Genome-wide association study of occupational attainment as a proxy for cognitive reserve.

Occupational attainment, which represents middle-age cognitive activities, is a known proxy marker of cognitive reserve for Alzheimer's disease. Previous genome-wide association studies have identified numerous genetic variants and revealed the genetic architecture of educational attainment, another marker of cognitive reserve. However, the genetic architecture and heritability for occupational attainment remain elusive. We performed a large-scale genome-wide association study of occupational attainment with 248 847 European individuals from the UK Biobank using the proportional odds logistic mixed model method. In this analysis, we defined occupational attainment using the classified job levels formulated in the UK Standard Occupational Classification system considering the individual professional skill and academic level. We identified 30 significant loci (P < 5 × 10-8); 12 were novel variants, not associated with other traits. Among them, four lead variants were associated with genes expressed in brain tissues by expression quantitative trait loci mapping from 10 brain regions: rs13002946, rs3741368, rs11654986 and rs1627527. The single nucleotide polymorphism-based heritability was estimated to be 8.5% (standard error of the mean = 0.004) and partitioned heritability was enriched in the CNS and brain tissues. Genetic correlation analysis showed shared genetic backgrounds between occupational attainment and multiple traits, including education, intelligence, leisure activities, life satisfaction and neuropsychiatric disorders. In two-sample Mendelian randomization analysis, we demonstrated that high occupation levels were associated with reduced risk for Alzheimer's disease [odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.65-0.92 in inverse variance weighted method; OR = 0.73, 95% CI = 0.57-0.92 in the weighted median method]. This causal relationship between occupational attainment and Alzheimer's disease was robust in additional sensitivity analysis that excluded potentially pleiotropic single nucleotide polymorphisms (OR = 0.72, 95% CI = 0.57-0.91 in the inverse variance weighted method; OR = 0.72, 95% CI = 0.53-0.97 in the weighted median method). Multivariable Mendelian randomization confirmed that occupational attainment had an independent effect on the risk for Alzheimer's disease even after taking educational attainment into account (OR = 0.72, 95% CI = 0.54-0.95 in the inverse variance weighted method; OR = 0.68, 95% CI = 0.48-0.97 in the weighted median method). Overall, our analyses provide insights into the genetic architecture of occupational attainment and demonstrate that occupational attainment is a potential causal protective factor for Alzheimer's disease as a proxy marker of cognitive reserve.

Association Between Subjective-Objective Discrepancy of Sleeping Time and Health-Related Quality of Life: A Community-Based Polysomnographic Study.

OBJECTIVE: This study aimed to investigate the existence of a difference in quality of life (QOL) between individuals with and without significant subjective-objective discrepancy (SOD) in total sleep time (TST). METHODS: From the Sleep Heart Health Study 2, 2540 individuals who had completed polysomnography, a morning sleep survey, and the 36-item Short-Form Health Survey (SF-36) were included in the analyses. The participants were classified as normoestimators (estimation of TST <±60 minutes), underestimators (underestimation of TST ≥60 minutes), or overestimators (overestimation of TST ≥60 minutes). The standardized SF-36 QOL scores were compared among the three groups. An adjusted partial correlation analysis was conducted between SOD and QOL. RESULTS: Of the 2540 participants, 1617 (63.7%), 433 (17.0%), and 490 (19.3%) were assigned to the normoestimator, underestimator, and overestimator groups, respectively. The bodily pain and social functioning components of the SF-36 score were significantly lower in the underestimators than in the normoestimators, whereas the physical functioning component was significantly lower in the overestimators than in the normoestimators. The absolute value of SOD in the TST showed a significant negative correlation with the physical and mental components of the SF-36. CONCLUSIONS: QOL was significantly better in the normoestimator than in the other groups and linearly correlated with the absolute value of SOD. This study suggests that a high prevalence of positive and negative sleep misperception in a community population can be a potential factor associated with poor QOL and potential comorbidities.

