between Aß burden, depression, and DMN FC. Independent component analysis showed increased anterior DMN FC and decreased posterior DMN FC in the depression group compared with the no depression group. Global cerebral Aß retention was positively correlated with anterior and negatively correlated with posterior DMN FC. Anterior DMN FC was positively correlated with severity of depression, whereas posterior DMN FC was negatively correlated with cognitive function. In addition, the effects of global cerebral Aß retention on severity of depression were mediated by subgenual anterior cingulate FC. Our results of anterior and posterior DMN FC dissociation pattern may be pivotal in linking cerebral Aß pathology and LLD in the course of AD progression. Further longitudinal studies are needed to confirm the causal relationships between cerebral Aß retention and LLD.

Pre-transplant Dementia is Associated with Poor Survival After Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study with Propensity Score Matched Control.

OBJECTIVE: No previous study examined impact of dementia in the outcome of allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to investigate overall survival (OS) of patients with dementia after receiving HSCT. METHODS: Among 8,230 patients who underwent HSCT between 2002 and 2018, 5,533 patients younger than 50 years were first excluded. Remaining patients were divided into those who were and were not diagnosed with dementia before HSCT (dementia group: n = 31; no dementia: n = 2,666). Thereafter, among 2,666 participants without dementia, 93 patients were selected via propensity-matched score as non-dementia group. Patients were followed from the day they received HSCT to the occurrence of death or the last follow-up day (December 31, 2018), whichever came first. RESULTS: With median follow-up of 621 days for dementia group and 654 days for non-dementia group, 2 year-OS of dementia group was lower than that of non-dementia group (53.3% [95% confidence interval, 95% CI, 59.0-80.2%] vs. 68.8% [95% CI, 38.0-68.2%], p = 0.076). In multivariate analysis, dementia had significant impacts on OS (hazard risk = 2.539, 95% CI, 1.166-4.771, p = 0.017). CONCLUSION: Our results indicated that patients diagnosed with dementia before HSCT have 2.539 times higher risk of mortality after transplantation than those not having dementia. With number of elderly needing HSCT is increasing, further work to establish treatment guidelines for the management of HSCT in people with dementia is needed.

Rapid Onset of Intranasal Esketamine in Patients with Treatment Resistant Depression and Major Depression with Suicide Ideation: A Meta-Analysis

Objective: We performed a meta-analysis of randomized double-blinded placebo controlled trials (DB-RCTs) to investigate efficacy and safety of intranasal esketamine in treating major depressive disorder (MDD) including treatment resistant depression (TRD) and major depression with suicide ideation (MDSI). Methods: Mean change in total scores on Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to different time-points were our primary outcome measure. Secondary efficacy measures included rate of remission of depression and resolution of suicidality. Results: Eight DB-RCTs (seven published and one un-published) covering 1,488 patients with MDD were included. Esketamine more significantly improved MADRS total scores than placebo starting from 2-4 hours after the first administration (standardized mean difference, -0.41 [95% CI, -0.58 to -0.25], p < 0.00001), and this superiority maintained until end of double-blinded period (28 days). Sub-group analysis showed that superior antidepressant effects of esketamine over placebo in TRD and MDSI was observed from 2-4 hours, which was maintained until 28 days. Resolution of suicide in MDSI was also greater for esketamine than for placebo at 2-4 hours (OR of 2.04, 95% CIs, 1.37 to 3.05, p = 0.0005), but two groups did not statistically differ at 24 hours and day 28. Total adverse events (AEs), and other common AEs including dissociation, blood pressure increment, nausea, vertigo, dysgeusia, dizziness, and somnolence were more frequent in esketamine than in placebo group. Conclusion: Esketamine showed rapid antidepressant effects in patients with MDD, including TRD and MDSI. The study also suggested that esketamine might be associated with rapid anti-suicidal effects for patients with MDSI.

Differential Impact of Education on Gray Matter Volume According to Sex in Cognitively Normal Older Adults: Whole Brain Surface-Based Morphometry.

