Decline of instrumental activities of daily living is a risk factor for nutritional deterioration in older adults: a prospective cohort study.

BACKGROUND: The association between functional capacity and the subsequent risk of nutritional deterioration is yet to be understood. The purpose of this study was to elucidate the relationship between functional capacity, comprising instrumental activities of daily living (IADL), intellectual activity, and social function, and future decline in nutritional status. METHODS: The current study is a two-year prospective cohort study. A total of 468 community-dwelling older adults without nutritional risks were enrolled. We used the Mini Nutritional Assessment Screening Form. Functional capacity, including IADL, intellectual activity, and social function, was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline. The nutritional status was reassessed at a 2-year follow-up. Risk ratios (RR) of functional capacity for the incidence of nutritional decline were estimated. RESULTS: Low functional capacity was significantly associated with future deterioration of nutritional status (RR 1.12, 95% confidence interval [CI] 1.02-1.25). Of the subdomains of functional capacity, IADL decline (adjusted RR 2.21, 95% CI 1.18-4.13) was an independent risk factor for the incidence of nutritional risk. Intellectual and social activities were not significant. CONCLUSION: Decline in functional capacity, especially IADL, is a risk factor for future deterioration in nutritional status. Further studies are required to elucidate the effect of interventions for IADL decline on maintaining nutritional status in older adults.

Association Between Timed Up-and-Go Test and Future Changes in the Frailty Status in a Longitudinal Study of Japanese Community-Dwelling Older Adults.

Purpose: This study aimed to evaluate the relationship between timed up-and-go (TUG) test time and changes in frailty status in a longitudinal cohort study of rural Japanese older adults. Patients and Methods: This prospective cohort study included 545 community-dwelling older adults. Initial and 2-year follow-up surveys were conducted. We compared the number of the Japanese version of the Cardiovascular Health Study components during the follow-up period and classified the participants into three groups: the favorable change, unchanged as prefrail, and unfavorable change groups. Associations between changes in frailty status and TUG time in the first survey were examined. The predictive ability of the TUG test was determined using the receiver operating characteristic (ROC) curve. Results: The favorable change group comprised 315 individuals (57.8%), the unchanged as prefrail group 105 (19.2%), and the unfavorable change group 125 (22.9%). TUG time was associated with the favorable and unfavorable changes after adjustment for covariates (OR 0.79, 95% CI 0.68-0.92, P=0.001 and OR 1.27, 95% CI 1.09-1.49, P=0.002). The ROC curve of TUG time as a predictor of unfavorable changes showed an area under the curve of 0.59. A cut-off point of TUG was calculated as 6.3 s with 49.6% sensitivity and 66.0% specificity. Conclusion: TUG time in the first survey was significantly associated with changes in frailty status 2 years later. However, its predictive value as a stand-alone test is limited and has the potential to predict future changes in the frailty status in older adults in combination with other tests.

[Association between physical activity and apathy among community-dwelling older adults].

AIM: To determine the association between physical activity and apathy in community-dwelling older adults. METHODS: This was a cross-sectional study. Apathy was assessed using three sub-items from the Geriatric Depression Scale 15 (GDS-3A) on apathy syndrome. Physical activity was measured using a wrist-worn accelerometer. Exercise intensity was classified as sedentary behavior, light-intensity physical activity, or moderate-to-vigorous-intensity physical activity. A logistic regression analysis was used to examine the association between apathy and physical activity for each exercise intensity level. RESULTS: Seven-hundred and eighty-four participants (age 72.7±5.9 years old) were included. Of those, 103 (13.1%) were in the apathy group. A multivariate analysis adjusted for demographic factors revealed that decreased total physical activity (odds ratio [OR] = 0.947, 95% confidence interval [CI] = 0.912-0.984, p = 0.005), light-intensity physical activity (OR = 0.941, 95% CI = 0.899-0.985, p = 0.009), and increased sedentary behavior (OR = 1.002, 95% CI = 1.001-1.003, p = 0.007) were associated with a greater OR of apathy, although moderate-to-vigorous-intensity physical activity was not significant (OR = 0.916, 95% CI = 1.826-1.017, p = 0.100). However, in the final model adjusted for depressive symptoms and functional factors, the association was not found to be significant, and a strong association was observed between depressive symptoms and apathy. CONCLUSION: Physical activity in older adults with apathy symptoms was decreased in this study. However, the associations seemed to be strongly affected by depressive symptoms, and physical activity was not independently associated with apathy.

