Decline In Grip Strength Research Articles

The Effect of Monosodium Glutamate Ingestion on Spatial Memory and Cognitive Behaviour in Wistar Rats

Monosodium glutamate (MSG), one of the most widely used food-additives in commercial foods gives a special aroma (umami) to processed foods. It’s vital to brain metabolism and function. Adverse effects of MSG have been widely reported. However, there is scarcity of literature on the action of MSG on spatial memory and cognition. Hence, there is need to assess the effect of MSG ingestion on spatial memory and cognitive behavior in Wistar rats. 25 Wistar rats were randomly selected into five groups and treated for three weeks thus: Group 1 (control), Group 2 (0.7 mL MSG), Group 3 (1 mL MSG), Group 4 (1.5 mL MSG) Group 5 (0.1 mL Epinephrine). Neurobehavioral (Barnes, navigation, and handgrip) activities exhibited by the various groups were recorded and analyzed using ANOVA. In the Barnes maze test, there was a significant decrease (p<0.05) in escape time in group 4 when compared to the control for weeks 1 and 3. In week 1 of the Navigation maze test, group 4 animals spent less time (p<0.05) to navigate the maze when compared to the control. In week 1 and 3 of the handgrip test, animals in groups 2, 3 and 5 had a significant decline (p<0.05) in grip strength when compared to the control group; However, in week 2, only the animals in group 5 had a decline in grip strength (p<0.05) when compared to control. MSG did not cause any form of neurotoxicity, cognitive or motor decline in rats.

Longitudinal changes in physical and cognitive functions among participants with and without rheumatoid arthritis in community-dwelling middle-aged and older adults.

This study evaluated the chronological changes in physical and cognitive functions in middle-aged and older adults with and without rheumatoid arthritis (RA). 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. 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). 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.

Grip Strength and Sports Performance in Competitive Master Weightlifters.

Grip strength (GS) is correlated with major muscle group strength; weakness and asymmetry in older adults are predictive of future disease and functional limitation risk. GS at different ages and hand symmetry for Olympic-style weightlifters and their association with performance have not been established. GS was measured in 164 athletes participating in the 2022 World Master Weightlifting Championships. The objectives wereto study the magnitude of the age-associated decline in GS in weightlifters and the association of GS with weightlifting performance. Hand symmetry was considered as a potential factor in successful lifts. Ages ranged from 35 to 90 (mean 53 years). Participants reported weekly training averages of 8.3 h of weightlifting and 4.1 additional hours of physical activities. The age-associated decline in GS was less steep than the decline in weightlifting performance. GS was lower in weightlifters compared to athletes in other sports that require grasping or force application (t = -2.53, p=0.053 for females; t = -2.62, p= 0.029 for males). The rate of decline was similar across different populations (weightlifters, other athletes, community-dwelling adults). Height and age were associated with GS, but performance level and training hours were not. GS was associated with snatch performance (t = 3.56, p < 0.001) but not with clean and jerk (t = 0.48, p = 0.633).

PS-BPC06-8: FACTORS ASSOCIATED WITH POTENTIAL COGNITIVE FUNCTIONAL CHANGES IN OLDER PATIENTS WITH HYPERTENSION

Objective: There are many cases of potentially impaired cognitive function in older patients with hypertension. Therefore, we investigated factors associated with one-year changes in cognitive function in older hypertensive patients during outpatient visits. Design and method: We included 223 hypertensive patients (age 76.3 ± 6.3 years, 106 males) aged 65 years or older who attended outpatient hypertension clinics at six specialized institutions nationwide and had no prior diagnosis of dementia. We obtained the mini-mental state examination (MMSE) from all participants. We defined the impaired cognitive function as an MMSE score of 27 or less. At baseline and one year later, the participants were evaluated for comprehensive geriatric assessment, including MMSE, and muscle strength, with the converted group defined as having new cognitive decline at one year and the reverted group as having cognitive improvement one year after the cognitive decline. All participants gave informed consent, and our institutional review board approved the study protocol. Results: At baseline, 81 of 223 elderly hypertensive patients had impaired cognitive function. At one-year follow-up, 40 of 142 patients in the maintained cognitive function group were classified as converted, and 33 of 81 patients in the impaired cognitive function group were classified as converted. The converted group was older than the cognitively intact group (76.8 vs. 73.9 years, p &lt; 0.05), had higher home blood pressure, and had more significant grip strength loss over the year. Multivariate analysis identified age (odds ratio 1.1, 95% CI 1.0–1.2) and change in grip strength (odds ratio 0.84, 95% CI 0.72–0.99) as factors associated with the converted group. The reverted group was younger, had a higher percentage of males, and had weaker grip strength than the group with persistent cognitive decline. In multivariate analysis, grip strength (odds ratio 0.80, 95%CI 0.68–0.94) was extracted as a factor associated with the revert group. Conclusions: Potential cognitive decline was observed in 36% of older patients with hypertension. Furthermore, we examined a high rate of cases of cognitive function change over one year. Age and grip strength decline was considered responsible for cognitive conversion and baseline grip strength for revert, respectively.