Background: The effect of educational status on brain structural measurements depends on demographic and clinical factors in cognitively healthy older adults. Objectives: The current study aimed to evaluate the impact of interaction between years of education and sex on gray matter volume and to investigate whether cortical volume has a differential impact on cognitive function according to sex. Methods: One hundred twenty-one subjects between 60 and 85 years old were included in this study. Gray matter volume was evaluated by whole brain surface-based morphometry. Multiple regression analysis was used to analyze the effects of sex-cortical volume interactions on cognitive functions. Results: There was a significant interaction between years of education and sex on the cortical volume of the left inferior temporal gyrus after adjusting for age, APOE ε4 allele prevalence, and total intracranial volume. In addition, we found a significant impact of the interaction between adjusted left inferior temporal volume and sex on CERAD-K total scores. Conclusion: These findings have significant implications for the understanding of how sex could affect the role of cognitive reserve for cortical atrophy in cognitively intact older adults.

Development of Random Forest Algorithm Based Prediction Model of Alzheimer's Disease Using Neurodegeneration Pattern.

OBJECTIVE: Alzheimer's disease (AD) is the most common type of dementia and the prevalence rapidly increased as the elderly population increased worldwide. In the contemporary model of AD, it is regarded as a disease continuum involving preclinical stage to severe dementia. For accurate diagnosis and disease monitoring, objective index reflecting structural change of brain is needed to correctly assess a patient's severity of neurodegeneration independent from the patient's clinical symptoms. The main aim of this paper is to develop a random forest (RF) algorithm-based prediction model of AD using structural magnetic resonance imaging (MRI). METHODS: We evaluated diagnostic accuracy and performance of our RF based prediction model using newly developed brain segmentation method compared with the Freesurfer's which is a commonly used segmentation software. RESULTS: Our RF model showed high diagnostic accuracy for differentiating healthy controls from AD and mild cognitive impairment (MCI) using structural MRI, patient characteristics, and cognitive function (HC vs. AD 93.5%, AUC 0.99; HC vs. MCI 80.8%, AUC 0.88). Moreover, segmentation processing time of our algorithm (<5 minutes) was much shorter than of Freesurfer's (6-8 hours). CONCLUSION: Our RF model might be an effective automatic brain segmentation tool which can be easily applied in real clinical practice.

Differential Risk of Incident Fractures Depending on Intensity and Frequency of Physical Activity According to Cognitive Status: A Nationwide Longitudinal Study.

Background: Previous studies have demonstrated an increased risk of fractures in subjects with various degrees of cognitive impairments. Recently, there has been growing recognition of the vital effect of physical activity (PA) on delay and prevention of fractures in older adults. Objectives: This study aimed to evaluate the optimal intensity and frequency of PA needed to prevent fractures in cognitively preserved older adults (CP), participants with subjective cognitive decline (SCD), and dementia patients using a large-scale nationwide cohort study. Methods: Data from a nationwide health screening program for individuals at the transitional age of 66 years were used in this study. A total of 968,240 subjects was enrolled, followed from 2007 to 2014, and classified as CP (n = 759,874), SCD (n = 195,365), or dementia group (n = 13,001). Adjusted hazard ratios (aHRs) by demographic and known risk factors for fractures were evaluated to identify the impact of various frequency and intensity PA on the occurrence of hip, vertebral, and limb fractures. Results: In CP participants, the most noticeable reduction of hip and vertebral fracture risk was shown in those performing vigorous-intensity PA at least three times per week. In the SCD group, the risk decrement in hip and vertebral fractures was most prominent in subjects who performed multiple-intensity PAs at least three times a week regardless of intensity. In the dementia group, only high-frequency walking and high-frequency & multiple-intensity PA decreased the risk of hip fractures compared with absence of PA. Conclusion: These findings suggest a role for various PA intensity and frequency levels to prevent hip and vertebral fractures according to cognitive status. Further study is needed to validate the effects of PA intensity and frequency proposed in this study on fractures according to cognitive status.

