Factors Associated with Increased Burden of Caregivers of People with Dementia with Lewy Bodies.

The burden of caregivers of people with dementia with Lewy bodies (DLB) is high; however, factors related to their caregiving burden are not fully clarified. We herein investigated factors associated with increasing caregiver burden for caregivers of people with DLB. To explore factors associated with caregiver burden, a linear regression analysis was conducted using the J-ZBI_8 total score as the dependent variable and a total of 36 factors as independent variables. This analysis included 252 pairs of people with DLB and their caregivers. Caregivers' mean J-ZBI_8 was 8.4, indicating that caregiver burden was generally high. First, we identified 20 factors associated with caregiver burden in univariable analysis. Finally, multivariable analysis found three significant factors: irritability (ß = 0.208, p < 0.001), use of "short stay" or "small-scale, multifunctional home care" (ß = 0.208, p < 0.001), and nighttime behavior (ß = 0.138, p = 0.020) were significantly associated with J-ZBI_8 total scores. Irritability and nighttime behavior were found to be contributing factors to caregiver burden. High caregiver burden among caregivers of people with DLB may result in the use of social services providing overnight stays, but to what extent such services reduce caregiver burden is unknown.

The Effects of Dietary Intervention and Macrophage-Activating Factor Supplementation on Cognitive Function in Elderly Users of Outpatient Rehabilitation.

BACKGROUND: Age, genetic, and environmental factors are noted to contribute to dementia risk. Neuroplasticity, protection from degeneration and cell death, and early intervention are desirable for preventing dementia. The linkage between neurons and microglia has been a research focus. In this study, we examined the effects of dietary modification (a reduction in advanced glycation end products [AGEs]) and macrophage-activating factor (MAF; a macrophage regulator) supplementation on cognitive function in elderly participants undergoing rehabilitation. METHODS: Participants were older than 60 years of age and had been attending a daycare rehabilitation facility for at least three months without cognitive dysfunction, severe anemia, terminal cancer, or neurodegenerative diseases such as Parkinson's disease. The exercise protocol at the rehabilitation facility was not changed during the study period. Forty-three participates were randomly divided into three groups: a control group receiving placebo, a group receiving dietary guidance, and a group receiving dietary guidance and MAF supplementation. The amyloid-ß40/42 ratio, dietary AGE intake, plasma AGE levels, dietary caloric intake, and mild cognitive impairment (MCI) screen test were evaluated. RESULTS: Four participants withdrew from the study. MCI screening scores significantly improved in the MAF supplementation group, especially after 6 months. Dietary modulation was also more effective than placebo at improving cognitive function after 12 months. Only the control group exhibited significantly increased plasma AGEs while the dietary modulation and MAF supplementation groups showed no change in plasma AGEs after 12 months. CONCLUSIONS: MAF supplementation improved cognitive function, especially after 6 months, in elderly people undergoing rehabilitation. Dietary modulation was also effective for improving cognitive function after 12 months compared to that in the control group. It was difficult to supervise meals during dietary guidance at the daycare service. However, simple guidance could show improvements in cognitive function through diet.

Post hoc analysis of the characteristics and treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers and their physicians' awareness of those treatment needs according to the duration after diagnosis of DLB.

