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Background@#and Purpose: Dementia subtypes, including Alzheimer’s dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18 F-Fluorodeoxyglucose Positron Emission Tomography ( 18 F-FDG PET) in differentiating these subtypes for precise treatment and management. @*Methods@#A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18 F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the goldstandard clinical diagnosis for dementia subtypes. @*Results@#From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88–0.98) and specificity was 0.84 (95% CI, 0.70–0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70–0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80–0.91) and the specificity was 0.88 (95% CI, 0.80–0.91). The studies mostly used case-control designs with visual and quantitative assessments. @*Conclusions@#18 F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.
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Background@#and purpose: The anti-aging standard forest healing program (ASFHP), which uses forest therapy, was reported to be effective in improving psychological, physical, and cognitive functions. However, there are several challenges to directly visiting the forest. This study aimed to investigate the impact of multi-session ASFHP with forest visit on the mental and physical health of the older people with visits to forest facilities and compared them with those of the same program conducted indoors. @*Methods@#Individuals aged over 70 years with concerns about cognitive decline were recruited at dementia relief centers and divided into control and experimental groups. A total of 33 people were administered ASFHP under the supervision of a forest therapy instructor. The control group stayed indoors, while the experimental group visited a forest healing center and repeated the program 20 weeks. @*Results@#The multiple-session ASFHP positively affected cognitive impairment screening test (CIST) total scores (p=0.002), memory (p=0.014), Korean version of the Repeatable Battery for the Assessment of Neuropsychological Status total scores (p<0.001), immediate recall (p=0.001), visuospatial/construction (p<0.001), language (p<0.001), forest healing standard questionnaire total scores (p=0.002), and cognitive function (p=0.019), regardless of location. The forest visits during the ASFHP showed positive effects on orientation (p=0.035), delayed recall (p=0.042), emotional stability (p=0.032), physical activity (p=0.005), and health (p=0.022). The CIST scores of the memory domain were the strongest indicator of the multiple-session ASFHP effects. @*Conclusions@#The 20-week multi-session ASFHP with forest visit showed effects on cognitive improvement and physical and emotional stability compared to indoor education.
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Objective@#We aimed to create an efficient and valid predicting model which can estimate individuals’ brain age by quantifying their regional brain volumes. @*Methods@#A total of 2,560 structural brain magnetic resonance imaging (MRI) scans, along with demographic and clinical data, were obtained. Pretrained deep-learning models were employed to automatically segment the MRI data, which enabled fast calculation of regional brain volumes. Brain age gaps for each subject were estimated using volumetric values from predefined 12 regions of interest (ROIs): bilateral frontal, parietal, occipital, and temporal lobes, as well as bilateral hippocampus and lateral ventricles. A larger weight was given to the ROIs having a larger mean volumetric difference between the cognitively unimpaired (CU) and cognitively impaired group including mild cognitive impairment (MCI), and dementia groups. The brain age was predicted by adding or subtracting the brain age gap to the chronological age according to the presence or absence of the atrophy region. @*Results@#The study showed significant differences in brain age gaps among CU, MCI, and dementia groups. Furthermore, the brain age gaps exhibited significant correlations with education level and measures of cognitive function, including the clinical dementia rating sum-of-boxes and the Korean version of the Mini-Mental State Examination. @*Conclusion@#The brain age that we developed enabled fast and efficient brain age calculations, and it also reflected individual’s cognitive function and cognitive reserve. Thus, our study suggested that the brain age might be an important marker of brain health that can be used effectively in real clinical settings.
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Objective@#The rising prevalence of mild cognitive impairment (MCI) has spurred interest in innovative cognitive rehabilitation approaches, including serious games. This review summarizes randomized clinical trials (RCTs) exploring the impact of serious games on MCI patients. @*Methods@#We conducted a comprehensive data search using key terms such as “gamification,” “digital therapy,” “cognition,” “mild cognitive impairment,” and “Alzheimer’s disease.” We exclusively considered published RCTs, excluding animal studies and basic research. @*Results@#We identified eight RCTs. Four RCTs examined the effects of serious games using cognitive training for MCI patients. Notably, one study found that non-specific training (Nintendo Wii) significantly enhanced cognitive function and quality of life compared to cognition-specific computer training (CoTras). Among the remaining three RCTs, one specifically demonstrated that personalized serious game-based cognitive training yielded superior cognitive outcomes and reduced depressive symptoms. One RCT focused on serious games incorporating physical exercise, highlighting the effectiveness of kinetic-based exergaming in enhancing overall cognition. Three RCT focused on combined cognitive training and physical exercise. A double-blind RCT revealed that progressive resistance training or standalone physical exercise outperformed the combined approach in improving executive function and global cognition. Two additional RCTs reported positive outcomes, including improvements in cognitive function and electroencephalogram patterns associated with game-based interventions. @*Conclusion@#Serious games, whether focusing on cognitive training, physical exercise, or a combination of both, have potential to improve cognitive and functional outcomes in individuals with MCI. Further research and standardization of protocols are needed to better understand the full potential of serious games in MCI.
