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1.  Lipopolysaccharide-Binding Protein, a Surrogate Marker of Microbial Translocation, Is Associated With Physical Function in Healthy Older Adults 
Physical function declines, and markers of inflammation increase with advancing age, even in healthy persons. Microbial translocation (MT) is the systemic exposure to mucosal surface microbes/microbial products without overt bacteremia and has been described in a number of pathologic conditions. We hypothesized that markers of MT, soluble CD14 (sCD14) and lipopolysaccharide (LPS) binding protein (LBP), may be a source of chronic inflammation in older persons and be associated with poorer physical function.
We assessed cross-sectional relationships among two plasma biomarkers of MT (sCD14 and LBP), physical function (hand grip strength, short physical performance battery [SPPB], gait speed, walking distance, and disability questionnaire), and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), TNF-α soluble receptor 1 [TNFsR1]) in 59 older (60–89 years), healthy (no evidence of acute or chronic illness) men and women.
LBP was inversely correlated with SPPB score and grip strength (p = .02 and p < .01, respectively) and positively correlated with CRP (p = 0.04) after adjusting for age, gender, and body mass index. sCD14 correlated with IL-6 (p = .01), TNF-α (p = .05), and TNFsR1 (p < .0001). Furthermore, the correlations between LBP and SPPB and grip strength remained significant after adjusting for each inflammatory biomarker.
In healthy older individuals, LBP, a surrogate marker of MT, is associated with worse physical function and inflammation. Additional study is needed to determine whether MT is a marker for or a cause of inflammation and the associated functional impairments.
PMCID: PMC3636679  PMID: 22960476
Microbial translocation; Inflammation; Physical function; Microbiome
2.  Comparing Pain Severity Versus Pain Location in the MOBILIZE Boston Study: Chronic Pain and Lower Extremity Function* 
This study compared measures of chronic pain, for example, number of pain sites and overall pain severity, in relation to lower extremity function in the older population.
Six hundred older adults (mean age 77.9 years, 64% female) were queried about presence of chronic pain. Number of pain sites was categorized as none, single site, multisite, or widespread. Pain severity was measured in quartiles of the Brief Pain Inventory pain severity subscale. Lower extremity function was assessed by the Short Physical Performance Battery (SPPB), a composite measure of gait speed, balance, and chair stands.
Many older persons reported multisite or widespread pain (40%). Increased pain sites and pain severity were associated with poorer SPPB performance after adjusting for age, sex, height, and weight. With further adjustment for education, comorbid conditions, and depressive symptoms, multisite pain (p < .001) and most severe pain (p < .05) were associated with poorer SPPB performance, but assessed together in the same model, only the association with multisite/widespread pain remained significant (p < .01). When specific joint pain sites were evaluated together, only knee pain was associated with lower SPPB score. Pain severity was independently associated with slower gait, pain location was associated with poorer balance, and chair stands performance was associated with both pain measures.
Although multisite pain rather than pain severity was more strongly associated with overall lower extremity function, differences emerged with specific SPPB subtests. Longitudinal studies are needed to understand risk for lower extremity function decline related to chronic pain characteristics in older adults.
PMCID: PMC2691797  PMID: 19228782
Pain; Mobility; Aging; Lower extremity function; Epidemiology
3.  Relationship Between Poor Physical Function, Inflammatory Markers, and Comorbidities in HIV-Infected Women on Antiretroviral Therapy 
Journal of Women's Health  2014;23(1):69-76.
Background: HIV-infected individuals may be at increased risk of poor physical function. Chronic inflammation has been associated with decreased physical function in the elderly and may also influence physical function in HIV-infected individuals.
Methods: This cross-sectional study assessed physical function in 65 HIV-infected women aged 40 and older on stable antiretroviral treatment using the Short Physical Performance Battery (SPPB): a standardized test of balance, walking speed, and lower- extremity strength developed for elderly populations. The relationship between low SPPB score, selected demographic and medical characteristics, and high inflammatory biomarker profile was analyzed using Fisher's exact test and Wilcoxon rank sum test.
Results: The median age of subjects was 49 years (interquartile range [IQR] 45–55), and the median CD4 T-cell count was 675 cells/mm3 (IQR 436–828). Thirteen subjects (20%) had a low SPPB score. Subjects with a low SPPB score were more likely to be cigarette smokers (p=0.03), had more medical comorbidities (p=0.01), and had higher levels of interleukin-6 (IL-6) (p<0.05). They also tended to be older (median age 55 vs. 48, p=0.06), more likely to have diabetes (p=0.07), and have higher levels of soluble tumor necrosis factor-1 (p=0.09).
Conclusions: Twenty percent of women aged 40 and older with well-treated HIV had poor physical-function performance, which was associated with the high burden of comorbidities in this population and with increased IL-6. However, it is unclear from this cross-sectional study whether increased inflammation was related to poor physical function or to other factors, such as age and medical comorbidities.
PMCID: PMC3880911  PMID: 24219874
4.  Relationship Between Renal Function and Physical Performance in Elderly Hospitalized Patients 
Rejuvenation Research  2012;15(6):545-552.