OBJECTIVES: To investigate the differences in patient/caregiver characteristics, their treatment needs, and the attending physician's understanding of those treatment needs according to the duration after diagnosis of dementia with Lewy bodies (DLB). METHODS: This was a post hoc analysis of a multicenter, cross-sectional, questionnaire survey study. A total of 263 patient-caregiver pairs were reclassified into two groups according to the median duration after diagnosis of DLB as follows: short (<24 months; S-group) and long (≥24 months; L-group) post-DLB diagnosis duration. Treatment need was defined as the symptom domain that caused the patient or caregiver the most distress. Concordance rates between patient-physician and caregiver-physician were calculated for physicians' understanding of treatment needs. RESULTS: In this analysis, 126 pairs (32 physicians) and 137 pairs (34 physicians) were classified as the S- and L-groups, respectively. Patient and caregiver characteristics were broadly similar between groups (mean age for patients 78.7 ± 6.6 vs. 79.8 ± 6.7, for caregivers 64.7 ± 12.9 vs. 64.9 ± 12.8; number of male/female for patients 61/65 vs. 67/70, for caregivers 34/92 vs. 38/99), but the prevalence of parkinsonism (82.5% vs. 66.7%) and autonomic dysfunction (49.6% vs. 33.3%), severity of parkinsonism (MDS-UPDRS Part III total scores, 29.2 ± 22.6 vs. 18.0 ± 16.4; Part II total score, 14.6 ± 12.0 vs. 7.6 ± 7.9), and caregiver burden (J-ZBI_8 score, 9.1 ± 6.7 vs. 7.5 ± 5.8) were higher in the L-group than the S-group. Regarding treatment needs, the invalid answer rates for patients were 34.9% and 46.8%, and those for caregivers were 28.6% and 34.9% in the S- and L groups, respectively. Patients' treatment needs did not significantly differ (p = 0.056), but S-group patients were more likely to select cognitive impairment (p = 0.045) as their treatment need, whereas L-group patients were more likely to select parkinsonism (p = 0.003). Caregivers' treatment needs significantly differed (p = 0.032) between groups. S-group caregivers were more likely to select cognitive impairment (p = 0.001), whereas L-group caregivers were more likely to select other symptom domains such as parkinsonism (S-group vs. L-group: 10.3% vs. 16.7%), psychiatric symptoms (20.6% vs. 24.6%), sleep-related disorder (4.0% vs. 7.1%), and autonomic dysfunction (4.8% vs. 9.5%). Concordance rates between patient-physician and caregiver-physician were low in both groups. CONCLUSIONS: There were some differences in characteristics according to the duration after diagnosis of DLB. Cognitive dysfunction may be a particular concern for patients and caregivers soon after diagnosis of DLB. Treatment needs of patients and caregivers for parkinsonism, psychiatric symptoms, sleep-related disorder, or autonomic dysfunction were different according to the duration after diagnosis of DLB. Physicians' perception of patients'/caregivers' treatment needs was poor regardless of the duration after diagnosis of DLB. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000041844).

Efficacy of highly bioavailable oral curcumin in asymptomatic or mild COVID-19 patients: a double-blind, randomized, placebo-controlled trial.

INTRODUCTION: Even after the peak of the COVID-19 pandemic, the number of mild cases remains high, requiring continuous control. Curcumin, owing to its anti-inflammatory properties, can suppress vital proliferation and cytokine secretion in animal models. We developed a highly absorbable curcumin, curcuRouge® (cR), which is approximately 100 times more orally bioavailable than conventional curcumin. We evaluated the effect of cR on the inhibition of disease progression in asymptomatic or mildly symptomatic COVID-19 patients. METHODS: This study evaluated the effect of 7-day oral intake of cR (360 mg twice daily). Patients within 5 days of COVID-19 diagnosis were randomly assigned to a placebo or cR group in a double-blind manner. RESULTS: Primary endpoint events [body temperature (BT) ≥ 37.5 °C and saturation of percutaneous oxygen (SpO2) < 96%] were fewer than expected, and the rate of these events was 2.8% in the cR group (2/71) and 6.0% in the placebo group (4/67); hazard ratio (HR) = 0.532, 95% confidence interval (CI) 0.097-2.902. Patients receiving cR tended to take fewer antipyretic medications than those receiving placebo (HR = 0.716, 95% CI 0.374-1.372). Among patients with a normal range of BT at baseline, the BT change rate was significantly (p = 0.014) lower in the cR group (- 0.34%) versus placebo (- 0.01%). CONCLUSION: The relative suppression of event rates and antipyretic medications taken, and significant decrease of subclinical BT support the anti-inflammatory effects of cR in asymptomatic or mildly symptomatic patients with COVID-19. TRIAL REGISTRATION: Japan Registry of Clinical Trials (CRB5200002).

Factors Associated with Quality of Life in Patients with Dementia with Lewy Bodies: Additional Analysis of a Cross-Sectional Study.