Impact of quality of life on future frailty status of rural Japanese community-dwelling older adults.

OBJECTIVES: We aimed to clarify the factors that contribute to the improvement or progression of frailty in rural Japanese community-dwelling older adults. METHODS: Of the 840 participants in the cohort study of independent older adults aged 65 years and older living in the Tamba-Sasayama area of Hyogo Prefecture (FESTA study) from September 2016 to December 2017, 551 participated in the 2-year follow-up survey from September 2018 to December 2019. METHODS: We evaluated clinical background, physical and cognitive function, total physical activity, daily protein intake, quality of life (QOL) using the WHOQOL-BREF (WHOQOL-26), and frailty status diagnosed using the Japanese version of the Cardiovascular Health Study. We compared the frailty status at the initial and follow-up examinations and classified the participants into three groups: improvement, unchanged, and worsening. Each parameter was compared among the three groups and the factors contributing to the improvement or worsening of frailty status were analyzed using a modified Poisson regression analysis. RESULTS: The median age at the first survey was 72 years (range: 68-76); 190 men and 361 women were enrolled. The improvement group consisted of individuals with a change in status from frail to prefrail/robust and from prefrail to robust (n = 114); the worsening group consisted of individuals with a change in status from robust to prefrail/frail and from prefrail to frail (n = 92). The physical domain of QOL was significantly associated with an improvement in frailty status independent of the frailty status at baseline. Contrastingly, any domains of QOL were not significantly associated with a worsening frailty status. CONCLUSIONS: This study demonstrated for the first time that QOL has a significant impact on the future improvement and progression of frailty status and that QOL conditions and frailty status affect older adults bidirectionally.

Relationship between Rate of Force Development of Tongue Pressure and Physical Performance.

In the assessment of skeletal muscle strength, rate of force development (RFD) is clinically identified as a functional index that reflects the effects of aging, but there are few reports on RFD of the tongue. The purpose of this study was to examine the relationship between RFD of tongue pressure (RFD-TP) and oral and whole-body physical performance in older adults, and to clarify its characteristics. We enrolled adults aged ≥65 years with pathological occlusal contact in premolar and molar regions of teeth in the Tamba-Sasayama area, Japan, from 2017 to 2018. Maximum tongue pressure (MTP) and the speed to reach the maximum tongue pressure (RFD-TP) were evaluated as measures of tongue function. Oral functions related to objective measures of tongue function, such as repetitive saliva swallowing test, oral diadochokinesis, and physical status or performance, such as mini mental state examination, body mass index, skeletal mass index, knee extension force, one-leg standing time, grip strength, walking speed, timed up-and-go test, and five-time chair stand speed was evaluated. No significant correlation was found between MTP and age, but RFD-TP had a significant negative correlation with age. Neither RFD-TP nor MTP showed a significant correlation with oral function. RFD-TP was associated with physical performance, such as knee extension force and one-leg standing time. RFD-TP is more sensitive to aging than MTP. In addition, RFD-TP is related to physical performance and may be useful for the early detection of frailty.

Estimation of Muscle Mass Using Creatinine/Cystatin C Ratio in Japanese Community-Dwelling Older People.

