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We investigated both independent and interconnected effects of 3 lifestyle factors on brain volume, measuring yearly changes using large-scale longitudinal magnetic resonance imaging, in middle-aged to older adults. We measured brain volumes in a cohort ( n = 984, 49–79 years) from the Korean Genome and Epidemiology Study group, using baseline and follow-up estimates after 4 years. In our analysis, the accelerated brain atrophy in normal aging was observed across regions (e.g., brain tissue: -0.098 ± 0.01 mL/y, p < 0.001). An independent lifestyle-specific trend of brain atrophy across time was also evident in men, where smoking ( p = 0.012) and physical activity ( p = 0.014) showed the strongest association with the atrophy rate. Linear regression analysis of the interconnected effect revealed that brain atrophy is mitigated by intense physical activity in smoking males. Lifestyle factors did not show any significant effect on brain volume in women. These results provide important information regarding lifestyle factors that affect brain aging in mid-to-late adulthood. Our findings may aid in the identification of preventive measures against dementia. [ABSTRACT FROM AUTHOR]

Background Sleep disturbances are closely related to migraine. Nevertheless, information regarding the impact of short sleep duration and poor sleep quality on the clinical presentation of migraine at population level is limited. Methods This study was a nationwide population-based survey on adults aged 19–69 years. Headache frequency (attacks/month) and intensity (visual analogue scale, 0–10) were documented. Short sleep duration and poor sleep quality were defined as average sleep duration <6 h/day and Pittsburgh Sleep Quality Index score >5, respectively. The association of sleep parameters with headache frequency and intensity was analysed among migraineurs. Results Of 2695 participants, 143 (5.3%) had migraine. Headache frequency was significantly higher among migraineurs with short sleep duration (2.0 [1.0–12.0] vs. 1.0 [0.3–4.0], p = 0.048) and poor sleep quality (2.0 [0.6–4.7] vs. 1.0 [0.2–3.0], p = 0.009) than among those without. However, headache intensity was similar between migraineurs with short sleep duration and poor sleep quality. Multiple linear regression analyses revealed that short sleep duration was a significant contributing factor for headache frequency (β = 0.210, p = 0.015). Conclusions Self-reported short sleep duration (<6 h per day) is associated with an increased headache frequency among migraineurs in a population-based setting. [ABSTRACT FROM AUTHOR]

Background Sleep disturbances are closely related to migraine. Nevertheless, information regarding the impact of short sleep duration and poor sleep quality on the clinical presentation of migraine at population level is limited. Methods This study was a nationwide population-based survey on adults aged 19-69 years. Headache frequency (attacks/month) and intensity (visual analogue scale, 0-10) were documented. Short sleep duration and poor sleep quality were defined as average sleep duration <6 h/day and Pittsburgh Sleep Quality Index score >5, respectively. The association of sleep parameters with headache frequency and intensity was analysed among migraineurs. Results Of 2695 participants, 143 (5.3%) had migraine. Headache frequency was significantly higher among migraineurs with short sleep duration (2.0 [1.0-12.0] vs. 1.0 [0.3-4.0], p = 0.048) and poor sleep quality (2.0 [0.6-4.7] vs. 1.0 [0.2-3.0], p = 0.009) than among those without. However, headache intensity was similar between migraineurs with short sleep duration and poor sleep quality. Multiple linear regression analyses revealed that short sleep duration was a significant contributing factor for headache frequency (β = 0.210, p = 0.015). Conclusions Self-reported short sleep duration (<6 h per day) is associated with an increased headache frequency among migraineurs in a population-based setting. [ABSTRACT FROM AUTHOR]

Objective We aimed to determine the association between psychomotor vigilance task (PVT) performance and sleep-related factors including sleep duration, daytime sleepiness, poor sleep quality, insomnia, and habitual snoring in a population-based sample. Methods This was a cross-sectional analysis from the ongoing prospective cohort study, the Korean Genome and Epidemiology Study. We measured PVT performance and documented demographics, sleep-related factors, life style, and medical conditions in community dwelling adults (N = 2499; mean age 57.1 ± 7.3; male 1259). Associations between PVT parameters and sleep-related factors were tested, adjusting for age, gender, smoking, alcohol use, education, body mass index, hypertension, diabetes, depression, and the interval between mid-sleep time and PVT test. Results High Epworth Sleepiness Scale (ESS, ≥8) was associated with slower mean reciprocal response speed (mean RRT) (3.69 ± 0.02 vs. 3.77 ± 0.01, p < 0.001), higher probability for increased lapses (≥4) (OR 1.48, CI 1.12–1.88, p = 0.001), and more negative RRT slope (−0.036 ± 0.002 vs. −0.030 ± 0.001, p = 0.02). Older age, female gender, low education level, depressive mood, and the interval between mid-sleep and PVT test were also associated with poor performance. Sleep duration, habitual snoring, insomnia, or poor sleep quality (the Pittsburgh Sleep Quality Index score > 5) was not related to PVT parameters. Conclusions At the population level, our results revealed important modifiers of PVT performance, which included subjective reports of daytime sleepiness. [ABSTRACT FROM AUTHOR]

Background and purpose: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted people's lifestyles, changing sleep patterns. This study investigated changes in sleep patterns and disturbances in South Koreans over the past decade, including during the pandemic. Methods: We compared data from the Korean Sleep Headache Society Phase I survey (n = 2484; conducted in 2010) and the National Sleep Survey of South Korea 2022 (n = 3729; conducted in 2022), involving participants aged 20–69 years. Changes in sleep schedule, sleep duration, social jet lag, insomnia, and daytime sleepiness were explored. Results: Workday bedtimes were advanced and free-day bedtimes and workday and free-day waking times were delayed during the pandemic. Increased circadian preference for eveningness and social jet lag were noted. A significant decrease in sleep duration and sleep efficiency, along with an increased prevalence of insomnia and daytime sleepiness, was noted with age- and sex-specific variations. Conclusions: Over the past decade, including during the COVID-19 pandemic, sleep habits have changed significantly and sleep problems worsened. This study emphasize the need for more comprehensive public health strategies and research to facilitate sleep recovery in the post-pandemic period within a society known for its high prevalence of sleep deprivation. [ABSTRACT FROM AUTHOR]

This study aimed to explore the association between restless legs syndrome and irritable bowel syndrome in an epidemiological cohort. We included 3365 adults, of whom 1602 were female (age 52.5 ± 7.5 years), who had participated in the Korean Genome and Epidemiology Study (2005-2006). The diagnosis of restless legs syndrome was based on the criteria proposed by the International Restless Legs Syndrome Study Group, and irritable bowel syndrome was defined according to the Rome II criteria. The prevalence of each condition was determined and their association was tested by logistic regression analysis. Age, sex, haemoglobin concentration, renal insufficiency, use of medications and depressive mood were all adjusted for. The prevalence of restless legs syndrome and irritable bowel syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P < 0.001). Subjects with restless legs syndrome were older (54.2 ± 8.4 versus 52.4 ± 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration (13.7 ± 1.5 versus 14.1 ± 1.6 g dL−1 P = 0.004) and higher highly sensitive C-reactive protein (1.8 ± 5.1 versus 1.4 ± 2.9 mg dL−1, P = 0.08). The adjusted odds ratio of restless legs syndrome in relation to irritable bowel syndrome was 2.59 (1.74-3.85, P < 0.001). Irritable bowel syndrome appeared to be associated with restless legs syndrome independently from other major risk factors for restless legs syndrome. Searching for the mechanisms underlying this association is indicated. [ABSTRACT FROM AUTHOR]