Effect of Cognitive Training in Fully Immersive Virtual Reality on Visuospatial Function and Frontal-Occipital Functional Connectivity in Predementia: Randomized Controlled Trial.

BACKGROUND: Cognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent. OBJECTIVE: We aimed to examine the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial processes, could improve visuospatial functioning, comprehensive neuropsychological functioning, psychiatric symptoms, and functional connectivity in the visual brain network in predementia. METHODS: Participants over 60 years old with subjective cognitive decline or mild cognitive impairment from a memory clinic were randomly allocated to the VR (n=23) or the control (n=18) group. The VR group participants received multidomain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month. The control group participants did not undergo any additional intervention except for their usual therapy such as pharmacotherapy. Participants of both groups were evaluated for cognitive function using face-to-face comprehensive neuropsychological tests, including the Rey-Osterrieth Complex Figure Test (RCFT) copy task; for psychiatric symptoms such as depression, apathy, affect, and quality of life; as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and after training. Repeated-measures analysis of variance was used to compare the effect of cognitive training between groups. Seed-to-voxel-based analyses were used to identify the cognitive improvement-related functional connectivity in the visual network of the brain. RESULTS: After VR cognitive training, significant improvement was found in the total score (F1,39=14.69, P=.001) and basic components score of the RCFT copy task (F1,39=9.27, P=.005) compared with those of the control group. The VR group also showed improvements, albeit not significant, in naming ability (F1,39=3.55, P=.07), verbal memory delayed recall (F1,39=3.03, P=.09), and phonemic fluency (F1,39=3.08, P=.09). Improvements in psychiatric symptoms such as apathy (F1,39=7.02, P=.01), affect (F1,39=14.40, P=.001 for positive affect; F1,39=4.23, P=.047 for negative affect), and quality of life (F1,39=4.49, P=.04) were found in the VR group compared to the control group. Improvement in the RCFT copy task was associated with a frontal-occipital functional connectivity increase revealed by rsfMRI in the VR group compared to the control group. CONCLUSIONS: Fully immersive VR cognitive training had positive effects on the visuospatial function, apathy, affect, quality of life, and increased frontal-occipital functional connectivity in older people in a predementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated designs over a longer duration may reveal greater improvements in cognition, psychiatric symptoms, and brain functional connectivity. TRIAL REGISTRATION: Clinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa.

Cognitive reserve and the effects of virtual reality-based cognitive training on elderly individuals with mild cognitive impairment and normal cognition.

BACKGROUND: Cognitive reserve (CR) is a concept proposed to account for discrepancies between the extent of brain pathology and clinical manifestations of that pathology. This study aimed to explore the associations between CR and the effects of cognitive training using fully immersive virtual reality (VR). METHODS: A total of 44 older adults (22 cognitively normal, 22 with mild cognitive impairment) underwent eight cognitive training sessions using VR for a period of 4 weeks. CR was assessed using the Cognitive Reserve Index questionnaire (CRIq). To evaluate baseline cognitive function and the effects of VR training, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery was administered to all participants before and after the training. RESULTS: Greater improvement in the total CERAD score was seen for cognitively normal participants with higher versus lower scores on the Education subdomain of the CRIq. Among patients with mild cognitive impairment, none of the CRIq subdomain scores (Education, Working Activity, Leisure Time) were related to a change in CERAD total scores. The CRIq total score did not predict the improvement of global cognition in either group. CONCLUSIONS: This study revealed different impacts of CR on cognitive training according to the participants' cognitive status. It also suggests that employing three proxies of CR rather than using a composite score would provide a more accurate understanding of one's CR.

Relationship between education, leisure activities, and cognitive functions in older adults.

