Sensorimotor Peripheral Nerve Function and Physical Activity in Older Men.

We determined whether sensorimotor peripheral nerve (PN) function was associated with physical activity (PA) in older men. The Osteoporotic Fractures in Men Study Pittsburgh, PA, site (n = 328, age 78.8 ± 4.7 years) conducted PN testing, including: peroneal motor and sural sensory nerve conduction (latencies, amplitudes: CMAP and SNAP for motor and sensory amplitude, respectively), 1.4g/10g monofilament (dorsum of the great toe), and neuropathy symptoms. ANOVA and multivariate linear regression modeled PN associations with PA (Physical Activity Scale for the Elderly [PASE] and SenseWear Armband). After multivariable adjustment, better motor latency was associated with higher PASE scores (160.5 ± 4.8 vs. 135.6 ± 6.7, p < .01). Those without versus with neuropathy symptoms had higher PASE scores (157.6 ± 5.3 vs. 132.9 ± 7.1, p < .01). Better versus worse SNAP was associated with slightly more daily vigorous activity (9.5 ± 0.8 vs. 7.3 ± 0.7, p = .05). Other PN measures were not associated with PA. Certain PN measures were associated with lower PA, suggesting a potential pathway for disability.

Fracture risk in diabetic elderly men: the MrOS study.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with increased fracture risk in women but few studies are available in men. To evaluate the relationship between diabetes and prospective non-vertebral fractures in elderly men, we used data from the Osteoporotic Fractures in Men (MrOS) study. METHODS: The MrOS enrolled 5,994 men (aged ≥65 years). Diabetes (ascertained by self-report, the use of medication for diabetes or an elevated fasting glucose level) was reported in 881 individuals, 80 of whom were using insulin. Hip and spine bone mineral density (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the men were followed for incident non-vertebral fractures using a triannual (3 yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional hazards model was used to assess the incident risk of fractures. RESULTS: In models adjusted for age, race, clinic site and total hip BMD, the risk of non-vertebral fracture was higher in men with diabetes compared with normoglycaemic men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46, 95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After multivariable adjustment, the risk of non-vertebral fracture remained higher only among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69). CONCLUSIONS/INTERPRETATION: Men with diabetes who are using insulin have an increased risk of non-vertebral fracture for a given age and BMD.

Patterns of 12-year change in physical activity levels in community-dwelling older women: can modest levels of physical activity help older women live longer?

Few studies have addressed changes in physical activity participation over time among the elderly. The authors hypothesized that there were distinct trajectories of physical activity level over time and identifiable predictors of such trajectories, as well as that the maintenance of regular physical activity, even below recommended levels, was associated with lower mortality risk. Using longitudinal data (1994-2009) from 433 initially high-functioning older women aged 70-79 years at baseline, a joint latent class and survival mixture model identified 4 activity trajectory classes: always active (16.6%), fast declining (19.2%), stable moderate (32.3%), and always sedentary (31.9%). Obesity, coronary artery disease, chronic obstructive pulmonary disease, depressive symptoms, low self-efficacy, mobility disability, and low energy were associated with sedentary behavior and/or a fast decline in activity. Women in the fast declining and always sedentary classes had hazard ratios for death of 2.34 (95% confidence interval: 1.20, 4.59) and 3.34 (95% confidence interval: 1.72, 6.47), respectively, compared with the always active class; no mortality difference was found between the stable moderate and always active groups (hazard ratio = 1.24, 95% confidence interval: 0.63, 2.47). Our findings suggest that physical activity does not have to be vigorous to be beneficial and that the gain may be the greatest among women who reported the lowest levels of activity.

Feed-forward loop between body composition, strength and performance in older adults.

Frailty syndrome is hypothesized to arise from malfunction in feedback mechanisms among interacting physiological systems. However, empirical evidence to support this hypothesis is not yet available. We present evidence of a feed-forward loop relationship between certain components of the frailty syndrome: body composition, strength and physical performance level. The evidence has been found by performing statistical analysis on measures from 878 females and 588 males aged 60-97, participating in the Rancho Bernardo Study, followed for at least three visits over 12 years. In the analysis, we have used fat mass and lean mass (measured by whole body DXA scans), grip strength (measured by dynamometer) and time to get up and walk a certain distance. The results provide evidence of a feed-forward loop between these variables. The results also suggest that adverse changes in body composition would not only reduce the physical performance and grip strength, but the changes would further result in adverse changes in body composition. Our findings support the hypothesis that feed-forward loops are present between the components of the frailty syndrome at the time of development of frailty, which itself may be a manifestation of dysregulated energetics.