Background: Quality of life (QOL) and treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers are important factors to consider when developing treatment strategies. Objective: To investigate factors associated with QOL in patients with DLB, and to examine factors associated with activities of daily living (ADL) if ADL was associated with QOL. Methods: We previously conducted a questionnaire survey study to investigate the treatment needs of patients with DLB and their caregivers. This pre-specified additional analysis evaluated the Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form-8 for QOL, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II total score for ADL. Results: In total, 231 patient- caregiver pairs and 38 physicians were included. Multivariable analysis of QOL showed that the MDS-UPDRS Part II total score (standard regression coefficient [ß], - 0.432) was associated with the PCS, and presence of depression (ß, - 0.330) was associated with the MCS. The severity of postural instability/gait disorder (PIGD) (ß, 0.337) and rigidity (ß, 0.266), presence of hallucinations (ß, 0.165), male sex (ß, 0.157), and use of "short stay" or "small-scale, multifunctional home care" (ß, 0.156) were associated with worsened ADL. Conclusions: In patients with DLB, QOL was negatively impacted by severity of ADL disability and depression, and ADL was negatively impacted by severity of PIGD and rigidity, hallucinations, male sex, and use of "short stay" or "small-scale, multifunctional home care."

Effect of degalactosylated bovine glycoprotein formulations MAF and M сapsules on lymphopenia and clinical outcomes in hospitalized COVID-19 patients: a randomized clinical trial.

BACKGROUND: Targeting mucosal immunity of the gut, which is known to provide antigen processing, while avoiding excessive or unnecessary inflammation, was tested as a way to modulate COVID-19 severity. METHODS: Randomized open-label trial in 204 adults hospitalized with non-critical COVID-19 who received for 14 days in addition to standard of care (SOC) degalactosylated bovine glycoproteins formulations of either MAF capsules (MAF group) or M capsules (M group) or SOC only (control group). RESULTS: Median recovery time when patients did not require supplemental oxygen was 6 days in both study groups compared to 9 days in the control (MAF vs. control; P = 0.020 and M vs. control; P = 0.004). A greater reduction in mortality was seen in the MAF group compared to the control by day 14 (8.3% vs. 1.6%; P = 0.121) and by day 29 (15.3% vs. 3.2%; P = 0.020), and similarly in the M group by day 14 (8.3% vs. 2.9%; P = 0.276) and by day 29 (15.3% vs. 2.9%; P = 0.017). The proportion of those who had baseline absolute lymphocyte count (ALC) lower than 0.8 × 109/L was 13/63 (20.6%), 17/69 (24.6%), and 18/72 (25.0%) of patients in MAF, M, and control group respectively. Day 29 mortality among these lymphopenic patients was three times higher than for the intent-to-treat population (21% vs. 7%) and consisted in above subgroups: 2/13 (15%), 2/17 (12%), and 6/18 (33%) of patients. The decreased mortality in both study subgroups correlated with greater ALC restoration above 0.8 × 109/L level seen on day 14 in 91% (11/12) and 87.5% (14/16) of survivors in MAF and M subgroups respectively compared to 53.3% (8/15) of survivors in control subgroup. Incidences of any ALC decrease below the baseline level on day 14 occurred in 25.4% of patients in the MAF group and 29.0% of patients in the M group compared to 45.8% in control and ALC depletion by ≥ 50% from the baseline level consisted of 7.9%, 5.8%, and 15.3% of cases in these groups respectively. CONCLUSION: This study showed that both study agents prevented ALC depletion and accelerated its restoration, which is believed to be one of the mechanisms of improved crucial clinical outcomes in hospitalized COVID-19 patients. TRIAL REGISTRATION: The trial was registered after the trial start in ClinicalTrials.gov NCT04762628, registered 21/02/2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT04762628 .

Five percent weight loss is a significant 1-year predictor and an optimal 5-year cut-off for reducing the number of obesity-related cardiovascular disease risk components: the Japan Obesity and Metabolic Syndrome Study.

