Binaural beats at 0.25 Hz shorten the latency to slow-wave sleep during daytime naps.

Binaural beats can entrain neural oscillations and modulate behavioral states. However, the effect of binaural beats, particularly those with slow frequencies (< 1 Hz), on sleep remains poorly understood. We hypothesized that 0.25-Hz beats can entrain neural oscillations and enhance slow-wave sleep by shortening its latency or increasing its duration. To investigate this, we included 12 healthy participants (six women; mean age, 25.4 ± 2.6 years) who underwent four 90-min afternoon nap sessions, comprising a sham condition (without acoustic stimulation) and three binaural-beat conditions (0, 0.25, or 1 Hz) with a 250-Hz carrier tone. The acoustic stimuli, delivered through earphones, were sustained throughout the 90-min nap period. Both N2- and N3- latencies were shorter in the 0.25-Hz binaural beats condition than in the sham condition. We observed no significant results regarding neural entrainment at slow frequencies, such as 0.25 and 1 Hz, and the modulation of sleep oscillations, including delta and sigma activity, by binaural beats. In conclusion, this study demonstrated the potential of binaural beats at slow frequencies, specifically 0.25 Hz, for inducing slow-wave sleep in generally healthy populations.

Efficacy and Safety of Valbenazine in Elderly and Nonelderly Japanese Patients With Tardive Dyskinesia: A Post Hoc Analysis of the J-KINECT Study.

PURPOSE: The efficacy and safety of valbenazine, a selective vesicular monoamine transporter 2 inhibitor, has been confirmed for treatment of tardive dyskinesia (TD) in patients aged ≥65 years in non-Asian clinical trials; however, data are lacking in elderly Asian patients. This post hoc analysis of J-KINECT aimed to evaluate the efficacy and safety of valbenazine in elderly Japanese patients with TD. METHODS: J-KINECT was a randomized, double-blind, placebo-controlled study with a 6-week double-blind, placebo-controlled period; 42-week double-blind, valbenazine extension period; and 4-week posttreatment observation period. Outcomes were summarized by age (≥65 years [elderly] and <65 [nonelderly]) and treatment group. RESULTS: The safety analysis set included 100 and 153 patients aged ≥65 and <65 years, respectively (intention-to-treat set: 98 and 151 patients, respectively). In the elderly group, the difference versus placebo in least-squares mean change from baseline in the Abnormal Involuntary Movement Scale total score at week 6 was -3.1 (95% confidence interval: -4.5, -1.7) and -5.5 (-7.0, -3.9) with valbenazine 40 and 80 mg, respectively; in the nonelderly group, respective differences were -1.5 (-2.6, -0.4) and -2.5 (-3.6, -1.3). Both age groups showed improvement in Clinical Global Impression of Change-Tardive Dyskinesia scores with valbenazine. The incidence of treatment-emergent adverse events (TEAEs) leading to treatment discontinuation was higher in the elderly versus nonelderly group. There was no trend toward higher incidences of TEAEs or related TEAEs in the elderly group. CONCLUSIONS: The findings suggest that valbenazine may be used effectively and safely as a treatment for TD, even in elderly patients.

Analysis of Antipsychotic Dosage in Patients With Tardive Dyskinesia: A Case-Control Study Using the Claims Database of the Corporate Health Insurance Association.