Differential Effects of the Interaction Between the Education and APOE ε4 Allele on Amyloid-beta Retention and Memory Performances in Cognitively Normal Older Adults and Alzheimer's Disease Patients.

BACKGROUND: Despite the effect of education and APOE ε4 allele on amyloid-beta (Aß) retention and memory, previous studies have not dealt with an interaction between two factors on Aß deposition and memory function in the course of Alzheimer's disease (AD). OBJECTIVE: To evaluate education by APOE ε4 allele interactions for Aß retention and neuropsychological test scores in cognitively normal older adults without Aß deposition [CN(Aß-), n=45] and Alzheimer's disease patients with Aß retention [AD(Aß+), n=33]. METHODS: Multiple regression analyses (adjusted for age, gender) were conducted to examine the effects of education, APOE ε4 allele, and the interaction between the two factors on global, regional Aß load quantified using [18F]flutemetamol standardized uptake value ratio with the pons as a reference region, and on neuropsychological test scores in each group. RESULTS: The interaction between education and APOE ε4 allele had an effect on amyloid load in parietal lobes (uncorrected p<0.05) and striatum (Bonferroni corrected p<0.05) in each CN(Aß-) and AD(Aß+). There was also an interaction effect of education and APOE ε4 allele on the memory performance in each CN(Aß-) and AD(Aß+) (uncorrected p<0.05). APOE ε4 carriers of both groups showed opposing slopes with each other in the correlation between the education years and Aß load, memory performance. CONCLUSION: The current results suggest a possible explanation of the differential effects of education and APOE ε4 allele interactions on AD pathology and memory function at the beginning and end of AD progress. However, further study with a validating cohort is needed for confirming this explanation.

Differences in cortical structure between cognitively normal East Asian and Caucasian older adults: a surface-based morphometry study.

There is a growing literature on the impact of ethnicity on brain structure and function. Despite the regional heterogeneity in age-related changes and non-uniformity across brain morphometry measurements in the aging process, paucity of studies investigated the difference in cortical anatomy between the East Asian and Caucasian older adults. The present study aimed to compare cortical anatomy measurements, including cortical thickness, volume and surface area, between cognitively normal East Asian (n = 171) and Caucasian (n = 178) older adults, using surface-based morphometry and vertex-wise group analysis of high-dimensional structural magnetic resonance imaging (MRI) data. The East Asian group showed greater cortical thickness and larger cortical volume in the right superior temporal gyrus, postcentral gyrus, bilateral inferior temporal gyrus, and inferior parietal cortex. The Caucasian group showed thicker and larger cortex in the left transverse temporal cortex, lingual gyrus, right lateral occipital cortex, and precentral gyrus. Additionally, the difference in surface area was discordant with that in cortical thickness. Differences in brain structure between the East Asian and Caucasian might reflect differences in language and information processing, but further studies using standardized methods for assessing racial characteristics are needed. The research results represent a further step towards developing a comprehensive understanding of differences in brain structure between ethnicities of older adults, and this would enrich clinical research on aging and neurodegenerative diseases.

Association of Alcohol Intake and Fracture Risk in Elderly Varied by Affected Bones: A Nationwide Longitudinal Study.

OBJECTIVE: Previous studies investigating association of alcohol intake and fracture risk in elderly yielded conflicting results. We first examined the association between alcohol intake and total fracture risk in elderly subjects and further analyzed whether the association varied by fracture locations. METHODS: This is a nationwide population-based cohort study which included all people aged 66 (n=1,431,539) receiving the National Screening Program during 2009-2014. Time-to-event were defined as duration from study recruitment, the day they received health screening, to the occurrence of fracture. RESULTS: Total fracture was significantly lower in mild drinkers [adjusted hazard ratio (aHR)=0.952; 95% confidence interval (95% CI) =0.931-0.973] and higher in heavy drinkers (aHR=1.246; 95% CI=1.201-1.294) than non-drinkers. Risk pattern of alcohol consumption and fracture differed according to affected bones. Similar J-shaped trends were observed for vertebra fractures, but risk of limb fracture showed a linear relationship with alcohol intake. For hip fracture, risk decrement was more pronounced in mild and moderate drinkers, and significant increment was noted only in very severe drinkers [≥60 g/day; (aHR)=1.446; 1.162-1.801]. CONCLUSION: Light to moderate drinking generally lowered risk of fractures, but association between alcohol and fracture risk varied depending on the affected bone lesions.

