Geriatric prognostic scoring system predicts survival after hepatectomy for elderly patients with liver cancer.

Aim: The number of elderly patients with liver cancer is increasing with the aging society. The Geriatric Prognostic Scoring System is useful in predicting the postoperative prognosis for elderly patients with gastrointestinal cancer. The aim of the present study was to assess the predictive ability of the geriatric prognostic scoring system for postoperative survival in elderly patients with liver cancer. Methods: Eighty-eight patients aged ≥75 years who were treated for primary liver cancer and metastatic liver tumor were retrospectively analyzed. The Geriatric Prognostic Score (GPS) was created by several clinical parameters such as age, sex, type of cancer, stage, performance status, body mass index, and comprehensive geriatric assessment. Each patient was divided into two groups of high-risk to low-risk according to their GPS: ≧30 high-risk group and <30 low-risk. The predictive ability of geriatric prognostic scoring system for postoperative survival was assessed in univariate and multivariate analyses. Results: Of the 88 patients, 75 were diagnosed as hepatocellular carcinoma and 13 as colorectal liver metastasis. After geriatric prognostic scoring system assessments, 26 patients were diagnosed as high-risk and the remaining 62 as low-risk. The 3-year overall survival rates were 78.5% in the low-risk group and 35.1% in the high-risk group (p < 0.001). The univariate and multivariate analyses of overall survival identified high GPS as an independent significant factor (p < 0.001). Conclusions: We could conclude that the geriatric prognostic scoring system is useful in predicting patients' prognosis after hepatectomy and it can provide helpful information to surgeons for determining treatment strategies for elderly patients with liver cancer.

Usefulness of the serum creatinine/cystatin C ratio as a blood biomarker for sarcopenia components among age groups in community-dwelling older people: The SONIC study.

AIM: The serum creatinine/cystatin C ratio (CCR) or sarcopenia index is considered a useful marker of muscle mass. However, its usefulness in late-stage older adults remains unclear. We aimed to determine the usefulness of CCR as an indicator of sarcopenia in community-dwelling Japanese adults aged >75 years. METHODS: Our study recruited participants aged 70, 80, and 90 ± 1 years during the baseline years, and included a 3-year follow-up in the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians study. From 2015 to 2018, 955 participants were eligible: 367 in their 70s, 304 in their 80s, and 284 in their 90s. The diagnostic components of sarcopenia, including "low muscle mass, plus low muscle strength, and/or low physical performance," were evaluated using the bioelectrical impedance analysis-measured skeletal muscle mass index (SMI), handgrip strength, and short physical performance battery (SPPB) score, respectively, in accordance with the Asia Working Group for Sarcopenia 2019 criteria. Separate analyses were performed between each component and CCR, adjusting for sex, body mass index, and other blood biomarkers in each group. RESULTS: The relationship between CCR and sarcopenia components was significant for handgrip strength (ß = 0.21, 0.13, 0.19, and P < 0.0001, =0.0088, <0.0001, for the 70s, 80s, and 90s age groups, respectively); however, it was limited for SMI (ß = 0.14; P = 0.0022, only for the 90s) and not significant for the SPPB score. CONCLUSION: CCR is a limited indicator of sarcopenia in late-stage older adults. Although its association with muscle strength was significant, its relationship with muscle mass and physical performance was less pronounced. Geriatr Gerontol Int 2024; ••: ••-••.

Exploring the association between number of teeth, food intake, and cognitive function: A 9-year longitudinal study.

