Association between Circulating Levels of CXCL9 and CXCL10 and Physical Frailty in Older Adults.

INTRODUCTION: Dysregulation of pro-inflammatory chemokines is considered a potential mechanism for the development of age-related medical conditions such as frailty. However, evidence linking circulating chemokines with frailty remains lacking. MATERIALS AND METHODS: We performed a case-control study including 48 cases and 48 controls aged 65-90 years, using the National Center for Geriatrics and Gerontology outpatient registry data. Cases were outpatients with physical frailty and low habitual daily activity. Controls were robust outpatients who performed habitual daily activities. The Japanese version of the Cardiovascular Health Study criteria was used to diagnose physical frailty, and the modified Baecke questionnaire was used to evaluate habitual daily activities. Serum CXCL9 and CXCL10 levels were measured using enzyme-linked immunosorbent assay. RESULTS: The median age (interquartile range) in cases and controls was 78 (73-83) and 76 (72-80) years, with the proportions of men were 47.9% and 43.8%, respectively. In the logistic regression model with adjustment for age, sex, and other confounding factors, the multivariable odds ratios (95% confidence intervals) for the highest versus lowest tertile of CXCL9 and CXCL10 levels were 7.90 (1.61-49.80) and 1.61 (0.42-6.30), respectively. However, we did not observe a linear association between CXCL9 levels and physical frailty components. DISCUSSION/CONCLUSION: Our preliminary data exhibit that circulating CXCL9 levels were positively associated with the odds of physical frailty. However, these findings lack evidence of a dose-response relationship between CXCL9 levels and physical frailty components. Further research with a larger sample size is required to confirm these findings.

Longitudinal Changes in Physical and Cognitive Functions among Participants with and without Rheumatoid Arthritis in Community-Dwelling Middle-Aged and Older Adults.

BACKGROUND: This study evaluated the chronological changes in physical and cognitive functions in middle-aged and older adults with and without rheumatoid arthritis (RA). METHODS: This population-based case-control longitudinal study included individuals aged 40-79 years at baseline who agreed to participate. We identified 42 participants with RA and randomly selected 84 age- and sex-matched controls. Physical function was assessed according to gait speed, grip strength, and skeletal muscle mass. Cognitive function was assessed based on the information, similarities, picture completion, and digit symbol substitution test scores of the Wechsler Adult Intelligence Scale-Revised Short Form. The general linear mixed models comprised the fixed effects of the intercept, case, age, time in years since baseline, and case×time interaction, which were used to examine longitudinal changes in physical and cognitive functions. RESULTS: Regardless of RA status, grip strength decreased and the picture completion score increased in the group aged <65 years, while skeletal muscle mass index and gait speed decreased in the group aged ≥65 years. The interaction of case×follow-up years for grip strength in the group aged ≥65 years was significant (p=0.03). The decline in grip strength in the control group (slope=-0.45) was greater than that in the RA group (slope=-0.19). CONCLUSION: Chronological changes in physical and cognitive functions were comparable between participants with and without RA; however, the decline in grip strength in the control group was greater among older adults with RA.

Relationships of habitual daily alcohol consumption with all-day and time-specific average glucose levels among non-diabetic population samples.