Objective: This study aimed to identify the amount of weight loss needed in patients with obesity to improve metabolic syndrome (MetS), a risk factor for cardiovascular disease (CVD), over a long period of time. Methods: A total of 576 patients with obesity were enrolled in this study. Effects of continuous physician-supervised weight loss on the cumulative MetS components excluding abdominal circumference (defined as obesity-related CVD risk score) were investigated during a 5-year follow-up period. The extent of weight loss required to reduce the obesity-related CVD risk components was assessed using receiver operating characteristic (ROC) curve analyses. Results: Of the 576 participants, 266 completed 5-year follow-up, with 39.1% and 24.1% of them achieving ≥5.0% and ≥7.5% weight loss at the 5-year follow-up, respectively. The area under the ROC curve for reducing the obesity-related CVD risk components was 0.719 [0.662-0.777] at 1 year and 0.694 [0.613-0.775] at 5 years. The optimal cut-off value for weight loss was 5.0% (0.66 sensitivity and 0.69 specificity) and the value with 0.80 specificity was 7.5% (0.45 sensitivity) at 5 years. Greater reductions in weight were associated with greater improvements in the obesity-related CVD risk score at all follow-up periods (P-trend <0.001). Obesity-related CVD risk score was significantly improved by 5.0-7.5% and ≥7.5% weight loss at 1 year (P = 0.029 and P < 0.001, respectively) and ≥7.5% weight loss at 5 years (P = 0.034). Conclusions: A weight loss of ≥5.0% at 1 year and ≥7.5% at 5 years could reduce the number of obesity-related CVD risk components in patients with obesity.

Impact of coronavirus disease 2019 on medical practice in endocrine and metabolic diseases in Japan: a nationwide surveillance study conducted by the Japan Endocrine Society.

We investigated the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the management of endocrine and metabolic disorders in Japan. We conducted a cross-sectional nationwide questionnaire survey targeting board-certified endocrinologists under the auspices of the Japan Endocrine Society. The questionnaire consisted of multiple-choice questions and open-ended responses. Out of approximately 2,700 specialists, 528 (19.5%) opted to participate, suggesting a high level of interest in COVID-19 management among endocrinologists. The study found that almost half of participants had encountered cases of endocrine and metabolic disorders following COVID-19 infection or vaccination. Conditions related to thyroid diseases, glucose metabolism disorders/diabetes, and hypothalamic-pituitary disorders were particularly prevalent. Diabetes and obesity were identified as having high rates of severe cases or fatalities due to COVID-19. The study also highlighted challenges in routine diagnosis and treatment, emphasizing the potential benefits of combining remote consultations with in-person visits to optimize the frequency of examinations and check-ups during infectious disease outbreak which disrupts access to healthcare providers. The insights obtained from this survey are expected to contribute to ensuring appropriate healthcare provision for patients with endocrine and metabolic disorders by using flexible consultation formats, particularly even in the conditions where medical access may be limited due to future outbreaks of emerging or re-emerging infectious diseases.

Differences in the treatment needs of patients with dementia with Lewy bodies and their caregivers and differences in their physicians' awareness of those treatment needs according to the clinical department visited by the patients: a subanalysis of an observational survey study.

BACKGROUND: We investigated whether the treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers, along with their attending physicians' perception of those treatment needs, differ according to the clinical department visited by the patients. METHODS: This was a subanalysis of a multicenter, cross-sectional, observational survey study. Data from the main study were classified according to the clinical department visited by the patient: psychiatric group (P-group), geriatric internal medicine group (G-group), and neurology group (N-group). The treatment needs of patients and caregivers were defined as "the symptom that causes them the most distress", and the frequency of each answer was tabulated. RESULTS: This subanalysis included 134, 65, and 49 patient-caregiver pairs in the P-, G-, and N-groups, respectively. Statistically significant differences in patient background characteristics such as patient age; initial symptom domains; use of cholinesterase inhibitors, levodopa, antipsychotics, and Yokukansan; and total scores of the Mini-Mental State Examination, Neuropsychiatric Inventory-12, and Movement Disorder Society-Unified Parkinson's Disease Rating Scale Parts II and III were shown among the three subgroups. While there were no differences in patients' treatment needs among the subgroups, residual analysis showed that in the N-group, parkinsonism was more of a problem than other symptom domains (p = 0.001). There were significant differences in caregivers' treatment needs among the three subgroups (p < 0.001). The patient-physician concordance rates for the symptom domains that caused patients the most distress were: P-group, 42.9% (kappa coefficient [κ] = 0.264); G-group, 33.3% (κ = 0.135), and N-group, 67.6% (κ = 0.484). The caregiver-physician concordance rates for the symptom domains that caused the caregivers the most distress were: P-group, 54.8% (κ = 0.351), G-group, 50.0% (κ = 0.244), and N-group, 47.4% (κ = 0.170). CONCLUSION: This subanalysis revealed differences in the treatment needs of patients with DLB and their caregivers according to the clinical department they attended. There might be a lack of awareness of those treatment needs by the attending physicians, regardless of their specialty. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000041844.