Pre-transplant depression decreased overall survival of patients receiving allogeneic hematopoietic stem cell transplantation: a nationwide cohort study.

Studies investigating association of depression with overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) yielded conflicting results. A nationwide cohort study, which included all adult patients [n = 7,170; depression group, 13.3% (N = 956); non-depression group, 86.7% (N = 6,214)] who received allo-HSCT from 2002 to 2018 in South Korea, analyzed risk of pre-transplant depression in OS of allo-HSCT. Subjects were followed from the day they received allo-HSCT, to occurrence of death, or last follow-up day (December 31, 2018). Median age at allo-HSCT for depression and non-depression groups were 50 and 45 (p < 0.0001), respectively. Two groups also differed in rate of females (depression group, 55.8%; non-depression group, 43.8%; p < 0.0001) and leukemia (depression group, 61.4%; non-depression group, 49.7%; p < 0.0001). After a median follow-up of 29.1 months, 5-year OS rate was 63.1%. Cox proportional-hazard regression evaluated an adjusted risk of post-transplant mortality related to depression: OS decreased sequentially from no depression (adjusted hazard ratio [aHR] = 1) to pre-transplant depression only (aHR = 1.167, CI: 1.007-1.352, p = 0.04), and to having both depression and anxiety disorder (aHR = 1.202, CI: 1.038-1.393, p = 0.014) groups. Pre-transplant anxiety (anxiety only) did not have significant influence in OS. Additional medical and psychiatric care might be necessary in patients who experienced depression, especially with anxiety, before allo-HSCT.

Differential Impact of Cigarette Smoking on Fracture Risks in Subjective Cognitive Decline and Dementia: A Nationwide Longitudinal Study.

OBJECTIVE: We aimed to explore the differential impact of cigarette smoking on fracture risks in SCD and dementia. METHODS: A nationwide population-based cohort study design was used. Out of all the people aged 66 (n=1,555,103) who went through the National Screening Program from 2009-2014, 968,240 participants with eligible data were included in the study. Time-to-event was calculated as the duration between the NSPTA and fracture incidence. Cox proportional-hazard regression analyses were conducted to evaluate the risk of fractures. RESULTS: Increased risk of all [adjusted hazard ratio (aHR)=1.184; 95% confidence interval (CI)=1.184, 1.093-1.283], hip (aHR=1.518; 95% CI=1.168-4.972), vertebral (aHR=1.235; 95% CI=1.101-1.386) fractures were increased in current smokers with more than 20 or more pack years (≥20 py) of SCD group, after adjusting for all relevant confounding factors. In dementia group, however, current smokers ≥20 py were at reduced risk of hip fractures (aHR=0.249; 95% CI=0.089-0.97). CONCLUSION: There was a disparate influence of cigarette smoking on the fracture risks in SCD and dementia group. Further studies are warranted to explicate this phenomenon, and personalized preventive measures according to one's cognitive status are imperative, since risk factors of fractures can exert disparate influence on patients at different stage of cognitive trajectory.

Agomelatine for the Treatment of Generalized Anxiety Disorder: A Meta-Analysis.

