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Background: Few studies have examined the association of neighborhood environment and mortality among community-dwelling older populations. Geographic Information Systems-based measures of neighborhood physical environment may provide new insights on the health effects of the social and built environment.Method: We studied 4 379 community-dwelling older adults in the United States aged 65 years and older from the Cardiovascular Health Study. Principal component analysis was used to identify neighborhood components from 48 variables assessing facilities and establishments, demographic composition, socioeconomic status, and economic prosperity. We used a Cox model to evaluate the association of neighborhood components with 5-year mortality. Age, sex, race, education, income, marital status, body mass index, smoking status, disability, coronary heart disease, and diabetes were included as covariates. We also examined the interactions between neighborhood components and sex and race (Black vs White or other).Results: We identified 5 neighborhood components, representing facilities and resources, immigrant communities, community-level economic deprivation, resident-level socioeconomic status, and residents' age. Communities' economic deprivation and residents' socioeconomic status were significantly associated with 5-year mortality. We did not find interactions between sex or race and any of the 5 neighborhood components. The results were similar in a sensitivity analysis where we used 10-year mortality as the outcome.Conclusions: We found that communities' economic status but not facilities in communities was associated with mortality among older adults. These findings revealed the importance and benefits living in a socioeconomically advantaged neighborhood could have on health among older residents with different demographic backgrounds. [ABSTRACT FROM AUTHOR]

Background: Animal studies suggest that gut microbiome metabolites such as trimethylamine N-oxide (TMAO) may influence cognitive function and dementia risk. However potential health effects of TMAO and related metabolites remain unclear.Objective: We examined prospective associations of TMAO, γ-butyrobetaine, crotonobetaine, carnitine, choline, and betaine with risk of cognitive impairment and dementia among older adults aged 65 years and older in the Cardiovascular Health Study (CHS).Methods: TMAO and metabolites were measured in stored plasma specimens collected at baseline. Incident cognitive impairment was assessed using the 100-point Modified Mini-Mental State Examination administered serially up to 7 times. Clinical dementia was identified using neuropsychological tests adjudicated by CHS Cognition Study investigators, and by ICD-9 codes from linked Medicare data. Associations of each metabolite with cognitive outcomes were assessed using Cox proportional hazards models.Results: Over a median of 13 years of follow-up, 529 cases of cognitive impairment, and 522 of dementia were identified. After multivariable adjustment for relevant risk factors, no associations were seen with TMAO, carnitine, choline, or betaine. In contrast, higher crotonobetaine was associated with 20-32% higher risk of cognitive impairment and dementia per interquintile range (IQR), while γ-butyrobetaine was associated with ∼25% lower risk of the same cognitive outcomes per IQR.∥Conclusion:These findings suggest that γ-butyrobetaine, crotonobetaine, two gut microbe and host metabolites, are associated with risk of cognitive impairment and dementia. Our results indicate a need for mechanistic studies evaluating potential effects of these metabolites, and their interconversion on brain health, especially later in life. [ABSTRACT FROM AUTHOR]

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65-98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07-.14) at baseline, and the prevalence of frailty (FI > .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = -.31) and grip strength (r = -.46), and strongly associated with a modified Fried's frailty phenotype (p < .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual's vulnerability to and risk of disease. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults.Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.Results: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12).Discussion: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES The extent to which the prevalence of muscle weakness in the US population varies by different putative grip strength constructs developed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) has not been described. DESIGN Cross‐sectional analysis. SETTING Two nationally representative cohorts—2010 and 2012 waves of the Health and Retirement Survey and round 1 (2011) of the National Health and Aging Trends Survey. PARTICIPANTS Adults aged 65 years and older (n = 12,984) were included in these analyses. MEASUREMENTS We analyzed three constructs of muscle weakness developed by the SDOC, and found to be associated with mobility disability for men and women, respectively: absolute grip strength (<35.5 kg and 20 kg); grip strength standardized to body mass index (<1.05 kg/kg/m² and 0.79 kg/kg/m²); and grip strength standardized to weight (<0.45 kg/kg and 0.337 kg/kg). We estimated the prevalence of muscle weakness defined by each of these constructs in the overall older US population, and by age, sex, race, and ethnicity. We also estimated the sensitivity and specificity of each of the grip strength constructs to discriminate slowness (gait speed <0.8 m/s) in these samples. RESULTS: The prevalence of muscle weakness ranged from 23% to 61% for men and from 30% to 66% for women, depending on the construct used. There was substantial variation in the prevalence of muscle weakness by race and ethnicity. The sensitivity and specificity of these measures for discriminating slowness varied widely, ranging from 0.30 to 0.92 (sensitivity) and from 0.17 to 0.88 (specificity). CONCLUSIONS: The prevalence of muscle weakness, defined by the putative SDOC grip strength constructs, depends on the construct of weakness used. J Am Geriatr Soc 68:1438‐1444, 2020. See related editorial by Cesari et al in this issue [ABSTRACT FROM AUTHOR]