Previous reports have shown that cigarette smoking is associated with white matter hyperintensities (WMHs). However, it remains unclear whether this is true for all ages. We investigated the association between cigarette smoking, WMHs, and age. We retrospectively reviewed charts from 595 patients, who presented as outpatients from January 2007 to March 2010. Grading of periventricular WMHs (PVWMHs) and the scores of deep WMHs (DWMHs) was determined based on criteria established by the Rotterdam Scan Study. We compared the degree of WMHs between smokers and non-smokers, and those younger than the age of 65 years versus those above. In younger age group, smokers had higher grades of PVWMHs and more microbleeds than non-smokers. In the older age group, total burden of DWMHs was much greater in smokers than nonsmokers. Multivariate regression analysis showed that cigarette smoking was an independent risk factor for PVWMHs in the younger age group and for DWMHs in the older age group. The location of WMHs in association with smoking seems to differ among age groups. Age should be considered when interpreting the effects of smoking on the brain. [ABSTRACT FROM AUTHOR]

Abstract: We have previously reported that TTF-1, a homeodomain-containing transcription factor, regulates circadian rhythm of pituitary adenylate cyclase-activating polypeptide gene expression in the rat hypothalamus. In this study we found that TTF-1 mRNA was specifically expressed in the rat suprachiasmatic nucleus (SCN) and colocalized with Period 2 (Per2), a circadian feedback loop controller. Interaction between TTF-1 and Per1 and Per2 was demonstrated by immunoprecipitation and immunoblot assays. Moreover, TTF-1 and Per proteins additively stimulated a transcriptional activity of angiotensinogen (AoGen) gene. TTF-1 also activated in vitro rhythm of AoGen transcription determined by secretary alkaline phosphatase (SEAP) reporter system in the NIH3T3 cells. These results suggest that TTF-1 plays a role in the circadian rhythm regulation of the AoGen gene expression via interacting with Per proteins in the rat SCN. [Copyright &y& Elsevier]

Migraine attacks have a time preference of headache attack (TPHA). Chronotype is the propensity for an individual to sleep at a particular time during a 24-h period. However, limited evidence exists regarding the association between TPHA and chronotype in individuals with migraine or tension-type headache (TTH). The aim of the present study is to investigate TPHA and chronotype in individuals with migraine and TTH, which are two of the most common primary headaches. One hundred sixty-nine first-visit migraine and TTH participants were consecutively enrolled. Information on sleep onset time and wake up time on workdays and free days, and TPHA were investigated with a face-to-face interview using a questionnaire booklet. Chronotype was assessed, using the midpoint of sleep on free days, corrected for sleep extension on free days (MSFsc), by subtracting one-half of the average weekly sleep duration. Headache frequency per month, headache intensity, impact of headache, sleep quality, daytime sleepiness, insomnia severity, and mood status were also assessed. Time preference of headache attack was reported for 45.5% and 44.8% of participants with migraine and TTH, respectively. Migraineurs with TPHA had an earlier MSFsc than did migraineurs without TPHA (1:18 a.m. ± 282 min vs. 4:18 a.m. ± 186 min; p =.022). Among migraineurs with TPHA, a later MSFsc was associated with a later preferential time of attack (β = 1.3, 95% confidence interval [CI] = 0.6–2.1, p =.004). A later MSFsc was significantly correlated with a higher headache frequency per month among migraineurs with TPHA (β = 1.9, 95% CI = 0.3–3.4, p =.023), but was not significantly correlated among migraineurs without TPHA (β = 1.4, 95% CI −1.7–4.4, p =.332). Among TTH participants with TPHA, MSFsc was not significantly associated with a preferential time of attack (β = −0.2, 95% CI = −1.0 to 0.6, p =.611). Headache frequency was not associated with MSFsc among TTH participants with TPHA (β = 0.2, 95% CI = −1.2 to 1.6, p =.792) or among TTH participants without TPHA (β = 0.4, 95% CI = −0.5 to 1.3, p =.354). In conclusion, approximately one-half of participants with migraine and TTH reported having TPHA. Migraineurs with TPHA had an earlier chronotype than did migraineurs without TPHA. A later chronotype was associated with increased headache frequency and a later time of attack among migraineurs with TPHA. Among participants with TTH, TPHA and headache frequency were not significantly associated with chronotype. [ABSTRACT FROM AUTHOR]

Abstract: An association between zolpidem administration and sleep-related eating disorder (SRED) has been suggested. The authors observed zolpidem-induced SRED in restless legs syndrome (RLS). With the review of previous reports, we identified a common occurrence of RLS in zolpidem-induced SRED. [Copyright &y& Elsevier]

To examine the association of subjective age (SA) with sleep quality in an adult population. In the Korean Sleep and Headache Study, 2,349 participants (49.2% men; 48.1 ± 16.4 years old) were interviewed face-to-face using structured questionnaires between September and December 2018. SA was assessed by asking participants their perceived age in years and then compared with their chronological age (CA). Participants were assigned to three groups: feeling younger, feeling their age, and feeling older. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Association between SA and sleep quality was analyzed with multiple linear regression controlling for demographics, psychosocial, and sleep characteristics. The group feeling older (n = 404, 17.2%; men, 58.2%; age, 46.5 ± 16.2 years) had worse sleep quality than the groups feeling younger and feeling their age (PSQI score, 4.3 ± 2.7, 3.8 ± 2.4, 3.4 ± 2.1, respectively, p <.001; prevalence of poor sleep quality, 29.0%, 18.4%, 13.5% respectively, p <.001). The association between SA and the PSQI score remained significant after adjusting for confounders (β = 1.05, 95% confidence interval 0.26, 1.83; p <.001). Stratified analyses by sex and CA showed that the association between SA and the PSQI score was significant only in women and in middle-aged and older group (aged 50–79), suggesting that sex and CA modified the association. Age perception was associated with self-reported sleep quality, independent of CA. SA may be a useful marker that complements the conventional assessment of subjective sleep quality. [ABSTRACT FROM AUTHOR]