PLASMA PROTEOMIC SIGNATURE OF DECLINE IN GAIT SPEED AND GRIP STRENGTH

Abstract Physical function predicts health-related quality of life. The biological mechanisms underlying declines in physical function with age remain unclear. We examined the plasma proteomic profile associated with longitudinal changes of physical functions measured by gait speed and grip strength in community-dwelling adults. We applied aptamer-based platform to assay 1,161 plasma proteins on 2,871 participants (60% women, aged 76 years) in Cardiovascular Health Study (CHS) in 1992/1993 and 1,550 participants (55% women, aged 54 years) in Framingham Offspring Study (FOS) in 1991-1995. Gait speed and grip strength were measured annually for 6 years in CHS and at cycles 7 (1998-2001) and 8 (2005-2008) in FOS. The associations of individual protein levels (log-transformed and standardized) with longitudinal changes of gait speed and grip strength in two populations were examined separately by linear mixed effect models. Meta-analyses were implemented using random effect models with a Bonferroni correction for multiple testing. We found that plasma levels of 18 and 12 proteins were associated with changes in gait speed and grip strength, respectively (Bonferroni-corrected p &amp;lt; .05). The proteins most strongly associated with gait speed decline were growth/differentiation factor 15 (GDF-15) (uncorrected Meta-analytic p = 1.60E-15), pleiotrophin (PTN) (1.29E-08), and metalloproteinase inhibitor 1 (TIMP-1) (2.02E-08). For grip strength decline, the strongest associations were for GDF-15 (1.39E-07), carbonic anhydrase III (6.60E-07), and TIMP-1 (3.21E-06). Several statistically significant proteins are involved in the alternative complement pathway, extracellular matrix remodeling or immune function. These novel proteomic biomarkers may inform our understanding of the pathophysiology of functional decline.

Hand Grip Strength Predicts Mortality and Quality of Life in Heart Failure: Insights From the Singapore Cohort of Patients With Advanced Heart Failure

Frailty is prevalent among patients with heart failure (HF) and is associated with increased mortality rates and worse patient-centered outcomes. Hand grip strength (GS) has been proposed as a single-item marker of frailty and a potential screening tool to identify patients most likely to benefit from therapies that target frailty so as to improve quality of life (QoL) and clinical outcomes. We assessed the association of longitudinal decline in GS with all-cause mortality and QoL. Decline in GS is associated with increased risk of all-cause mortality and worse overall and domain-specific (physical, functional, emotional, social) QoL among patients with advanced HF. We used data from a prospective, observational cohort of patients with New York Heart Association class III or IV HF in Singapore. Patients' overall and domain-specific QoL were assessed, and GS was measured every 4 months. We constructed a Kaplan-Meier plot with GS at baseline dichotomized into categories of weak (≤ 5th percentile) and normal (> 5th percentile) based on the GS in a healthy Singapore population of the same sex and age. Missing GS measurements were imputed using chained equations. We jointly modeled longitudinal GS measurements and survival time, adjusting for comorbidities. We used mixed effects models to evaluate the associations between GS and QoL. Among 251 patients (mean age 66.5 ± 12.0 years; 28.3% female), all-cause mortality occurred in 58 (23.1%) patients over a mean follow-up duration of 3.0 ± 1.3 years. Patients with weak GS had decreased survival rates compared to those with normal GS (log-rank P = 0.033). In the joint model of longitudinal GS and survival time, a decrease of 1 unit in GS was associated with a 12% increase in rate of mortality (hazard ratio: 1.12; 95% confidence interval: 1.05-1.20; P = < 0.001). Higher GS was associated with higher overall QoL (β (SE) = 0.36 (0.07); P = < 0.001) and higher domain-specific QoL, including physical (β [SE] = 0.13 [0.03]; P = < 0.001), functional (β [SE] = 0.12 [0.03]; P = < 0.001), and emotional QoL (β [SE] = 0.08 [0.02]; P = < 0.001). Higher GS was associated with higher social QoL, but this was not statistically significant (β [SE] = 0.04 [0.03]; P = 0.122). Among patients with advanced HF, longitudinal decline in GS was associated with worse survival rates and QoL. Further studies are needed to evaluate whether incorporating GS into patient selection for HF therapies leads to improved survival rates and patient-centered outcomes.