Age-wise examination of the association of obesity based on body mass index and waist circumference with metabolic diseases in comprehensive health checkup participants.

Aim: Body mass index and waist circumference are used for obesity diagnosis and screening of visceral fat; however, their evidence in older adults is insufficient. This study investigated the age-specific association of body mass index and waist circumference with metabolic diseases, assessing their applicability as diagnostic criteria for individuals aged ≥65 years. Methods: Analysis included 46,324 individuals aged ≥18 years, categorized into five age groups: 18-44, 45-54, 55-64, 65-74, and ≥75 years. Logistic regression analyses identified associations between obesity and metabolic diseases, stratified by age and sex. Results: Men with obesity based on body mass index had a significantly high risk of hypertension, diabetes mellitus, and dyslipidemia across all age groups (all, p < 0.05). Obesity based on waist circumference was significantly positively associated with all metabolic diseases (all, p < 0.05). Women with obesity based on body mass index and waist circumference had a significantly high risk of all metabolic diseases across all age groups (all, p < 0.05), except for diabetes mellitus in individuals aged ≥75 years. Conclusions: Participants with obesity based on body mass index and waist circumference exhibited a high risk of hypertension, diabetes mellitus, and dyslipidemia among those aged 18-74 years and men aged ≥75 years. This study contributes to the early prevention and control of metabolic diseases.

Imeglimin Exhibits Novel Anti-Inflammatory Effects on High-Glucose-Stimulated Mouse Microglia through ULK1-Mediated Suppression of the TXNIP-NLRP3 Axis.

Type 2 diabetes mellitus (T2DM) is an epidemiological risk factor for dementia and has been implicated in multifactorial pathologies, including neuroinflammation. In the present study, we aimed to elucidate the potential anti-inflammatory effects of imeglimin, a novel antidiabetic agent, on high-glucose (HG)-stimulated microglia. Mouse microglial BV2 cells were stimulated with HG in the presence or absence of imeglimin. We examined the effects of imeglimin on the levels of proinflammatory cytokines, intracellular reactive oxygen species (ROS), mitochondrial integrity, and components related to the inflammasome or autophagy pathways in these cells. Our results showed that imeglimin suppressed the HG-induced production of interleukin-1beta (IL-1ß) by reducing the intracellular ROS levels, ameliorating mitochondrial dysfunction, and inhibiting the activation of the thioredoxin-interacting protein (TXNIP)-NOD-like receptor family pyrin domain containing 3 (NLRP3) axis. Moreover, the inhibitory effects of imeglimin on the TXNIP-NLRP3 axis depended on the imeglimin-induced activation of ULK1, which also exhibited novel anti-inflammatory effects without autophagy induction. These findings suggest that imeglimin exerted novel suppressive effects on HG-stimulated microglia through the ULK1-TXNIP-NLRP3 axis, and may, thereby, contribute to the development of innovative strategies to prevent T2DM-associated cognitive impairment.

Eating problems in people with dementia with Lewy bodies: Associations with various symptoms and the physician's understanding.