Chronic kidney disease (CKD) is increasingly recognized as a cause of worsening physical functioning in older patients. The Short Physical Performance Battery (SPPB) is highly reliable in older populations, but no data on older hospitalized patients with different degrees of kidney function are available. We aimed at testing the association between estimated glomerular filtration rate (eGFR) and SPPB, either global score (range 0–12) or its individual components (muscle strength, balance, and walking speed, each ranging from 0 to 4), in a sample of older hospitalized patients. Our series consisted of 486 patients aged 65 or more consecutively enrolled in 11 acute care medical wards participating to a multicenter observational study. eGFR was obtained by the Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) equation. Physical performance was objectively measured by the SPPB. The relationship between eGFR and SPPB was investigated by multiple linear regression analysis. Physically impaired patients (SPPB total score<5) were older, had lower serum albumin and Mini-Mental State Examination (MMSE) scores as well as higher overall co-morbidity, prevalence of stroke, cancer, and anemia compared to those with intermediate (SPPB=5–8) and good physical performance (SPPB=9–12). Fully adjusted multivariate models showed that eGFR (modeled as 10 mL/min per 1.73 m2 intervals) was independently associated with the SPPB total score (B=0.49; 95% confidence interval [CI]=0.18–0.66; p=0.003), balance (B=0.30; 95% CI=0.10–0.49; p=0.005), and muscle strength (B=0.06; 95% CI=0.01–0.10; p=0.043), but not with walking speed (B=−0.04; 95% CI=−0.09–0.11; p=0.107). In conclusion, reduced renal function is associated with poorer physical performance in older hospitalized patients. SPPB is worthy of testing to monitor changes in physical performance in elderly CKD patients.
PMCID: PMC3549205  PMID: 22950422
5.  Validity and reliability of the Short Physical Performance Battery (SPPB) 
Colombia Médica : CM  null;44(3):165-171.
To assess the validity (convergent and construct) and reliability of the Short Physical Performance Battery (SPPB) among non-disabled adults between 65 to 74 years of age residing in the Andes Mountains of Colombia.
Design Validation study; Participants:
150 subjects aged 65 to 74 years recruited from elderly associations (day-centers) in Manizales, Colombia. Measurements: The SPPB tests of balance, including time to walk 4 meters and time required to stand from a chair 5 times were administered to all participants. Reliability was analyzed with a 7-day interval between assessments and use of repeated ANOVA testing. Construct validity was assessed using factor analysis and by testing the relationship between SPPB and depressive symptoms, cognitive function, and self rated health (SRH), while the concurrent validity was measured through relationships with mobility limitations and disability in Activities of Daily Living (ADL). ANOVA tests were used to establish these associations.
Test-retest reliability of the SPPB was high: 0.87 (CI95%: 0.77-0.96). A one factor solution was found with three SPPB tests. SPPB was related to self-rated health, limitations in walking and climbing steps and to indicators of disability, as well as to cognitive function and depression. There was a graded decrease in the mean SPPB score with increasing disability and poor health.
The Spanish version of SPPB is reliable and valid to assess physical performance among older adults from our region. Future studies should establish their clinical applications and explore usage in population studies.
PMCID: PMC4002038  PMID: 24892614
SPPB; aging; reliability; validity; validation studies; disability; Colombia
6.  Physical function and self-rated health status as predictors of mortality: results from longitudinal analysis in the ilSIRENTE study 
BMC Geriatrics  2008;8:34.
Physical function measures have been shown to predict negative health-related events in older persons, including mortality. These markers of functioning may interact with the self-rated health (SRH) in the prediction of events. Aim of the present study is to compare the predictive value for mortality of measures of physical function and SRH status, and test their possible interactions.
Data are from 335 older persons aged ≥ 80 years (mean age 85.6 years) enrolled in the "Invecchiamento e Longevità nel Sirente" (ilSIRENTE) study. The predictive values for mortality of 4-meter walk test, Short Physical Performance Battery (SPPB), hand grip strength, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and a SRH scale were compared using proportional hazard models. Kaplan-Meier survival curves for mortality and Receiver Operating Characteristic (ROC) curve analyses were also computed to estimate the predictive value of the independent variables of interest for mortality (alone and in combination).
During the 24-month follow-up (mean 1.8 years), 71 (21.2%) events occurred in the study sample. All the tested variables were able to significantly predict mortality. No significant interaction was reported between physical function measures and SRH. The SPPB score was the strongest predictor of overall mortality after adjustment for potential confounders (per SD increase; HR 0.64; 95%CI 0.48–0.86). A similar predictive value was showed by the SRH (per SD increase; HR 0.76; 95%CI 0.59–0.97). The chair stand test was the SPPB subtask showing the highest prognostic value.
All the tested measures are able to predict mortality with different extents, but strongest results were obtained from the SPPB and the SRH. The chair stand test may be as useful as the complete SPPB in estimating the mortality risk.
PMCID: PMC2628909  PMID: 19102751
7.  Association Between Inflammatory Components and Physical Function in the Health, Aging, and Body Composition Study: A Principal Component Analysis Approach 
In older adults, studies demonstrate an inverse relationship between physical function and individual inflammatory biomarkers. Given that the inflammatory response is a complex system, a combination of biomarkers may increase the strength and consistency of these associations. This study uses principal component analysis to identify inflammatory “component(s)” and evaluates associations between the identified component(s) and measures of physical function.