Detection and spatial distribution analyses of interictal epileptiform discharges (IEDs) are important for diagnosing, classifying, and treating focal epilepsy. This study proposes deep learning-based models to detect focal IEDs in electroencephalography (EEG) recordings of the frontal, temporal, and occipital scalp regions. This study included 38 patients with frontal (n = 15), temporal (n = 13), and occipital (n = 10) IEDs and 232 controls without IEDs from a single tertiary center. All the EEG recordings were segmented into 1.5-s epochs and fed into 1- or 2-dimensional convolutional neural networks to construct binary classification models to detect IEDs in each focal region and multiclass classification models to categorize IEDs into frontal, temporal, and occipital regions. The binary classification models exhibited accuracies of 79.3–86.4%, 93.3–94.2%, and 95.5–97.2% for frontal, temporal, and occipital IEDs, respectively. The three- and four-class models exhibited accuracies of 87.0–88.7% and 74.6–74.9%, respectively, with temporal, occipital, and non-IEDs F1-scores of 89.9–92.3%, 84.9–90.6%, and 84.3–86.0%; and 86.6–86.7%, 86.8–87.2%, and 67.8–69.2% for the three- and four-class (frontal, 50.3–58.2%) models, respectively. The deep learning-based models could help enhance EEG interpretation. Although they performed well, the resolution of region-specific focal IED misinterpretations and further model improvement are needed. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of sleep duration on brain structures in the presence versus absence of sleep apnea in middle-aged and older individuals. The study investigated a population-based sample of 2,560 individuals, aged 49-80 years. The presence of sleep apnea and self-reported sleep duration were examined in relation to gray matter volume (GMV) in total and lobar brain regions. We identified ranges of sleep duration associated with maximal GMV using quadratic regression and bootstrap sampling. A significant quadratic association between sleep duration and GMV was observed in total and lobar brain regions of men with sleep apnea. In the fully adjusted model, optimal sleep durations associated with peak GMV between brain regions ranged from 6.7 to 7.0 hours. Shorter and longer sleep durations were associated with lower GMV in total and 4 sub-regions of the brain in men with sleep apnea. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate whether the impact of obstructive sleep apnea (OSA) on glucose metabolism was different according to the presence or absence of obesity.Research Design and Methods: A total of 1,344 subjects >40 years old from the Korean Genome and Epidemiology Study were included. OSA was detected by home portable sleep monitoring. Plasma glucose, HbA1c, and insulin resistance were compared according to OSA and obesity status. The associations between OSA and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and diabetes were evaluated in subjects with and without obesity after adjusting for several confounding variables. The effect of visceral obesity on this association was evaluated in 820 subjects who underwent abdominal computed tomography scanning.Results: In subjects without obesity, fasting glucose, 2-h glucose after 75-g glucose loading, and HbA1c were higher in those with OSA than in those without after controlling for age, sex, and BMI. In addition, the presence of OSA in nonobese subjects was associated with a higher prevalence of IFG + IGT and diabetes after adjusting for several confounding variables (odds ratio 3.15 [95% CI 1.44-6.90] and 2.24 [1.43-3.50] for IFG + IGT and diabetes, respectively). Further adjustment for visceral fat area did not modify this association. In contrast, in those with obesity, none of the abnormal glucose tolerance categories were associated with OSA.Conclusions: The presence of OSA in nonobese individuals is significantly associated with impaired glucose metabolism, which can be responsible for future risk for diabetes and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract: Thyroid transcription factor-1 (TTF-1) belongs to the Nkx family of homeodomain-containing proteins and regulates expression of several important genes in the brain. Our previous studies showed that TTF-1 plays an important role in water homeostasis in the subfornical organ of rats and is involved in cerebrospinal fluid formation by regulation of aquaporin-1 transcription in the choroid plexus. In this study, we examined changes in TTF-1 transcription in response to hypertonicity using promoter assays. TTF-1 was synthesized in several osmosensitive regions of the rat brain. TTF-1 promoter activity was diminished by treatment with hypertonic solutions in a time- and dose-dependent manner in brain-derived cell lines. Additionally, TTF-1 was involved in the regulation of angiotensinogen (Aogen) transcription under a hyperosmotic condition through specific binding domains in the Aogen promoter. These results suggest a possible role of TTF-1 in brain fluid homeostasis in response to changes in the osmotic environment. [Copyright &y& Elsevier]

Abstract: TTF-1 is a member of the NKx family of homeodomain genes, and is required for morphogenesis and fetal diencephalon development. Our previous studies have shown that TTF-1 expression is maintained in some regions of the postnatal rat brain and transactivates the gene expression of several neuropeptides. In this study, a potential role for TTF-1 in the regulation of feeding behavior was identified. Immunohistochemical analysis showed that TTF-1 is present in several hypothalamic nuclei of the adult rat brain involved in the control of feeding behavior. Food deprivation for two days markedly increased the hypothalamic levels of TTF-1 mRNA and protein. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased TTF-1 protein abundance in the hypothalamus. This TTF-1 decrease was followed by a significant decrease in neuropeptide Y mRNA content and an increase in proopiomelanocortin mRNA content, and in turn resulted in a decrease of the animal’s food intake and body weight. These results suggest a novel role for TTF-1 in the regulation of feeding behavior in the rat hypothalamus. [Copyright &y& Elsevier]

The aims of this analysis were to: (1) determine the value of ictal SPECT in the localization of neocortical epileptogenic foci, (2) evaluate the relationships between the results of ictal SPECT and other potential affecting factors, and (3) compare traditional visual analysis and the subtraction method. We retrospectively analyzed 81 consecutive patients with neocortical epilepsy who underwent epilepsy surgery and achieved a favourable surgical outcome, including 36 patients with normal MRI. Side-by-side visual analysis and subtraction images were classified as correctly localizing,correctly lateralizing, or non-localizing/non-lateralizing images according to the resected lobe. Side-by-side visual analysis and subtraction SPECT correctly localized the epileptogenic lobe in 58.9% and 63.0% of patients, respectively. The two methods were complementary and the diagnostic sensitivity of ictal SPECT using the two methods was 79.0%. Ictal SPECT using the visual method correctly localized the epileptogenic lobe more frequently in patients with a localizing pattern of ictal scalp EEG at the time of radioligand injection. When using subtraction images, an injection delay of less than 20 s after seizure onset was significantly correlated with correct localization. The subtraction method was superior to the visual method for localizing frontal lobe epilepsy (FLE) and parietal lobe epilepsy (PLE), and in patients with non-localizing/non-lateralizing EEG at onset. Ictal SPECT analyses using visual and subtraction methods are useful and complementary for the localization of the epileptogenic foci of neocortical epilepsy. Early radioligand injection and ictal EEG patterns are related to ictal SPECT localization. The subtraction method may be more useful in some epileptic syndromes. [ABSTRACT FROM AUTHOR]

The fine structure of sleep electrocortical activity reflects health and disease. The current study provides normative data for sleep structure and electroencephalography (EEG) spectral power measures derived from overnight polysomnography (PSG) and examines the effect of age and sex among Korean middle‐aged and older adults with or without obstructive sleep apnea (OSA). We analysed home PSG data from 1,153 adult participants of an ongoing population‐based cohort study, the Korean Genome and Epidemiology Study. Sleep stages were visually scored and spectral power was measured on a single‐channel EEG (C4‐A1). We computed spectral power for five frequency ranges. The EEG power was reported in relative (%) and log‐transformed absolute values (µV2). With ageing, the proportion of N1 sleep increased, whereas N3 decreased, which is more noticeable in men than in women. The amount of N3 was relatively low in this cohort. With ageing, relative delta power decreased and alpha and sigma power increased for the whole sleep period, which was more pronounced during REM sleep in non‐OSA. For men compared with women, relative theta power was lower during REM and sigma and beta were higher during N1 sleep. The differences of relative powers by age and sex in OSA were comparable to those in non‐OSA. In a community‐based Korean population, we present normative data of sleep structure and spectral power for middle‐aged or older adults of a non‐Caucasian ethnicity. The values varied with age and sex and were not influenced by sleep apnea. [ABSTRACT FROM AUTHOR]

Migraine neither presents with a definitive single symptom nor has a distinct biomarker; thus, its diagnosis is based on combinations of typical symptoms. We aimed to identify natural subgroups of migraine based on symptoms listed in the diagnostic criteria of the third edition of the International Classification of Headache Disorders. Latent class analysis (LCA) was applied to the data of the Korean Sleep-Headache Study, a nationwide population-based survey. We selected a three-class model based on Akaike and Bayesian information criteria and characterized the three identified classes as "mild and low frequency," "photophobia and phonophobia," and "severe and high frequency." In total, 52.0% (65/125) of the participants were classified as "mild and low frequency," showing the highest frequency of mild headache intensity but the lowest overall headache frequency. Meanwhile, "photophobia and phonophobia" involved 33.6% (42/125) of the participants, who showed the highest frequency of photophobia and phonophobia. Finally, "severe and high frequency" included 14.4% (18/125) of the participants, and they presented the highest frequency of severe headache intensity and highest headache frequency. In conclusion, LCA is useful for analyzing the heterogeneity of migraine symptoms and identifying migraine subtypes. This approach may improve our understanding of the clinical characterization of migraine. [ABSTRACT FROM AUTHOR]