This study aimed to reveal the relationship between life activities and cognitive function and to evaluate the interaction between education and various leisure activities in predicting cognitive function. Using a cross-sectional research design with retrospective data, a total of 210 healthy Korean older adults participated and reported their years of education, working, and lifelong leisure activities. Cognitive function was measured using the Mini Mental State Examination. A hierarchical multiple regression analysis showed that education was positively associated with cognitive function, whereas working activity was not. Craft activities positively predicted cognitive function. Furthermore, education moderated the relationship between leisure activities and cognitive function. Only low-educated participants showed a decrease in cognitive function as they performed domestic chores and an increase in cognitive function as they participated in social activities and volunteering. High-educated participants showed no relation between leisure activities and cognitive function. The results of the current study suggest that the relationship between various leisure activities and cognitive function can vary based on the nature of the leisure activity and educational level. Professionals examining older adults' cognitive function should pay closer attention to educational level, as well as life styles (i.e. leisure activities), to provide appropriate interventions.

Comparison of Psychiatric Symptoms in Patients With Obstructive Sleep Apnea, Simple Snoring, and Normal Controls.

OBJECTIVE: Patients with sleep-related breathing disorders are known to have more severe psychiatric symptoms than good sleepers. The aim of this study was to compare the psychiatric symptoms of participants with obstructive sleep apnea (OSA), those with simple snoring (SS), and normal controls (NC). METHODS: A total of 386 participants (260 with OSA, 75 with SS, and 51 NC) completed self-report questionnaires including the Symptoms Checklist 90-Revised and underwent nocturnal polysomnography. The scores of nine primary symptom dimensions and three global distress indices of the Symptoms Checklist 90-Revised were compared among the three groups, adjusting for age, sex, and body mass index. RESULTS: Participants with suspected OSA (OSA + SS) reported more severe psychiatric symptoms than the NC group. Compared with the participants with OSA, those with SS manifested more severe obsessive-compulsive (1.4 (1.0) versus 1.1 (0.7), p = .008) and depressive (1.2 (1.2) versus 0.8 (0.8), p = .031) symptoms and higher Global Severity Index (1.0 (0.9) versus 0.7 (0.6), p = .039) and Positive Symptom Distress Index (2.0 (0.8) versus 1.7 (0.6), p = .009). Only higher Pittsburgh Sleep Quality Index values predicted higher Global Severity Index (B = 0.11, p = .041) and Positive Symptom Distress Index (B = 0.46, p = .007) in suspected OSA participants. CONCLUSIONS: This study found that individuals with suspected OSA experienced more severe psychiatric symptoms than NCs and that psychiatric symptoms were more severe in the SS group than in the OSA group. The psychiatric symptoms of suspected OSA patients were associated with subjective sleep quality rather than with the apnea-hypopnea index.

Low white-matter integrity between the left thalamus and inferior frontal gyrus in patients with insomnia disorder

Background: Previous studies have reported functional and structural abnormalities in the thalamus and the pars triangularis of the inferior frontal gyrus in patients with insomnia disorder. However, no studies have been conducted on the white-matter tracts between these 2 brain regions. We aimed to compare the white-matter integrity and structure of the left thalamus­pars triangularis tracts between patients with insomnia and controls, and to characterize the relationship between white-matter integrity and clinical features in patients with insomnia. Methods: In total, 22 participants with insomnia disorder and 27 controls underwent overnight polysomnography and brain magnetic resonance imaging, and then completed self-report clinical questionnaires and neurocognitive tests for spatial planning. Structural and diffusion measures such as fractional anisotropy, axial diffusivity, radial diffusivity and trace were analyzed in group comparison and correlation analyses. Results: The insomnia group showed significantly lower fractional anisotropy (F = 8.647, p = 0.02) and axial diffusivity (F = 5.895, p = 0.038) in the left thalamus­pars triangularis tracts than controls. In patients with insomnia, fractional anisotropy in the tracts was correlated with the results of the Stockings of Cambridge test (r = 0.451, p = 0.034), and radial diffusivity was correlated with Epworth Sleepiness Scale score (r = 0.437, p = 0.042). Limitations: Limitations included analyses of limited brain regions and the cross-sectional design. Conclusion: The insomnia group showed decreased integrity in the left thalamus­pars triangularis tracts, and integrity was correlated with cognition and daytime sleepiness. These results may imply that insomnia is characterized by disintegration of the white-matter tract between the left thalamus and inferior frontal gyrus.