OBJECTIVES: Eating problems frequently occur in people with dementia with Lewy bodies (DLB), but few studies have investigated the clinical background of this phenomenon. This study examined the relationship between eating problems and various symptoms of DLB and the relation between the treatment needs for DLB people with eating problems and the understanding of their eating problems by caregivers and physicians. DESIGN, MEASUREMENTS, AND PARTICIPANTS: This was a subanalysis of a cross-sectional, questionnaire-based survey study. Two hundred sixty-one subjects with DLB were divided into subjects with or without eating problems. Logistic or linear regression analysis was used to investigate the factors influencing eating problems. The treatment needs of DLB people for their eating problems and the understanding of these needs by caregivers and physicians were calculated as participant-caregiver and participant-physician kappa coefficient. RESULTS: Of the 261 participants, 27% suffered from eating problems. The presence of eating problems in participants with DLB was related to depression (p = 0.01, OR : 2.19, 95% CI: 1.23-3.91) and apathy (p = 0.01, OR 2.15, 95% CI: 1.20-3.87), while the worsening of eating problems was related to dysphagia (ß = 0.24, p = 0.03), apathy (ß = 0.23, p = 0.05), and nighttime behavior (ß = 0.24, p = 0.04). The participant-physician kappa coefficient for physician understanding of constipation, weight loss, dysphagia, weight gain, and increase in appetite was significantly lower than the corresponding participant-caregiver kappa coefficient (p-value of five symptoms < 0.01). CONCLUSIONS: Physicians need to pay more attention to eating problems and their neuropsychiatric background in the long-term support and management of DLB subjects.

Impact of smoking initiation age on nicotine dependency and cardiovascular risk factors: a retrospective cohort study in Japan.

Aims: Initiating smoking in early adolescence results in challenges with smoking cessation and is associated with high risk of cardiovascular disease. Recently, the initiation of smoking has transitioned from adolescence to young adulthood. However, there are few reports on the impact of initiating smoking at a later age. This study investigated the impact of the age of smoking initiation on nicotine dependency, smoking cessation rates, and cardiovascular risk factors, using a cut-off point of 20 years, within the Japanese population. Methods and results: This retrospective cohort study encompassed 1382 smokers who sought smoking cessation treatment at Kyoto Medical Centre Hospital between 2007 and 2019. Clinical indicators were evaluated by adjusting for age at the time of hospital visit and sex. The smoking cessation rate was further adjusted for treatment medication. The group with a smoking initiation age of <20 years reported a higher number of cigarettes/day (P = 0.002), higher respiratory carbon monoxide levels (P < 0.001), a higher Fagerström Test for Nicotine Dependence (FTND) score (P < 0.001), and a higher Self-rating Depression Scale score (P = 0.014). They also reported lower diastolic blood pressure (P = 0.020) and a lower successful smoking cessation rate [odds ratio: 0.736, 95% confidence interval (0.569, 0.951)] than the group with a smoking initiation age of ≥20 years. When smokers were divided into four groups based on the age they started smoking, the FTND score for those who started at 20-21 years was significantly higher than the score for those who started at 22 years or older. Conclusion: In young adulthood, initiating smoking later (beyond 20 years old) was associated with lower nicotine dependency and fewer depressive tendencies, as well as a higher success rate in smoking cessation among Japanese smokers. The results might suggest that raising the legal smoking initiation age from 20 to 22 years old or older could be effective in reducing nicotine dependency in smokers.

A body shape index is useful for BMI-independently identifying Japanese patients with obesity at high risk of cardiovascular disease.