OBJECTIVES: This study aimed to investigate the association between the number of teeth, food intake, and cognitive function in Japanese community-dwelling older adults. METHODS: This 9-year longitudinal study included a total of 293 analyzable participants who participated in baseline and follow-up surveys. Dental status (number of teeth and periodontal pocket depth), dietary assessment using the brief-type self-administered diet history questionnaire, cognitive function, and the following confounding factors were evaluated: educational level, financial satisfaction, living situation, smoking and drinking habits, history of chronic diseases, apolipoprotein E-ε4 carrier, body mass index, handgrip strength, instrumental activities of daily living, and depressive symptomatology. The Japanese version of the Montreal Cognitive Assessment was used to evaluate cognitive function. A multinomial logistic regression analysis for the intake level of each food categorized into three groups (low, moderate, high), and a generalized estimating equation (GEE) for cognitive function over nine years were performed. RESULTS: After controlling for confounding factors, the number of teeth was shown to be associated with the intake of green-yellow vegetables and meat. Furthermore, the GEE indicated that the lowest quartile of intake of green-yellow vegetables significantly associated with lower cognitive function (unstandardized regression coefficient [B] = -0.96, 95 % confidence interval [CI]: -1.72 to -0.20), and the lowest quartile of intake of meat significantly associated with lower cognitive function (B = -1.42, 95 % CI: -2.27 to -0.58). CONCLUSIONS: The intake of green and yellow vegetables and meat, which is influenced by the number of teeth, was associated with cognitive function in Japanese community-dwelling older adults. CLINICAL SIGNIFICANCE: There are few studies that have examined the association between oral health, food intake, and cognitive function. This 9-year longitudinal study suggests that it is important to maintain natural teeth to enable the functional means to consume green-yellow vegetables and meat, and thereby help maintain cognitive function.

Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice.

This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild-type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to the autophagosome pathway. Moreover, although IL-15 KO mice maintained gastrocnemius muscle mass, they exhibited a decrease in autophagy induction. IL-15 TG mice exhibited a decrease in gastrocnemius muscle mass and an increase in forelimb grip strength and SDH activity in skeletal muscle. In the gastrocnemius muscle, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α (AMPKα) to total AMPKα and unc-51-like autophagy activating kinase 1 and Beclin1 protein expression were higher in the IL-15 TG group than in the WT group. IL-15 gene deficiency induces a decrease in autophagy induction. In contrast, IL-15 overexpression could improve muscle quality by activating autophagy induction while decreasing muscle mass. The regulation of IL-15 in autophagy in skeletal muscles may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.NEW & NOTEWORTHY IL-15 gene deficiency can decrease autophagy induction. However, although IL-15 overexpression induced a decrease in muscle mass, it led to an improvement in muscle quality. Based on these results, understanding the role of IL-15 in regulating autophagy pathways within skeletal muscle may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.

The Contributions of Knee Extension Strength and Hand Grip Strength to Factors Relevant to Physical Frailty: The Tanno-Sobetsu Study.

Sarcopenia is the core factor of frailty. This study specifically focused on lower limb muscle strength and examined muscle indices that indicate the risk of frailty or pre-frailty in older adults. The study included 327 community-dwelling individuals aged ≥65 years (43.7% male) who participated in the cohort. Frailty was defined based on five symptoms: weight loss, low activity level, exhaustion, weakness and slowness. Participants were classified into frail (three or more applicable), pre-frail (one to two applicable) and non-frail groups. Muscle strength (knee extension strength, toe grip strength and hand grip strength) were assessed, and appendicular muscle mass was assessed via a bioelectrical impedance analysis. The adjusted odds ratio (OR) of muscle indices for with frailty (frail group vs. pre-frail group) or pre-frailty (pre-frail group vs. non-frail group) were calculated. The prevalence of frail and pre-frail was 7% and 40%, respectively. Adjusted for age, sex, albumin and medical history, knee extension strength was significantly associated with frailty (odds ratio 0.95, 95% CI 0.92-0.98), while hand grip strength was associated with pre-frailty (odds ratio 0.92, 95% CI 0.88-0.97) but not with other muscle indices. This study is significant for identifying knee extension strength as a factor relevant to frailty in older adults considered pre-frailty, emphasizing the importance of this specific muscle measure in predicting and managing frailty.

Knee Extensor Weakness Potently Predicts Postoperative Outcomes in Older Gastrointestinal Cancer Patients.