Principal component analysis with a varimax rotation was used to identify two components from eight inflammatory biomarkers measured in 1,269 older persons. The study sample is a subset of the Health, Aging, and Body Composition study.
The two components explained 56% of the total variance in the data (34%, component 1 and 22%, component 2). Five markers (tumor necrosis factor-alpha [TNF-α], sTNFRI, sTNFRII, interleukin [IL]-6sR, IL-2sR) loaded highest on the first component (TNF-α related), whereas three markers (C-reactive protein [CRP], IL-6, plasminogen activator inhibitor-1) loaded highest on the second component (CRP related). After adjusting for age, sex, race, site, sampling indicator, total lean and fat mass, physical activity, smoking, and anti-inflammatory drug use, knee strength and a physical performance battery score were inversely related to the TNF-α-related component, but not to the CRP-related component (knee strength: β^TNFα = −2.71, p = .002; β^CRP = −0.88, p = .325; physical performance battery score: β^TNFα = −0.05, p < .001; β^CRP = −0.02, p = .171). Both components were positively associated with 400-m walk time, inversely associated with grip strength, and not associated with 20-m walking speed.
At least two inflammatory components can be identified in an older population, and these components have inconsistent associations with different aspects of physical performance.
PMCID: PMC2800809  PMID: 19228783
Inflammation; Physical function; Aging; Principal component analysis
8.  Association of C-reactive protein and muscle strength in the English Longitudinal Study of Ageing 
Age  2009;31(3):171-177.
Sarcopenia has been associated with systemic inflammation and a range of other biological risk factors. The purpose of this study was to assess the systemic inflammation–muscle strength relationship in a large representative community-based cohort of older adults, and to determine the independence of this association from other biological and psychosocial risk factors. Participants were 1,926 men and 2,260 women (aged 65.3 ± 9.0 years) from the English Longitudinal Study of Ageing, a study of community dwelling older adults. We assessed hand grip strength and lower body strength (time required to complete five chair stands). Biological measures included C-reactive protein (CRP), fibrinogen, cholesterol, haemoglobin, glycated haemoglobin, adiposity, and blood pressure. Approximately 33% of the sample demonstrated elevated concentrations (≥3 mg/L) of CRP. After adjustments for age, smoking, physical activity, education, inflammatory diseases, and all other biological factors, elevated CRP was associated with poorer hand grip strength and chair stand performance in women but only chair stand performance in men. Low haemoglobin levels were consistently associated with poorer performance on both tests in women and men. These results confirm an independent association between low grade systemic inflammation (as indexed by CRP) and muscle strength that appears to be more robust in women.
PMCID: PMC2734243  PMID: 19466582
Inflammation; Muscle strength; Sarcopenia; Community sample
9.  Use of the Short Physical Performance Battery Score to Predict Loss of Ability to Walk 400 Meters: Analysis From the InCHIANTI Study 
Early detection of mobility limitations remains an important goal for preventing mobility disability. The purpose of this study was to examine the association between the Short Physical Performance Battery (SPPB) and the loss of ability to walk 400 m, an objectively assessed mobility outcome increasingly used in clinical trials.
The study sample consisted of 542 adults from the InCHIANTI study aged 65 and older, who completed the 400 m walk at baseline and had evaluations on the SPPB and 400 m walk at baseline and 3-year follow-up. Multiple logistic regression models were used to determine whether SPPB scores predict the loss of ability to walk 400 m at follow-up among persons able to walk 400 m at baseline.
The 3-year incidence of failing the 400 m walk was 15.5%. After adjusting for age, sex, education, body mass index, Mini-Mental State Examination, number of medical conditions, and 400 m walk gait speed at baseline, SPPB score was significantly associated with loss of ability to walk 400 m after 3 years. Participants with SPPB scores of 10 or lower at baseline had significantly higher odds of mobility disability at follow-up (odds ratio [OR] = 3.38, 95% confidence interval [CI]: 1.32–8.65) compared with those who scored 12, with a graded response across the range of SPPB scores (OR = 26.93, 95% CI: 7.51–96.50; OR = 7.67, 95% CI: 2.26–26.04; OR = 8.28, 95% CI: 3.32–20.67 for SPPB ≤ 7, SPPB 8, and SPPB 9, respectively).
The SPPB strongly predicts loss of ability to walk 400 m. Thus, using the SPPB to identify older persons at high risk of lower body functional limitations seems a valid means of recognizing individuals who would benefit most from preventive interventions.
PMCID: PMC2655026  PMID: 19182232
Mobility; 400 m walk; Incidence of disability; Functional limitation; Aging
10.  Total and Abdominal Adiposity Are Associated With Inflammation in Older Adults Using a Factor Analysis Approach 
Obesity-related increases in multiple inflammatory markers may contribute to the persistent subclinical inflammation common with advancing age. However, it is unclear if a specific combination of markers reflects the underlying inflammatory state. We used factor analysis to identify inflammatory factor(s) and examine their associations with adiposity in older adults at risk for disability.
Adiponectin, CRP, IL-1ra, IL-1sRII, IL-2sRα, IL-6, IL-6sR, IL-8, IL-15, sTNFRI, sTNFRII, and TNF-α were measured in 179 participants from the Lifestyle Interventions and Independence for Elders Pilot (Mean ± SD age 77 ± 4 years, 76% white, 70% women). Body mass index, waist circumference, and total fat mass were assessed by anthropometry and dual-energy x-ray absorptiometry.