PURPOSE: This study aimed to assess the association between antipsychotic doses and the risk of tardive dyskinesia (TD) in clinical practice using a Japanese claims database from 2010 to 2020. METHODS: The study population included patients 15 years or older with a diagnosis record of schizophrenia, depression, or bipolar disorder who were prescribed antipsychotics. Using a case-control design, we categorized patients newly diagnosed with TD as cases, with corresponding 1:10 matching in the control group. The primary endpoint was the relative risk of TD in the >median dose and ≤median dose groups, as determined using conditional logistic regression analysis adjusted for age. RESULTS: The analysis population included 58,452 patients, and the median daily antipsychotic dose was 75 mg/d of chlorpromazine equivalent (CPZE). Of these, 80 were identified as TD cases, and doses >75 mg/d were associated with a significantly increased risk of TD at the last prescription and the maximum dose, respectively, before the date of the first diagnosis of TD. Post-hoc analysis further showed a significant association between doses ≥300 mg/d and the risk of TD compared to doses ≤75 mg/d and doses >75 to <300 mg/d. Comparing ≥300 mg/d versus >75 to <300 mg/d, the odd ratios at the last prescription and maximum dose before the first diagnosis of TD were 3.40 and 3.50, respectively. CONCLUSIONS: In the Japanese medical claims database of patients receiving relatively low doses of antipsychotics, doses >75 mg/d were associated with an increased risk of TD in a dose-dependent manner.

Self-Reported Sleep Duration and Bedtime Are Associated with Dementia Risk in Community-Dwelling People Aged 40-74 Years: The Murakami Cohort Study.

Background: Sleep is a potentially modifiable factor associated with dementia, including Alzheimer's disease, but current evidence supporting this is insufficient. Objective: This study aimed to determine whether sleep duration and bedtime patterns are associated with the risk of dementia among middle-aged and older people. Methods: This cohort study had an eight-year follow-up period. Participants were 13,601 community-dwelling people aged 40-74 years living in Murakami (Niigata, Japan). Data were collected using a self-administered questionnaire. Predictors were self-reported sleep duration and bedtime, and the outcome was newly-diagnosed dementia determined using the long-term care insurance database. Covariates were demographic characteristics, body mass index, smoking, alcohol consumption, total physical activity, insomnia symptoms, disease history, and either bedtime or sleep duration. Cox proportional hazard models were used to calculate hazard ratios (HRs). Results: The mean age of participants at baseline was 59.2 years. Over a mean follow-up period of 8.0 years, 319 cases of dementia were observed. A long self-reported sleep duration relative to the reference sleep duration (7 hours) was associated with increased dementia risk, with the "8 hours" group (adjusted HR = 1.30, 95% CI:0.99-1.73) and "≥9 hours" group (adjusted HR = 1.46, 95% CI:1.00-2.15) having an increased risk (marginally significant) relative to the reference group. Early bedtime was associated with increased dementia risk (adjusted p for trend = 0.0010), with the "21 : 00 or earlier" group (adjusted HR = 1.61, 95% CI:1.14-2.28) having an increased risk relative to the reference ("23 : 00"). Conclusions: A long self-reported sleep duration and early bedtime are both associated with increased dementia risk in middle-aged and older people.

Low plasma 25-hydroxyvitamin D levels are not associated with a high risk of recurrent falls in community-dwelling Japanese adults: the Murakami cohort study.

Reports on the association between vitamin D levels and fall risk have been mixed, and long-term follow-up studies are lacking. This 5-year cohort study of 5,343 community-dwelling Japanese people aged 40-74 years found that low vitamin D levels are not associated with a high risk of recurrent falls. PURPOSE: Findings of cohort studies on the association between plasma 25-hydoxyvitamin D (25[OH]D) levels and fall risk have been mixed, and long-term follow-up studies are lacking. The present study investigated whether low plasma 25(OH)D levels are longitudinally associated with a high risk of recurrent falls in adults. METHODS: This 5-year cohort study included 5,343 community-dwelling Japanese people aged 40-74 years. Baseline blood collection and a questionnaire survey were conducted in 2011-2013. Plasma 25(OH)D levels were determined and divided into quintiles after stratification by season, sex, and age group. Information on recurrent falls occurring in the year before the survey 5 years later was obtained, and participants with two or more falls were considered to have experienced recurrent falls. Covariates were sex, age, marital status, education, occupation, BMI, total physical activity levels, calcium intake, vitamin K intake, smoking, drinking, and disease history. RESULTS: Mean age and 25(OH)D levels were 60.9 years and 50.9 nmol/L, respectively. In the follow-up survey, 209 recurrent falls were reported. Plasma 25(OH)D levels were not significantly associated with the occurrence of recurrent falls in men, women, or men/women-combined (adjusted P for trend = 0.1198, 0.8383, and 0.2355, respectively). In men and men/women-combined, adjusted ORs for recurrent falls in the lowest quintile were significantly lower (adjusted OR = 0.42 and 0.59, respectively) than the middle quintile (reference). CONCLUSION: Low plasma 25(OH)D levels are not associated with a high risk of recurrent falls in middle-aged and older people. Further longitudinal studies will be needed to confirm our findings in other populations.