OBJECTIVES: Muscle weakness, assessed by grip strength, has been shown to predict postoperative mortality in older patients with cancer. Because lower extremity muscle strength well reflects physical performance, we examined whether lower knee extension muscle strength predicts postoperative mortality better than grip strength in older patients with gastrointestinal cancer. DESIGN: Prospective, observational study in a single institution. SETTING AND PARTICIPANTS: A total of 813 patients (79.0 ± 4.2 years, 66.5% male) aged 65 years or older with gastrointestinal cancer who underwent preoperative evaluation of grip strength and isometric knee extension muscle strength between April 2012 and April 2019 were included. METHODS: The study participants were prospectively followed up for postoperative mortality. Muscle weakness was defined as the lowest quartile of grip strength or knee extension strength (GS-muscle weakness and KS-muscle weakness, respectively). RESULTS: Among the study participants, 176 patients died during a median follow-up of 716 days. In the Kaplan-Meier analysis, we found that patients with both GS-muscle weakness and KS-muscle weakness had a lower survival rate than those without muscle weakness. As expected, higher clinical stages and abdominal and thoracic surgeries compared with endoscopic surgery were associated with increased all-cause mortality. In addition, we found that KS-muscle weakness, but not GS-muscle weakness, was an independent prognostic factor after adjusting for sex, body mass index, cancer stage, surgical technique, and surgical site in the Cox proportional hazard model. CONCLUSIONS AND IMPLICATIONS: In older patients with gastrointestinal cancer, muscle weakness based on knee extension muscle strength can be a better predictor of postoperative prognosis than muscle weakness based on grip strength.

Clinical features of sleep apnea syndrome and cognitive impairment in multiple sclerosis.

BACKGROUND: Complications of obstructive sleep apnea (OSA) have been reported in patients with multiple sclerosis (MS). Patients with sleep apnea syndrome (SAS) due to OSA also show cognitive decline, with similar clinical characteristics to that manifested in MS. SAS due to OSA is a treatable condition, and the associated cognitive decline is expected to improve. This study investigates clinical features of SAS in people living with MS and contribute to improve cognitive dysfunction of MS. METHODS: A case-control study was conducted. Cognitive functions were evaluated by the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test 2 (PASAT-2) and 3 (PASAT-3). The Respiratory Event Index (REI) was measured using Out of Center Sleep Testing (OCST). We defined subjects with REI ≥ 5 as OSA and divided participants into two groups with or without SAS due to OSA. Cognitive and respiratory characteristics were statistically compared between patients with MS and healthy controls. RESULTS: We enrolled 67 people living with MS and 31 age- and sex-matched controls. OCST detected OSA in people living with MS and controls, and the prevalence rates were 28.4 % and 25.8 %, respectively. REI values (5.2 ± 7.9 vs 3.9 ± 5.2, p = 0.509) and number of participants with REI ≥ 5 (19 vs 8, p = 0.793) were similar between the MS and control group. The SDMT, PASAT-2, and PASAT-3 scores were significantly lower in the MS group than the control group (p < 0.001, p = 0.001, and p < 0.001, respectively). The interaction effect of MS and SAS on cognitive function was not significant in the SDMT (p = 0.078), but in the PASAT-2 (p = 0.043) and PASAT-3 (p = 0.020). CONCLUSION: This study revealed the prevalence rates of SAS in Japanese people living with MS and the usefulness of OCST for detection of SAS. This study also revealed that concomitant SAS can facilitate cognitive decline in people living with MS. These findings suggest that an appropriate intervention for OSA can be beneficial for people living with MS with cognitive decline.

Age Group Differences in the Association Between Sleep Status and Frailty Among Community-Dwelling Older Adults: The SONIC Study.

Objective: We aimed to determine whether the association of sleep status with frailty differs between age groups of older adults. Method: This cross-sectional study was part of the observational Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study. Subjects were community-dwelling older adults in their 70s and 80s. Frailty was evaluated using the Japanese version of the Cardiovascular Health Study criteria (J-CHS). Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep status. Poor sleep quality was defined as a PSQI global score ≥6. Sleep duration was categorized as short (<6 hr), normal (6-8), and long (>8). We performed multivariable logistic regression to investigate the association between sleep status and frailty separately for each age group adjusted for multiple covariates. Results: In those in their 70s, long sleep duration and sleep medication use were independently associated with frailty. In those in their 80s, poor sleep quality was independently associated with frailty. Conclusions: The association between sleep status and frailty was different between age groups. The findings underscore the importance of incorporating the evaluation of sleep quantity and non-pharmacological therapies in those in their 70s and the evaluation of sleep quality in those in their 80s to help prevent the onset of frailty.

Relationship between the number of teeth, occlusal force, occlusal contact area, and dietary hardness in older Japanese adults: The SONIC study.