Plasma proteomic signature of decline in gait speed and grip strength.

The biological mechanisms underlying decline in physical function with age remain unclear. We examined the plasma proteomic profile associated with longitudinal changes in physical function measured by gait speed and grip strength in community-dwelling adults. We applied an aptamer-based platform to assay 1154 plasma proteins on 2854 participants (60% women, aged 76 years) in the Cardiovascular Health Study (CHS) in 1992-1993 and 1130 participants (55% women, aged 54 years) in the Framingham Offspring Study (FOS) in 1991-1995. Gait speed and grip strength were measured annually for 7 years in CHS and at cycles 7 (1998-2001) and 8 (2005-2008) in FOS. The associations of individual protein levels (log-transformed and standardized) with longitudinal changes in gait speed and grip strength in two populations were examined separately by linear mixed-effects models. Meta-analyses were implemented using random-effects models and corrected for multiple testing. We found that plasma levels of 14 and 18 proteins were associated with changes in gait speed and grip strength, respectively (corrected p< 0.05). The proteins most strongly associated with gait speed decline were GDF-15 (Meta-analytic p= 1.58 × 10-15 ), pleiotrophin (1.23 × 10-9 ), and TIMP-1 (5.97 × 10-8 ). For grip strength decline, the strongest associations were for carbonic anhydrase III (1.09 × 10-7 ), CDON (2.38 × 10-7 ), and SMOC1 (7.47 × 10-7 ). Several statistically significant proteins are involved in the inflammatory responses or antagonism of activin by follistatin pathway. These novel proteomic biomarkers and pathways should be further explored as future mechanisms and targets for age-related functional decline.

Associations of physical activity participation trajectories with subsequent motor function declines and incident frailty: A population-based cohort study

Maintaining physical function and delaying frailty are of significant importance in both quality of life and health longevity for successful aging. The objective of this study is to investigate whether different trajectories of long-term physical activity (PA) participation are associated with subsequent motor function declines and incident frailty in middle-aged and elderly adults. Data from 8,227 aged ≥ 50 years adults enrolled in the English Longitudinal Study of Aging were analyzed. Long-term PA participation trajectories were assessed using group-based trajectory modeling over the first 6-year period from wave 1 (2002-2003) to wave 4 (2008-2009). The longitudinal associations of PA trajectories with motor function declines and incident frailty were evaluated by a linear mixed model and Cox regression model, respectively, with follow-up of 10 years from wave 4 to wave 9 (2018-2019). Five distinct trajectories of long-term PA participation were identified in the aging cohort, including persistently low-active trajectory (N = 2,039), increasing active trajectory (N = 1,711), declining active trajectory (N = 216), persistently moderate-active trajectory (N = 2,254), and persistently high-active trajectory (N = 2,007). Compared with the persistently low-active group, the participants in persistently moderate- and high-active groups experienced significantly decelerated grip strength decline, decreased gait speed decline, and faster chair rises after multiple-adjustment. Similarly, participants maintaining moderate- and high-active PA were also associated with a lower risk of incident frailty (multiple-adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-0.80, and 0.42, 95% CI: 0.36-0.49, respectively), compared with those with persistently low PA. Notably, the participants with the increasing active trajectory got similar health benefits as those with persistently moderate and high levels of PA. In addition to persistent PA, increasing PA was linked to a slower decline in motor function and lower risk of incident frailty in the cohort. Our findings suggest that regular PA is never too late.