Prevalence and correlates of sleep-disordered breathing in older men: osteoporotic fractures in men sleep study.

OBJECTIVES: To determine the prevalence and distribution of sleep-disordered breathing and associated correlates in a large cohort of older men using several standardized definitions. DESIGN: Cross-sectional analyses. SETTING: Six U.S. communities. PARTICIPANTS: Polysomnography was performed on 2,911 participants of the Outcomes of Sleep Disorders in Older Men Sleep Study (mean age+/-standard deviation 76.38+/-5.53; body mass index 27.17+/-3.8 kg/m(2)). MEASUREMENTS: Three outcomes were assessed: sleep-disordered breathing (respiratory disturbance index > or =15), obstructive apnea (obstructive apnea index > or =5), and central apnea (central apnea index > or =5). RESULTS: The prevalence of moderate-severe sleep-disordered breathing was estimated to be 21.4% to 26.4%. Multivariable logistic regression models demonstrated that age (adjusted odds ratio (AOR) per 5-year increase =1.24, 95% confidence interval (CI)=1.15-1.34), obesity (AOR=2.54, 95% CI=2.09-3.09), Asian versus Caucasian race (AOR=2.14, 95% CI=1.33-3.45), snoring (AOR=2.01, 95% CI=1.62-2.49), sleepiness (AOR=1.41, 95% CI=1.11-1.79), hypertension (AOR=1.26, 95% CI=1.06-1.50), cardiovascular disease (AOR=1.24, 95% CI=1.19-1.29), and heart failure (AOR=1.81, 1.31-2.51) were independently associated with sleep-disordered breathing; snoring (AOR=2.10, 95% CI=1.67-2.70), age (AOR per 5-year increase=1.27, 95% CI=1.18-1.38), obesity (AOR=1.48, 95% CI=1.21-1.82), and heart failure (AOR=1.60, 95% CI=1.15-2.24) were associated with obstructive apnea; and age (AOR=1.33, 1.17-1.50) and heart failure (AOR=1.88, 95% CI=1.17-3.04) were associated with central apnea. CONCLUSION: Regardless of definition, a high prevalence of sleep disorders is observed in community-dwelling older men. Qualitatively similar associations were observed between sleep disorders and snoring, obesity, and comorbidities, as reported for middle aged populations. Asian race was associated with sleep-disordered breathing.

Comparison of Handgrip and Leg Extension Strength in Predicting Slow Gait Speed in Older Adults.

OBJECTIVES: To compare the relative predictive power of handgrip and leg extension strength in predicting slow walking. DESIGN: Report of correlative analysis from two epidemiological cohort studies. SETTING: Foundation of the National Institutes of Health Sarcopenia Project. PARTICIPANTS: Men and women aged 67 to 93 (N=6,766). MEASUREMENTS: Leg strength, handgrip strength, and gait speed were measured. Strength cutpoints associated with slow gait speed were developed using classification and regression tree analyses and compared using ordinary least squares regression models. RESULTS: The cutpoints of lower extremity strength associated with slow gait speed were 154.6 N-m in men and 89.9 N-m in women for isometric leg extension strength and 94.5 N-m in men and 62.3 N-m in women for isokinetic leg extension strength. Weakness defined according to handgrip strength (odds ratios (OR)=1.99 to 4.33, c-statistics=0.53 to 0.67) or leg strength (ORs=2.52 to 5.77; c-statistics=0.61 to 0.66) was strongly related to odds of slow gait speed. Lower extremity strength contributed 1% to 16% of the variance and handgrip strength contributed 3% to 17% of the variance in the prediction of gait speed depending on sex and mode of strength assessment. CONCLUSION: Muscle weakness of the leg extensors and forearm flexors is related to slow gait speed. Leg extension strength is only a slightly better predictor of slow gait speed. Thus, handgrip and leg extension strength appear to be suitable for screening for muscle weakness in older adults.

Prevalence and associations of respiratory-related leg movements: the MrOS sleep study.