Efficacy and Safety of Valbenazine in Japanese Patients With Tardive Dyskinesia and Schizophrenia/Schizoaffective Disorder or Bipolar Disorder/Depressive Disorder: Primary Results and Post Hoc Analyses of the J-KINECT Study.

PURPOSE: This post hoc analysis investigated whether a patient's underlying psychiatric disease (schizophrenia/schizoaffective disorder [SCHZ] or bipolar disorder/depressive disorder [MOOD]) influenced the efficacy or safety of valbenazine for tardive dyskinesia (TD) in an Asian population. METHODS: We analyzed data from J-KINECT, a multicenter, phase II/III, randomized, double-blind study, which consisted of a 6-week placebo-controlled period followed by a 42-week extension where Japanese patients with TD received once-daily 40- or 80-mg valbenazine. We compared the change from baseline in Abnormal Involuntary Movement Scale total score and Clinical Global Impression of TD score between patients with SCHZ and those with MOOD, and incidence of treatment-emergent adverse events. RESULTS: Of 256 patients included in the placebo-controlled period, 211 continued to the long-term extension. The mean change from baseline in Abnormal Involuntary Movement Scale total score at week 6 (95% confidence interval) was -1.8 (-3.2 to -0.5) and -3.3 (-4.7 to -1.9) in the valbenazine 40- and 80-mg groups, respectively (SCHZ group), and -2.4 (-3.9 to -0.9) and -3.5 (-5.1 to -1.9) in the valbenazine 40- and 80-mg groups, respectively (MOOD group), demonstrating improvement at either dose level over placebo, regardless of the underlying disease. These results were maintained to week 48, and improvements of Clinical Global Impression of TD scores were similar. There were no notable differences in the incidence of serious or fatal treatment-emergent adverse events by underlying disease; differences in the incidence of worsening schizophrenia and depression were attributed to underlying disease progression. CONCLUSIONS: Safety and efficacy of long-term valbenazine therapy for TD did not vary according to underlying psychiatric disease.

Chronic Pain in the Lower Extremities and Low Back is Associated With Recurrent Falls in Community-Dwelling Japanese People Aged 40-74 Years.

OBJECTIVE: To determine the longitudinal association between chronic pain in the lower extremities and low back and the odds of recurrent falls in middle-aged and older people. DESIGN: A cohort study. SETTING: Communities in Japan. PARTICIPANTS: Participants were 7540 community-dwelling volunteers aged 40-74 years (N=7540). The baseline survey was a self-administered questionnaire conducted between 2011-2013. Predictors were presence of chronic pain in the knee, foot or ankle, and low back, with the degree of pain categorized as none, very mild/mild, moderate, or severe/very severe. Covariates in the multivariate model of chronic pain in a site were demographics, body mass index, physical activity level, disease history, and chronic pain in the other 2 sites. Logistic regression analysis was used to calculate odds ratios (ORs). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Recurrent falls in the year before the 5-year follow-up survey. RESULTS: Mean participant age was 60.2 years. Higher degrees of chronic pain were associated with higher odds of recurrent falls for the knee (P=.0002) with a higher OR of 1.48 (95% CI: 1.11-1.97), for the foot or ankle (P=.0001) with a higher OR of 1.97 (95% CI: 1.36-2.86), and for the low back (P=.0470) with a higher OR of 1.45 (95% CI: 1.09-1.91) in those with any degree of pain relative to those without pain. Higher degrees of chronic knee pain were associated with higher odds of recurrent falls in women (P=.0005), but not in men (P=.0813). Meanwhile, higher degrees of chronic low back pain were associated with the odds of recurrent falls in men (P=.0065), but not in women (P=.8735). CONCLUSIONS: Chronic pain in the knee, foot or ankle, and lower back was independently and dose-dependently associated with a higher risk of recurrent falls. A marked sex-dependent difference was also noted in the association.