[18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive Aphasia.

BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and ß-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS: Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for ß-amyloid. CONCLUSIONS: These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

fMRI brain activation in patients with insomnia disorder during a working memory task.

PURPOSE: This study used functional magnetic resonance imaging (fMRI) to investigate differences in the functional brain activation of patients with insomnia disorder (n = 21, mean age = 36.6) and of good sleepers (n = 26, mean age = 33.2) without other comorbidities or structural brain abnormalities during a working memory task. METHODS: All participants completed a clinical questionnaire, were subjected to portable polysomnography (PSG), and performed the working memory task during an fMRI scan. The subjects who were suspected of major sleep disorder and comorbid psychiatric disorders except insomnia disorder were excluded. To compare the brain activation on working memory from the insomnia group with those from the good-sleeper group, a two-sample t test was performed. Statistical significance was determined using 3DClustSim with the updated algorithm to obtain a reasonable cluster size and p value for each analysis. RESULTS: We observed higher levels of brain activation in the right lateral inferior frontal cortex and the right superior temporal pole in the insomnia group compared to good sleepers (cluster-based multiple comparison correction, p < 0.001, k = 34 @ α = 0.01). CONCLUSION: Thus, patients with insomnia disorder showed increased brain activation during working memory relative to good sleepers, and this may be indicative of compensatory brain activation to maintain cognitive performance in patients with insomnia disorder without other comorbidities.

Montreal cognitive assessment reflects cognitive reserve.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is known to have discriminative power for patients with Mild Cognitive Impairment (MCI). Recently Cognitive Reserve (CR) has been introduced as a factor that compensates cognitive decline. We aimed to assess whether the MoCA reflects CR. Furthermore, we assessed whether there were any differences in the efficacy between the MoCA and the Mini-Mental State Examination (MMSE) in reflecting CR. METHODS: MoCA, MMSE, and the Cognitive Reserve Index questionnaire (CRIq) were administered to 221 healthy participants. Normative data and associated factors of the MoCA were identified. Correlation and regression analyses of the MoCA, MMSE and CRIq scores were performed, and the MoCA score was compared with the MMSE score to evaluate the degree to which the MoCA reflected CR. RESULTS: The MoCA reflected total CRIq score (CRI; B = 0.076, P < 0.001), CRI-Education (B = 0.066, P <  0.001), and CRI-Working activity (B = 0.025, P = 0.042), while MMSE reflected total CRI (B = 0.044, P <  0.001) and CRI-Education (B = 0.049, P <  0.001) only. The MoCA differed from the MMSE in the reflection of total CRI (Z = 2.30). CONCLUSION: In this study, we show that the MoCA score reflects CR more sensitively than the MMSE score. Therefore, we suggest that MoCA can be used to assess CR and early cognitive decline.

The quality of life of suspected obstructive sleep apnea patients is related to their subjective sleep quality rather than the apnea-hypopnea index.

PURPOSE: The relationship between the severity of the apnea-hypopnea index (AHI) and the quality of life (QOL) in patients with obstructive sleep apnea (OSA) has been inconsistent in previous studies. This study aimed to identify the core factor associated with the QOL of suspected OSA patients and to compare the QOL of subjects with OSA and simple snoring (SS). METHODS: Two hundred eighty-five subjects who were clinically suspected to have OSA underwent nocturnal polysomnography (PSG) and completed self-report questionnaires including the World Health Organization Quality of Life Short Form (WHOQOL-BREF) and the Pittsburgh Sleep Quality Index (PSQI). The effects of the clinical and PSG variables on the QOL score were analyzed using multiple stepwise regression analyses, and the QOL of OSA and SS groups was compared. RESULTS: In correlation analyses, the most significant factor that correlated with the QOL of the subjects was the PSQI total score (p < 0.001), while the AHI was not related to the WHOQOL-BREF total score. In multiple linear regression analysis, the PSQI total score was the most significant factor associated with the QOL of participants (p < 0.001). The mean score of the WHOQOL-BREF did not differ significantly between the OSA group and the SS group. CONCLUSION: This study suggests that the main factor affecting the QOL of suspected OSA subjects is their subjective sleep quality. We therefore conclude that patients with OSA symptoms estimate their QOL based on their subjective sleep perception rather than AHI.