OBJECTIVES: Obstructive respiratory events often terminate with an associated respiratory-related leg movement (RRLM). Such leg movements are not scored as periodic leg movements (periodic limb movements during sleep, PLMS), although the criteria for distinguishing RRLM from PLMS differ between the American Academy of Sleep Medicine (AASM) and the World Association of Sleep Medicine (WASM)/ International Restless Legs Syndrome Study Group (IRLSSG) scoring manuals. Such LMs may be clinically significant in patients with obstructive sleep apnea (OSA). The prevalence and correlation of RRLM in men with OSA were examined. METHODS: A case-control sample of 575 men was selected from all men with an apnea-hypopnea index (AHI, ≥3% desaturation criteria) ≥ 10 and good data from piezoelectric leg movement sensors at the first in-home sleep study in the MrOS cohort (mean age = 76.8 years). Sleep studies were rescored for RRLMs using five different RRLM definitions varying in both latency of leg movement onset from respiratory event termination and duration of the leg movement. The quartile of RRLM% (the number of RRLM/the number of hypopneas + apneas) was derived. RESULTS: The nonparametric densities of RRLM% were most influenced by alterations in the latency rather than the duration of the LM. The most liberal RRLM definition (latency 0-5 s, duration 0.5-10 s) led to a median RRLM% of 23.4 (interquartile range 12.41, 37.12) in this sample. The average AHI and arousal index increased as the quartile of RRLM% increased, as well as the prevalence of chronic obstructive pulmonary disease (COPD). The prevalence of those with a history of hypertension decreased as RRLM% increased. The non-Caucasian race was associated with lower RRLM%. CONCLUSION: Within an elderly sample with moderate to severe OSA, piezoelectric-defined RRLM% is associated with a number of sleep-related and demographic factors. Further study of the optimal definition, predictors, and consequences of RRLM is warranted.

Strength and function response to clinical interventions of older women categorized by weakness and low lean mass using classifications from the Foundation for the National Institute of Health sarcopenia project.

BACKGROUND: The Foundation for the National Institutes of Health Sarcopenia Project developed data-driven cut-points for clinically meaningful weakness and low lean body mass. This analysis describes strength and function response to interventions based on these classifications. METHODS: In data from four intervention studies, 378 postmenopausal women with baseline and 6-month data were evaluated for change in grip strength, appendicular lean mass corrected for body mass index, leg strength and power, and short physical performance battery (SPPB). Clinical interventions included hormones, exercise, and nutritional supplementation. Differences in outcomes were evaluated between (i) those with and without weakness and (ii) those with weakness and low lean mass or with one but not the other. We stratified analyses by slowness (walking speed ≤ 0.8 m/s) and by treatment assignment. RESULTS: The women (72±7 years; body mass index of 26±5kg/m(2)) were weak (33%), had low lean mass (14%), or both (6%). Those with weakness increased grip strength, lost less leg power, and gained SPPB score (p < .05) compared with nonweak participants. Stratified analyses were similar for grip strength and SPPB. With lean mass in the analysis, individuals with weakness had larger gains in grip strength and SPPB scores regardless of low lean mass (p < .01). CONCLUSIONS: Older women with clinically meaningful muscle weakness increased grip strength and SPPB, regardless of the presence of low lean mass following treatment with interventions for frailty. Thus, results suggest that muscle weakness, as defined by the Foundation for the National Institutes of Health Sarcopenia Project, appears to be a treatable symptom.

Analyzing feed-forward loop relationship in aging phenotypes: physical activity and physical performance.

We present evidence of feed-forward loop relationships and positive association between physical activity and performance levels, which are components of frailty, using measures from 431 high functioning women initially aged 70-79 years followed over 7 visits. Physical activity levels were assessed using a questionnaire. Grip strength was measured using a handheld dynamometer and usual walking speed was measured over 4-m. The results suggest that a reduction in physical activity would not only degrade physical performance, but it would further reduce physical activity through declines in physical performance. As both physical activity and physical performance impact frailty, improvement of physical activity could help reduce frailty directly as well as indirectly via improved physical performance. Our findings support a priori hypothesis that feed-forward loops are present in the phenotype of frailty, which is due to dysregulated energetics. A methodologically broader implication is that we introduce modeling and analysis of feed-forward loop data here. The feed-forward loop, as we define it, is different from the concept of feedback loops used in biochemical systems. Generalizing our model of two-variable feed-forward loop, three, four or multivariable feed-forward loop can be applied to other biological systems.

Macronutrients, diet quality, and frailty in older men.