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Objective@#Cognitive reserve has emerged as a concept to explain the variable expression of clinical symptoms in the pathology of Alzheimer’s disease (AD). The association between years of education, a proxy of cognitive reserve, and resting-state functional connectivity (rFC), a representative intermediate phenotype, has not been explored in the preclinical phase, considering risk factors for AD. We aimed to evaluate whether the relationship between years of education and rFC in cognitively preserved older adults differs depending on amyloid-beta deposition and APOE ε4 carrier status as effect modifiers. @*Methods@#A total of 121 participants underwent functional magnetic resonance imaging, [ 18F] flutemetamol positron emission tomography-computed tomography, APOE genotyping, and a neuropsychological battery. Potential interactions between years of education and AD risk factors for rFC of AD-vulnerable neural networks were assessed with wholebrain voxel-wise analysis. @*Results@#We found a significant education years-by-APOE ε4 carrier status interaction for the rFC from the seed region of the central executive (CEN) and dorsal attention networks. Moreover, there was a significant interaction of rFC between right superior occipital gyrus and the CEN seed region by APOE ε4 carrier status for memory performances and overall cognitive function. @*Conclusion@#In preclinical APOE ε4 carriers, higher years of education were associated with higher rFC of the AD vulnerable network, but this contributed to lower cognitive function. These results contribute to a deeper understanding of the impact of cognitive reserve on sensitive functional intermediate phenotypic markers in the preclinical phase of AD.
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Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a “breakthrough therapy” for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin’s potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials, DB-RCTs) trials exploring psilocybin’s impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over 6 months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.
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Objective@#Apolipoprotein E (APOE) gene is known to influence cerebral functional connectivity (FC) in Alzheimer’s disease continuum. We investigated association between APOE allotypes and FC, structural connectivity, and cortical thickness in amyloid-PET negative cognitive normal older adults (CN). @*Methods@#A total of 188 CN (37 had ε2/ε2 or ε2/ε3 [ε2 group], 113 had ε3/ε3 [ε3 group], and 38 had ε3/ε4 or ε4/ε4 [ε4 group]) were recruited. Voxel-based morphometry and cortical thickness analysis were used to investigate differences in cortical thickness between three APOE allotypes. To investigate integrity of structural connectivity, we analyzed diffusion weighted imaging using fractional anisotropy and mean diffusivity. In terms of FC, differences of FC in default mode network (DMN) among APOE allotypes were measured using functional magnetic resonance imaging. @*Results@#There were no significant differences in age, sex, education, cerebral beta-amyloid (Aβ) deposition severity, or neuropsychological profiles. No significant differences were found in cortical thickness and structural connectivity among the APOE allotypes. However, FC within the DMN was significantly lower in ε4 and ε2 carriers compared to ε3 homozygotes. @*Conclusion@#This study suggests that both ε4 and ε2 exhibit APOE-associated DMN FC changes before Aβ deposition, structural changes, and neurodegeneration.
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Objective@#Granulocyte colony-stimulating factor (G-CSF) is a growth factor used to regulate the mobilization of bone marrow progenitor cells and has been shown to promote brain repair and reduce inflammation. This study aimed to investigate the pro-cognitive and neuroplastic effects of G-CSF in healthy adults. @*Methods@#Sixteen healthy adults or donors of hematopoietic stem cell transplantation received G-CSF injections for 5 consecutive days, and their blood samples were collected before, immediately after, and 3 weeks after the G-CSF injections. Twelve subjects underwent neuropsychological testing before and 12 weeks after the G-CSF injections. @*Results@#The study found that G-CSF administration resulted in significant improvements in cognitive function, as measured by the Rey– Osterrieth Complex Figure test for immediate recall, delayed recall, and recognition score at 12 weeks after the injections. The blood levels of brain-derived neurotrophic factor, interleukin-4, and interleukin-8 were significantly increased immediately after the injections and returned to baseline levels after 3 weeks. There was no significant change in the plasma level of Multimer Detection System-oligomerized amyloid beta. @*Conclusion@#Our results might suggest that G-CSF has neuroplastic and pro-cognitive effects in healthy adults. However, further study containing a larger sample size is needed to confirm our findings.