OBJECTIVES: Sarcopenia is defined as a combination of low skeletal muscle mass index (SMI), weak muscle strength, and reduced physical function. Recently, many studies have reported that the creatinine/cystatin C ratio (Cr/CysC) is useful for evaluating muscle mass. We designed a cross-sectional study with separate model development and validation groups to develop a prediction equation to estimate bioimpedance analysis (BIA)-measured SMI with Cr/CysC. DESIGN: The current study was a retrospective cross-sectional study. SETTING AND PARTICIPANTS: The model development group included 908 subjects (288 men and 620 women) from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, and the validation group included 263 subjects (112 men and 151 women) from participants in the medical checkup program at the Anti-Aging Center in Ehime Prefecture. MEASURES: Multivariate regression analysis indicated that age, hemoglobin (Hb), body weight (BW), and Cr/CysC were independently associated with SMI in both men and women. The SMI prediction equation was developed as follows: Men:4.17-0.012×Age+1.24×(Cr/CysC)-0.0513×Hb+0.0598×BW Women:3.55-0.00765×Age+0.852×(Cr/CysC)-0.0627×Hb+0.0614×BW RESULTS: The SMI prediction equation was applied to the validation group and strong correlations were observed between the BIA-measured and predicted SMI (pSMI) in men and women. According to the receiver operator characteristic (ROC) analysis, the areas under the curve were 0.93 (specificity 89.0%, sensitivity 87.2%) among men and 0.88 (specificity 83.6%, sensitivity 79.6%) among women for using pSMI to identify low SMI in the model development group. The pSMI also indicated high accuracy in ROC analysis for low SMI in the validation group. The Bland-Altman plot regression showed good agreement between BIA-measured and pSMI. CONCLUSIONS AND IMPLICATIONS: Our new prediction equation to estimate SMI is easy to calculate in daily clinical practice and would be useful for diagnosing sarcopenia.

Low back pain is closely associated with frailty but not with sarcopenia: Cross-sectional study of rural Japanese community-dwelling older adults.

AIM: We speculated that low back pain, which is the most common ailment in older adults, is associated with frailty and/or sarcopenia and contributes to the progression of either condition. Our objective was to evaluate the relationship between low back pain, sarcopenia and frailty in rural Japanese community-dwelling older adults. METHODS: We recruited 730 participants aged ≥65 years who underwent a comprehensive health examination between November 2016 and December 2018. The Oswestry Disability Index (ODI) was used to assess low back pain quantitatively, and scores were compared for the frail groups determined by the Japanese version of Cardiovascular Health Study, and the sarcopenia groups as determined by the Asian Working Group for Sarcopenia 2019. RESULTS: Among 730 participants, the prevalence of low back pain was 57.8%. There were significant differences in the ODI scores between the robust, prefrail and frail groups (P < 0.001). In contrast, there were no significant differences in the ODI scores among the robust, low appendicular skeletal muscle and sarcopenia groups. Logistic regression analysis showed that the prevalence of low back pain and the ODI scores were significantly associated with frailty after adjustment for age, sex and body mass index (odds ratio 3.41, 95% confidence interval 1.39-8.39, P = 0.008, and odds ratio 1.06, 95% confidence interval 1.04-1.09, P < 0.001, respectively). CONCLUSIONS: To the best of our knowledge, this study is the first to show the close association between low back pain and frailty, and suggests that not only the decline in physical function but also neuropsychiatric factors, including chronic pain, constitute a vicious cycle of frailty in community-dwelling older adults. Geriatr Gerontol Int 2021; 21: 54-59.

Relationships between cystatin C- and creatinine-based eGFR in Japanese rural community- dwelling older adults with sarcopenia.