IL-2sRα, sTNFRI, and sTNFRII loaded highest on the first factor (factor 1). CRP, IL-1ra, and IL-6 loaded highest on the second factor (factor 2). Factor 2, but not factor 1, was positively associated with 1-SD increments in waist circumference (β = 0.160 ± 0.057, p = .005), body mass index (β = 0.132 ± 0.053, p = .01), and total fat mass (β = 0.126 ± 0.053, p = .02) after adjusting for age, gender, race/ethnicity, site, smoking, anti-inflammatory medications, comorbidity index, health-related quality of life, and physical function. These associations remained significant after further adjustment for grip strength, but only waist circumference remained associated with inflammation after adjusting for total lean mass. There were no significant interactions between adiposity and muscle mass or strength for either factor.
Greater total and abdominal adiposity are associated with higher levels of an inflammatory factor related to CRP, IL-1ra, and IL-6 in older adults, which may provide a clinically useful measure of inflammation in this population.
PMCID: PMC3437966  PMID: 22451470
Aging; Adiposity; Inflammation; Muscle impairment; Factor analysis
11.  Health-Related Quality of Life in Older Adults at Risk for Disability 
The number of older adults living in the U.S. continues to increase, and recent research has begun to target interventions to older adults who have mobility limitations and are at risk for disability. The objective of this study is to describe and examine correlates of health-related quality of life in this population subgroup using baseline data from a larger intervention study.
The Lifestyle Interventions and Independence for Elders–Pilot study (LIFE–P) was a randomized, controlled trial that compared a physical activity intervention to a non-exercise educational intervention with 424 older adults at risk for disability. Baseline data (collected April–December 2004; analyzed in 2006) included demographics, medical history, the Quality of Well-Being Scale (QWB-SA), a timed 400 m walk, and the Short Physical Performance Battery (SPPB). Descriptive HRQOL data are presented. Hierarchical linear regression models were used to examine correlates of HRQOL.
The mean QWB-SA score for the sample was 0.630 on an interval scale ranging from 0.0 (death) to 1.0 (asymptomatic, optimal functioning). The mean of 0.630 is 0.070 lower than a comparison group of healthy older adults. The variables associated with lower HRQOL included white ethnicity, more comorbid conditions, slower 400-m walk times, and lower SPPB balance and chair stand scores.
Older adults who are at risk for disability had reduced HRQOL. Surprisingly, however, mobility was a stronger correlate of HRQOL than an index of comorbidity, suggesting that interventions addressing mobility limitations may provide significant health benefits to this population.
PMCID: PMC1995005  PMID: 17826582
12.  Lifetime occupation and physical function: a prospective cohort study on persons aged 80 years and older living in a community 
Several studies have reported predictors for loss of mobility and impairments of physical performance among frail elderly people.
To evaluate the relationship between lifetime occupation and physical function in persons aged 80 years or older.
Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study (a prospective cohort study performed in a mountain community in Central Italy). Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4-metre walking speed, balance, and chair stand tests. Muscle strength was measured by hand grip strength. Lifetime occupation was categorised as manual or non-manual work.
Mean age of participants was 85.9 (SD 4.9) years. Of the total sample, 273 subjects (75%) had a history of manual work and 91 subjects (25%) a history of non-manual work. Manual workers had significant lower grip strength and physical performance battery score (indicating worse performance) than non-manual workers. After adjustment for potential confounders (including age, gender, education, depression, cognitive performance scale score, physical activity, number of diseases, hearing impairment, history of alcohol abuse, smoking habit, and haemoglobin level), manual workers had significantly worse physical function (hand grip strength: non-manual workers 32.5 kg, SE 1.4, manual workers 28.2 kg, SE 0.8; physical performance battery score: non-manual workers 7.1, SE 0.4, manual workers 6.1, SE 0.2).
A history of manual work, especially when associated with high physical stress, is independently associated with low physical function and muscle strength in older persons.
PMCID: PMC2092516  PMID: 16782827
13.  Lifetime occupation and physical function: a prospective cohort study on persons aged 80 years and older living in a community 
Several studies have reported predictors for loss of mobility and impairments of physical performance among frail elderly people.
To evaluate the relationship between lifetime occupation and physical function in persons aged 80 years or older.
Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study (a prospective cohort study performed in a mountain community in Central Italy). Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4‐metre walking speed, balance, and chair stand tests. Muscle strength was measured by hand grip strength. Lifetime occupation was categorised as manual or non‐manual work.
Mean age of participants was 85.9 (SD 4.9) years. Of the total sample, 273 subjects (75%) had a history of manual work and 91 subjects (25%) a history of non‐manual work. Manual workers had significant lower grip strength and physical performance battery score (indicating worse performance) than non‐manual workers. After adjustment for potential confounders (including age, gender, education, depression, cognitive performance scale score, physical activity, number of diseases, hearing impairment, history of alcohol abuse, smoking habit, and haemoglobin level), manual workers had significantly worse physical function (hand grip strength: non‐manual workers 32.5 kg, SE 1.4, manual workers 28.2 kg, SE 0.8; physical performance battery score: non‐manual workers 7.1, SE 0.4, manual workers 6.1, SE 0.2).