BACKGROUND: Frailty, a phenotype of multisystem impairment and expanding vulnerability, is associated with higher risk of adverse health outcomes not entirely explained by advancing age. We investigated associations of macronutrients, dietary fiber, and overall diet quality with frailty status in older community-dwelling men. METHODS: Participants were 5,925 men aged ≥ 65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study at six U.S. centers. Diet was assessed at baseline with a food frequency questionnaire. We assessed frailty status (robust, intermediate, or frail) at baseline and at a second clinic visit (a mean of 4.6 years later) using a slightly modified Cardiovascular Health Study frailty index. We used multinomial logistic regression to assess associations between macronutrient intake, dietary fiber, and the Diet Quality Index Revised with frailty status at baseline and at the second clinic visit. RESULTS: At baseline, 2,748 (46.4%) participants were robust, 2,681 (45.2%) were intermediate, and 496 (8.4%) were frail. Carbohydrate, fat, protein, and dietary fiber showed no consistent associations with frailty status. Overall diet quality exhibited fairly consistent associations with frailty status. The Diet Quality Index Revised was inversely associated with frail status relative to robust status at the baseline visit (odds ratio for Q5 vs Q1 = 0.44, 95% confidence interval: 0.30, 0.63; p for trend < .0001) and at the second clinic visit (odds ratio for Q5 vs Q1 = 0.18, 95% confidence interval: 0.03, 0.97; p for trend = .0180). CONCLUSIONS: Overall diet quality was inversely associated with prevalent and future frailty status in this cohort of older men.

Objective measures of activity level and mortality in older men.

OBJECTIVES: To examine associations between objective measures of activity level and mortality risk in older men. DESIGN: Prospective cohort study. SETTING: Six U.S. sites. PARTICIPANTS: Men aged 71 and older followed an average of 4.5 years (N = 2,918). MEASUREMENTS: Time awake spent in sedentary behavior (metabolic equivalent (MET) level ≤1.50), light activity (MET level 1.51-2.99), and at least moderate activity (MET level ≥3.00) measured using an activity monitor worn for 5 days or longer and expressed as quartiles. Deaths were confirmed with death certificates; cause of death was adjudicated by review of certificates and records. RESULTS: During follow-up, 409 (14%) men died. After multivariable adjustment, comparing Q4 with Q1, more time spent in sedentary behavior (Q4 vs Q1, hazard ratio (HR) = 1.51, 95% confidence interval (CI) = 1.10-2.08), less time spent in light activity (Q1 vs Q4, HR = 1.54, 95% CI = 1.06-2.24), and less time spent in at least moderate activity (Q1 vs Q4, HR = 1.56, 95% CI = 1.09-2.25) were similarly associated with greater mortality risk primarily due to higher risks of cardiovascular and noncardiovascular, noncancer death. The association between time spent in sedentary behavior and mortality varied according to time spent at higher activity level. More time spent in sedentary behavior was associated with greater risk of death in men spending 1.2 (median) h/d or more in at least moderate activity (Q4 vs Q1, HR = 2.09, 95% CI = 1.26-3.49) but not in those spending less time (Q4 vs Q1, HR = 1.02, 95% CI = 0.62-1.66) (P = .005 for interaction). CONCLUSION: In older men exceeding current guidelines on physical activity, more time spent in sedentary behavior is associated with greater mortality risk.

The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates.

BACKGROUND: Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts. METHODS: The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups. RESULTS: The pooled sample included 26,625 participants (57% women, mean age in men 75.2 [±6.1 SD] and in women 78.6 [±5.9] years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength <26kg for men and <16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index <0.789 for men and <0.512 for women. CONCLUSIONS: These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations.

Grip strength cutpoints for the identification of clinically relevant weakness.

BACKGROUND: Weakness is common and contributes to disability, but no consensus exists regarding a strength cutpoint to identify persons at high risk. This analysis, conducted as part of the Foundation for the National Institutes of Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness associated with mobility impairment, defined as gait speed less than 0.8 m/s. METHODS: In pooled cross-sectional data (9,897 men and 10,950 women), Classification and Regression Tree analysis was used to derive cutpoints for grip strength associated with mobility impairment. RESULTS: In men, a grip strength of 26-32 kg was classified as "intermediate" and less than 26 kg as "weak"; 11% of men were intermediate and 5% were weak. Compared with men with normal strength, odds ratios for mobility impairment were 3.63 (95% CI: 3.01-4.38) and 7.62 (95% CI 6.13-9.49), respectively. In women, a grip strength of 16-20 kg was classified as "intermediate" and less than 16 kg as "weak"; 25% of women were intermediate and 18% were weak. Compared with women with normal strength, odds ratios for mobility impairment were 2.44 (95% CI 2.20-2.71) and 4.42 (95% CI 3.94-4.97), respectively. Weakness based on these cutpoints was associated with mobility impairment across subgroups based on age, body mass index, height, and disease status. Notably, in women, grip strength divided by body mass index provided better fit relative to grip strength alone, but fit was not sufficiently improved to merit different measures by gender and use of a more complex measure. CONCLUSIONS: Cutpoints for weakness derived from this large, diverse sample of older adults may be useful to identify populations who may benefit from interventions to improve muscle strength and function.