Cutaneous allodynia (CA) is a pain in response to non-nociceptive stimulation and a marker of central sensitisation. Probable migraine (PM) is a migraine subtype that fulfils all but one criterion of migraine. Headache intensity and the disability of individuals with PM are similar or lower than individuals with migraine. This study compared CA prevalence and characteristics of PM and migraine using a nationally representative sample in Korea. The Allodynia Symptom Checklist-12 (ASC-12) was used to assess CA (ASC-12 score ≥ 3). PM and migraine prevalence were 11.6% and 5.0%, respectively. CA prevalence did not significantly differ between PM and migraine (14.5% vs. 16.0%, p = 0.701). Participants with PM with CA reported a higher monthly headache frequency (3.3 ± 4.3 vs. 1.8 ± 3.6, p = 0.044), more severe headache intensity (Visuals Analogue Scale, 6.0 [4.0–7.0] vs. 5.0 [3.0–6.0], p = 0.002), and higher impact of headache (Headache Impact Test-6, 56.3 ± 7.2 vs. 48.3 ± 8.0, p < 0.001) than those without CA. Multiple regression analyses revealed that headache frequency and intensity, anxiety, and depression were significant factors for CA in participants with PM. In conclusion, CA prevalence among participants with PM and migraine were comparable. Anxiety, depression, and headache frequency and intensity were significant factors for CA in participants with PM. [ABSTRACT FROM AUTHOR]

Background: A close association has been reported between depression and migraine. However, information concerning the impacts of migraine on the clinical presentation and prevalence of depression in a population-based study is currently limited.Methods: Data from the Korean Headache-Sleep Study, a nationwide survey about headache and sleep for adults aged 19-69 years were used. Depression was defined when Patient Health Questionnaire-9 score ≥ 10.Results: Of 2,695 participants who included in this study, 116 (4.3%), 143 (5.3%), and 1130 (41.9%) had depression, migraine, and non-migraine headache, respectively. Migraine (24/116 [20.5%] vs. 119/2579 [4.7%], p < 0.001) and non-migraine headache (67/116 [58.1%] vs. 1063/2579 [41.3%], p < 0.001) was more prevalent in the group of participants with depression than among participants without depression. Among participants with depression, there was no statistically differences in total Patient Health Questionnaire-9 (PHQ-9) scores among migraine, non-migraine headache, and non-headache groups (median with interquartile range, 12.0 [10.2-18.0] vs. 13.0 [11.0-16.0] vs. 12.0 [10.0-15.2], p = 0.514). Among subcomponent scores of PHQ-9, all subcomponent scores did not significantly differ by headache status except feeling tired or having little energy scores (non-migraine headache 2.0 [2.0-3.0] vs. non-headache 2.0 [1.0-2.0], p = 0.010).Limitations: Diagnosis of depression based on PHQ-9 questionnaire and small sample size in subgroup analyses.Conclusions: Participants with depression exhibit an increased risk of migraine and non-migraine headache compared with participants without depression. Among participants with depression, the severity of depression did not significantly differ on the basis of headache status. [ABSTRACT FROM AUTHOR]

Background: Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is related to iron–dopamine dysregulation and immune system alteration. We aimed to assess the effects of serum hepcidin, an iron-regulating hormone, in drug-naive RLS patients compared to healthy controls and to evaluate its role in helping to predict clinical improvement after treatment with dopamine agonist. Methods: Nonanemic and drug-naive RLS patients (n = 18) and healthy controls (n = 15) were enrolled. The serum hepcidin and iron-related values in the serum were measured upon the first visit in both groups and 12 weeks later after dopaminergic treatment in 12 patients. Information about sociodemographic characteristics, sleep-related profiles, mood and anxiety was obtained upon the first visit in all participants as well as after treatment in RLS patients. Results: Serum hepcidin levels exhibited no significant differences between patients with drug-naïve RLS and healthy controls at diagnosis (7.1 ± 2.4 vs. 7.0 ± 3.2 ng/mL, p = 0.357). Decreased hepcidin levels were significantly associated with decreased RLS severity (β = 0.002, 95% CI = 0.00−0.00, p = 0.005) and improved quality of life (β = 0.002, 95% CI = 0.00−7.01, p = 0.044) in a dose-dependent manner after 12 weeks of treatment with a dopamine agonist. This association was independent of age, sex, inflammatory markers, sleep quality, insomnia, daytime sleepiness, depression and anxiety. Conclusions: This study demonstrates the role of hepcidin in evaluating the positive therapeutic response in RLS. [ABSTRACT FROM AUTHOR]

Anxiety, depression, and insomnia are highly prevalent among migraineurs and are associated with negative health consequences. Anxiety and depression, however, unlike insomnia, are usually underdiagnosed, due to less self-reporting of these two conditions. The aim of the present study was to evaluate the risk of anxiety and depression in migraineurs with self-reported insomnia, using a general population-based sample. We used data from a nationwide population-based survey on headache and sleep, the Korean Headache-Sleep Study. Of all 2,695 participants, 143 (5.3%), 268 (10.0%), 116 (4.3%), and 290 (10.8%) were classified as having migraine, anxiety, depression, and self-reported insomnia, respectively. The risk of anxiety (odds ratio [OR] = 7.0, 95% confidence interval [CI] = 3.0–16.7) and depression (OR = 3.3, 95% CI = 1.3–8.5) was significantly increased in migraineurs with self-reported insomnia. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for anxiety in migraineurs with self-reported insomnia were 46.5%, 89.0%, 64.5%, and 79.5%, respectively. For depression, the sensitivity, specificity, PPV, and NPV were 41.7%, 82.4%, 32.3%, and 87.5%, respectively. Self-reported insomnia is likely to be comorbid with anxiety and depression in migraineurs and could thus be a useful predictor of anxiety and depression in migraine. [ABSTRACT FROM AUTHOR]