A history of manual work, especially when associated with high physical stress, is independently associated with low physical function and muscle strength in older persons.
PMCID: PMC2092516  PMID: 16782827
lifetime occupation; physical performance; aging;  ilSIRENTE study
14.  Effects of a 6-month multimodal training intervention on retention of functional fitness in older adults: A randomized-controlled cross-over design 
Older adults have the highest rates of disability, functional dependence and use of healthcare resources. Training interventions for older individuals are of special interest where regular physical activity (PA) has many health benefits. The main purpose of this study was to assess the immediate and long-term effects of a 6-month multimodal training intervention (MTI) on functional fitness in old adults.
For this study, 117 participants, 71 to 90 years old, were randomized in immediate intervention group and a control group (delayed intervention group). The intervention consisted of daily endurance and twice-a-week strength training. The method was based on a randomized-controlled cross-over design. Short Physical Performance Battery (SPPB), 8 foot up-and-go test, strength performance, six min walking test (6 MW), physical activity, BMI and quality of life were obtained at baseline, after a 6-month intervention- and control phase, again after 6-month crossover- and delayed intervention phase, and after anadditional 6-month follow-up.
After 6 months of MTI, the intervention group improved in physical performance compared with the control group via Short Physical Performance Battery (SPPB) score (mean diff = 0.6, 95 % CI: 0.1, 1.0) and 8-foot up-and-go test (mean diff = −1.0 s, 95 % CI: -1.5, -0.6), and in endurance performance via 6-minute walking test (6 MW) (mean diff = 44.2 meters, 95 % CI: 17.1, 71.2). In strength performance via knee extension the intervention group improved while control group declined (mean diff = 55.0 Newton, 95 % CI: 28.4, 81.7), and also in PA (mean diff = 125.9 cpm, 95 % CI: 96.0, 155.8). Long-term effects of MTI on the particpants was assesed by estimating the mean difference in the variables measured between time-point 1 and 4: SPPB (1.1 points, 95 % CI: 0.8, 1.4); 8-foot up-and-go (−0.9 s, 95 % CI: -1.2, -0.6); 6 MW (18.7 m, 95 % CI: 6.5, 31.0); knee extension (4.2 Newton, 95 % CI: -10.0, 18.3); hand grip (6.7 Newton, 95 % CI: -4.4, 17.8); PA (−4.0 cpm, 95 % CI: -33.9, 26.0); BMI (−0.6 kg/m2, 95 % CI: -0.9, -0.3) and Icelandic quality of life (0.3 points, 95 % CI: -0.7, 1.4).
Our results suggest that regular MTI can improve and prevent decline in functional fitness in older individuals, influence their lifestyle and positively affect their ability to stay independent, thus reducing the need for institutional care.
Trial registration
This study was approved by the National Bioethics Committee in Iceland, VSNb20080300114/03-1
PMCID: PMC3522556  PMID: 22963328
Physical activity; Functional fitness; SPPB; 6 MW; Strength; Cross-over design
15.  Education-related differences in physical performance after age 60: a cross-sectional study assessing variation by age, gender and occupation 
BMC Public Health  2013;13:641.
Having a low level of education has been associated with worse physical performance. However, it is unclear whether this association varies by age, gender or the occupational categories of manual and non-manual work. This study examined whether there are education-related differences across four dimensions of physical performance by age, gender or occupational class and to what extent chronic diseases and lifestyle-related factors may explain such differences.
Participants were a random sample of 3212 people, 60 years and older, both living in their own homes and in institutions, from the Swedish National Study on Aging and Care, in Kungsholmen, Stockholm. Trained nurses assessed physical performance in grip strength, walking speed, balance and chair stands, and gathered data on education, occupation and lifestyle-related factors, such as physical exercise, body mass index, smoking and alcohol consumption. Diagnoses of chronic diseases were made by the examining physician.
Censored normal regression analyses showed that persons with university education had better grip strength, balance, chair stand time and walking speed than people with elementary school education. The differences in balance and walking speed remained statistically significant (p < 0.05) after adjustment for chronic diseases and lifestyle. However, age-stratified analyses revealed that the differences were no longer statistically significant in advanced age (80+ years). Gender-stratified analyses revealed that women with university education had significantly better grip strength, balance and walking speed compared to women with elementary school education and men with university education had significantly better chair stands and walking speed compared to men with elementary school education in multivariate adjusted models. Further analyses stratified by gender and occupational class suggested that the education-related difference in grip strength was only evident among female manual workers, while the difference in balance and walking speed was only evident among female and male non-manual workers, respectively.
Higher education was associated with better lower extremity performance in people aged 60 to 80, but not in advanced age (80+ years). Our results indicate that higher education is associated with better grip strength among female manual workers and with better balance and walking speed among female and male non-manual workers, respectively.
PMCID: PMC3733740  PMID: 23842209
Educational status; Aging; Chronic diseases; Muscle strength; Walking; Postural balance
16.  Lower Extremity Muscle Mass Predicts Functional Performance in Mobility-Limited Elders 
This study examined the influence of lower extremity body composition and muscle strength on the severity of mobility-disability in community-dwelling older adults.