BACKGROUND AND AIM: Obesity with multiple metabolic syndrome (MetS) components and/or with skeletal muscle loss is at high risk of cardiovascular disease (CVD). This study aimed to clarify the utility of anthropometric indices for identifying patients with overweight/obese at high risk of CVD based on having multiple MetS components and skeletal muscle loss. METHODS & RESULTS: This cross-sectional study included 188 overweight/obese (BMI ≥25 kg/m2, Japanese patients; 73 men and 115 women, mean age 55.7 years). First, we performed correlation analysis among seven anthropometric indices, body mass index (BMI), percentage body fat, waist circumference (WC), waist-to-hip ratio (WHpR), waist-to-height ratio (WHtR), a body shape index (ABSI), and body roundness index (BRI). Unlike the others, only ABSI was not correlated with BMI. Then, we conducted receiver operating characteristic analysis to assess the predictive abilities of anthropometric indices for having multiple MetS components. WC, WHpR, WHtR, BRI, and ABSI had significant predictive abilities for having multiple MetS components. Furthermore, multiple regression analysis showed that only ABSI had significantly negative associations with all sarcopenia-evaluated indices (skeletal muscle mass index [SMI], handgrip strength [HGS], and muscle quality [MQ]), irrespective of sex and age. Finally, an analysis of covariance showed that the high ABSI group had significantly lower SMI and HGS than the low ABSI group, irrespective of sex and age. CONCLUSION: ABSI was deemed useful for BMI-independently identifying Japanese patients with overweight/obese at high risk of CVD based on having multiple MetS components and skeletal muscle loss. Clinical trials (the unique trial number and the name of the registry) ID: UMIN000042726.

Understanding impacts of COVID-19 restrictions on glycemic control for patients with diabetes in Japan.

Objective: This study evaluated the changes in the status of glycemic control and lipid management in patients with diabetes under COVID-19 containment restrictions, in order to better understand the impacts of events causing lifestyle restrictions. Patient characteristics with worsened glycemic control were also assessed. Methods: We conducted a retrospective and observational cohort study using the electronic health records of 5,169 patients with diabetes seeking medical care in two healthcare centers. Laboratory test results including glycemic and lipid goal attainment rates were compared between pre-COVID-19 (January to December 2019) and the first wave of COVID-19 (February to June 2020). Multiple regression models were used to evaluate the association between glycated hemoglobin (HbA1c) at baseline and during the first wave with covariates such as concomitant medications and comorbidities. Results: The HbA1c goal achievement rate improved significantly from 39.0% to 43.1% (p < 0.0001) overall, and more patients reached their glycemic target during COVID-19 restrictions. No significant changes were observed in lipid control. An indexed change in HbA1c level showed that glycemic control improved in 2,230 patients and worsened in 1,619 patients. Administration of insulin, GLP-1, and sulfonylureas were each identified as factors correlated with elevated HbA1c, during the first wave of COVID-19. Conclusion: Although the glycemic control in patients with diabetes improved overall under COVID-19 restrictions, those on insulin, GLP-1, or sulfonylureas worsened. These findings suggest the need to better understand what drives differences in glycemic control to better support people with diabetes for future epidemiological outbreaks. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01302-5.

Comparative efficacy and safety of adjunctive drugs to levodopa for fluctuating Parkinson's disease - network meta-analysis.

It remains unclear which adjunctive drug for Parkinson's disease (PD) in combination with levodopa is more effective, tolerable, and safe. We aimed to compare the efficacy, tolerability, and safety among anti-PD drugs from several classes in patients with fluctuating PD who received levodopa through network meta-analysis (NMA). Twelve anti-PD drugs belonging to 4 different drug classes (dopamine agonists, monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, and an adenosine A2A receptor antagonist) were selected. We systematically searched PubMed, Embase, and the Cochrane Library for eligible randomized controlled trials (RCTs) comparing placebo with anti-PD drug or among anti-PD drugs in patients with PD who experienced motor fluctuations or wearing-off and received levodopa. We included 54 RCTs in the analysis. The NMA was performed under a frequentist framework using a random-effects model. The efficacy outcome was change in daily off-time, and the tolerability outcome was discontinuation due to all causes. Safety outcomes included discontinuation due to adverse events (AEs) and the incidence of AEs, dyskinesia, hallucination, and orthostatic hypotension. According to the surface under the cumulative ranking curve (SUCRA) in the NMA, ropinirole transdermal patch (SUCRA, 0.861) ranked the highest in efficacy, followed by pramipexole (0.762), ropinirole extended release (ER) (0.750), and safinamide (0.691). In terms of tolerability, ropinirole (0.954) ranked the highest, followed by pramipexole (0.857), safinamide (0.717), and ropinirole ER (0.708). Each anti-PD drug had different SUCRA ranking profiles for the safety outcomes. These findings suggest that ropinirole, pramipexole, and safinamide are well-balanced anti-PD drugs that satisfy both efficacy and tolerability outcomes.