Predictors of Continuous Positive Airway Pressure Adherence and Comparison of Clinical Factors and Polysomnography Findings Between Compliant and Non-Compliant Korean Adults With Obstructive Sleep Apnea.

OBJECTIVE: Continuous positive airway pressure (CPAP) is the preferred treatment for obstructive sleep apnea (OSA). However, compliance with CPAP therapy varies among studies, and studies on its predictors are insufficient in Korea. This study aimed to identify factors that predict compliance with CPAP therapy in patients with OSA. METHODS: We retrospectively reviewed medical records, polysomnography (PSG) records, and self-report questionnaires of patients w ith OSA. Criteria for compliance was the use of CPAP devices for ≥4 h per night for ≥70% of the consecutive 30 nights (i.e., 21 days) during the first 3 months of treatment initiation. The patients were classified into two groups: compliant and non-compliant. Logistic regression analyses were performed to identify the clinical factors and PSG parameters associated with CPAP compliance. RESULTS: Of the 188 participants, 80 were classified into the compliant group and 108 into the non-compliant group. The ratios of stage N1 (p=0.011) and health insurance coverage (p=0.007) were significantly associated with compliance with CPAP, with an explanatory power of 18.6% (R2=0.186, p<0.001). CONCLUSION: Stage N1 ratio and health insurance coverage were significant predictors of CPAP compliance. It is necessary to confirm whether the relationship between a high stage N1 ratio and compliance can be reproduced in a larger sample and in individuals from other countries.

Significant association between increased risk of emergency department visits for psychiatric disorders and air pollutants in South Korea.

BACKGROUND: The association between air pollutants and psychiatric disorders has been investigated in many countries. However, results for the association between air pollutants and emergency room (ER) visits for psychiatric disorders are inconsistent. Further, systematic large-scale studies relating to the same are lacking, especially in South Korea. OBJECTIVE: We aimed to investigate the acute and short-term cumulative effect of air pollutants on ER visits for psychiatric disorders in South Korea. METHODS: The data on nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) and ER visits due to nine representative psychiatric disorders were collected from eight major cities in South Korea for three years. We estimated the relative risk (RR) at lag 0 and a cumulative 11-day RR by increasing a 10-unit for PM and 0.01-unit for NO2 using the Distributed Lag Nonlinear Model. RESULTS: During the study period, a total of 79,092 ER visits for psychiatric disorders were identified and tested for association with NO2, PM2.5, and PM10. The RR at lag 0 of depression per 0.01-unit increase in NO2 was the highest (3.127; 95% confidence interval [CI] 2.933 to 3.332) among the psychiatric disorders. The RRs at lag 0 of anxiety disorders per 10-unit increase in PM2.5 (1.709; 95% CI 1.424 to 2.053) and PM10 (2.168; 95% CI 1.957 to 2.403) were the highest among the psychiatric disorders. SIGNIFICANCE: Air pollutants increased ER visits for psychiatric disorders with the highest RR of depression due to NO2 and anxiety disorder due to PM2.5 and PM10. These results contribute evidence to the positive association between ambient exposure to air pollution and aggravation of psychiatric disorders, indicating air pollution may be a modifiable risk factor in mental health management. IMPACT STATEMENT: We investigated the effect of air pollution on emergency room visits caused by major psychiatric disorders in prominent cities in South Korea. Using the Distributed Lag Nonlinear Model, an advanced analysis method, we calculated the acute effect and short-term cumulative effect. Air pollutants increased ER visits for psychiatric disorders with the highest relative risk of depression due to NO2 and anxiety disorder due to PM2.5 and PM10. These results reveal an association between ambient exposure to air pollution and aggravation of psychiatric disorders and suggest that air pollution may be a modifiable risk factor in mental health management.