BACKGROUND: Alcohol consumption is a prevalent behavior that is bi-directionally related to the risk of type 2 diabetes. However, the effect of daily alcohol consumption on glucose levels in real-world situations in the general population has not been well elucidated. This study aimed to clarify the relationship between alcohol consumption and all-day and time-specific glucose levels among non-diabetic individuals. METHODS: We investigated 913 non-diabetic males and females, aged 40-69 years, during 2018-2020 from four communities across Japan. The daily alcohol consumption was assessed using a self-report questionnaire. All-day and time-specific average glucose levels were estimated from the interstitial glucose concentrations measured using the Flash glucose monitoring system for a median duration of 13 days. Furthermore, we investigated the association between all-day and time-specific average glucose levels and habitual daily alcohol consumption levels, using never drinkers as the reference, and performed multiple linear regression analyses after adjusting for age, community, and other diabetes risk factors for males and females separately. RESULTS: All-day average glucose levels did not vary according to alcohol consumption categories in both males and females. However, for males, the average glucose levels between 5:00 and 11:00 h and between 11:00 and 17:00 h were higher in moderate and heavy drinkers than in never drinkers, with the difference values of 4.6 and 4.7 mg/dL for moderate drinkers, and 5.7 and 6.8 mg/dL for heavy drinkers. Conversely, the average glucose levels between 17:00 and 24:00 h were lower in male moderate and heavy drinkers and female current drinkers than in never drinkers; the difference values of mean glucose levels were -5.8 for moderate drinkers, and -6.1 mg/dL for heavy drinkers in males and -2.7 mg/dL for female current drinkers. CONCLUSIONS: Alcohol consumption was associated with glucose levels in a time-dependent biphasic pattern.

Predictive validity of the modified Kihon Checklist for the incidence of functional disability among older people: A 3-year cohort study from the JAGES.

AIM: The original Kihon Checklist, validated to predict the incidence of functional disability, has been modified to capture both functional ability (can/cannot) and performing state (do/do not). However, the predictive validity of the modified Kihon Checklist remains unverified. Therefore, this study intends to verify the predictive validity of the modified Kihon Checklist and to clarify whether predictive discrimination differs between the classification method of functional ability and performing state. METHODS: The participants comprised 67 398 older people who responded to the Japan Gerontological Evaluation Study (2016). They were followed for 3.1 years on average. Cox's proportional hazards model with incidence of functional disability as the endpoint was used to calculate the hazard ratio, adjusted for sex and age. The independent variables were judged by two classification methods, functional ability and performing state, using nine indicators based on the modified Kihon Checklist. Additionally, we examined whether the two classification methods produced different C-index estimates. RESULTS: Incidence of functional disability occurred in 6232 participants (9.2%). The adjusted hazard ratio of those to whom the nine indicators applied was significantly higher than that of those to whom they did not. The range of the hazard ratio was 1.50-3.82 for both classification methods. The C-index was slightly higher when the classification was based on performing state than when it was based on on functional ability. CONCLUSIONS: Although predictive discrimination was slightly higher for the performing state than for functional ability, the predictive validity of the modified Kihon Checklist was confirmed for both. Geriatr Gerontol Int 2022; 22: 667-674.

Home-Based Frailty Prevention Program for Older Women Participants of Kayoi-No-Ba during the COVID-19 Pandemic: A Feasibility Study.

This study presents a single-arm intervention that aimed to determine the feasibility of a three-month home-based exercise program to prevent the progression of frailty during COVID-19. We recruited four groups of Kayoi-no-ba, or community salons for frailty prevention, and a total of 69 community-dwelling older women who belonged to one of the Kayoi-no-ba in a preliminary study for a follow-up study. The intervention program was developed on the basis of the 5A approach, and the focus group by the volunteer leaders of Kayoi-no-ba. We adapted the National Center for Geriatrics and Gerontology Home Exercise Program for Older People for 10-min daily home-based exercise. For feasibility outcomes, 91.3% of the participants completed the intervention program, whereas the percentage of exercise performed was 86.5% during the intervention period. For health-related outcomes, the five times sit-to-stand test exhibited significant improvement after the intervention. The results of feasibility outcomes indicate that the program may be feasible due to the high rates of completion and exercise performed. Additionally, improvement was noted for the health indicators of the five times sit-to-stand test, which may help prevent frailty. The feasibility trial has provided the necessary data to design a future-cluster randomized controlled trial.