Ergonomic Assessment of Surgeon Characteristics and Laparoscopic Device Strain in Gynecologic Surgery

To evaluate whether surgeon characteristics, including sex and hand size, were associated with grip strength decline with laparoscopic advanced energy devices. Prospective cohort study. Ergonomic simulation at an academic tertiary care site and the Society of Gynecologic Surgeons 47th Annual Meeting. Thirty-eight participants (19 women and 19 men) were recruited. Surgeon anthropometric measurements were collected. Each participant completed a 120-second trial of maximum voluntary effort with 3 laparoscopic advanced energy devices (LigaSure, HALO PKS, and ENSEAL). Grip strength was measured using a handheld dynamometer. Subjects completed the NASA Raw Task Load Index scale after each device trial. Grip strengths and ergonomic workload scores were compared using Student t tests and Wilcoxon rank sum tests where appropriate. Univariate and multivariate models analyzed hand size and ergonomic workload. Women had lower baseline grip strength (288 vs 451 N) than men, as did participants with glove size <7 compared with ≥7 (231 vs 397 N). Normalized grip strength was not associated with surgeon sex (p=.08), whereas it was significantly associated with surgeon glove size (p <.01). Grip strength decline was significantly greater for smaller compared to larger handed surgeons for LigaSure (p=.02) and HALO PKS devices (p <.01). The ergonomic workload of device use was significantly greater for smaller compared to larger handed surgeons (p <.01). Surgeon handspan significantly predicted grip strength decline with device use, even after accounting for potential confounders (R2=.23, β=.8, p <.01). Surgeons with smaller hand size experienced a greater grip strength decline and greater ergonomic workload during repetitive laparoscopic device use. No relationship was found between surgeon sex and grip strength decline or ergonomic workload. Laparoscopic device type was also identified as a significant main effect contributing to grip strength decline. These findings point toward ergonomic strain stemming from an improper fit between the laparoscopic device and the surgeon's hand during device use.

Sex Differences in Age-Associated Rate of Decline in Grip Strength When Engaging in Vigorous Physical Activity.

Handgrip strength (GS) is used as an indicator of overall muscle strength and health outcomes for aging adults. GS has also been evaluated as a potential link with sport performances. We quantified the age-associated decline in grip strength for males and females engaged in weekly vigorous physical activity, differentiated by body mass, and investigated whether there was an acceleration of decline at any age. The Survey of Health, Ageing and Retirement in Europe is a multinational complex panel data survey with a target population of individuals aged 50 years or older. Data from 48,070 individuals from 20 European countries, collected from 2004 to 2015, were used in multivariable regression models to study the association of age and body weight with grip strength for individuals engaged in vigorous physical activity at least once a week. The annual rate of change in GS differed for males and females; it was constant from ages 50 to 55 years and then accelerated for females, possibly due to the menopausal transition. In contrast, the decline in GS accelerates with each year of increase in age for males. Higher body mass was associated with an increase in GS, but the increase was less pronounced for older males. The increase in GS diminished with a body mass above the median even with engagement in weekly vigorous physical activities. GS reference values for individuals engaged in vigorous physical activity add to existing reference values for general populations.

Early Adaptation To Increased Mechanical Loading After Disuse: Muscle Response In Male And Female Rats