• Several metabolites and specific pathway are altered in the hippocampus by SF. • The metabolite profiles vary according to the duration of SF. • The alanine, aspartate, and glutamate metabolism pathway is the most altered pathway. Sleep fragmentation (SF) commonly occurs in several pathologic conditions and is especially associated with impairments of hippocampus-dependent neurocognitive functions. Although the effects of SF on hippocampus in terms of protein or gene levels were examined in several studies, the impact of SF at the metabolite level has not been investigated. Thus, in this study, the differentially expressed large-scale metabolite profiles of hippocampus in a rat model of SF were investigated using untargeted metabolomics approaches. Forty-eight rats were divided into the following 4 groups: 4-day SF group, 4-day exercise control (EC) group, 15-day SF group, and 15-day EC group (n = 12, each). SF was accomplished by forced exercise using a walking wheel system with 30-s on/90-s off cycles, and EC condition was set at 10-min on/30-min off. The metabolite profiles of rat hippocampi in the SF and EC groups were analyzed using liquid chromatography/mass spectrometry. Multivariate analysis revealed distinctive metabolic profiles and marker signals between the SF and corresponding EC groups. Metabolic changes were significant only in the 15-day SF group. In the 15-day SF group, L-tryptophan, myristoylcarnitine, and palmitoylcarnitine were significantly increased, while adenosine monophosphate, hypoxanthine, L-glutamate, L-aspartate, L-methionine, and glycerophosphocholine were decreased compared to the EC group. The alanine, aspartate, and glutamate metabolism pathway was observed as the common key pathway in the 15-day SF groups. The results from this untargeted metabolomics study provide a perspective on metabolic impact of SF on the hippocampus. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to investigate sex differences in the prevalence and clinical presentation of migraine and probable migraine in a general population‐based sample. Background: While there is research on sex differences in clinical characteristics and their impact on migraine headache, only few studies have investigated sex differences in probable migraine in population‐based settings. Moreover, compared with Western countries, the prevalence of probable migraine in Asia is relatively high. This cross‐sectional study was designed to investigate sex differences in the prevalence and clinical presentation of migraine and probable migraine in a general population‐based sample. Methods: We used the data of the Korean Headache‐Sleep Study, which is a nationwide survey on headache and sleep. Results: We interviewed 7430 people, and 3114 of them agreed to participate in our study (rejection rate, 58.1%). Among these people, 419 withdrew their participation during the interview. Ultimately, 2695 people completed our survey (cooperation rate, 36.3%). The prevalence of overall migraine and probable migraine was 350/1350 (25.9%) for women and 172/1345 (12.8%) for men (P < .001, respectively). The prevalence of migraine (107/1350 [7.9%] vs 36/1345 [2.7%], P < .001) and probable migraine (243/1350 [18.0%] vs 136/1345 [10.1%], P < .001) was significantly higher among women than among men. Headache frequency per month (median [interquartile range]) (1.0 [0.3–3.0] vs 0.8 [0.3–2.0], P = .037), the visual analog scale score for headache intensity (5.0 [4.0–7.0] vs 5.0 [3.0–6.0], P = .019), and the impact of headache {Headache Impact Test‐6 score (47.0 [42.0–54.0] vs 44.0 [42.0–51.8], P = .013)} were significantly higher among women with probable migraine than men. Headache frequency per month (2.0 [0.4–4.0] vs 1.0 [0.3–2.0], P = .073), headache intensity (6.0 [5.0–8.0] vs 6.0 [4.2–7.0], P = .281), and the impact of headache (55.0 [48.0–61.0] vs 49.0 [46.3–60.8], P = .225) were not significantly different between women and men with migraine. Other comorbidities or associated symptoms, such as anxiety and depression, were not significantly different between women and men with migraine and probable migraine, except for nausea in probable migraine. Conclusion: Women experience more severe symptoms and a higher impact of headache than men among participants with probable migraine. Our findings suggest that women with PM need a more intensive evaluation and treatment than men with PM. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence, sleep characteristics, and comorbidities associated with a high risk for obstructive sleep apnea (OSA) in the Korean adult population. Methods: We analyzed data from 2,740 subjects who responded to a nationwide questionnaire survey of sleep characteristics. Those who qualified under two or more symptom categories of the Berlin questionnaire were defined as “at high risk for OSA”. We investigated their socio-demographic information, sleep habits, and medical and psychiatric comorbidities. Logistic regression analyses were performed to identify factors and consequences significantly associated with a high risk for OSA. Results: The prevalence of a high risk for OSA was 15.8% (95% confidence interval [CI] 14.5–17.2%). Multiple logistic regression analysis showed that old age (≥ 70 years, odds ratio [OR] 2.68) and body mass index ≥ 25 kg/m2 (OR 10.75) were significantly related with a high risk for OSA, whereas regular physical activity (OR 0.70) had a protective effect. Subjective sleep characteristics associated with a high risk for OSA were perceived insufficient sleep (OR 1.49), excessive daytime sleepiness (OR 1.88), and insomnia (OR 3.70). In addition, hypertension (OR 5.83), diabetes mellitus (OR 2.54), hyperlipidemia (OR 2.85), and anxiety (OR 1.63) were comorbid conditions independently associated with a high risk for OSA. Conclusions: This is the first study to demonstrate the prevalence of a high risk for OSA in a nationwide representative sample of the Korean adult population. These findings elucidate the epidemiology and clinical characteristics of those at high risk for OSA. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate sleep characteristics associated with drowsy driving in an adult population.Methods: The study subjects consisted of 1675 adults aged 19 years or older who completed a population-based questionnaire survey on sleep habits. Experiences of drowsy driving were obtained from self-reported data. We investigated sleep-related variables including sleep duration, sleep efficiency, chronotype, subjective sleep perception, daytime sleepiness, sleep quality, and snoring. We performed multivariate logistic regression analysis to determine sleep characteristics independently associated with drowsy driving.Results: The mean age of the subjects was 43.2 years, and 66.3% were men. The prevalence of self-reported drowsy driving was 23.6% (396 of 1675), and 33.1% of subjects experienced dozing at the wheel at least once a month. Multivariate analysis demonstrated that men, office and manual workers, excessive daytime sleepiness, depression, habitual snoring, and perceived insufficient sleep were independently associated with drowsy driving. Subgroup analyses revealed that reduced weekday sleep duration was a risk factor of drowsy driving in adults with perceived sufficient sleep. On the other hand, frequent alcohol drinking significantly increased risk of drowsy driving in the subgroup with perceived sleep insufficiency. Furthermore, ordinal regression analyses confirmed the association between sleep characteristics and drowsy driving across different drowsy driving frequencies.Conclusion: Excessive daytime sleepiness, depression, habitual snoring, and perceived insufficient sleep were sleep-related risk factors for drowsy driving. In addition to maintaining healthy sleep habits, individuals at high risk should be encouraged to evaluate underlying sleep disorders or psychiatric problems to prevent drowsy driving. [ABSTRACT FROM AUTHOR]

Background: Tension-type headache (TTH) represents the most common type of headache among the general population. Although such headaches are usually mild in severity, some individuals with TTH experience severe symptoms and psychiatric comorbidities. Such patients may also experience sleep disturbances, which have been associated with headache exacerbation. Nevertheless, information regarding the prevalence and impact of insomnia among individuals with TTH in a population-based setting is limited. Therefore, the aim of the present study was to evaluate the prevalence and impact of insomnia among individuals with TTH using data from the Korean Headache-Sleep Study (KHSS). Methods: We analysed data from the KHSS-a nation-wide, cross-sectional, population-based survey on headache and sleep involving Korean adults aged 19 to 69 years. Insomnia was defined as an Insomnia Severity Index score ≥ 10. Results: Among 2695 participants, 570 (21.2%) and 290 (10.8%) were classified as having TTH and insomnia, respectively. Among individuals with TTH, 113 (19.8%) met the criteria for probable migraine (PM). The prevalence of insomnia among individuals with TTH was significantly higher than that among individuals without headache (13.2% vs. 5.8%, p < 0.001). However, among the TTH group, the prevalence of insomnia did not significantly differ between participants fulfilling PM criteria and those not fulfilling PM criteria (14.2% vs. 12.9%, p = 0.725). Among individuals with TTH, headache frequency [median and interquartile range (IQR): 1.0 (0.3-3.0) vs. 0.4 (0.2-1.0), p = 0.002], visual analogue scale scores for headache intensity [median and IQR: 5.0 (4.0-7.0) vs. 4.0 (3.0-6.0), p < 0.001], Headache Impact Test-6 scores [median and IQR: 46.0 (40.0-52.0) vs. 42.0 (38.0-46.0), p < 0.001], anxiety prevalence (28.0% vs. 6.7%, p < 0.001), and depression prevalence (21.3% vs. 1.6%, p < 0.001) were significantly higher in those with insomnia than in those without insomnia. Conclusions: Our findings indicate that insomnia is prevalent among individuals with TTH. Moreover, insomnia was associated with exacerbation of headache symptoms and psychiatric comorbidities. Therefore, identification of insomnia among individuals with TTH is required to improve the management of headache symptoms in such patients. [ABSTRACT FROM AUTHOR]

This study investigates health behaviors, health-related quality of life (HRQOL) and sleep among chronotypes in a community-based sample (n = 2,976). Analysis of covariance indicated evening types (E-types) had a significantly higher percentage of current smokers and more sleep-interfering behaviors compared to intermediate and morning types (M-type), and also lower physical activity and more sleep disturbance compared to M-types. E-types also had worse mental HRQOL compared to both chronotypes, and worse physical HRQOL compared to M-types. Exploratory analyses indicated E-types consumed more caffeinated beverages at night, smoked or ate heavy meals before bedtime, kept irregular sleep-wake schedules, and took more naps. Mediational analyses indicated that sleep-interfering behavior partially mediated the relationship between chronotype and sleep disturbance, and physical activity partially mediated the relationship between chronotype and mental HRQOL. E-types had more unhealthy behaviors, which may subsequently place them at higher risk for health problems. [ABSTRACT FROM AUTHOR]