Chronic obstructive pulmonary disease and the mortality risk in male older adults: Role of socioeconomic factors.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a common disease among older adults, leading to mortality. Although COPD is also associated with socioeconomic factors, little is known about the impact of COPD on mortality accounting for them. We examined the association between COPD and mortality among older male adults, adjusting for socioeconomic factors. METHODS: This study recruited functionally independent male older adults from the Japan Gerontological Evaluation Study. Participants answered self-reported questionnaires mailed in 2013, followed up to 2016. Participants with COPD were screened as those with higher scores than the upper quantile of the modified International Primary Care Airway Group questionnaire. Regarding individual socioeconomic factors, educational attainment, household equivalized income, living arrangements, and social participation was assessed. The Cox proportional hazards model was applied to examine the association between screened COPD and mortality. RESULTS: Data of 6,662 male older adults were analyzed (mean age [standard deviation]: 73.0 [5.8] years). During the observation periods, 394 deaths (5.9%) occurred. Screened COPD was associated with an increased mortality risk, even after adjusting for socioeconomic factors (hazard ratio, 1.56; 95% confidence interval, 1.25-1.94). In the stratified analysis among current smokers, the mortality risk of screened COPD was high in those with lower education, higher income, living alone, and less social participation. CONCLUSIONS: Those with screened COPD had an increased mortality risk, even after adjusting for socioeconomic factors. The risk was higher among those with lower education and less social relationships. Detection and treatment of COPD should be performed considering individual socioeconomic backgrounds.

Impact of social support on severity of depressive symptoms by remission status in patients with rheumatoid arthritis.

OBJECTIVES: We aimed to examine the psychosocial characteristics of patients with rheumatoid arthritis (RA) by remission status and determine the impacts of social support on severity of depressive symptoms. METHODS: We enrolled RA patients aged 40-79 years who visited university hospitals' outpatient clinics. Severity of depressive symptoms (Beck Depression Inventory-II), physical disability (Health Assessment Questionnaire), and support were evaluated. Furthermore, RA disease activity was evaluated by 28-point Disease Activity Score (DAS28) calculation. The independent impacts of instrumental and emotional social support on depressive symptoms by remission status defined as DAS28 score < 2.6 were estimated by multivariable regression analysis. RESULTS: This study included 360 RA patients. In the remission group, emotional support showed a statistically significant negative impact on depressive symptoms, whereas instrumental support had an extremely limited contribution to severity of depressive symptoms. In the non-remission group, instrumental support showed a negative tendency of impact on severity of depressive symptoms, whereas emotional support had a wide range of influence. CONCLUSIONS: Favourable association between emotional support and depressive symptoms is confirmed only among RA patients in remission status. The influence of emotional support in non-remission patients and that of instrumental support regardless of remission status are inconclusive.

Comparison of frailty associated factors between older adult patients with rheumatoid arthritis and community dwellers.

PURPOSE: To determine whether frailty associated factors differ between community dwellers and older adult patients with rheumatoid arthritis (RA). METHODS: We used the cross-sectional data for patients with RA from the RA epidemiological quality-of-life study (n = 210, mean age 71.8 ± 3.7 years) and community dwellers from the Japan Gerontological Evaluation Study (n = 53,255, mean age 71.7 ± 4.0 years). Frailty status was assessed using the Kihon Checklist (KCL), and the primary outcome was frailty (KCL score ≥8 points). Information on predictor variables, including age, sex, marital status, educational level, body mass index (BMI), drinking and smoking status and social participation were obtained from a standardized questionnaire. We employed Poisson regression to calculate the prevalence ratio (PR) of frailty according to its predictors. RESULTS: We found frailty in 37.6% of the patients with RA and 15.7% of the community dwellers. In the multivariate models, BMI and social participation were independently associated with frailty in patients with RA (BMI <18.5: PR, 1.62; 95% confidence interval [CI] 1.09-2.41. BMI ≥25.0: PR, 1.81; 95% CI 1.20-2.71. Active social participation: PR, 0.61; 95% CI 0.42-0.87) and community dwellers (BMI <18.5: PR, 1.77; 95% CI 1.67-1.88. BMI ≥25.0: PR, 1.27; 95% CI 1.22-1.33. Active social participation: PR, 0.46; 95% CI 0.44-0.48). All other predictors were significantly associated with frailty in the community dwellers. CONCLUSION: Maintaining appropriate body weight and participating in social activities are important for preventing frailty in patients with RA as well as community dwellers.