On top of musculoskeletal alterations during spaceflight, reloading upon return induces muscle deterioration and prolongs recovery. Astronauts will return to the lunar surface by 2024, and plan for a future landing on Mars, where they will experience gravity shifts. PURPOSE: To understand the impact of acute gravitational reloading following disuse in both sexes. METHODS: 141 Adult Wistar rats were unloaded for 14d to establish muscle deconditioning, and then exposed to either 4 h or 24 h or partial weight-bearing (PWB) at 20, 40, or 100% of normal loading to simulate early adaptation to the Moon, Mars, and Earth’s gravity, respectively. Muscle strength, function and composition were assessed. Gene expression was performed in the soleus muscle using RTqPCR. RESULTS: After 14d of unloading, males lost more weight and displayed a greater decline in grip strength than females (-53.7% vs -35.9%, p < 0.0001), which was associated with greater atrophy of the soleus (p = 0.009). After 4 h of reloading, males displayed increased grip force while females did not. After 24 h, only males reloaded at PWB100 and PWB20 had a significant increase in grip strength but no change in gastrocnemius mass. Soleus mass decreased in females but increased in all males. In the soleus, myofiber size was greater in reloaded animals compared to HLS, but more so in males reloaded at PWB40 (p = 0.0002). Compared to HLS animals, gastrocnemius, myofiber size was higher in reloaded males but identical in reloaded females, regardless of the PWB level. Interestingly, reloaded males showed an increased proportion of type 1 myofibers, while females displayed an increase in hybrid myofibers. Gene expression highlighted that males were able to significantly upregulate several genes involved in muscle regeneration, including Pax7, MyoD, MyoG, Ubr5, as early as after 4 hr of reloading, while females did not. CONCLUSION: Early adaptation to PWB after unloading results in a rapid increase in grip strength in males, but not in females. Moreover, the ability for males to induce gene expression immediately following reloading might contribute to the improve muscle function. Muscle composition during recovery seems to be plastic and sex-dependent, suggesting a complex set of influences on muscle recovery after disuse. This work was supported by NASA (80NSSC19K1598).

Functional performance, nutritional status and level of physical activity of elderly

The elderly is a risk group for changes in health conditions and as well as in functional performance related to the decline in grip strength and reduced walking speed, which can compromise the performance of activities of daily living. Based on this, the objective was to analyze the factors associated with functional performance in the elderly. For that, a cross-sectional study was developed involving a group of 179 elderly people who received medical care at an outpatient clinic of the public health network. Muscle strength and gait speed were measured. Nutritional status was determined by Body Mass Index (BMI), calf circumference (CC), waist circumference (WC) and waist-to-hip ratio (WHR). Level of physical activity was measured by the adapted version of the Minnesota Leisure Activities Questionnaire. Low muscle strength was found in 20.7% of the elderly and slow gait in 20.1%. Increased risk of cardiovascular disease was found in 40.8% considering WC, and 35.2% by WHR. Most of the elderly had low weight and no loss of muscle mass. Loss of muscle strength was associated with sex and CC and gait speed were associated with sex, age, and presence of a partner (p &lt; 0.05). The chance of loss of muscle strength and lower gait speed was higher in elderly women. Loss of muscle mass due to CC was associated with the chance of loss of strength, and the chance of reduced walking speed was greater among the elderly individuals aged 75 years and over.

Milk intake across adulthood and muscle strength decline from mid- to late life: the MRC National Survey of Health and Development.

Milk is a source of several nutrients which may be beneficial for skeletal muscle. Evidence that links lower milk intake with declines in muscle strength from midlife to old age is lacking. We used data from the Medical Research Council National Survey of Health and Development to test sex-specific associations between milk consumption from age 36 to 60-64 years, low grip strength (GS) or probable sarcopenia, and GS decline from age 53 to 69 years. We included 1340 men and 1383 women with at least one measure of both milk intake and GS. Milk intake was recorded in 5-d food diaries (aged 36, 43, 53 and 60-64 years), and grand mean of total, reduced-fat and full-fat milk each categorised in thirds (T1 (lowest) to T3 (highest), g/d). GS was assessed at ages 53, 60-64, and 69 years, and probable sarcopenia classified at the age of 69 years. We employed logistic regression to examine the odds of probable sarcopenia and multilevel models to investigate decline in GS in relation to milk intake thirds. Compared with T1, only T2 (58·76-145·25 g/d) of reduced-fat milk was associated with lower odds of sex-specific low GS at the age of 69 years (OR (95 % CI): 0·59 (0·37, 0·94), P = 0·03). In multilevel models, only T3 of total milk (≥ 237·52 g/d) was associated with stronger GS in midlife in men (β (95 % CI) = 1·82 (0·18, 3·45) kg, P = 0·03) compared with T1 (≤ 152·0 g/d), but not with GS decline over time. A higher milk intake across adulthood may promote muscle strength in midlife in men. Its role in muscle health in late life needs further examination.