Cutpoints for low appendicular lean mass that identify older adults with clinically significant weakness.

BACKGROUND: Low lean mass is potentially clinically important in older persons, but criteria have not been empirically validated. As part of the FNIH (Foundation for the National Institutes of Health) Sarcopenia Project, this analysis sought to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that discriminate the presence or absence of weakness (defined in a previous report in the series as grip strength <26kg in men and <16kg in women). METHODS: In pooled cross-sectional data stratified by sex (7,582 men and 3,688 women), classification and regression tree (CART) analysis was used to derive cutpoints for appendicular lean body mass (ALM) that best discriminated the presence or absence of weakness. Mixed-effects logistic regression was used to quantify the strength of the association between lean mass category and weakness. RESULTS: In primary analyses, CART models identified cutpoints for low lean mass (ALM <19.75kg in men and <15.02kg in women). Sensitivity analyses using ALM divided by body mass index (BMI: ALMBMI) identified a secondary definition (ALMBMI <0.789 in men and ALMBMI <0.512 in women). As expected, after accounting for study and age, low lean mass (compared with higher lean mass) was associated with weakness by both the primary (men, odds ratio [OR]: 6.9 [95% CI: 5.4, 8.9]; women, OR: 3.6 [95% CI: 2.9, 4.3]) and secondary definitions (men, OR: 4.3 [95% CI: 3.4, 5.5]; women, OR: 2.2 [95% CI: 1.8, 2.8]). CONCLUSIONS: ALM cutpoints derived from a large, diverse sample of older adults identified lean mass thresholds below which older adults had a higher likelihood of weakness.

Criteria for clinically relevant weakness and low lean mass and their longitudinal association with incident mobility impairment and mortality: the foundation for the National Institutes of Health (FNIH) sarcopenia project.

BACKGROUND: This analysis sought to determine the associations of the Foundation for the National Institutes of Health Sarcopenia Project criteria for weakness and low lean mass with likelihood for mobility impairment (gait speed ≤ 0.8 m/s) and mortality. Providing validity for these criteria is essential for research and clinical evaluation. METHODS: Among 4,411 men and 1,869 women pooled from 6 cohort studies, 3-year likelihood for incident mobility impairment and mortality over 10 years were determined for individuals with weakness, low lean mass, and for those having both. Weakness was defined as low grip strength (<26kg men and <16kg women) and low grip strength-to-body mass index (BMI; kg/m(2)) ratio (<1.00 men and <0.56 women). Low lean mass (dual-energy x-ray absorptiometry) was categorized as low appendicular lean mass (ALM; <19.75kg men and <15.02kg women) and low ALM-to-BMI ratio (<0.789 men and <0.512 women). RESULTS: Low grip strength (men: odds ratio [OR] = 2.31, 95% confidence interval [CI] = 1.34-3.99; women: OR = 1.99, 95% CI 1.23-3.21), low grip strength-to-BMI ratio (men: OR = 3.28, 95% CI 1.92-5.59; women: OR = 2.54, 95% CI 1.10-5.83) and low ALM-to-BMI ratio (men: OR = 1.58, 95% CI 1.12-2.25; women: OR = 1.81, 95% CI 1.14-2.87), but not low ALM, were associated with increased likelihood for incident mobility impairment. Weakness increased likelihood of mobility impairment regardless of low lean mass. Mortality risk patterns were inconsistent. CONCLUSIONS: These findings support our cut-points for low grip strength and low ALM-to-BMI ratio as candidate criteria for clinically relevant weakness and low lean mass. Further validation in other populations and for alternate relevant outcomes is needed.

Serum albumin in relation to change in muscle mass, muscle strength, and muscle power in older men.