Background Although probable migraine (PM) is common among headache sufferers, there is little knowledge of the prevalence and impacts of comorbid anxiety and depression in patients with PM. We assessed the prevalence and impact of anxiety and depression among PM sufferers in the general population. Methods We recruited Korean individuals aged 19-69 years via stratified random sampling and assessed headache type, anxiety, and depression among them using structured interviews. Results In a representative sample of 2695 individuals, 143 (5.3%) and 379 (14.1%) had migraine and PM, respectively. Fewer patients with PM had anxiety (17.7% vs. 30.1%, p = 0.002) and depression (8.7% vs. 16.8%, p = 0.007) compared to those with migraine. Prevalence of anxiety and depression was lower in people with PM than in those with migraine in univariable analysis, but insignificant after including headache intensity and headache frequency for adjustment. Headache frequency, headache intensity, and impact of headache were significantly higher among PM and migraine patients with anxiety and depression than among those without. Conclusions The prevalence of anxiety and depression was lower among individuals with PM compared to those with migraine. However, they were still prevalent and associated with an exacerbation of symptoms among individuals with PM. [ABSTRACT FROM AUTHOR]

To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer's disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50-65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011-2012. Nineteen OSA subjects (Apnea-Hypopnea Index [AHI] ≥15/h, 21.2±5.1/h; age 58.5±4.1 years; 9 male) and 19 controls (AHI 1.8±1.3/h; age 58.5±4.2 years; 9 male) underwent 60-min dynamic 11C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Sleep disorder and sleep complaints are common in subjects with migraine. Although the association between sleep disorders and migraine has been reported, the association between perceived insufficient sleep and migraine has rarely reported. The aim of this study is to evaluate the association between insufficient sleep and migraine using the data of the Korean Headache-Sleep Study (KHSS). Methods: The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep for Korean adults aged 19 to 69 years. A difference of one hour or more between sleep need and average sleep time indicated insufficient sleep. Results: Of 2,695 participants, 727 (27.0%) individuals were classified as having insufficient sleep. The prevalence of insufficient sleep among individuals with migraine (45.5%) was significantly higher compared to that among individuals with non-migraine headache (32.9%, p = 0.004) or among non-headache (20.4%, p < 0.001). Average sleep time did not differ among migraine, non-migraine headache, and non-headache groups (7.3 ± 1.2 vs. 7.2 ± 1.2 vs. 7.3 ± 1.4, p = 0.207). Multivariable logistic regression analyses demonstrated that migraine had an increased odds ratio (OR) for insufficient sleep after adjusting for sociodemographic variables, short sleep time, insomnia, poor sleep quality, anxiety, and depression (OR = 1.8, 95% confidence interval [CI] = 1. 2 - 2.7, p = 0.002). Conclusions: The prevalence of insufficient sleep was significantly higher among migraineurs compared to that in non-migraine headache or non-headache group. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown a significant association between restless legs syndrome (RLS) and primary headache disorders. Nevertheless, information regarding the association between tension-type headache (TTH) and RLS is limited. This study aimed to investigate the association between RLS and TTH in a population-based sample. Methods: We selected a stratified random population sample of Koreans aged 19-69 years and assessed them using a semi-structured interview designed to identify RLS, headache type, and clinical characteristics of TTH. We determined the prevalence and clinical impact of RLS in participants with TTH. Results: Of the 2695 participants, 570 (21.2%) and 142 (5.3%) were classified as having TTH and RLS, respectively. Among the 570 individuals with TTH, 113 (19.8%) also met the criteria for probable migraine (PM). The prevalence of RLS was significantly higher among individuals with TTH than among those with non-headache (6.0% vs 3.6%, p = 0.018). The prevalence of RLS was significantly higher in subjects with TTH who fulfilled PM criteria than in those with non-headache participants (8.0% vs. 3.6%, p = 0.018). However, RLS prevalence in individuals with TTH who did not fulfil PM criteria did not differ from that of participants with non-headache (5.5% vs. 3.6%, p = 0.063). TTH participants with RLS had higher visual analogue scale scores for headache intensity (5.1 ± 2.0 vs. 4.3 ± 1.8, p = 0.038), and higher prevalence of anxiety (20.6% vs. 8.8%, p = 0.022) and depression (14.7% vs. 3.5%, p = 0.002) than TTH participants without RLS. Multivariable analyses revealed that headache aggravation by movement (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.1-5.2) and depression (OR = 3.5, 95% CI = 1.1-11.4) were significant indicators of RLS among individuals with TTH. Conclusions: The prevalence of RLS was higher among individuals with TTH than among those with non-headache. Some clinical presentations varied in accordance with the presence of RLS among participants with TTH. [ABSTRACT FROM AUTHOR]

Although tension-type headache (TTH) is a frequent type of headache disorder and imposes a significant burden, there is scant information about the prevalence and impact of comorbid anxiety and depression among individuals with TTH. We investigated the prevalence and clinical impact of anxiety and depression among patients with TTH in the general population. We recruited Korean participants aged 19–69 years using a two-stage clustered random sampling method. To identify the presence of headache type, anxiety, and depression, we used a semi-structured interview using certain questionnaires. To assess the level of anxiety and depression, we used the Goldberg Anxiety Scale and Patient Health Questionnaire-9, respectively. Among 2,695 participants, 570 people (21.2%) had TTH during previous 1 year. In participants with TTH, the prevalence of anxiety (9.5% vs. 5.3%, p = 0.001) and depression (4.2% vs. 1.8%, p = 0.001) was significantly higher than that of non-headache participants. The prevalence of anxiety among TTH participants with >15 attacks per month [21.4%, odds ratio (OR): 4.0] and 1–14 attacks per month (13.1%, OR: 2.2) was higher than that in those with <1 attack per month (6.4%), however this tendency was not observed in participants with depression. Visual Analogue Scale (VAS) score [median 5.0 vs. 4.0, p = 0.010] and Headache Impact Test-6 (HIT-6) score [median 45.5 vs. 42.0, p < 0.001] were significantly higher among those with anxiety. Furthermore, VAS scores [median 5.0 vs. 4.0, p = 0.010] and HIT-6 scores [median 45.5 vs. 42.0, p = 0.027] were also significantly higher among TTH patients with depression than among those without depression. In conclusion, anxiety and depression were more prevalent in participants with TTH than in non-headache participants. These two conditions were associated with an exacerbation of headache symptoms in individuals with TTH. [ABSTRACT FROM AUTHOR]

Background: Insomnia is a common complaint among individuals with migraine. The close association between insomnia and migraine has been reported in clinic-based and population-based studies. Probable migraine (PM) is a migrainous headache which fulfills all but one criterion in the migraine diagnostic criteria. However, an association between insomnia and PM has rarely been reported. This study is to investigate the association between insomnia and PM in comparison with migraine using data from the Korean Headache-Sleep Study. Methods: The Korean Headache-Sleep Study is a nation-wide cross-sectional survey for all Korean adults aged 19-69 years. The survey was performed via face-to-face interview using a questionnaire on sleep and headache. If an individual's Insomnia Severity Index score was ≥15.5, she/he was diagnosed as having insomnia. Results: Of 2695 participants, the prevalence of migraine, PM and insomnia was 5.3, 14.1 and 3.6 %, respectively. The prevalence of insomnia among subjects with PM was not significantly different compared to those with migraine (8.2 % vs. 9.1 %, p = 0.860). However, insomnia prevalence in subjects with PM was significantly higher than in non-headache controls (8.2 % vs. 1.8 %, p < 0.001). Insomnia Severity Index score was significantly higher in subjects with migraine compared to those with PM (6.8 ± 5.8 vs. 5.5 ± 5.8, p = 0.012). Headache frequency and Headache Impact Test-6 score were significantly higher in subjects with migraine and PM with insomnia compared to those without insomnia. Multivariable linear analyses showed that anxiety, depression, headache frequency and headache intensity were independent variables for contributing the ISI score among subjects with PM. Conclusions: The prevalence of insomnia among subjects with PM was not significantly different compared to those with migraine. Anxiety, depression, headache frequency and headache intensity were related with ISI score in subjects with PM. [ABSTRACT FROM AUTHOR]