Depression, physical function, and disease activity associated with frailty in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the clinical and psychosocial backgrounds of frailty in rheumatoid arthritis (RA) patients. METHODS: Patients with RA between 40 and 79 years of age who visited university hospitals in an urban area were recruited. Well-validated self-reported questionnaires were used to evaluate patient physical function (Health Assessment Questionnaire, HAQ), depressive symptoms (Beck Depression Inventory-II, BDI-II), and frailty (Kihon Checklist). A 28-point Disease Activity Score (DAS-28) was calculated to evaluate RA disease activity. RESULTS: A total of 375 RA patients, 323 of whom were women, were enrolled (average age: 65.2 ± 9.7 years; average disease duration: 16.6 ± 11.9 years). The prevalence rates of frailty, working-age (40-64 years), young-old (65-74 years), and old-old (≥75 years) patients were 18.5, 28.8, and 36.6%, respectively. Higher age and longer disease duration were associated with frailty. Multivariable logistic regression analysis revealed that HAQ, DAS-28, and BDI-II scores were independently associated with frailty in RA patients. CONCLUSION: Frailty is common, even among working-age RA patients. Physical function, disease activity, and depressive symptoms were independently associated with frailty. A multidisciplinary intervention approach, along with adequate pharmacological therapy, may promote successful aging in patients with RA.

Joint impact of muscle mass and waist circumference on type 2 diabetes in Japanese middle-aged adults: The Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: Although evidence about skeletal muscle mass loss and type 2 diabetes risk has accumulated, little information is available on the combined effect of skeletal muscle mass and abdominal obesity on type 2 diabetes. We examined whether skeletal muscle mass and abdominal obesity were synergistically associated with the prevalence of type 2 diabetes. METHODS: Skeletal muscle mass and waist circumference (WC) were measured in 1515 Japanese aged 40 to 69 years. Relative muscle mass was calculated as percentage of total skeletal muscle mass in body weight (SMM%). Type 2 diabetes was identified as fasting serum glucose ≥7.0 mmol/L (126 mg/dL), nonfasting serum glucose ≥11.1 mmol/L (200 mg/dL), glycosylated hemoglobin ≥ 6.5%, and/or diabetes medication use. RESULTS: The multivariable-adjusted odds ratio (OR) of prevalent diabetes from the lowest to the third quartile of SMM% compared to the highest quartile gradually increased in both sexes. The association between a high WC and prevalent diabetes was similar. The multivariable-adjusted OR (95% confidence intervals) for the prevalence of type 2 diabetes in the low skeletal muscle mass/high WC group was 3.19 (1.78-5.71) for men and 4.46 (2.09-9.51) for women compared with the high skeletal muscle mass/low WC group. The relative excess risk due to interaction was 2.2 (0.5-3.9) in men and 2.8 (0.2-5.3) in women for an excess burden of type 2 diabetes for low skeletal muscle mass and high WC. CONCLUSIONS: Low skeletal muscle mass and abdominal obesity were synergistically associated with presence of type 2 diabetes.

Rhythmic arm swing enhances long latency facilitatory effect of transcranial magnetic stimulation on soleus motoneuron pool excitability.

The purpose of this study was to investigate whether rhythmic arm swing modulates the long latency effect of transcranial magnetic stimulation (TMS) on soleus motoneuron pool excitability. Ten healthy humans rhythmically swung the left arm back and forth in a sitting position. The soleus H-reflex was evoked when the arm was in the backward swing phase. Conditioning TMS was delivered over the motor cortex 8 ms before the soleus H-reflex was evoked. The soleus H-reflex amplitude in both legs was depressed by the rhythmic arm swing. In contrast, rhythmic arm swing enhanced the facilitatory effect of conditioning TMS over the motor cortex contralateral to the arm swing side on the soleus H-reflex ipsilateral to the arm swing side. This finding indicates that rhythmic arm swing enhances some polysynaptic facilitatory pathways from the motor cortex contralateral to the arm swing side to the soleus motoneuron pool ipsilateral to the arm swing side.