PURPOSE: Individuals with impaired masticatory function tend to prefer soft foods, which results in decreased masticatory muscle activity. This study examined the association between the oral condition (number of teeth, occlusal force, and occlusal contact area) and dietary hardness using a daily dietary questionnaire. METHODS: This cross-sectional study evaluated 1841 participants aged 69-71 and 79-81 years. Registered dentists examined the number of teeth, occlusal force, and occlusal contact area. Dietary hardness was defined as the estimated masticatory muscle activity required for a habitual diet. Habitual diet during the preceding month was assessed using a brief self-administered diet history questionnaire. Confounding factors, such as age, sex, socioeconomic status, smoking habits, history of chronic diseases (hypertension, hyperlipidemia, and diabetes), and cognitive function were also evaluated. Multivariate linear regression analyses were performed to assess the association between dietary hardness and each oral condition. RESULTS: Occlusal force (standardized regression coefficients [ß]=0.08, P < 0.01) and occlusal contact area (ß=0.06, P < 0.01) were significantly associated with dietary hardness after adjusting for the confounding factors. Number of teeth was not significantly associated with dietary hardness. In addition, the associations between dietary hardness, sex, and a history of diabetes were stronger than those between dietary hardness and oral factors. CONCLUSIONS: Occlusal force and contact area were significantly associated with dietary hardness as estimated from the masticatory muscle activity using a daily diet questionnaire.

Factors associated with weight loss by age among community-dwelling older people.

BACKGROUND: Factors associated with weight loss in community-dwelling older people have been reported in several studies, but few studies have examined factors associated with weight loss by age groups. The purpose of this study was to clarify factors associated with weight loss by age in community-dwelling older people through a longitudinal study. METHODS: Participants in the SONIC study (Longitudinal Epidemiological Study of the Elderly) were community-dwelling people aged 70 or older. The participants were divided into two groups: 5% weight loss and maintenance groups, and compared. In addition, we examined factors affecting weight loss by age. The analysis method used was the χ2 test, and the t-test was used for comparison of the two groups. Factors associated with 5% weight loss at 3 years were examined using logistic regression analysis with sex, age, married couple, cognitive function, grip strength, and the serum albumin level as explanatory variables. RESULTS: Of the 1157 subjects, the proportions showing 5% weight loss after 3 years among all subjects, those aged 70 years, 80 years, and 90 years, were 20.5, 13.8, 26.8, and 30.5%, respectively. In logistic regression analysis, factors associated with 5% weight loss at 3 years by age were influenced by BMI of 25 or higher (OR = 1.90, 95%CI = 1.08-3.34, p = 0.026), a married couple (OR = 0.49, 95% = 0.28-0.86, p = 0.013), serum albumin level below 3.8 g/dL (OR = 10.75, 95% = 1.90-60.73, p = 0.007) at age 70, and the grip strength at age 90 (OR = 1.24, 95%CI = 1.02-1.51, p = 0.034), respectively. CONCLUSIONS: The results suggest that factors associated with weight loss by age in community-dwelling older people through a longitudinal study differ by age. In the future, this study will be useful to propose effective interventions to prevent factors associated with weight loss by age in community-dwelling older people.

Ultrasound evaluation of vagus nerve cross-sectional area in a community-dwelling elderly Japanese cohort.

OBJECTIVES: Although the vagus nerve (VN) is easily observed by ultrasonography, few studies have evaluated the cross-sectional area (CSA) of the VN in healthy older individuals from East Asia. In this study, we aimed to report reference values for the CSA of the VN in community-dwelling elderly Japanese individuals and to identify any associated medical history and/or lifestyle factors. METHODS: The present study included 336 participants aged ≥ 70 years from a prospective cohort study conducted in Yahaba, Japan from October 2021 to February 2022. The CSA of the VN was measured bilaterally at the level of the thyroid gland by ultrasonography. Simple linear regression analysis and generalized estimating equation were conducted to identify the associations between clinical and background factors and the CSA of the VN. RESULTS: In our cohort, the median CSA of the VN was 1.3 mm2 (interquartile range [IQR] 1.1-1.6) on the right side and 1.2 mm2 (IQR 1.0-1.4) on the left side. Generalized estimating equation showed that history of head injury (ß = 0.19, p < .01), current smoking habit (ß = -0.09, p = .03), and BMI (ß = 0.02, p < .01) were independently associated with the CSA of the VN. CONCLUSION: We have reported reference VN CSA values for community-dwelling elderly Japanese individuals. In addition, we showed that the CSA of the VN was positively associated with a history of head injury and BMI and inversely associated with current smoking habit.