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that migraine and sleep disturbances are closely associated. Excessive daytime sleepiness (EDS) is a common symptom of various types of sleep disturbance. Findings from clinic-based studies suggest that a high percentage of migraineurs experience EDS. However, the prevalence and clinical impact of EDS among migraineurs at the population level have rarely been reported. The objective of this study was to investigate the prevalence and impact of EDS among migraineurs using a population-based sample in Korea. Methods: We selected a stratified random sample of Koreans aged 19 to 69 years and evaluated them using a semi-structured interview designed to identify EDS, headache type, and the clinical characteristics of migraine. If the score on the Epworth Sleepiness Scale (ESS) was more than or equal to 11, the participant was classified as having EDS. Results: Of the 2,695 participants that completed the interview, 143 (5.3 %) and 313 (11.6 %) were classified as having migraine and EDS, respectively. The prevalence of EDS was significantly higher in participants with migraine (19.6 %) and non-migraine headache (13.4 %) compared to non-headache controls (9.4 %). Migraineurs with EDS had higher scores on the Visual Analogue Scale (VAS) for headache intensity (6.9 ± 1.8 vs. 6.0 ± 1.9, p = 0.014) and Headache Impact Test-6 (59.8 ± 10.2 vs. 52.5 ± 8.2, p < 0.001) compared to migraineurs without EDS. Conclusions: Approximately 20 % of migraineurs had EDS in this population-based sample. Excessive daytime sleepiness was associated with an exacerbation of some migraine symptoms. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to document the frequency of sleep problems including poor sleep quality, excessive daytime sleepiness, and insomnia in subjects with epilepsy compared with healthy controls and to determine the factors associated with these sleep disturbances. Methods We recruited 180 patients with epilepsy (age: 43.2 ± 15.6 years, men: 50.0%) and 2836 healthy subjects (age: 44.5 ± 15.0 years, men: 49.8%). Sleep and the anxiety/mood profiles were measured using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index, Goldberg Anxiety Scale, and Patient Health Questionnaire—9 depression scale. Associations of sleep problems with epilepsy and other factors were tested by multiple logistic regression analysis, adjusted for age, gender, body mass index, alcohol intake, smoking, perceived sleep insufficiency, and habitual snoring. Results Sleep disturbances were more common in the group with epilepsy than in the controls (53.3% vs. 25.5%; p < 0.001). Poor sleep quality, excessive daytime sleepiness, and insomnia were significantly associated with epilepsy (odds ratio [95% confidence interval]: 3.52 [2.45–5.05], 2.10 [1.41–3.12], 5.91 [3.43–10.16], respectively). Depressive mood, anxiety, and perceived sleep insufficiency contributed to the presence of sleep disturbances. In the group with epilepsy, seizure remission for the past year related to a lower frequency of insomnia, whereas age, sex, type of epilepsy, and number of antiepileptic drugs were not correlated with sleep problems. Conclusion Epilepsy was significantly associated with the higher frequency of sleep disturbances, which supports the importance of screening sleep problems in patients with epilepsy and providing available intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND A chemosensitizing effect of levetiracetam (LEV) has been suggested because LEV inhibits O-6 methylguanine-DNA methyltransferase (MGMT). However, the survival benefit of LEV has not been clinically documented. The objective of this study was to assess the survival benefit of LEV compared with other antiepileptic drugs as a chemosensitizer to temozolomide for patients with glioblastoma. METHODS In total, 103 consecutive patients with primary glioblastoma who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and 58 patients (56%) received LEV during temozolomide chemotherapy for at least 3 months. A Cox regression survival analysis was performed to adjust for confounding factors, including age, extent of lesion, Karnofsky performance scale score, extent of removal, and MGMT promoter methylation status. RESULTS The median progression-free survival (PFS) and overall survival (OS) for patients who received LEV in combination with temozolomide (PFS: median, 9.4 months; 95% confidence interval [CI], 7.5-11.3 months; OS: median, 25.7 months; 95% CI, 21.7-29.7 months) were significantly longer than those for patients who did not receive LEV (PFS: median, 6.7 months; 95% CI, 5.8-7.6 months; OS: median, 16.7 months; 95% CI, 12.1-21.3 months; P = .010 and P = .027, respectively). In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (hazard ratio [HR], 0.37; P = .016), MGMT promoter methylation (HR, 0.30; P = .002), and receipt of LEV (HR, 0.31; P < .001. CONCLUSIONS LEV may provide a survival benefit in patients with glioblastoma who receive temozolomide-based chemotherapy. A prospective randomized study may be indicated. Cancer 2015;121:2926-2932. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Pandemics in poultry caused by the highly pathogenic avian influenza ( HPAI) A virus occur too frequently globally, and there is growing concern about the HPAI A virus due to the possibility of a pandemic among humans. Thus, it is important to develop a vaccine against HPAI suitable for both humans and animals. Various approaches are underway to develop such vaccines. In particular, an edible vaccine would be a convenient way to vaccinate poultry because of the behaviour of the animals. However, an edible vaccine is still not available. In this study, we developed a strategy of effective vaccination of mice by the oral administration of transgenic Arabidopsis plants ( HA- TG) expressing haemagglutinin ( HA) in the endoplasmic reticulum ( ER). Expression of HA in the ER resulted in its high-level accumulation, N-glycosylation, protection from proteolytic degradation and long-term stability. Oral administration of HA- TG with saponin elicited high levels of HA-specific systemic IgG and mucosal IgA responses in mice, which resulted in protection against a lethal influenza virus infection with attenuated inflammatory symptoms. Based on these results, we propose that oral administration of freeze-dried leaf powders from transgenic plants expressing HA in the ER together with saponin is an attractive strategy for vaccination against influenza A virus. [ABSTRACT FROM AUTHOR]

Continuation of sleep is important for learning and memory. Some proteins are differentially expressed in specific brain regions by normal sleep/wake cycle or sleep deprivation, suggesting that specific proteins are regulated by sleep/wake cycle and could play an important role in regulation of normal brain function associated with sleep in the regions. The hippocampus is a major region of the brain accounting for memory formation and organization, and its specific function could be altered by change of synapse-related molecular components. To examine sleep fragmentation-induced alteration of proteins in the hippocampus, two-dimensional gel electrophoresis was performed. Thirty-six male Wistar rats were randomly divided into the home cage group, sleep fragmentation group, and exercise control group. Four day sleep fragmentation was accomplished by a forced walking wheel system with a wheel on/off cycle of 30-s on/90-s off to mimic the arousal that is common in patients with severe sleep apnea. Time interval of exercise control was set at 10 min on/30 min off. Of 58 spots that were differentially expressed among the groups, one protein was consistently reduced in the sleep fragmented group compared to other groups. The protein was identified as synapsin IIa by MALDI-TOF mass spectrometry. Real-time polymerase chain reaction and Western blot analysis confirmed downregulated expression of synapsin IIa and another isoform, synapsin IIb. The results suggest that sleep fragmentation induces molecular changes accounting for neurotransmitter release, integrity of the reserve synaptic vesicle pool, and synaptic plasticity. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The present study utilized a population-based sample investigating the following aims: (1) compare the longitudinal course of insomnia in middle-aged and older adults and (2) examine age-related differences on subjective complaint and objective performance in middle-aged and older adults based on the course of insomnia. Methods: 1657 middle-aged adults (48.16% male, mean age=55.35±4.03years) and 405 older adults (48.40% male, mean age=70.13±3.88years) from the Korean Genome and Epidemiology Study (KoGES) were classified into 4 groups — no insomnia (NI), single episode insomnia (SEI), remitted persistent insomnia (PI-R), and ongoing persistent insomnia (PI-O) based on their course of insomnia over 5 time points spaced two years apart. Their performance on the psychomotor vigilance task (PVT) and subjective daytime sleepiness were compared across different insomnia groups, and the results were compared between middle-aged adults and older adults. Results: Analysis of covariance indicated that subjective daytime sleepiness was significantly different across the insomnia groups in middle-aged adults based on insomnia group (P=<.0001), but, did not affect objective vigilance performance. In contrast, older adults displayed significantly different PVT response time, but not daytime sleepiness, based on insomnia group (P=0.03). Conclusion: Insomnia impacts psychomotor performance and subjective sleepiness differently, based on age group. There may be underlying processes associated with the aging that amplifies the impact of insomnia on vigilance performance, yet lessens perceived sleepiness in older adults. [Copyright &y& Elsevier]