Differences in metabolic characteristics between Metabolically Healthy Obesity (MHO) and Metabolically Unhealthy Obesity (MUO) in weight reduction therapy.

Metabolically Healthy Obesity (MHO) is generally recognized as the absence of any metabolic disorders and cardiovascular diseases, including type 2 diabetes, dyslipidemia, and hypertension, in obese individuals; however, it is not clearly defined. Therefore, the present study investigated differences in metabolic characteristics between individuals with MHO and Metabolically Unhealthy Obesity (MUO) during weight reduction therapy. The key factors defining MHO and the importance of weight reduction therapy for MHO were also examined. Cohort data from the Japan Obesity and Metabolic Syndrome (JOMS) study were analyzed. Subjects were divided into the MHO (n = 25) and MUO (n = 120) groups. Prior to weight reduction therapy, serum adiponectin levels were significantly higher in the MHO group than in the MUO group. Serum adiponectin levels also negatively correlated with the area of subcutaneous adipose tissue (SAT) and Homeostasis model assessment (HOMA)-R in the MHO group, but not in the MUO group. Collectively, the present results suggest the importance of adiponectin for maintaining metabolic homeostasis in the MHO group. On the other hand, no significant differences were observed in inflammatory markers between the MHO and MUO groups, suggesting the presence of chronic inflammation in both groups. Furthermore, a positive correlation was noted between changes in serum cystatin C levels and waist circumference in the MHO group, which indicated that despite the absence of metabolic disorders, the MHO group exhibited anti-inflammatory responses during weight reduction therapy. These results underscore the significance of weight reduction even for individuals with MHO.

Novel pathological implications of serum uric acid with cardiovascular disease risk in obesity.

AIMS: This cohort study intended to elucidate the association between serum uric acid (SUA) levels and cardiovascular disease events in Japanese patients with obesity. METHODS: Altogether, 450 obese Japanese outpatients were enrolled in a multicenter prospective cohort Japan, the Japan Obesity and Metabolic Syndrome Study. Primary analysis regarding the measurements of cardiovascular risk factors, including SUA levels, and the occurrence of macrovascular complications was based on following the participants over a 5-year period. RESULTS: Of the eligible patients, 335 (74.4%) were followed into the fifth year. During the study period, 15 coronary heart disease, 7 stroke, and 6 arteriosclerosis obliterans events occurred in 39 patients. The CVD incidence rate was 15.8 per 1000 person-years. In the analysis of adjusted models for traditional risk factors, hyperuricemia was a significant factor for the incidence of CVD events, especially in female obese patients. Additionally, we estimated the association between SUA levels and CVD events using cubic spline models, which showed a U-shaped association in both male and female patients. CONCLUSIONS: SUA is an effective predictor of CVD events in female obese patients and a risk factor for CVD incident in obese patients.

Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP-NLRP3 Axis.

Type 2 diabetes mellitus is associated with an increased risk of dementia, potentially through multifactorial pathologies, including neuroinflammation. Therefore, there is a need to identify novel agents that can suppress neuroinflammation and prevent cognitive impairment in diabetes. In the present study, we demonstrated that a high-glucose (HG) environment elevates the intracellular reactive oxygen species (ROS) levels and triggers inflammatory responses in the mouse microglial cell line BV-2. We further found that thioredoxin-interacting protein (TXNIP), a ROS-responsive positive regulator of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, was also upregulated, followed by NLRP3 inflammasome activation and subsequent interleukin-1beta (IL-1ß) production in these cells. Conversely, caspase-1 was not significantly activated, suggesting the involvement of noncanonical pathways in these inflammatory responses. Moreover, our results demonstrated that taxifolin, a natural flavonoid with antioxidant and radical scavenging activities, suppressed IL-1ß production by reducing the intracellular ROS levels and inhibiting the activation of the TXNIP-NLRP3 axis. These findings suggest the novel anti-inflammatory effects of taxifolin on microglia in an HG environment, which could help develop novel strategies for suppressing neuroinflammation in diabetes.