Body mass index, height, and osteoporotic fracture risk in community-dwelling Japanese people aged 40-74 years.

INTRODUCTION: The association between body size and fracture risk is complex and varies by sex and ethnicity. This study aimed to examine associations of body mass index (BMI) and height with osteoporotic fracture risk in middle-aged and older people. MATERIALS AND METHODS: This 10-year cohort study included 13,151 community-dwelling Japanese people aged 40-74 years. A self-administered questionnaire survey was conducted at baseline to obtain information on demographic characteristics, body size, lifestyle, and disease history. BMI (kg/m2) was categorized as underweight (< 18.5), low-normal (18.5-21.7), high-normal (21.8-24.9), overweight (25.0-29.9), and obese (≥ 30.0). Height was categorized into quartiles. All incident cases of major osteoporotic fractures, including fractures of the distal radius, neck of the humerus, neck or trochanter of the femur, and vertebrae, were obtained from medical records during follow-up. RESULTS: Mean participant age was 58.8 years. In men, the underweight group had a significantly higher hazard ratio (HR) for total fracture (adjusted HR = 2.46), and the obese group had significantly higher HRs for total (adjusted HR = 3.01) and vertebral (HR = 3.77) fractures relative to the reference (overweight) group. No significant associations were observed between BMI and risk of any fracture in women. Higher quartiles of height were associated with higher vertebral fracture risk (adjusted P for trend = 0.023) only in women. CONCLUSION: BMI and osteoporotic fracture risk showed a U-shaped association in men, whereas higher height was associated with higher vertebral fracture risk in women, suggesting sex-dependent differences in these associations.

Sex Differences in the Association Between Body Mass Index and Dementia Risk in Community-Dwelling Japanese People Aged 40-74 Years.

BACKGROUND: The association between body mass index (BMI) and dementia risk is heterogeneous across age groups and might be influenced by sex. OBJECTIVE: This study aimed to clarify sex differences in the association between BMI and dementia risk in community-dwelling people. METHODS: This cohort study with an 8-year follow-up targeted 13,802 participants aged 40-74 years at baseline in 2011-2013. A self-administered questionnaire requested information on body size, including height, weight, and waist circumference (the values of which were validated by direct measurement), socio-demographics, lifestyle, and disease history. BMI was calculated and categorized as < 18.5 (underweight), 18.5-20.6 (low-normal), 20.7-22.6 (mid-normal), 22.7-24.9 (high-normal), 25.0-29.9 (overweight), and≥30.0 kg/m2 (obese). Incident cases of dementia were obtained from the long-term care insurance database. A Cox proportional hazards model was used to calculate multivariable-adjusted hazard ratios (HRs). RESULTS: The mean age of participants was 59.0 years. In men, higher BMI was associated with lower dementia risk (fully-adjusted p for trend = 0.0086). In women, the association between BMI and dementia risk was U-shaped; the "underweight," "low-normal," and "overweight" groups had a significantly higher risk (fully-adjusted HR = 2.12, 2.08, and 1.78, respectively) than the reference ("high-normal" group). These findings did not change after excluding dementia cases which occurred within the first four years of the follow-up period. CONCLUSION: Overweight/obese women, but not men, had an increased risk of dementia, suggesting that sex differences in adiposity might be involved in the development of dementia.

Alcohol consumption, smoking, and risk of dementia in community-dwelling Japanese people aged 40-74 years: The Murakami cohort study.