Effects of luseogliflozin treatment on hyperglycemia-induced muscle atrophy in rats.

Diabetes mellitus is recognized as a risk factor for sarcopenia. Luseogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces inflammation and oxidative stress by improving hyperglycemia, subsequently improving hepatosteatosis or kidney dysfunction. However, the effects of SGLT2 inhibitor on the regulation of skeletal muscle mass or function in hyperglycemia are still unknown. In this study, we investigated the effects of luseogliflozin-mediated attenuation of hyperglycemia on the prevention of muscle atrophy. Twenty-four male Sprague-Dawley rats were randomly divided into four groups: control, control with SGLT2 inhibitor treatment, hyperglycemia, and hyperglycemia with SGLT2 inhibitor treatment. The hyperglycemic rodent model was established using a single injection of streptozotocin, a compound with preferential toxicity toward pancreatic beta cells. Muscle atrophy in streptozotocin-induced hyperglycemic model rats was inhibited by the suppression of hyperglycemia using luseogliflozin, which consequently suppressed hyperglycemia-mediated increase in the levels of advanced glycation end products (AGEs) and activated the protein degradation pathway in muscle cells. Treatment with luseogliflozin can restore the hyperglycemia-induced loss in the muscle mass to some degree partly through the inhibition of AGEs-induced or homeostatic disruption of mitochondria-induced activation of muscle degradation.

[Relationship between glycemic control and mental health in community-dwelling older people with diabetes mellitus: The SONIC study].

AIM: The purpose of this study was to examine the relationship between glycemic control and mental health in community-dwelling older people with diabetes mellitus (DM) from insights that contribute to the management of diabetes in consideration of quality of life (QOL). METHODS: We used the data of the Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) study, a prospective cohort study of community-dwelling older people. The present study included 2,051 older subjects of 70±1 years, 80±1 years and 90±1 years of age. We conducted medical interviews, blood sampling, and the subjects were asked to complete a questionnaire (WHO-5-J) at the venue. Three hundred sixty-eight people were diagnosed with DM. The subjects of this study were 192 people who were undergoing drug therapy for glycemic control. A multiple regression analysis was performed to clarify the relationship between glycemic control (divided as follows: HbA1c<7.0%, good control group; HbA1c≥7.0%, poor control group) and the WHO-5-J score, as the dependent variable, after adjusting for any confounding factors. RESULTS: In subjects of 70 years of age, a negative association was found between glycemic control and the WHO-5-J score, with the good control group showing a significantly lower score (ß: -0.468, p<0.01) in comparison to the poor control group. In detail, we observed a significant difference in the sub-items of WHO-5-J, question item 3, "I have felt active and vigorous" at 70 years of age (good control group, 2.56±1.37; poor control group, 3.21±1.18; p=0.021) and question item 5, "My daily life has been filled with things that interest me" (good control group, 2.44±1.21; poor control group, 3.11±1.11; p=0.009). As for the two questions, the WHO-5-J scores were lower in the good control group. These associations showed no statistical significance at 80 years of age or 90 years of age. CONCLUSION: The results obtained in this study indicated that strict glycemic control management of diabetes mellitus may lead to a lower mental QOL in younger elderly individuals (70 years of age). Therefore, it is important to pay attention to the mental burdens of the management of glycemic control in older people with DM.

Longitudinal association of hypertension and dyslipidemia with cognitive function in community-dwelling older adults: the SONIC study.