Fifty-seven older males and females (age 74.2 ± 7 yrs; BMI 28.9 ± 6 kg/m2) underwent an objective assessment of lower extremity functional performance, the Short Physical Performance Battery test (SPPB). Participants were subsequently classified as having moderate (SPPB score > 7: n = 38) or severe mobility impairments (SPPB score ≤7: n = 19). Body composition was assessed using dual-energy X-ray absorptiometry and provided measures of bone mineral density (BMD), total leg lean mass (TLM) and total body fat. Maximal hip extensor muscle strength was estimated using the bilateral leg press exercise. Multiple logistic regression analysis was utilized to identify the significant independent variables that predicted the level of mobility-disability.
TLM was a strong independent predictor of the level of functional impairment, after accounting for chronic medical conditions, BMD, body fat, body weight and habitual physical activity. In a separate predictive model, reduced muscle strength was also a significant predictor of severe functional impairment. The severity of mobility-disability was not influenced by gender (p = 0.71). A strong association was elicited between TLM and muscle strength (r = 0.78, p < 0.01).
These data suggest that lower extremity muscle mass is an important determinant of physical performance among functionally-limited elders. Such findings may have important implications for the design of suitable strategies to maintain independence in older adults with compromised physical functioning. Additional studies are warranted to assess the efficacy of lifestyle, exercise or therapeutic interventions for increasing lean body mass in this population.
PMCID: PMC2544628  PMID: 18615232
Aging; Sarcopenia; Mobility; Muscle Mass; Strength
17.  Body Mass Index, Muscle Strength and Physical Performance in Older Adults from Eight Cohort Studies: The HALCyon Programme 
PLoS ONE  2013;8(2):e56483.
To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity.
Cross-sectional data from eight UK cohort studies (total N = 16 444) participating in the Healthy Ageing across the Life Course (HALCyon) research programme, ranging in age from 50 to 90+ years at the time of physical capability assessment, were used. Regression models were fitted within each study and meta-analysis methods used to pool regression coefficients across studies and to assess the extent of heterogeneity between studies.
Higher BMI was associated with poorer performance on chair rise (N = 10 773), walking speed (N = 9 761) and standing balance (N = 13 921) tests. Higher BMI was associated with stronger grip strength in men only. Stronger grip strength was associated with better performance on all tests with a tendency for the associations to be stronger in women than men; for example, walking speed was higher by 0.43 cm/s (0.14, 0.71) more per kg in women than men. Both BMI and grip strength remained independently related with performance after mutual adjustment, but there was no evidence of effect modification. Both BMI and grip strength exhibited non-linear relations with performance; those in the lowest fifth of grip strength and highest fifth of BMI having particularly poor performance. Findings were similar when waist circumference was examined in place of BMI.
Older men and women with weak muscle strength and high BMI have considerably poorer performance than others and associations were observed even in the youngest cohort (age 53). Although causality cannot be inferred from observational cross-sectional studies, our findings suggest the likely benefit of early assessment and interventions to reduce fat mass and improve muscle strength in the prevention of future functional limitations.
PMCID: PMC3577921  PMID: 23437142
18.  Effects of a weight loss plus exercise program on physical function in overweight, older women: a randomized controlled trial 
Obesity and a sedentary lifestyle are associated with physical impairments and biologic changes in older adults. Weight loss combined with exercise may reduce inflammation and improve physical functioning in overweight, sedentary, older adults. This study tested whether a weight loss program combined with moderate exercise could improve physical function in obese, older adult women.
Participants (N = 34) were generally healthy, obese, older adult women (age range 55–79 years) with mild to moderate physical impairments (ie, functional limitations). Participants were randomly assigned to one of two groups for 24 weeks: (i) weight loss plus exercise (WL+E; n = 17; mean age = 63.7 years [4.5]) or (ii) educational control (n = 17; mean age = 63.7 [6.7]). In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions within their community each week. During exercise sessions, participants engaged in brisk walking and lower-body resistance training of moderate intensity. Participants in the educational control group attended monthly health education lectures on topics relevant to older adults. Outcomes were: (i) body weight, (ii) walking speed (assessed by 400-meter walk test), (iii) the Short Physical Performance Battery (SPPB), and (iv) knee extension isokinetic strength.
Participants randomized to the WL+E group lost significantly more weight than participants in the educational control group (5.95 [0.992] vs 0.23 [0.99] kg; P < 0.01). Additionally, the walking speed of participants in the WL+E group significantly increased compared with that of the control group (reduction in time on the 400-meter walk test = 44 seconds; P < 0.05). Scores on the SPPB improved in both the intervention and educational control groups from pre- to post-test (P < 0.05), with significant differences between groups (P = 0.02). Knee extension strength was maintained in both groups.
Our findings suggest that a lifestyle-based weight loss program consisting of moderate caloric restriction plus moderate exercise can produce significant weight loss and improve physical function while maintaining muscle strength in obese, older adult women with mild to moderate physical impairments.
PMCID: PMC3131984  PMID: 21753869
obesity; weight loss; physical function; oxidative stress; inflammation; walking speed
19.  Angiotensin-Converting Enzyme Inhibitor Use by Older Adults Is Associated with Greater Functional Responses to Exercise 
To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training.
Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability.
Four academic research centers within the United States.
Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers.
A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA).
Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)).
Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91). The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively).
For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers.