OBJECTIVES: To investigate the relationship between serum albumin and change in muscle mass, grip strength, and leg power. DESIGN: Prospective cohort. SETTING: Six U.S. academic medical centers. PARTICIPANTS: Community-dwelling men aged 65 and older participating in the Osteoporotic Fractures in Men (MrOS) Study. MEASUREMENTS: Serum albumin was measured at baseline in 5,534 participants. Baseline serum albumin was examined in relation to change in appendicular skeletal muscle (ASM) mass, grip strength, and leg power after 2 and 4.6 years. Two-year change in serum albumin was examined with respect to simultaneous change in these outcomes in 1,267 participants. RESULTS: Baseline serum albumin <40 g/L was not associated with 2- or 4.6-year change in ASM mass, grip strength, or leg power before or after adjustment for confounders. There was no association between serum albumin change and change in grip strength. A statistically significant trend was observed between serum albumin change and change in ASM mass, but there was substantial overlap across confidence intervals (CIs). Participants with a marked decrease (>3 g/L) and mild decrease (1-2 g/L) in serum albumin over 2 years exhibited a modest change of -8.9 W (95% CI = -25.6 to -7.8 W) and -6.3 W (95% CI = -21.2 to -8.5 W) of leg power, respectively (P for trend = .02), compared with those with no decrease in albumin concentration. CONCLUSION: Serum albumin demonstrated modest and inconsistent trends with loss of muscle mass and function. Low serum albumin within the normal range is not a risk factor for this process in elderly men.

Sleep disturbances and risk of frailty and mortality in older men.

OBJECTIVE: To test the hypothesis that non-frail older men with poorer sleep at baseline are at increased risk of frailty and death at follow-up. METHODS: In this prospective cohort study, subjective (questionnaires) and objective sleep parameters (actigraphy, in-home overnight polysomnography) were measured at baseline in 2505 non-frail men aged ≥67years. Repeat frailty status assessment performed an average of 3.4 years later; vital status assessed every four months. Sleep parameters expressed as dichotomized predictors using clinical cut-points. Status at follow-up exam classified as robust, intermediate (pre-frail) stage, frail, or died in interim. RESULTS: None of the sleep disturbances were associated with the odds of being intermediate/frail/dead (vs. robust) at follow-up. Poor subjective sleep quality (multivariable odds ratio [MOR] 1.26, 95% CI 1.01-1.58), greater nighttime wakefulness (MOR 1.31, 95% CI 1.04-1.66), and greater nocturnal hypoxemia (MOR 1.47, 95% CI 1.02-2.10) were associated with a higher odds of frailty/death at follow-up (vs. robust/intermediate). Excessive daytime sleepiness (MOR 1.60, 95% CI 1.03-2.47), greater nighttime wakefulness (MOR 1.57, 95% CI 1.12-2.20), severe sleep apnea (MOR 1.74, 95% CI 1.04-2.89), and nocturnal hypoxemia (MOR 2.28, 95% CI 1.45-3.58) were associated with higher odds of death (vs. robust/intermediate/frail at follow-up). The association between poor sleep efficiency and mortality nearly reached significance (MOR 1.48, 95% CI 0.99-2.22). Short sleep duration and prolonged sleep latency were not associated with frailty/death or death at follow-up. CONCLUSIONS: Among non-frail older men, poor subjective sleep quality, greater nighttime wakefulness, and greater nocturnal hypoxemia were independently associated with higher odds of frailty or death at follow-up, while excessive daytime sleepiness, greater nighttime wakefulness, severe sleep apnea and greater nocturnal hypoxemia were independently associated with an increased risk of mortality.

Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study.

OBJECTIVES: To determine the cross-sectional and longitudinal associations between 25-hydroxyvitamin D (25(OH)D) levels and frailty status in older men. DESIGN: Prospective cohort study. SETTING: Six U.S. community-based centers. PARTICIPANTS: One thousand six hundred six men aged 65 and older. MEASUREMENTS: 25(OH)D (liquid chromatography tandem mass spectroscopy) and frailty status (criteria similar to those used in the Cardiovascular Health Study) measured at baseline; frailty status assessment repeated an average of 4.6 years later. Frailty status was classified as robust, intermediate, or frail at baseline and robust, intermediate, frail, or dead at follow-up. RESULTS: After adjusting for multiple potential confounders, men with 25(OH)D levels less than 20.0 ng/mL had 1.5 times higher odds (multivariate odds ratio (MOR)=1.47, 95% confidence interval (CI)=1.07-2.02) of greater frailty status at baseline than men with 25(OH)D levels of 30.0 ng/mL or greater (referent group), whereas frailty status was similar in men with 25(OH)D levels from 20.0 to 29.9 ng/mL and those with levels of 30.0 ng/mL or greater (MOR=1.02, 95% CI=0.78-1.32). However, in 1,267 men not classified as frail at baseline, there was no association between lower baseline 25(OH)D level and odds of greater frailty status at the 4.6-year follow-up. Findings were the same when 25(OH)D was expressed in quartiles or as a continuous variable. CONCLUSION: Lower levels of 25(OH)D (<20.0 ng/mL) in community-dwelling older men were independently associated with greater evidence of frailty at baseline but did not predict greater risk of greater frailty status at 4.6 years.