The associations among cognitive function, hypertension, and dyslipidemia in older adults are controversial. Therefore, we investigated the associations among cognitive decline, hypertension, dyslipidemia, and their combination in community-dwelling older people in their 70s, 80s, and 90s in the long-term observational Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians (SONIC) study. We administered the Montreal Cognitive Assessment Japanese version (MoCA-J) by trained geriatricians and psychologists, and conducted blood testing and blood pressure (BP) measuring by medical staff involving 1186 participants. We performed multiple regression analysis to assess the relationships among hypertension, dyslipidemia, their combination, and lipid and BP levels with cognitive function at the 3-year follow-up after adjusting for covariate factors. At the baseline, the percentage of the combination of hypertension and dyslipidemia was 46.6% (n = 553), hypertension was 25.6% (n = 304), dyslipidemia was 15.0% (n = 178), and that without hypertension or dyslipidemia was 12.7% (n = 151). Conducting multiple regression analysis, no significant correlation was found between the combination of hypertension and dyslipidemia and MoCA-J score. In the group with the combination, high high-density lipoprotein cholesterol (HDL) levels resulted in higher MoCA-J scores at the follow-up (ß = 0.06; P < 0.05) and high diastolic BP (DBP) also resulted in higher MoCA-J scores (ß = 0.08; P < 0.05). The results suggest that high HDL and DBP levels of individuals with HT & DL and high SBP levels of individuals with HT were associated with cognitive function in community-dwelling older adults. In the SONIC study, which is an epidemiological study of Japanese older persons aged 70 years or older, a disease-specific examination suggested that high HDL and DBP levels of individuals with hypertension & dyslipidemia and high SBP levels of individuals with hypertension were associated with maintaining cognitive function in community-dwelling older adults.

Lower cognitive function as a risk factor for anemia among older Japanese women from the longitudinal observation in the SONIC study.

AIM: The aging-related increase in the incidence of anemia potentially affects the mortality risk. Lower cognitive function is common among older adults, and anemia is one of the causes of cognitive decline. However, to the best of our knowledge, no study has investigated whether cognitive decline is a risk factor for anemia in older people. Therefore, in this study, we used a 3-year longitudinal evaluation to examine the association of cognitive function with anemia in community-dwelling older adults. METHODS: This longitudinal study enrolled participants without anemia (diagnosed based on the World Health Organization's criteria) at baseline. Cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment. Multiple logistic regression models were used to examine the association between cognitive function at baseline and the presence of anemia 3 years later. RESULTS: Participants were in the 69-71 and 79-81 years age groups, and 974 older people (48.6% men) were enrolled, of whom 126 (12.9%) had anemia after 3 years. After adjusting, cognitive function at baseline was associated with anemia in women, but not in men. CONCLUSIONS: Older Japanese women with lower cognitive function have an increased risk for anemia 3 years later. The adoption of a lifestyle that utilizes or improves cognitive function might be important to prevent anemia in older women. Geriatr Gerontol Int 2023; 23: 334-340.

Preserved Lower Limb Muscle Mass Prevents Insulin Resistance Development in Nondiabetic Older Adults.

OBJECTIVE: To investigate roles of sarcopenia indexes in prediction of development of insulin resistance in nondiabetic older adults. DESIGN: A 2-year follow-up cohort. SETTING AND PARTICIPANTS: The Tanno-Sobetsu study, a prospective observational cohort, included 194 community-dwelling nondiabetic older adults during 2017-2019. METHODS: Lower limb, upper limb, appendicular, and trunk muscle masses by a bioelectrical impedance analysis, grip strength, knee extension torque, and walking speed were measured in study participants aged ≥65 years (79 men and 115 women) at baseline. Muscle mass and strength were divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). Insulin resistance was assessed by homeostasis model (HOMA-IR) at baseline, and the study participants whose HOMA-IR was less than 1.73 at baseline were followed for a maximum of 2 years. The study endpoint was development of insulin resistance defined as HOMA-IR ≥1.73. The adjusted hazard ratio (HR) of each sarcopenia component for development of insulin resistance was calculated. RESULTS: Lower limb muscle mass (HR 0.88, 95% CI 0.79-0.98) and appendicular muscle mass (HR 0.89, 95% CI 0.81-0.99), but not other sarcopenia components, were associated with the development of insulin resistance, independently of sex and age, HOMA-IR, and waist circumference at baseline. CONCLUSIONS AND IMPLICATIONS: The loss of lower limb muscle mass is a significant risk factor for development of insulin resistance independently of obesity in nondiabetic older adults. The lower limb muscle mass may be a novel target of interventions for the prevention of diabetes in older adults.

A characteristic N-glycopeptide signature associated with diabetic cognitive impairment identified in a longitudinal cohort study.