Effects of the APOEɛ4 Allele on the Relationship Between Tau and Amyloid-ß in Early- and Late-Onset Alzheimer's Disease.

BACKGROUND: Little is known regarding the differential effects of the apolipoprotein E (APOE) ɛ4 on the regional topography of amyloid and tau in patients with both early-onset (EOAD) and late-onset Alzheimer's disease (LOAD). OBJECTIVE: To compare the distribution and association of tau, amyloid, and cortical thickness among groups classified by the presence of APOEɛ4 allele and onset age. METHODS: A total of 165 participants including 54 EOAD patients (29 ɛ4-; 25 ɛ4+), 45 LOAD patients (21 ɛ4-; 24 ɛ4+), and 66 age-matched controls underwent 3T MRI, 18F-THK5351 (THK) and 18F-flutemetamol (FLUTE) PET scans, APOE genotyping, and neuropsychological tests. Data for voxel-wise and standardized uptake values from PET scans were analyzed in the context of APOE and age at onset. RESULTS: EOAD ɛ4- patients showed greater THK retention in the association cortices, whereas their EOAD ɛ4+ counterparts had more retention in medial temporal areas. THK topography of LOAD ɛ4+ was similar to EOAD ɛ4 + . THK correlated positively with FLUTE and conversely with mean cortical thickness, being lowest in EOAD ɛ4-, highest in LOAD ɛ4-, and modest in ɛ4+ groups. Even in the APOEɛ4+ groups, THK tended to correlate with FLUTE and mean cortical thickness in the inferior parietal region in EOAD and in the medial temporal region in LOAD. LOAD ɛ4- manifested with prevalent small vessel disease markers and the lowest correlation between THK retention and cognition. CONCLUSION: Our observations suggest the differential effects of the APOEɛ4 on the relationship between tau and amyloid in EOAD and LOAD.

Difference in spectral power density of sleep electroencephalography between individuals without insomnia and frequent hypnotic users with insomnia complaints.

Previous spectral analysis studies on insomnia have shown inconsistent results due to their heterogeneity and small sample sizes. We compared the difference of electroencephalogram (EEG) spectral power during sleep among participants without insomnia, insomniacs with no hypnotic use, hypnotic users with no insomnia complaints, and hypnotic users with insomnia complaints using the Sleep Heart Health Study data, which is large sample size and has good quality control. The fast Fourier transformation was used to calculate the EEG power spectrum for total sleep duration within contiguous 30-s epochs of sleep. For 1985 participants, EEG spectral power was compared among the groups while adjusting for potential confounding factors that could affect sleep EEG. The power spectra during total sleep differed significantly among the groups in all frequency bands (pcorr < 0.001). We found that quantitative EEG spectral power in the beta and sigma bands of total sleep differed (pcorr < 0.001) between participants without insomnia and hypnotic users with insomnia complaints after controlling for potential confounders. The higher beta and sigma power were found in the hypnotic users with insomnia complaints than in the non-insomnia participants. This study suggests differences in the microstructures of polysomnography-derived sleep EEG between the two groups.

Mood and Sleep Status and Mental Disorders During Prolonged Winter-Over Residence in Two Korean Antarctic Stations.