Mortality risk in older men associated with changes in weight, lean mass, and fat mass.

OBJECTIVES: To evaluate risk of all-cause mortality associated with changes in body weight, total lean mass, and total fat mass in older men. DESIGN: Longitudinal cohort study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Four thousand three hundred thirty-one ambulatory men aged 65 to 93 at baseline. MEASUREMENTS: Repeated measurements of body weight and total lean and fat mass were taken using dual-energy X-ray absorptiometry 4.6 ± 0.4 years apart. Percentage changes in these measures were categorized as gain (+5%), loss (-5%), or stable (-5% to +5%). Deaths were verified centrally according to death certificate reviews, and proportional hazard models were used to estimate the risk of mortality. RESULTS: After accounting for baseline lifestyle factors and medical conditions, a higher risk of mortality was found for men with weight loss (hazard rat (HR)=1.84, 95% confidence interval (CI)=1.50-2.26), total lean mass loss (HR=1.78, 95% CI=1.45-2.19), and total fat mass loss (HR=1.72, 95% CI=1.34-2.20) than for men who were stable for each body composition measure. Men with total fat mass gain had a slightly greater mortality risk (HR=1.29, 95% CI=0.99-1.67) than those who remained stable. These associations did not differ according to baseline age, obesity, or self-reported health status (P for interactions >.10), although self-reported weight loss intent altered mortality risks with total fat mass (P for interaction=.04) and total lean mass (P for interaction=.09) change. CONCLUSION: Older men who lost weight, total lean mass, or total fat mass had a higher risk of mortality than men who remained stable.

Sleep disturbances and frailty status in older community-dwelling men.

OBJECTIVES: To test the hypothesis that sleep disturbances are independently associated with frailty status in older men. DESIGN: Cross-sectional analysis of prospective cohort study. SETTING: Six U.S. centers. PARTICIPANTS: Three thousand one hundred thirty-three men aged 67 and older. MEASUREMENTS: Self-reported sleep parameters (questionnaire); objective parameters of sleep-wake patterns (actigraphy data collected for an average of 5.2 nights); and objective parameters of sleep-disordered breathing, nocturnal hypoxemia, and periodic leg movements with arousals (PLMAs) (in-home overnight polysomnography). Frailty status was classified as robust, intermediate stage, or frail using criteria similar to those used in the Cardiovascular Health Study frailty index. RESULTS: The prevalence of sleep disturbances, including poor sleep quality, excessive daytime sleepiness, short sleep duration, lower sleep efficiency, prolonged sleep latency, sleep fragmentation (greater nighttime wakefulness and frequent, long wake episodes), sleep-disordered breathing, nocturnal hypoxemia, and frequent PLMAs, was lowest in robust men, intermediate in men in the intermediate-stage group, and highest in frail men (P-for-trend < or =.002 for all sleep parameters). After adjusting for multiple potential confounders, self-reported poor sleep quality (Pittsburgh Sleep Quality Index > 5, multivariable odds ratio (MOR)=1.28, 95% confidence interval (CI)=1.09-1.50), sleep efficiency less than 70% (MOR=1.37, 95% CI=1.12-1.67), sleep latency of 60 minutes or longer (MOR=1.42, 95% CI=1.10-1.82), and sleep-disordered breathing (respiratory disturbance index > or =15, MOR=1.38, 95% CI=1.15-1.65) were each independently associated with higher odds of greater frailty status. CONCLUSION: Sleep disturbances, including poor self-reported sleep quality, lower sleep efficiency, prolonged sleep latency, and sleep-disordered breathing, are independently associated with greater evidence of frailty.