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Objective@#We aimed to evaluate the impact of interaction between APOE ε4 carrier status and body composition measurements on intra- and inter-regional functional connectivity (FC) in mild cognitive impairment (MCI) patients with Aβ deposition. @*Methods@#MCI patients with and without APOE ε4 allele (carrier, n=86; non-carrier, n=95) underwent neuropsychological battery, resting-state functional magnetic resonance imaging scans, positron emission tomography scans with [18 F]flutemetamol, and bioelectrical impedance analysis for measuring body composition. We employed a priori defined regions of interest to investigate the intra- and inter-network FC profiles of default mode network (DMN), central executive network (CEN), and salience network. @*Results@#There was a significant interaction of APOE ε4 carrier status with body fat mass index, visceral fat area, and waist-hip circumference ratio for inter-network FC between DMN and CEN, contributing higher fat-related body composition measurements in the APOE ε4 carrier with lower DMN-CEN FC. @*Conclusion@#The present results highlight the detrimental effect of APOE ε4 carrier status on the associations between the fat-related body composition measurements and FC in the MCI patients with Aβ accumulation.
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Coronavirus disease 2019 (COVID-19) has multiple negative impacts on the psychiatric health of both those previously infected and not infected with severe acute respiratory syndrome coronavirus 2. Moreover, the negative impacts of COVID-19 are closely associated with geographical region, culture, medical system, and ethnic background. We summarized the evidence of the impact of COVID-19 on the psychiatric health of the Korean population. This narrative review included thirteen research articles, which investigated the impact of COVID-19 on the psychiatric health of Koreans. COVID-19 survivors were reported to have a 2.4 times greater risk of developing psychiatric disorders compared to members of a control group, and anxiety and stress-related disorders were the most common newly diagnosed psychiatric illnesses. Studies also reported that COVID-19 survivors had a 3.33-fold higher prevalence of insomnia, a 2.72-fold higher prevalence of mild cognitive impairment, and a 3.09-fold higher prevalence of dementia compared to the control group. In addition, more than four studies have highlighted that the medical staff members, including nurses and medical students, exhibit a greater negative psychiatric impact of COVID-19. However, none of the articles investigated the biological pathophysiology or mechanism linking COVID-19 and the risk of diverse psychiatric disorders. Moreover, none of the studies were actual prospective studies. Thus, longitudinal studies are needed to more clearly elucidate the effect of COVID-19 on the psychiatric health of the Korean population. Lastly, studies focusing on preventing and treating COVID-19–associated psychiatric problems are needed to provide a benefit in real clinical settings.
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The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) first was published in 2002, and has been revised four times, in 2006, 2012, 2017, and 2021. In this review, we compared recommendations from the recently revised KMAP-DD 2021 to four global clinical practice guidelines (CPGs) for depression published after 2010. The recommendations from the KMAP-DD 2021 were similar to those from other CPGs, although there were some differences. The KMAP-DD 2021 reflected social culture and the healthcare system in Korea and recent evidence about pharmacotherapy for depression, as did other recently published evidence-based guidelines. Despite some intrinsic limitations as an expert consensus-based guideline, the KMAP-DD 2021 can be helpful for Korean psychiatrists making decisions in clinical settings by complementing previously published evidence-based guidelines, especially for some clinical situations lacking evidence from rigorously designed clinical trials.
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Objective@#The aim of the present study is to identify the factors that affect retention in outpatients with psychiatric disorders as indicators of treatment adherence, including Minnesota Multiphasic Personality Inventory (MMPI) scores. @*Methods@#The medical records of 146 patients diagnosed with major depressive disorder, bipolar disorder, or anxiety disorder for at least 10 years and discharged were retrospectively reviewed in the present study. The subjects were categorized based on the duration of outpatient treatment as ＜ 6 months (L6) or ≥ 6 months (M6) groups and reclassified as ＜ 36 months (L36) and ≥ 36 months (M36) groups. The demographic, clinical, and personality characteristics of the groups were compared. @*Results@#Patients in M6 and M36 groups were more likely to have a higher educational level compared with those in the L6 and L36 groups, respectively. Patients in the M6 group showed significantly lower hypomania (Ma) scores on the MMPI test than did patients in the L6 group. @*Conclusion@#The association between high Ma score on the MMPI test and early discontinuation of treatment suggests that impulsivity, hostility, and disinhibition confer higher risk of nonadherence.
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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.
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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.