OBJECTIVE: Despite multiple drugs available, a large proportion of patients with generalized anxiety disorder (GAD) do not show adequate response and remission. Thus, additional novel pharmacological agents are needed to increase treatment option for GAD. We aimed to investigate efficacy and safety of agomelatine in the treatment of GAD by conducting a meta-analysis. METHODS: An extensive search of multiple databases and clinical trial registries were conducted. Mean change in total scores on Hamilton Anxiety Rating Scale (HAM-A) from baseline to endpoint was our primary outcome measure. Secondary efficacy measures included response and remission rates, as defined by a 50% or greater reduction in HAM-A total scores and a score of 7 or less in HAM-A total scores at study endpoint respectively. RESULTS: Four published double blinded, randomized, placebo-controlled trials were included in this meta-analysis. Agomelatine more significantly (standardized mean difference = -0.56, p = 0.004) improved HAM-A total scores than placebo. The odds ratios (ORs) of agomelatine over placebo for response and remission rates were 3.75 (p < 0.00001) and 2.74 (p < 0.00001), respectively. Agomelatine was generally well tolerated with insignificance in dropout rate, somnolence, headache, nasopharyngitis, and dizziness compared with placebo. However, agomelatine showed significantly higher incidence of liver function increment (OR = 3.13, p = 0.01) and nausea (OR = 3.27, p = 0.02). CONCLUSION: We showed that agomelatine may be another treatment option in patients with GAD. However, the results should be interpreted and translated into clinical practice with caution because the meta-analysis was based on limited numbers of clinical trials.

Effects of Moderate Intensity Exercise on the Cortical Thickness and Subcortical Volumes of Preclinical Alzheimer's Disease Patients: A Pilot Study.

OBJECTIVE: We aimed to explore the impact of moderate intensity exercise on the cortical thickness and subcortical volumes of preclinical Alzheimer's disease (AD) patients. METHODS: Sixty-three preclinical AD patients with magnetic resonance imaging (MRI) and 18-florbetaben positron emission tomography (PET) data were enrolled in the study. Information on demographic characteristics, cognitive battery scores, self-reported exercise habits were attained. Structural magnetic resonance images were analyzed and processed using Freesurfer v6.0. RESULTS: Compared to Exercise group, Non-Exercise group demonstrated reduced cortical thickness in left parstriangularis, rostral middle frontal, entorhinal, superior frontal, lingual, superior parietal, lateral occipital, inferior parietal gyrus, temporal pole, precuneus, insula, fusiform gyrus, right precuneus, superiorparietal, lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, superior frontal, lingual, middle temporal gyrus, insula, supramarginal, parahippocampal, paracentral gyrus. Volumes of right thalamus, caudate, putamen, pallidum, hippocampus, amygdala were also reduced in Non-Exercise group. CONCLUSION: Moderate intensity exercise affects cortical and subcortical structures in preclinical AD patients. Thus, physical exercise has a potential to be an effective intervention to prevent future cognitive decline in those at high risk of AD.

Relationship between Delusion of Theft and Cognitive Functions in Patients with Mild Alzheimer's Disease.

Although delusion of theft (DT) is the most frequent type of delusion in Alzheimer's disease (AD), its relationship to cognitive functions remains unclear. The aim of this study was to demonstrate the relationship between DT and cognitive functions in mild AD. Two hundred eighty-nine mild AD patients were enrolled in this study. These subjects were classified into three groups: patients with no delusions (ND, n=82), patients with paranoid delusions (PD, n=114) and patients with DT (n=93). Cognitive functions and their associations with the degree of delusion were compared among the three groups. The results showed that verbal Fluency scores were significantly lower in the PD group than in the DT and ND groups. Word List Recall scores were significantly lower in the DT group than in the PD and ND groups. Interestingly, delusion severity measured with the Neuropsychiatric Inventory delusion subscale correlated negatively with the Word List Recall scores in the DT group. In this study, we demonstrated that episodic memory functions in mild AD patients were associated with DT, but not with PD. Further studies might be needed to clarify the pathophysiology of delusions associated with AD.

Serotonin Transporter and COMT Polymorphisms as Independent Predictors of Health-related Quality of Life in Patients with Panic Disorder.

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.