Protein intake, physical activity and grip strength in European and North American community-dwelling older adults: a pooled analysis of individual participant data from four longitudinal ageing cohorts.

Higher dietary protein, alone or in combination with physical activity (PA), may slow the loss of age-related muscle strength in older adults. We investigated the longitudinal relationship between protein intake and grip strength, and the interaction between protein intake and PA, using four longitudinal ageing cohorts. Individual participant data from 5584 older adults (52% women; median: 75, IQR: 71.6, 79.0 years) with up to 8.5 years (mean: 4.9, SD: 2.3 years) of follow-up from the Health ABC, NuAge, LASA and Newcastle 85+ cohorts were pooled. Baseline protein intake was assessed with food frequency questionnaires and 24h recalls and categorized into <0.8, 0.8-<1.0, 1.0-<1.2 and ≥1.2 g/kg adjusted body weight (aBW)/d. The prospective association between protein intake, its interaction with PA, and grip strength (sex- and cohort-specific) was determined using joint models (hierarchical linear mixed effects and a link function for Cox proportional hazards models). Grip strength declined on average by 0.018 SD (95%CI: -0.026, -0.006) every year. No associations were found between protein intake, measured at baseline, and grip strength, measured prospectively, or rate of decline of grip strength in models adjusted for sociodemographic, anthropometric, lifestyle and health variables (e.g., protein intake ≥1.2 vs <0.8 g/kg aBW/d: β= -0.003, 95%CI: -0.014,0.005 SD per year). There also was no evidence of an interaction between protein intake and PA. We failed to find evidence in this study to support the hypothesis that higher protein intake, alone or in combination with higher PA, slowed the rate of grip strength decline in older adults.

Decreased Diastolic Blood Pressure and Average Grip Strength in Adults With Type 1 Diabetes Compared With Controls: An Analysis of Data From the Canadian Longitudinal Study on Aging

ObjectivesOur aim in this study was to determine whether aging individuals with type 1 diabetes (T1D) have differences in cardiovascular health, assessed by blood pressure, and skeletal muscle function, assessed by grip strength, compared with matched nondiabetic controls (CON). MethodsThis investigation was a retrospective cohort analysis using baseline and 3-year follow-up data from the Canadian Longitudinal Study on Aging. Bivariate and multivariate regression analyses were used to examine the association between sociodemographic, health, behavioural and T1D-specific variables on blood pressure and grip strength in T1D and CON groups. Generalized estimating equations were used to model the average population changes in blood pressure and grip strength from baseline to follow up. ResultsThe sample included 126 individuals (63 T1D and 63 CON). Systolic blood pressure was not significantly different between groups at baseline or follow up (p>0.05). However, compared with CON, diastolic blood pressure was significantly lower at both time-points in the T1D group (p<0.001). Grip strength was consistently lower among persons with T1D (p=0.03). In the multivariate regression model, body mass index, age and sex were significantly associated with diastolic blood pressure and grip strength in both groups. In the T1D group, disease duration accounted for a large proportion of the variance in diastolic blood pressure and grip strength (17% and 9%, respectively). The rate of decline in diastolic blood pressure and grip strength did not differ between groups (p>0.05). ConclusionsDiastolic blood pressure and grip strength appear to be consistently lower and differentially regulated in individuals with T1D vs CON. Aging individuals with T1D may be at risk of premature morbidity and mortality.

Grip Strength in Patients with Gastrointestinal Diseases.