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Objectives@#The Korean Medication Algorithm Project for Depressive Disorder 2021 (KMAP-DD 2021) was a revision of previous works. The main purpose of the current study was to amend guidelines for the treatment of a major depressive disorder (MDD) for children and adolescents. @*Methods@#The survey consisted of 21 questionnaires for children and adolescents. A total of 33 of the 46 experts in child and adolescent psychiatry answered the survey. @*Results@#Antidepressant (AD) monotherapy was selected as the 1st line option for MDD with mild to moderate severity. As the 1st line of treatment for MDD severe without psychotic features in children and adolescents, AD monotherapy and AD augmented with atypical antipsychotics (AAP) were recommended. For MDD with psychotic features, AD augmented with AAP was preferred as the 1st line of treatment. @*Conclusion@#We developed an algorithm for child and adolescent populations with depressive disorders, more specifically than the KMAP-DD 2017. We expect this algorithm will provide clinicians useful information and help in the treatment of children and adolescents with depressive disorders.
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Objectives@#The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was developed in 2002 and revised in 2006, 2012, 2017. In 2021, the fifth edition was published.This edition reflected new findings and the latest trends in the areas of pharmacological treatment. The aim of this study is to present strategies and treatment options according to the subtype of depression using data from the KMAP-DD-2021. @*Methods@#Ninety-seven psychiatrists with clinical experience in depressive disorder were selected. The questionnaires for KMAP-DD 2021 were sent to participants via mail. KMAP-DD 2021 consists of overall treatment strategies and treatment options under specific circumstances.Each treatment strategy or treatment option was evaluated with an overall score of nine and was divided into the three phases of recommendation that include primary, secondary, and tertiary. @*Results@#For persisting depressive disorder, antidepressant monotherapy including selective serotonin reuptake inhibitor (SSRI) (escitalopram, fluoxetine, sertraline, paroxetine), serotoninnorepinephrine reuptake inhibitor (SNRI) (desvenlafaxine, venlafaxine, duloxetine, milnacipran), vortioxetine, and mirtazapine, was recommended as first-line medications. For melancholia of major depressive disorder, SSRI, SNRI, vortioxetine, and mirtazapine also were recommended as first-line medications. For mixed features, SSRI, bupropion, mirtazapine, SNRI, except for duloxetine, and milnacipran were recommended as first-line medications. For anxious distress, SSRI, mirtazapine, and SNRI, except milnacipran, were recommended as first-line medications. @*Conclusion@#The preferences of antidepressants by experts differed according to the subtype of depression. These findings suggest that experts treat patients with a major depressive disorder after considering the subtype of depression involved.
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Objectives@#The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) is a consensus-based medication guideline. To reflect advances in pharmacotherapy for depressive disorders, we have undertaken a fourth revision of the KMAP-DD. @*Methods@#The review committee for the new version of the KMAP-DD (KMAP-DD 2021) included 143 Korean psychiatrists with clinical experience in the field of depressive disorders. Each treatment strategy or treatment option was evaluated with an overall score of nine, and the treatment option was categorized into the three levels of recommendation of primary, secondary, and tertiary. @*Results@#The first-line pharmacotherapeutic strategy for mild to moderate major depressive episodes (MDE) was antidepressant (AD) monotherapy. For severe MDE without psychotic features, AD monotherapy or the combination of AD and atypical antipsychotics (AAP) was the first-line strategy. The combination of AD and AAP was recommended as the first-line for the MDE with psychotic features as well. When treatment response to initial AD monotherapy was insufficient, a combination of AAP or another AD was recommended. In the case of unsatisfactory response to initial treatment with an AD and AAP combination, switching to another AAP or adding another AD was recommended. @*Conclusion@#Generally, there were no significant changes in the recommendations for MDE management in the KMAP-DD 2021 compared to previous versions. However, it was notable that the preference for the use of AAP and AD with the novel mechanism of action including vortioxetine and agomelatine increased.
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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.
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Objective@#The aim of the present study is to identify the factors that affect retention in outpatients with psychiatric disorders as indicators of treatment adherence, including Minnesota Multiphasic Personality Inventory (MMPI) scores. @*Methods@#The medical records of 146 patients diagnosed with major depressive disorder, bipolar disorder, or anxiety disorder for at least 10 years and discharged were retrospectively reviewed in the present study. The subjects were categorized based on the duration of outpatient treatment as ＜ 6 months (L6) or ≥ 6 months (M6) groups and reclassified as ＜ 36 months (L36) and ≥ 36 months (M36) groups. The demographic, clinical, and personality characteristics of the groups were compared. @*Results@#Patients in M6 and M36 groups were more likely to have a higher educational level compared with those in the L6 and L36 groups, respectively. Patients in the M6 group showed significantly lower hypomania (Ma) scores on the MMPI test than did patients in the L6 group. @*Conclusion@#The association between high Ma score on the MMPI test and early discontinuation of treatment suggests that impulsivity, hostility, and disinhibition confer higher risk of nonadherence.
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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.