BACKGROUND: Identifying a biomarker for the decline in cognitive function in patients with diabetes is important. Therefore, we aimed to identify the N-glycopeptides on plasma proteins associated with diabetic cognitive impairment in participants in a longitudinal study using N-glycoproteomics. METHODS: We used samples from the 3-year SONIC (Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians) longitudinal cohort study of older Japanese people in the general population. First, we placed the participants with diabetes into two groups: those that did or did not have cognitive decline over a 6-year period. Next, their plasma protein profiles were compared between baseline and the 6-year time point using two-dimensional fluorescence difference gel electrophoresis. Finally, an N-glycoproteomic study of the focused proteins was performed using an enrichment technique and liquid chromatography-tandem mass spectrometry. RESULTS: Approximately 500 N-glycopeptides, derived from 18 proteins, were identified in each sample, from among which we identified the N-glycopeptides that were associated with diabetic cognitive impairment using multivariate analysis. We found that N-glycopeptides with sialylated tri- or tetra-antennary glycans on alpha-2-macroglobulin, clusterin, serum paraoxonase/arylesterase 1, and haptoglobin were less abundant, whereas 3-sialylated tri-antennary N-glycopeptides on serotransferrin were more abundant. CONCLUSION: N-glycopeptides with sialylated multi-antennary glycans comprise a characteristic signature associated with diabetic cognitive impairment. GENERAL SIGNIFICANCE: The characterized N-glycopeptides represent potential biomarker candidates for diabetic cognitive impairment.

Preoperative Comprehensive Geriatric Assessment Predicts Postoperative Risk in Older Patients with Esophageal Cancer.

BACKGROUND: Preoperative risk assessment is important in older patients because they often have comorbidities and impaired organ function. We performed preoperative comprehensive geriatric assessment (CGA) for older patients with esophageal cancer. PATIENTS AND METHODS: A total of 217 patients over 75 years old who underwent esophagectomy for thoracic esophageal cancer were analyzed. The CGA was performed preoperatively and included the Mini-Mental State Examination (MMSE), Geriatric Depression Score (GDS), vitality index, Barthel index, and instrumental activities of daily living (IADL). We defined the robust group as patients with normal function on every instrument, and the pre-frail and frail groups as those with functional impairment on one instrument or two or more instruments, respectively. We assessed how the CGA correlated with postoperative complications and prognosis. RESULTS: Of the 217 patients, 86 (39.6%) were in the robust group, 68 (31.3%) in the pre-frail group, and 63 (29.0%) in the frail group. Postoperative pneumonia (P = 0.026) and anastomotic leakage (P = 0.032) were significantly more common in the frail group. The frail group had a significantly longer postoperative hospitalization period (P = 0.016) and significantly lower rate of discharge to home (P = 0.016). Overall survival (OS) was significantly worse in the frail group (5-year overall survival rate, frail group versus others, 37.8% versus 52.0%, P = 0.046), but it was not significant on multivariate analysis. CONCLUSIONS: The preoperative CGA in older patients with esophageal cancer was associated with risk of postoperative complications.

Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study.

OBJECTIVE: Nicotinamide adenine dinucleotide regulates various biological processes. Nicotinamide mononucleotide (NMN) increases its intracellular levels and counteracts age-associated changes in animal models. We investigated the safety and efficacy of oral nicotinamide mononucleotide supplementation in older patients with diabetes and impaired physical performance. METHOD: We carried out a 24-week placebo-controlled, double-blinded study of male patients with diabetes aged ≥65 years with reduced grip strength (<26 kg) or walking speed (<1.0 m/s). The primary end-points were to determine the safety of NMN oral administration (250 mg/day), and changes in grip strength and walking speed. The secondary end-points were to determine the changes in various exploratory indicators. RESULTS: We studied 14 participants aged 81.1 ± 6.4 years. NMN was tolerable without any severe adverse events. The changes in grip strength and walking speed showed no difference between the two groups: 1.25 kg (95% confidence interval -2.31 to 4.81) and 0.033 m/s (-0.021 to 0.087) in the NMN group, and -0.44 kg (-4.15 to 3.26) and 0.014 m/s (-0.16 to -0.13) in the placebo group, respectively. There were no significant differences in any exploratory indicators between the two groups. However, improved prevalence of frailty in the NMN group (P = 0.066) and different changes in central retinal thickness between the two groups (P = 0.051) was observed. CONCLUSION: In older male patients with diabetes and impaired physical performance, NMN supplementation for 24 weeks was safe, but did not improve grip strength and walking speed. Geriatr Gerontol Int 2023; 23: 38-43.