PMCID: PMC3625953  PMID: 22726232
aging; exercise; physical function; LIFE Study; ACE inhibitors
20.  Predictive Value of the Short Physical Performance Battery Following Hospitalization in Older Patients 
Hospitalization represents a stressful and potentially hazardous event for older persons. We evaluated the value of the Short Physical Performance Battery (SPPB) in predicting rates of functional decline, rehospitalization, and death in older acutely ill patients in the year after discharge from the hospital.
Prospective cohort study of 87 patients aged 65 years and older who were able to walk and with a Mini-Mental State Examination score ≥18 and admitted to the hospital with a clinical diagnosis of congestive heart failure, pneumonia, chronic obstructive pulmonary disease, or minor stroke. Patients were evaluated with the SPPB at hospital admission, were reevaluated the day of hospital discharge, and 1 month later. Subsequently, they were followed every 3 months by telephone interviews to ascertain functional decline, new hospitalizations, and vital status.
After adjustment for potential confounders, including self-report activity of daily living and comorbidity, the SPPB score at discharge was inversely correlated with the rate of decline in activity of daily living performance over the follow-up (p < .05). In a multivariable discrete-time survival analysis, patients with poor SPPB scores at hospital discharge (0–4) had a greater risk of rehospitalization or death (odds ratio: 5.38, 95% confidence interval: 1.82–15.9) compared with those with better SPPB scores (8–12). Patients with early decline in SPPB score after discharge also had steeper increase in activity of daily living difficulty and higher risk of rehospitalization or death over the next year.
In older acutely ill patients who have been hospitalized, the SPPB provides important prognostic information. Lower extremity performance-based functional assessment might identify older patients at high risk of poor outcomes after hospital discharge.
PMCID: PMC3011958  PMID: 20861145
SPPB; Hospitalization; Disability; Mortality; Prognosis
21.  Measures of Physical Performance Capture the Excess Disability Associated With Hip Pain or Knee Pain in Older Persons 
Hip pain (HP) and knee pain (KP) may specifically affect function and performance; few studies investigate the functional impact of HP or KP in the same population.
Population-based sample of older individuals living in the Chianti area (Tuscany, Italy) (1998–2000); 1006 persons (564 women and 442 men) were included in this analysis; 11.9% reported HP and 22.4% reported KP in the past 4 weeks. Self-reported disability and lower extremity performance, measured by 400-m walk test and by the short physical performance battery (SPPB, including standing balance, chair raising, and 4-m walk test), were compared in participants reporting HP or KP versus those free of these conditions; the relationship of HP or KP with performance and self-reported disability was studied, adjusting for age, sex, hip or knee flexibility, muscle strength, multiple joint pain, major medical conditions, and depression.
Participants reporting HP were more likely to report disability in shopping, cutting toenails, carrying a shopping bag, and using public transportation; those with KP reported more disability in cutting toenails and carrying a shopping bag. Participants reporting HP or KP had significantly lower SPPB scores. Adjusting by SPPB, pain no longer predicted self-reported disability, except for “HP—carrying a shopping bag.”
In our cohort of older persons, those with HP reported disability in a wider range of activities than those with KP. Physical performance measured by SPPB was impaired in both conditions. Reduced lower extremity performance captures the excess disability associated with either HP or KP.
PMCID: PMC2773811  PMID: 19797345
Hip pain; Knee pain; Older persons; Performance; Disability
22.  The Relationship of Reduced Peripheral Nerve Function and Diabetes With Physical Performance in Older White and Black Adults 
Diabetes Care  2008;31(9):1767-1772.
OBJECTIVE—Poor peripheral nerve function is prevalent in diabetes and older populations, and it has great potential to contribute to poor physical performance.
RESEARCH DESIGN AND METHODS—Cross-sectional analyses were done for the Health, Aging, and Body Composition (Health ABC) Study participants (n = 2,364; 48% men; 38% black; aged 73–82 years). Sensory and motor peripheral nerve function in legs/feet was assessed by 10- and 1.4-g monofilament perception, vibration detection, and peroneal motor nerve conduction amplitude and velocity. The Health ABC lower-extremity performance battery was a supplemented version of the Established Populations for the Epidemiologic Studies of the Elderly battery (chair stands, standing balance, and 6-m walk), adding increased stand duration, single foot stand, and narrow walk.
RESULTS—Diabetic participants had fewer chair stands (0.34 vs. 0.36 stands/s), shorter standing balance time (0.69 vs. 0.75 ratio), slower usual walking speed (1.11 vs. 1.14 m/s), slower narrow walking speed (0.80 vs. 0.90 m/s), and lower performance battery score (6.43 vs. 6.93) (all P < 0.05). Peripheral nerve function was associated with each physical performance measure independently. After addition of peripheral nerve function in fully adjusted models, diabetes remained significantly related to a lower performance battery score and slower narrow walking speed but not to chair stands, standing balance, or usual walking speed.
CONCLUSIONS—Poor peripheral nerve function accounts for a portion of worse physical performance in diabetes and may be directly associated with physical performance in older diabetic and nondiabetic adults. The impact of peripheral nerve function on incident disability should be evaluated in older adults.
PMCID: PMC2518342  PMID: 18535192
23.  The physical capability of community-based men and women from a British cohort: the European Prospective Investigation into Cancer (EPIC)-Norfolk study 
BMC Geriatrics  2013;13:93.