We sought to elucidate factors contributing to the grip strength (GS) decline in patients with gastrointestinal diseases (Ga-Ds, n = 602, 379 males, median age = 72 years). The GS decline in males and females was defined as <28 kg and <18 kg, respectively, following the current Asian guidelines. The median GS (male) was 28.8 kg, and GS decline (male) was found in 169 patients (44.6%). The median GS (female) was 17.5 kg, and GS decline (female) was found in 122 patients (54.7%). Advanced cancer was identified in 145 patients (24.1%). In terms of the univariate analysis of parameters of the GS decline, age (p < 0.0001), gender (p = 0.0181), body mass index (BMI, p = 0.0002), ECOG-PS (p < 0.0001), SARC-F score (p < 0.0001), hemoglobin value (p < 0.0001), total lymphocyte count (p < 0.0001), serum albumin value (p < 0.0001), C reactive protein (CRP) value (p < 0.0001), and estimated glomerular filtration rate were statistically significant. In terms of the multivariate analysis, age (p < 0.0001), BMI (p = 0.0223), hemoglobin value (p = 0.0186), serum albumin value (p = 0.0284), the SARC-F score (p = 0.0003), and CRP value (p < 0.0001) were independent parameters. In conclusion, the GS decline in patients with Ga-Ds is closely associated with not only the primary factor (i.e., aging) but also secondary factors such as inflammatory factors and nutritional factors.

Coexistent physical and cognitive decline and the development of fear of falling among Korean older adults

Although hand grip strength and cognitive function are associated with fear of falling (FOF), little is known about whether coexisting physical and cognitive decline is jointly related to FOF. This study examines whether grip strength and cognitive function interact to shape FOF and FOF-related activity restriction (FAR) among Korean older adults. This study used seven waves of the Korean Longitudinal Study of Ageing (N=3373 older adults aged 65 or over). Grip strength was assessed by a handgrip dynamometer, and cognitive function by Korean Mini-mental State Examination (K-MMSE). Fixed effects models were estimated to account for time-invariant confounders such as genetic predispositions, innate ability, and health endowments. This study estimated a joint model that included interaction effects between grip strength and cognitive function. Declines in grip strength and cognitive function were independently associated with FOF. Fixed effects estimates suggested that, despite some attenuation, controlling for individual heterogeneity does not confound the associations. The interaction model showed that coexistence of low grip strength and cognitive decline leads to a greater risk of FOF and FAR than having a single condition. Similar patterns were found for FAR. This study provides evidence that coexistent cognitive and physical decline are a significant risk factor for FOF and FAR. Given the well-established adverse effects of FOF on older adults' health and well-being, results of this study lend support to interventions to target old adults with coexistent cognitive and physical decline to remove excessive concerns about FOF.

HDAC3 Inhibition Stimulates Myelination in a CMT1A Mouse Model

Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy, with currently no effective treatment or cure. CMT1A is caused by a duplication of the PMP22 gene, which leads to Schwann cell differentiation defects and dysmyelination of the peripheral nerves. The epigenetic regulator histone deacetylase 3 (HDAC3) has been shown to negatively regulate myelination as well as its associated signaling pathways, PI3K-AKT and MAPK-ERK. We showed that these signaling pathways are indeed downregulated in the C3-PMP22 mouse model, similar to what has been shown in the CMT1A rat model. We confirmed that early postnatal defects are present in the peripheral nerves of the C3-PMP22 mouse model, which led to a progressive reduction in axon caliber size and myelination. The aim of this study was to investigate whether pharmacological HDAC3 inhibition could be a valuable therapeutic approach for this CMT1A mouse model. We demonstrated that early treatment of CMT1A mice with the selective HDAC3 inhibitor RGFP966 increased myelination and myelin g-ratios, which was associated with improved electrophysiological recordings. However, a high dose of RGFP966 caused a decline in rotarod performance and a decline in overall grip strength. Additionally, macrophage presence in peripheral nerves was increased in RGFP966 treated CMT1A mice. We conclude that HDAC3 does not only play a role in regulating myelination but is also important in the neuroimmune modulation. Overall, our results indicate that correct dosing of HDAC3 inhibitors is of crucial importance if translated to a clinical setting for demyelinating forms of CMT or other neurological disorders.

Skeletal muscle mitoribosomal defects are linked to low bone mass caused by bone marrow inflammation in male mice.