Purpose: Antarctica is a region with extreme climate, characterized by extreme cold and photoperiod. No research has been conducted on the mental health of Korean Antarctic dispatchers. The aim of this study was to investigate the status of mental illness and changes in mood and sleep among Korean crew members staying for a long-term period in the Antarctic station. Methods: From 2017 to 2020, crew members who were dispatched from South Korea to two Antarctic stations for a one-year period participated in this study. The crew were evaluated for mood and sleep status and mental illness through psychological tests and interviews by board-certified psychiatrists once before departure and twice during their stay in Antarctica. The incidence of mental illness was confirmed and changes in sleep and depression were analyzed. Results: A total of 88 participants were included in the final analysis, and 7 of them (8.0%) were diagnosed with mental disorders such as insomnia in early winter. The total Beck Depression Inventory (BDI) score increased significantly in the early winter period, and the total Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Inventory (PSQI) scores increased in both early and late winter. The difference in changes in mood and sleep symptoms before, during, and after dispatch between the two stations was not significant. Conclusion: This is the first study to investigate the mental illness and mood and sleep status of Korean crews dispatched to Antarctica. In early winter, there were significant increases in mental illness and depressive symptoms, and a worsening of sleep status.

[18F]THK-5351 PET Patterns in Patients With Alzheimer's Disease and Negative Amyloid PET Findings.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) does not always mean amyloid positivity. [18F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [18F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings. METHODS: We performed 3.0-T magnetic resonance imaging, [18F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [18F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern. RESULTS: The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [18F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13). Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [18F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group. CONCLUSIONS: Approximately 70% of the patients with amyloid-negative AD showed abnormal [18F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.

Prevalence of DSM-5 mixed features: A meta-analysis and systematic review.

BACKGROUND: The definition of mixed features by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) remains controversal; however, there has been no systematic review of the prevalence of DSM-5 mixed features. We conducted a meta-analysis and systematic review to examine the prevalence of DSM-5-defined mixed features in major depressive episodes (MDE) and manic/hypomanic episodes. METHODS: We systematically searched all literature types (i.e., observational, cross-sectional, cohort, retrospective chart review, and post-hoc analysis) in electronic databases including MEDLINE, Embase, CINAHL, PsycINFO, and Web of Science from 2013 to 2020. RESULTS: A total of 17 studies with 20 samples were selected. The pooled prevalences of the mixed features in MDE and manic/hypomanic episodes were 11.6% (95% confidence interval [CI] = 7.9-16.7%) and 26.8 (95% CI = 17.0-39.5%), respectively. The prevalence of mixed features during major depressive disorder in East Asian countries was the lowest, which ranged from 0-2.2%. The subgroup analysis did not identify any influential factors for substantial heterogeneity. Most of the individual studies demonstrated moderate to high risk of bias. CONCLUSIONS: Despite the increasing attention and controversy surrounding DSM-5-defined mixed features, few studies have systematically estimated the prevalence. Future studies with appropriate design and sample sizes should measure the prevalence of mixed features during MDE and manic/hypomanic episodes.

Spectral Power Analysis of Sleep Electroencephalography in Subjects with Different Severities of Obstructive Sleep Apnea and Healthy Controls.

PURPOSE: Previous spectral analysis studies on obstructive sleep apnea (OSA) involved small samples, and the results were inconsistent. We performed a spectral analysis of sleep EEG based on different severities of OSA using the Sleep Heart Health Study data. This study aimed to determine the difference in EEG spectral power during sleep in the non-OSA group and with different severities of OSA in the general population. PATIENTS AND METHODS: The participants (n = 5,804) underwent polysomnography, and they were classified into non-OSA, mild OSA, moderate OSA, and severe OSA groups. The fast Fourier transformation was used to compute the EEG power spectrum for total sleep duration within contiguous 30-second epochs of sleep. The EEG spectral powers of the groups were compared using 4,493 participants after adjusting potential confounding factors that could affect sleep EEG. RESULTS: The power spectra differed significantly among the groups for all frequency bands (p corr < 0.001). We found that the quantitative EEG spectral powers in the beta and sigma bands of total sleep differed (p corr < 0.001) among the participants in the non-OSA group and with different severities of OSA, controlling for covariates. The beta power was higher and the sigma power was lower in the OSA groups than in the non-OSA group. The beta power decreased in the order of severe OSA, moderate OSA, mild OSA, and non-OSA. CONCLUSION: This study suggests that there are differences between the microstructures of PSG-derived sleep EEG of non-OSA participants and those with different severities of OSA.