OBJECTIVE: Alcohol drinking and tobacco smoking have impacts on lifestyle-related diseases, but their association with dementia remains a debated topic. This study aimed to examine longitudinal associations between alcohol consumption, smoking, and dementia risk in middle-aged and older Japanese people. METHODS: This study used a cohort design with an 8-year follow-up. Participants were community-dwelling Japanese people (N = 13,802) aged 40-74 years. The baseline survey, including a self-administered questionnaire, was conducted in 2011-2013. Predictors were alcohol consumption and tobacco smoking. The outcome was incident dementia obtained from a long-term care insurance database. Covariates were demographics, lifestyle factors, body mass index, general health status, and history of stroke, diabetes, and depression. RESULTS: Participant mean age was 59.0 years. The 1-149, 150-299, and 300-449 g ethanol/week groups had significantly lower adjusted hazard ratios (HRs) (0.62, 0.59, and 0.47, respectively) compared with the reference group, with no significant linear association. HRs increased toward 1 when past-drinkers and those with poor health status and a disease history were excluded (0.80, 0.66, and 0.82, respectively). Higher smoking levels were dose-dependently associated with a higher HR (adjusted P for trend = 0.0105), with the ≥20 cigarettes/day group having a significantly higher adjusted HR (1.80). Heavy drinkers (≥449 g ethanol/week) with smoking habits, but not those without smoking habits, had higher dementia risk (P for interaction = 0.0046). CONCLUSION: Light-to-moderate alcohol consumption is associated with decreased dementia risk, and smoking is dose-dependently associated with increased dementia risk, with an interaction between high alcohol consumption and smoking on dementia risk.

Urinary proteome profiles associated with cognitive decline in community elderly residents-A pilot study.

Non-invasive and simple methods enabling easy identification of individuals at high risk of cognitive decline are needed as preventive measures against dementia. This pilot study aimed to explore protein biomarkers that can predict cognitive decline using urine, which can be collected non-invasively. Study subjects were selected from participants in a cohort study of middle-aged and older community-dwelling adults who underwent cognitive testing using the Mini-Mental State Examination and provided spot urine samples at two time points with an interval of approximately 5 years. Seven participants whose cognitive function declined 4 or more points from baseline (Group D) and 7 sex- and age-matched participants whose cognitive function remained within the normal range during the same period (Group M) were selected. Urinary proteomics using mass spectrometry was performed and discriminant models were created using orthogonal partial least squares-discriminant analysis (OPLS-DA). OPLS-DA yielded two models that significantly discriminated between the two groups at baseline and follow-up. Both models had ORM1, ORM2, and SERPINA3 in common. A further OPLS-DA model using baseline ORM1, ORM2, and SERPINA3 data showed similar predictive performance for data at follow-up as it did for baseline data (sensitivity: 0.85, specificity: 0.85), with the receiver operating characteristic curve analysis yielding an area under the curve of 0.878. This prospective study demonstrated the potential for using urine to identify biomarkers of cognitive decline.

Low plasma 25-hydroxyvitamin D levels are associated with an increased risk of depressive symptoms in community-dwelling Japanese people aged between 40 and 74 years: The Murakami cohort study.