BackgroundMitochondrial oxidative phosphorylation (OxPhos) is a critical regulator of skeletal muscle mass and function. Although muscle atrophy due to mitochondrial dysfunction is closely associated with bone loss, the biological characteristics of the relationship between muscle and bone remain obscure. We showed that muscle atrophy caused by skeletal muscle‐specific CR6‐interacting factor 1 knockout (MKO) modulates the bone marrow (BM) inflammatory response, leading to low bone mass.MethodsMKO mice with lower muscle OxPhos were fed a normal chow or high‐fat diet and then evaluated for muscle mass and function, and bone mineral density. Immunophenotyping of BM immune cells was also performed. BM transcriptomic analysis was used to identify key factors regulating bone mass in MKO mice. To determine the effects of BM‐derived CXCL12 (C–X–C motif chemokine ligand 12) on regulation of bone homeostasis, a variety of BM niche‐resident cells were treated with recombinant CXCL12. Vastus lateralis muscle and BM immune cell samples from 14 patients with hip fracture were investigated to examine the association between muscle function and BM inflammation.ResultsMKO mice exhibited significant reductions in both muscle mass and expression of OxPhos subunits but increased transcription of mitochondrial stress response‐related genes in the extensor digitorum longus (P < 0.01). MKO mice showed a decline in grip strength and a higher drop rate in the wire hanging test (P < 0.01). Micro‐computed tomography and von Kossa staining revealed that MKO mice developed a low mass phenotype in cortical and trabecular bone (P < 0.01). Transcriptomic analysis of the BM revealed that mitochondrial stress responses in skeletal muscles induce an inflammatory response and adipogenesis in the BM and that the CXCL12–CXCR4 (C–X–C chemokine receptor 4) axis is important for T‐cell homing to the BM. Antagonism of CXCR4 attenuated BM inflammation and increased bone mass in MKO mice. In humans, patients with low body mass index (BMI = 17.2 ± 0.42 kg/m2) harboured a larger population of proinflammatory and cytotoxic senescent T‐cells in the BMI (P < 0.05) and showed reduced expression of OxPhos subunits in the vastus lateralis, compared with controls with a normal BMI (23.7 ± 0.88 kg/m2) (P < 0.01).ConclusionsDefects in muscle mitochondrial OxPhos promote BM inflammation in mice, leading to decreased bone mass. Muscle mitochondrial dysfunction is linked to BM inflammatory cytokine secretion via the CXCL12–CXCR4 signalling axis, which is critical for inducing low bone mass.

684 LONG-TERM CONDITIONS, MULTIMORBIDITY, LIFESTYLE FACTORS AND GRIP STRENGTH CHANGE OVER 9 YEARS IN 44,315 UK BIOBANK PARTICIPANTS

Abstract Introduction Weak grip strength is associated with a range of adverse health outcomes, and an accelerated decline in grip strength confers an even greater risk. To date there has been limited research into the factors associated with change in grip strength in mid-life. Using data from UK Biobank our aim was to investigate the associations of long-term conditions (LTCs), multimorbidity and lifestyle factors with patterns of change in grip strength. Methods We used data from 44,315 UK Biobank participants with grip strength measured at baseline (2006–10) and a subsequent study visit around nine years later. At baseline, participants’ LTCs were self-reported and categorised against a hierarchy. Multimorbidity was characterised by the number of LTC categories present (0, 1, 2 and 3+). Lifestyle factors (body mass index (BMI), smoking, diet and physical activity) were also assessed. Change in grip strength was grouped into four patterns: decline, stable low, stable high or reference (no change or increase) and used as the outcome in multinomial logistic regression models. Results Most LTC categories were associated with adverse patterns of change in grip strength (stable low and/or decline): for example, musculoskeletal/trauma conditions were associated with an increased risk of the stable low pattern (Relative Risk Ratio [RRR] = 1.63; 95% Confidence Interval [CI] 1.49–1.79). Multimorbidity and lifestyle factors had independent associations with grip strength change: those with 3+ categories of LTCs were more likely to experience decline in grip strength (RRR = 1.18;95% CI 1.08–1.28) compared to those with no LTCs. Low physical activity was associated with adverse patterns of grip strength, while raised BMI had divergent associations (both the decline and stable high patterns of grip strength change). Conclusion Individuals living with multimorbidity and those with lifestyle risk factors such as low physical activity are at increased risk of loss of strength over time.