BACKGROUND: Sarcopenia is prevalent in patients with chronic kidney disease (CKD). The indices of physical function, such as grip power and gait speed, decreased according to the decline in the estimated glomerular filtration rate (eGFR). METHODS: We examined the relationships between cystatin C-based GFR (eGFRcys), creatinine-based GFR (eGFRcre), their ratio (eGFRcys/eGFRcre) and sarcopenia in community-dwelling older adults in Japan. This cross-sectional study included 302 men aged 73.9 ± 6.2 years and 647 women aged 72.9 ± 5.8 years from a rural area in Hyogo Prefecture, Japan. eGFRcys and eGFRcre were simultaneously measured, and sarcopenia based on the Asia Working Group for Sarcopenia (AWGS) 2019 criteria was evaluated. RESULTS: eGFRcys and the eGFRcys/eGFRcre ratio were significantly correlated with grip power and gait speed (p < 0.001). The eGFRcys/eGFRcre ratio was also correlated with skeletal muscle mass index (SMI) (p < 0.01). Univariate logistic regression analysis showed eGFRcys and eGFRcys/eGFRcre ratio but not eGFRcre were associated with sarcopenia (p < 0.01). The presence of low eGFRcys (CKDcys) and low eGFRcys/eGFRcre ratio (< 1.0) but not that of low eGFRcre (CKDcre) were associated with sarcopenia (p < 0.01). In the multivariate logistic regression analysis, when the eGFRcys/eGFRcre ratio was added as a covariate to the basic model, it was significantly associated with sarcopenia in women (p < 0.05). Moreover, low eGFRcys/eGFRcre ratio (< 1.0) was associated with a higher risk of sarcopenia in men (p < 0.01). CONCLUSION: In conclusion, CKDcys but not CKDcre is associated with sarcopenia. A lower eGFRcys/eGFRcre ratio may be a practical screening marker of sarcopenia in community-dwelling older adults.

Physical frailty predicts the development of social frailty: a prospective cohort study.

BACKGROUND: It has not been clarified whether physical frailty symptoms predict social. frailty. The purpose of this study was to elucidate the effect of physical frailty on social frailty, and to determine which domains of physical frailty predict the development of social frailty. METHODS: We employed a two-year prospective cohort study. A total of 342 socially robust community-dwelling older adults were recruited. We used a modified social frailty screening index consisting of four social domains including financial difficulties, living alone, social activity, and contact with neighbors. Physical frailty status was also assessed at baseline. At the two-year follow-up, we assessed the development of social frailty. Social status was assessed using four social subdomains for the primary analysis. Social status was assessed using the two social subdomains of social activity and contact with neighbors, which would be affected by the physical frailty component, for the secondary analysis. The risk ratios (RR) of physical frailty for the development of social frailty were estimated. RESULTS: Although physical frailty symptoms were not a significant risk factor for future development of social frailty as assessed by four social subdomains (adjusted RR 1.39, 95% CI 0.95-2.15), it became significant when development of social frailty was assessed by the two social subdomains (adjusted RR 1.78, 95% CI 1.10-2.88). An analysis using the physical frailty subdomain showed that slow gait speed (adjusted RR 3.41, 95% CI 1.10-10.53) and weakness (adjusted RR 1.06, 95% CI 1.01-1.12) were independent risk factors for development of social frailty as assessed by two social subdomains. CONCLUSIONS: Physical frailty symptoms predict the development of social frailty. Among physical frailty subdomains, gait speed and muscle strength are critical independent risk factors for future decline in the social aspect. The prevention of physical frailty, especially by maintaining gait ability and muscle strength, may be effective for avoiding social frailty.

The Relationship between Dietary Habits and Frailty in Rural Japanese Community-Dwelling Older Adults: Cross-Sectional Observation Study Using a Brief Self-Administered Dietary History Questionnaire.

To develop effective nutritional interventions for preventing frailty, the specific problems associated with the dietary habits of individuals based on sex differences must be identified. The purpose of this study was to evaluate the association between dietary habits and frailty in rural Japanese community-dwelling older adults. We recruited 800 participants, aged 65 and older, who underwent a comprehensive health examination between November 2015 and December 2017. Dietary habits were assessed by a brief self-administered dietary history questionnaire. Frailty was determined using either the Kihon Checklist (KCL) or the Japanese version of the Cardiovascular Health Study (J-CHS). The percentage of frail older adults was 8.4% according to KCL and 4.0% according to J-CHS. Various kinds of nutrient intakes, including three major nutrients, minerals, and vitamins in frail men, according to KCL, were the lowest. By contrast, there were no differences in nutrient intake between the robust, prefrail, and frail female groups according to KCL. We found significant associations of the intakes of soluble dietary fiber, potassium, folate, and vitamin C with a frail status in men (p = 0.035, 0.023. 0.012, and 0.007, respectively), and an association of the intake of vitamin C with a frail status in women (p = 0.027) according to J-CHS. Attention should be paid to the diagnostic criteria of frailty and to sex differences, when nutritional interventions for the prevention of frailty are planned.