BACKGROUND: Association between vitamin D levels and the occurrence of depression are not always consistent. The present cohort study aimed to determine this association in older adults, using a method for measuring vitamin D levels which is more accurate than those used in previous studies. METHODS: Participants were 3447 individuals aged 40-74 years without depressive symptoms at baseline who participated in the 5-year follow-up survey. The baseline investigation, including a self-administered questionnaire survey and blood collection, was conducted in 2011-2013. Plasma 25-hydroxyvitamin D (25[OH]D) levels were measured, and divided into overall quartiles summed up by sub-quartiles and stratified by age, sex, and season. The outcome was depressive symptoms determined by the CES-D (11-item, cut-off score of 6/7) 5 years later. Covariates were demographics, lifestyles, baseline CES-D score, and disease history. RESULTS: Mean plasma 25(OH)D levels were 58.0 nmol/L in men and 45.7 in women (P < 0.0001), and cumulative incidences of depressive symptoms were 249/1577 (15.8 %) in men and 313/1870 (16.7 %) in women (P = 0.4526). The lower 25(OH)D quartile group had higher adjusted ORs in men and women combined (P for trend = 0.0107) and women (P for trend = 0.0003), but not in men. Adjusted ORs of the lowest quartile group were significantly higher than the highest group in men and women combined (OR = 1.39, 95 % CI: 1.06-1.81) and women (OR = 1.89, 95 % CI: 1.31-2.72). LIMITATION: Depressive symptoms were self-reported. CONCLUSIONS: Low vitamin D levels were associated with a high risk of depressive symptoms, especially in women. Women are thus considered a major target for preventing vitamin D deficiency to address depression.

Epidural Anesthesia and Continuous Epidural Analgesia in a Pediatric Patient With Pelizaeus-Merzbacher Disease: A Case Report.

Pelizaeus-Merzbacher disease (PMD) is a genetic leukodystrophy, which is a progressive and degenerative central nervous system abnormality caused by dysmyelination. Because the incidence of PMD is extremely low, only a few case reports have been published regarding its anesthetic management. In particular, epidural anesthesia has only been reported in one case of general anesthesia combined with caudal anesthesia. We performed general anesthesia combined with epidural anesthesia for the soft-tissue release surgery for bilateral hip subluxation in a six-year-old male patient diagnosed with PMD. General anesthesia was induced with sevoflurane in nitrous oxide and oxygen. Rocuronium was administered to facilitate tracheal intubation. After intubation, general anesthesia was maintained with sevoflurane in the air and oxygen. An epidural catheter was placed from L3/4. For epidural anesthesia and analgesia, 1% mepivacaine was used as needed, and 2 ml/h of 0.2% ropivacaine was started one hour before the end of surgery. During surgery, only epidural analgesia was provided as postoperative analgesia, and the patient did not complain of pain after extubation. Anesthesia lasted three hours and 55 minutes. No significant hemodynamic or respiratory changes occurred. Postoperatively, the patient received continuous epidural analgesia and regular oral acetaminophen, and pain control was good. The epidural catheter was removed on the second postoperative day. The postoperative course was good, and the patient was transferred to a pediatric rehabilitation hospital on the fifth postoperative day. No adverse events occurred and no neurological deficits were observed during hospitalization. In conclusion, anesthesiologists should pay attention to the possibility of perioperative aspiration, spasticity, and seizure, even with mild PMD. Proper preoperative evaluations, intraoperative monitoring, and anesthetic techniques will ensure safe anesthesia for PMD patients. Although regional anesthesia in patients with pre-existing neurologic deficits is controversial, we were able to safely perform epidural anesthesia and postoperative continuous epidural analgesia in a pediatric patient with PMD.

Influence of Surveillance Methods in the Detection of Sports Injuries and Illnesses.

Background: Epidemiological data on sports injuries and illnesses depend on the surveillance methodology and the definition of the health problems. The effect of different surveillance methods on the data collection has been investigated for overuse injuries, but not for other health problems such as traumatic injuries and illnesses. Purpose: The purpose of this study was to investigate the new surveillance method developed by the Oslo Sports Trauma Research Center (OSTRC), which is based on any complaint definition (new method), to identify health problems compared with the traditional surveillance method, which is based on time loss definition. Study design: Descriptive epidemiology study. Methods: A total of 62 Japanese athletes were prospectively followed-up for 18 weeks to assess differences in health problems identified by both new and traditional methods. Every week, the athletes completed the Japanese version of the OSTRC questionnaire (OSTRC-H2.​JP), whereas the teams' athletic trainers registered health problems with a time loss definition. The numbers of health problems identified via each surveillance method were calculated and compared with each other to assess any differences between their results. Results: The average weekly response rate to the OSTRC-H2.​JP was 82.1% (95% CI, 79.8-84.3). This new method recorded 3.1 times more health problems (3.1 times more injuries and 2.8 times more illnesses) than the traditional method. The difference between both surveillance methods' counts was greater for overuse injuries (5.3 times) than for traumatic injuries (2.5 times). Conclusions: This study found that the new method captured more than three times as many health problems as the traditional method. In particular, the difference between both methods' counts was greater for overuse injuries than for traumatic injuries. Level of evidence: 2b.

Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT).

AIM: Valbenazine is approved in the US for treatment of tardive dyskinesia (TD); however, efficacy/safety data in Asian populations are lacking. We assessed the efficacy/safety of valbenazine in Japanese patients. METHODS: This phase II/III, multicenter, randomized, double-blind, placebo-controlled study (NCT03176771) included adult psychiatric patients with TD, who were randomly allocated to receive placebo or valbenazine (once-daily 40- or 80-mg) for a 6-week, double-blind period, after which the placebo group was switched to valbenazine for a 42-week extension. The primary endpoint was change from baseline in Abnormal Involuntary Movement Scale (AIMS) total score at Week 6; clinical global impression of improvement of TD (CGI-TD) was also assessed. RESULTS: Of 256 patients, 86, 85, and 85 were allocated to the 40-mg valbenazine, 80-mg valbenazine, and placebo groups, respectively. Least-squares mean (95% confidence interval) change from baseline in AIMS score at Week 6 was -2.3 (-3.0 to -1.7) in the valbenazine 40-mg group, -3.7 (-4.4 to -3.0) in the 80-mg group, and -0.1 (-0.8 to 0.5) in the placebo group; both treatment groups showed statistically significant improvements vs. placebo. Patients switched to valbenazine at Week 6 showed similar improvements in AIMS scores, which were maintained to Week 48. Improvements in CGI-TD scores were observed for both treatment groups vs. placebo. Incidence of adverse events was highest in the 80-mg group; common events included nasopharyngitis, somnolence, schizophrenia worsening, hypersalivation, insomnia, and tremor. CONCLUSION: The efficacy/safety profile of valbenazine was similar to that of previous clinical trials, supporting its use for TD treatment in Japanese patients.

Physical activity and recurrent fall risk in community-dwelling Japanese people aged 40-74 years: the Murakami cohort study.

BACKGROUND: Falls are important causes of injury and mortality in older people, and associated medical costs can be enormous. Physical activity (PA) is a potential preventive factor for falls. However, few studies have examined the effect of different types of PA on fall prevention. This study aimed to evaluate the association between PA levels and the incidence of recurrent falls by type of PA in middle-aged and older people. METHODS: This cohort study targeted 7,561 community-dwelling individuals aged 40-74 years who did not experience recurrent falls in the year before baseline. Information on PA levels, demographics, body size, lifestyle, and fall/disease history was obtained using a self-administered questionnaire in the baseline survey. Levels of total PA, leisure-time PA, and non-leisure-time PA (occupation, commuting, and housework) were estimated using metabolic equivalent (MET) scores (MET-h/day; hours spent on a given activity per day multiplied by its MET intensity). PA levels were categorized into four groups. Falls were recorded as none, once, or twice or more (recurrent falls). The outcome of the study was the incidence of recurrent falls in the past year before a survey conducted 5 years after the baseline survey. Logistic regression analyses were performed to calculate odds ratios for recurrent falls. RESULTS: Higher total PA and non-leisure-time PA levels were associated with a higher risk of recurrent falls (P for trend = 0.0002 and 0.0001, respectively), with the highest total PA and non-leisure-time PA groups having a significantly higher adjusted OR (1.96 [95%CI:1.33-2.88] and 2.15 [95%CI:1.48-3.14], respectively) relative to the lowest group (reference). As for leisure-time PA, the medium group had a significantly lower adjusted OR (0.70 [95%CI:0.49-0.99]) relative to the reference group. By sex, the adjusted OR in the medium leisure-time PA group was significantly lower relative to the reference group in women (0.50 [95%CI: 0.29-0.85]) but not in men. CONCLUSIONS: Medium level leisure-time PA reduces the risk of recurrent falls in middle-aged and older people, whereas higher level non-leisure-time PA is associated with a higher risk of recurrent falls.