Introduction: Antiepileptic drugs are commonly given for perioperative prophylaxis after brain tumor surgery, and there has been growing interest in levetiracetam, a second-generation antiepileptic drug. This retrospective study compared the seizure outcomes, side effects and durability of levetiracetam with valproic acid after a craniotomy for supratentorial brain tumors. Methods: Between 2009 and 2012, 282 consecutive patients with a supratentorial brain tumor underwent a craniotomy at Seoul National University Bundang Hospital. Of these patients, 51 (18.1 %) and 231 (81.9 %) were pre-operatively administered levetiracetam and valproic acid, respectively. The postoperative seizure outcomes (within 1 month after surgery) and the long-term side effects of both drugs were evaluated. Results: Of the 51 patients in the levetiracetam group, 4 (7.8 %) experienced postoperative seizures after brain tumor surgery, and 15 (6.5 %) of the 231 patients in the valproic acid group experienced postoperative seizures ( p = 0.728). The long-term complication rate of the valproic acid group (26.8 %; 62/231) was significantly higher than that of the levetiracetam group (9.8 %; 5/51) [ p = 0.010]. In the valproic acid group, 10 hepatotoxicities, 20 hyperammonemias and 10 hematologic abnormalities (6 thrombocytopenias, 3 pancytopenias, and 1 leucopenia) occurred. Moreover, 89 patients (38.5 %) in the valproic acid group changed or added other anticonvulsants because of side effects or uncontrolled seizures, whereas only 9 patients (17.6 %) in the levetiracetam group changed or added other anticonvulsants ( p = 0.005). Conclusions: The postoperative seizure control rates of levetiracetam and valproic acid were not statistically significantly different; however, levetiracetam may be superior to valproic acid in terms of its safety and durability after supratentorial tumor surgery. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Our objective was to investigate if weekend catch-up sleep is independently related to a decrease in the risk for hypertension in Korean adults. Methods: The subjects included 2782 Korean adults ages 19years and older. Data on demographic variables, sleep duration (weekday and weekend), and hypertension were obtained using questionnaires. Logistic regression analyses were performed to test the association between hypertension and sleep duration (weekday and weekend catch-up sleep duration); we also adjusted for possible covariates. Results: After adjustment for confounding variables, we found that individuals who slept less than 6hours a night had an increased odds ratio (OR) for hypertension (OR, 1.73; 95% confidence interval [CI], 1.13–2.64) compared to individuals who slept 7 to <8hours a night. Furthermore, one hour of weekend catch-up sleep was significantly associated with decreased risk for hypertension (OR, 0.83; 95% CI, 0.72–0.95). There were significant differences for groups with and without subjective sleep insufficiency in the association between weekend catch-up sleep duration and the prevalence of hypertension; in addition, the effect of an extra hour of weekend catch-up sleep per night on hypertension was stronger in those subjects who experienced subjective sleep insufficiency (OR, 0.61; 95% CI, 0.46–0.82). Conclusions: Sleeping more on the weekend to compensate for weekday sleep deficit could lower the risk for hypertension in Korean adults, especially in Korean adults who have the subjective symptom of sleep insufficiency. [Copyright &y& Elsevier]

Abstract: Thyroid transcription factor 1 (TTF-1) is required for morphogenesis of the fetal diencephalon. Previous reports showed that mice carrying a TTF-1 null mutation lacked normal development of the pituitary gland. In this study, a role for TTF-1 in the regulation of growth hormone and prolactin transcription was identified. In-situ hybridization analysis demonstrated TTF-1 mRNA in the growth hormone-producing cells and prolactin-producing cells of the rat anterior pituitary gland. In the GH3 pituitary cell line, we identified TTF-1 as a factor functionally regulating growth hormone and prolactin transcription. TTF-1 activated prolactin transcription, but inhibited growth hormone transcription. Inhibition and activation of growth hormone and prolactin transcription, respectively, by TTF-1 disappeared upon deletion of the TTF-1 binding motifs within the promoters of these genes. These data suggest that TTF-1 plays a regulatory role in the transcription of growth hormone and prolactin genes and may regulate transdifferentiation of cells expressing these two hormones. [Copyright &y& Elsevier]

Background: Insomnia and migraine are closely related; insomnia aggravates migraine symptoms. This study was conducted to investigate the impact of migraine on the clinical presentation of insomnia symptoms.Methods: The data of the Korean Headache-Sleep Study (KHSS) were used in the present study. The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep in Korean adults aged 19 to 69 years. If a participant’s Insomnia Severity Index (ISI) score ≥ 10, she/he was classified as having insomnia. The clinical presentation of insomnia symptoms was assessed using total and subcomponent scores of the ISI.Results: Of 2695 participants, 290 (10.8%) and 143 (5.3%) individuals were assigned as having insomnia and migraine, respectively. The proportions of migraine (12.8% vs. 4.4%, p <  0.001) and non-migraine headache (59.0% vs. 39.9%, p <  0.001) were higher among individuals with insomnia compared to those without insomnia. Among participants with insomnia, total ISI scores were not significantly different among participants with migraine, non-migraine, and non-headache [median and interquartile range: 13.0 (11.0-17.5) vs. 13.0 (11.0-17.5) vs. 12.0 (11.0-16.0), p = 0.245]. ISI scores for noticeability of sleep problems to others were significantly higher among participants with migraine [3.0 (2.0-4.0) vs. 2.0 (2.0-3.0), p = 0.011] and non-migraine headache [3.0 (2.0-4.0) vs. 2.0 (2.0-3.0), p = 0.001] compared to those without headache history. Other ISI subcomponent scores did not significantly differ between headache status groups.Conclusions: Participants with insomnia had an increased risk of migraine and non-migraine headache compared to those without insomnia. Among participants with insomnia, overall insomnia severity was not significantly influenced by the headache status. [ABSTRACT FROM AUTHOR]

Background: Probable migraine (PM) is a subtype of migraine that is prevalent in the general population. Previous studies have shown that poor sleep quality is common among migraineurs and is associated with an exacerbation of migraine symptoms. However, information on the prevalence and clinical implication of poor sleep quality among individuals with PM is scarce. Thus, the aim of this study was to assess the prevalence and clinical impact of poor sleep quality in individuals with PM in comparison with those with migraine.Methods: Two-stage cluster random sampling was used to perform the survey for sleep and headache in Korean general population. Participants with Pittsburgh Sleep Quality Index > 5 were considered as having poor sleep quality.Results: Of 2695 participants, 379 (14.1%) had PM and 715 (26.5%) had poor sleep quality. Prevalence of poor sleep quality was 35.4% in the PM group, which was lower than that in the migraine group (47.6%, p = 0.011), but higher than that in the non-headache group (21.4%, p < 0.001). The PM participants with poor sleep quality showed increased headache frequency (median [interquartile range]: 2.0 [0.3-4.0] vs. 1.0 [0.2-2.0]; p = 0.001) and headache intensity (visual analogue scale, 6.0 [4.0-7.0] vs. 5.0 [3.5-6.0]; p = 0.003) compared to PM participants who had no poor sleep quality.Conclusions: Poor sleep quality was prevalent among participants with PM. It was associated with an exacerbation of PM symptoms. Our findings suggest that proper evaluation and treatment for poor sleep quality are needed in the management of PM. [ABSTRACT FROM AUTHOR]