Isotemporal substitution of sedentary time with physical activity and its associations with frailty status.

OBJECTIVES: Recently, isotemporal substitution has been developed to substitute activity time for an equivalent amount of another activity. This study employed this method to demonstrate the effects of replacing sedentary behavior (SB) time with an equivalent amount of light-intensity physical activity (LPA) and moderate-to-vigorous intensity physical activity (MVPA) on the risk for different severities of frailty. METHODS: A total of 886 older adults (average age 73.6 years, female 70%) participated in this cross-sectional study. Frailty status was assessed according to the cardiovascular health study criteria. MAIN OUTCOME MEASURES: Wrist-worn accelerometers were used to measure SB, LPA, and MVPA. Isotemporal substitution models were applied to show the estimated effects of substituting 30 min of SB with an equal amount of time spent in LPA or MVPA on the risk for pre-frailty and frailty. RESULTS: The physical activity level and SB were not associated with the incidence of pre-frailty. However, a 16% (OR: 0.84; 95% CI: 0.78-0.90) and 42% (OR: 0.58; 95% CI: 0.37-0.92) decrease in frailty risk was noted when SB was substituted with LPA and MVPA, respectively, in the crude model. In the adjusted model, the significant effect was sustained for LPA (OR: 0.86; 95% CI: 0.80-0.92) but not for MVPA (OR: 0.74; 95% CI: 0.47-1.17). CONCLUSIONS: This study indicates that replacing 30 min of SB with an equivalent amount of LPA decreases the risk for frailty in older adults. Moreover, increasing LPA seems more feasible than increasing MVPA in older adults, with substantial benefit.

Solid-state compatibility studies using a high-throughput and automated forced degradation system.

As the number of pharmaceutical candidate compounds increases, so does the need for development workflow that is capable of handling more compounds in shorter times. In this paper, the establishment of a high-throughput automated powder compatibility testing system is reported. The integrated robotic system automatically dispenses, weighs, and stores powder samples, and extracts and analyses drug substance using ultra-performance liquid chromatography (UPLC). Although automation of powder testing systems is generally accompanied by difficulties in accuracy and precision, mass tracking at every unit operation allowed the system to be validated. In a standard procedure, drug substance and an excipient were dispensed 1:1 (w/w), stored at 70 degrees C for 9 days, dissolved in solvents, and analyzed to examine the degradation of drug substance and the increases in related substances. The robot quantitatively discriminate between initial conditions of the incompatible powder mixtures of aspirin and magnesium stearate (Mg-St) prepared with or without the use of a whisk and shaker system, demonstrating the capability for evaluating powder mixtures with varying degrees of homogeneity where the contact area between excipient and drug substance differs. Differential scanning calorimetry (DSC), however, did not clearly distinguish between those powder samples, indicating that DSC is less sensitive to powder conditions. The incompatibility results of aspirin and Mg-St were comparable to those reported previously, demonstrating that the automated testing system is reliable. The robot reduced manual work to one sixth and cut down on the costs of outsourcing. An extensive impact is anticipated on development workflows because this system is applicable not only to compatibility testing but also to analytical method development for drug products.

Effective targets for constraint-induced movement therapy for patients with upper-extremity impairment after stroke.