Association between Sarcopenia and Depressive Symptoms in Community-Dwelling People Aged 40 Years and Older.

Several studies have reported an association between sarcopenia and depression. Their results, however, are inconsistent, partly due to small sample sizes and lack of consideration of important confounders. The present study aimed to cross-sectionally examine this association in community-dwelling people in Japan. This study used baseline data from the Yuzawa cohort study (age ≥ 40 years), with the final analysis population comprising 2,466 participants. A self-administered questionnaire was used to elicit information related to sarcopenia, depressive symptoms, demographic characteristics, anthropometrics, disease history, and lifestyles. Sarcopenia was diagnosed using SARC-F, a validated questionnaire including components of Strength, Assistance in walking, Rising from a chair, Climbing stairs, and Falls. Depressive symptoms were assessed using the 11-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). For depressive symptoms, prevalence ratios (PRs) were calculated, and odds ratio (ORs) were obtained using simple and multiple logistic regression analyses. Mean age of participants was 61.7 years (standard deviation = 11.8), and 10.5% and 34.7% had sarcopenia and depressive symptoms, respectively. Sarcopenic individuals had a significantly higher PR (2.00), unadjusted OR (3.67), and adjusted OR (4.96) compared to non-sarcopenic individuals, with an estimated adjusted PR of 2.7. There was a significant dose-dependent association between SARC-F scores and depressive symptoms in sarcopenic individuals (adjusted P for trend = 0.0028). In conclusion, sarcopenia and depressive symptoms were robustly associated in community-dwelling, middle-aged and older people in Japan. However, the direction of this association is unclear, and a future cohort study will be needed to determine causality.

Leisure-Time and Non-Leisure-Time Physical Activities are Dose-Dependently Associated With a Reduced Risk of Dementia in Community-Dwelling People Aged 40-74 Years: The Murakami Cohort Study.

OBJECTIVE: Although physical activity (PA) in late life is considered a preventive factor for dementia, effects of different types of PAs on the development of dementia in early old age are unclear. This study aimed to determine the effect of leisure-time and non-leisure-time PAs on dementia risk in middle-aged and older adults during an 8-year follow-up. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Participants were 13,773 community-dwelling individuals aged 40-74 years who completed the baseline self-administered questionnaire survey of the Murakami cohort study in 2011-2013. METHODS: Main predictors were leisure-time and non-leisure-time (commute, occupational work, and housework) PAs as assessed by MET score (MET-hour/d). The outcome was newly developed dementia determined using a long-term care insurance database. Covariates included demographics, lifestyle, body size, disease history, and PA level. Hazard ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: Mean age of participants was 59.0 (SD 9.3) years. Higher levels of leisure-time PA were associated with lower HRs (adjusted P for trend <.001), with all tertiles having significantly lower HRs (low: 0.71, 95% CI 0.51-0.99; medium: 0.59, 95% CI 0.43-0.81; high: 0.55, 95% CI 0.41-0.75) relative to the reference (zero). Higher quartiles of non-leisure-time PA were associated with lower adjusted HRs for dementia (adjusted P for trend < .001), with the second-fourth quartiles having significantly lower HRs (second: 0.73, 95% CI 0.54-0.98; third: 0.59, 95% CI 0.43-0.81; fourth: 0.55, 95% CI 0.41-0.75) relative to the lowest quartile. These associations were robust regardless of sex and age group. CONCLUSIONS AND IMPLICATIONS: Both leisure-time and non-leisure-time PAs are independently and robustly associated with a reduced risk of dementia.