The European Working Group for Sarcopenia in Older People (EWGSOP) published a case-finding algorithm for sarcopenia, recommending muscle mass measurement in older adults with low grip strength (women <20 kg; men <30 kg) or slow walking speed (≤0.8 m/s). However, the implications of adopting this algorithm into clinical practice are unclear. Therefore, we aimed to explore the physical capability of men and women from a British population-based cohort study.
In the European Prospective Investigation into Cancer-Norfolk study, 8,623 community-based adults (48-92 years old) underwent assessment of grip strength, walking speed, timed chair stands and standing balance. The proportion of older men and women (≥65 years) fulfilling EWGSOP criteria for muscle mass measurement was estimated. Additionally, cross-sectional associations of physical capability with age and sex were explored using linear and logistic regression.
Approximately 1 in 4 older participants (28.8%) fulfilled criteria for muscle mass measurement with a greater proportion of women than men falling below threshold criteria (33.6% versus 23.6%). Even after adjustment for anthropometry, women were 12.4 kg (95% Confidence Interval [CI] 12.0, 12.7) weaker, took 12.0% (95% CI 10.0, 14.0) longer to perform five chair stands and were 1.82 (95% CI 1.48, 2.23) times more likely to be unable to hold a tandem stand for 10 seconds than men, although usual walking speed was similar. Physical capability was inversely associated with age and per year, walking speed decreased by 0.01 m/s (95% CI 0.01, 0.01) and grip strength decreased by 0.49 kg (men; 95% CI 0.46, 0.51) and 0.25 kg (women; 95% CI 0.23, 0.27). Despite this, there was still variation within age-groups and not all older people had low physical capability.
Every effort to optimise functional health in later life should be made since poor function is not inevitable. However, if the EWGSOP sarcopenia case-finding algorithm is endorsed, large proportions of older people could qualify for muscle mass measurement which is not commonly available. Considering population ageing, further discussion is needed over the utility of muscle mass measurement in clinical practice.
PMCID: PMC3846689  PMID: 24020915
Ag(e)ing; Sarcopenia; Hand strength; Physical capability; Sex factors
24.  Gonadal Status and physical performance in older men 
Male aging is characterized by a progressive decline in serum testosterone levels and physical performance. Low testosterone levels may be implicated in the decline of physical performance and consequent mobility disability that occurs with aging. During the recent years many consensus reports have advocated that one of the potential effects of testosterone supplementation is the improvement in mobility. However, to the best of our knowledge no study has fully investigated the relationship between gonadal status and objective measures of physical performance in older men and their determinants.
We evaluated 455 ≥ 65 year old male participants of InCHIANTI study a population based study in two municipalities of Tuscany, Italy with complete data on testosterone levels, hand grip strength, cross-sectional muscle area (CSMA), short physical performance battery (SPPB). Linear models were used to test the relationship between gonadal status and determinants of physical performance.
According to baseline serum levels of total testosterone, three different groups of older men were created: 1) severely hypogonadal (N= 23),total testosterone levels ≤230 ng /dl; 2) moderately hypogonadal (N=88), total testosterone >230 and <350 ng/dL), and 3) eugonadal (N=344), testosterone levels ≥350 ng/dL. With increased severity of hypogonadal status, participants were significantly older while their BMI was substantially similar. In the age and BMI adjusted analysis, there was a significant difference in hemoglobin levels, hand grip strength and SPPB score (p for trend<0.001) among −3 groups, with severely hypogonadal men having lower values of hemoglobin, muscle strength and physical performance. We found no association between testosterone group assignment and calf muscle mass and 4 meter walking speed. In the multivariate analysis grip strength (p for trend=0.004) and haemoglobin (p for trend <0.0001) but not SPPB and other determinants of physical performance were significantly different between the 3 groups.
In older men, gonadal status is independently associated with some determinants (hemoglobin and muscle strength) of physical performance.
PMCID: PMC3142745  PMID: 20937007
testosterone; physical performance; older men
Clinical medicine. Geriatrics  2008;2008(1):9-15.
(a) To compare exercise performance and leisue-time physical activity (LTPA) between older men and women, (b) to assess the relationship between exercise performance and LTPA, and (c) to determine whether group differences in exercise performance persist after controlling for LTPA.
A total of 105 women and 155 men who were 65 years of age and older participated in this study. Subjects were characterized on exercise performance by a 6-minute walk test, and by a short physical performance battery (SPPB) consisting of a repeated chair rise test, a standing balance test, and a 4-meter walk test. Additionally, LTPA was assessed using the Minnesota LTPA questionnaire.
Women had a 7% lower SPPB value (P < 0.001), a 12% shorter 6-minute walk distance (P < 0.001), and a 28% lower LTPA value (P < 0.011) than the older men. LTPA was significantly related (P < 0.01) to both SPPB and 6-minute walk distance in the older men and women. Group differences in SPPB and 6-minute walk distance between older men and women were no longer present (P > 0.05) after controlling for LTPA.
Older women have impaired exercise performance and lower LTPA compared to older men. Furthermore, sex differences in exercise performance no longer exist after controlling for LTPA.
PMCID: PMC3679925  PMID: 23772175
Age; Exercise; Gender; Physical Function

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