OBJECTIVE: Examination of effectiveness of different sites of constraint-induced movement therapy (CI therapy) for upper-extremity impairment of patients after stroke. SUBJECTS: Patients exhibiting moderate to slight upper-extremity impairment after stroke. METHODS: The patients received a modified version of CI therapy for a cumulative total of 5 h daily for 10 days. Using Fugl-Meyer scores, shoulder/elbow/forearm, wrist and hand functions were separately assessed before and after treatment. To assess the site-specific effects of CI therapy, before and after scores were statistically compared at each site using Wilcoxon signed-rank tests. Relative effects were evaluated by paired comparison of the results at each site with, in turn, the results at every other site. Instances of single-score increments were, using standard chi-square tests, statistically isolated and compared. RESULTS: Nineteen patients, 12-169 (median 31) months after stroke, were enrolled in this study and completed the protocol. Age range was 40-81 (median 65) years old and pretreatment Fugl-Meyer total scores spanned 31-64 (median 48). Analyses detected statistically significant improvements for wrist, hand and coordination but not for shoulder/elbow/forearm subcomponents. For the hand, at least single-point increments were observed in 74% of the population, while only 47% showed similar increments for the shoulder/elbow/forearm, and 53% for the wrist. Statistical analysis revealed that a higher proportion had increments in hand scores. CONCLUSIONS: Statistical analysis shows that CI therapy is most beneficial for treating hand function, suggesting an efficient application of this treatment.

Enhanced pharmacological activity of recombinant human interleukin-11 (rhIL11) by chemical modification with polyethylene glycol.

In order to improve the pharmacological efficacy of recombinant human interleukin-11 (rhIL11) and to reduce the frequency of administration, we examined the feasibility of chemical modification of rhIL11 by polyethylene glycol. The rhIL11 was chemically modified by using branched type (PEG2), or linear type (PEG) polyethylene glycol-N-hydroxysuccinimide with various molecular weights. Plasma profiles of immunoreactive rhIL11 after i.v. injection of the 20 kDa PEG2 conjugated rhIL11 (PEG2 (20 K)-rhIL11) were determined by ELISA. Peripheral platelet counts after the administration of the various conjugates were measured. Pharmacokinetic analysis revealed that the mean residence time of PEG2 (20 K)-rhIL11 after i.v. injection extensively increased by a factor of ca 60 compared with the native rhIL11. Maximum peripheral platelet increase of 67% for PEG2 (20 K)-rhIL11 and that of 50% for PEG (20 K)-rhIL11 over the control was observed whereas no significant change was associated with the bolus i.v. injection of native rhIL11. On the other hand, the remaining biological activity of these PEGylated-rhIL11s was 14-16% of native rhIL11, suggesting that retention of rhIL11 in plasma is much effective in order to potentiate the pharmacological efficacy of the cytokine. Chemical modification of rhIL11 by PEG is a promising approach for improving the clinical efficacy of rhIL11 by prolonged retention in plasma.

Purification and substrate specificity of UDP-D-xylose:beta-D-glucoside alpha-1,3-D-xylosyltransferase involved in the biosynthesis of the Xyl alpha1-3Xyl alpha1-3Glc beta1-O-Ser on epidermal growth factor-like domains.

A unique O-glycan structure, Xylalpha1-3Xylalpha1-3Glcbeta1-O-Ser is found on the consensus sequence C-X-S-X-P-C (X denotes any amino acid) in epidermal growth factor (EGF)-like domains of plasma proteins such as clotting factor VII and IX. One of the enzymes involved in the biosynthesis of this trisaccharide, UDP-d-xylose:beta-d-glucoside 1,3-d-xylosyltransferase has been identified in HepG2 cells (Omichi, K., Aoki, K., Minamida, S., and Hase, S. Eur. J. Biochem. 245, 143-146 [1997]). Here, we report that this enzyme activity can be detected in bovine liver and that the enzyme has been purified from the microsomal fraction. The enzyme was purified 6200-fold in terms of specific activity and ran as a single band on native-PAGE and isoelectric focusing gel electrophoresis. The best acceptor substrate of those tested was the EGF-like domain of bovine factor IX carrying beta-glucoside at Ser53. The Km value for this substrate was 34 muM. Comparison of initial velocity with various acceptor substrates shows that this xylosyltransferase recognizes not only the glucose moiety to which xylose is transferred but also the tertiary structure of the EGF-like domain. With regard to the donor substrate, the enzyme does not recognize UDP-d-glucose but does recognize UDP-d-xylose.