BACKGROUND Despite readily available treatments, control of blood pressure (BP) with population aging remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both "untreated" and "treated but uncontrolled" high BP. METHODS We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and United States (US) in the ASPirin in Reducing Events in the Elderly study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mm Hg and/or the use of any BP lowering medication. "Controlled hypertension" was defined if participants were receiving antihypertensive medication and BP <140 and 90 mm Hg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control. RESULTS Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP ≥140/90 mm Hg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to "treated but uncontrolled" BP included older age, male, Black race (vs. White), using antihypertensive monotherapy (vs. multiple) and residing in Australia (vs. US). CONCLUSIONS High levels of "untreated" and "treated but uncontrolled" BP occur in healthy elderly people without CVD, suggesting there are opportunities for better BP control in the primary prevention of CVD in this population. CLINICAL TRIALS REGISTRATION NCT01038583. [ABSTRACT FROM AUTHOR]

Objectives: To explore whether baseline scores on the Mobility Assessment Tool—short form (MAT‐sf), a brief, animated, computer‐based means of assessing mobility that predicts mobility disability, are associated with number of hospitalizations and time to first hospitalization over a median follow‐up of 2.7 years. Design: Post hoc analysis of prospectively gathered data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a randomized clinical trial of lifestyle interventions to preserve mobility in older adults. Setting: Eight U.S. academic medical centers. Participants: Of 1,635 sedentary community‐dwelling older adults enrolled in LIFE, 1,574 completed baseline physical function screening including the MAT‐sf, with baseline scores ranging from 30.2 (low function) to 69.8 (high function) on a scale from 30 to 80. Measurements: Number of hospitalizations and time to first hospitalization, adjusted for age, sex, race, living alone, clinical site, baseline comorbidities, number of prescription medications, and cognition. Results: Of the 1,557 participants with data regarding hospitalization status, 726 (47%) had at least 1 hospitalization; 78% of these had 1 or 2 hospitalizations. For every 10‐point lower MAT‐sf score, the rate of all hospitalizations was 19% higher in those with lower scores (adjusted rate ratio=1.20, 95% confidence interval (CI)=1.08–1.32, p<.001). Lower baseline MAT‐sf scores were also associated with greater risk of first hospitalization (adjusted hazard ratio=1.20, 95% CI=1.09–1.32, p<.01, per 10‐point lower MAT‐sf score). Conclusion: Low MAT‐sf scores identify older adults at risk of hospitalization; further study is needed to test interventions to reduce hospitalizations in these individuals. [ABSTRACT FROM AUTHOR]

Background: Structured physical activity interventions delay the onset of disability for at-risk older adults. However, it is not known if at-risk older adults continue to participate in physical activity or maintain mobility benefits after cessation of structured intervention.Methods: One thousand six hundred and thirty-five sedentary men and women aged 70-89 years with Short Physical Performance Battery (SPPB) scores of 9 or less and able to walk 400 m were randomized to a structured, moderate-intensity physical activity (PA) program consisting of center-based (twice/week) and home-based (three to four times per week) aerobic, resistance, and flexibility training or a health education (HE) program combined with upper extremity stretching.Results: Most of the participants (88% of HE and 87% of PA) returned for a follow-up visit (POST) 1 year after cessation of formal intervention. The HE group reported about 1-hour less activity per week than the PA group at end of intervention (LAST TRIAL; -68.9; 95% confidence interval [CI] = -86.5 to -51.3) but similar weekly activity at POST (-13.5; 95% CI = -29.5 to 2.47). SPPB did not differ between the two groups at LAST TRIAL (-0.06; 95% CI = -0.31 to 0.19) nor POST (-0.18; 95% CI = -0.45 to 0.088).Conclusions: Although sedentary at-risk older adults increased their physical activity during a structured physical activity intervention, they did not continue at this level following the cessation of intervention. Future exercise interventions need to include novel methods to support older adults in continued physical activity following structured interventions. [ABSTRACT FROM AUTHOR]

Background: Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large long-term randomized trials are lacking.Objective: To determine whether a long-term, structured, moderate-intensity physical activity program is associated with a lower risk for frailty and whether frailty status alters the effect of physical activity on the reduction in major mobility disability (MMD) risk.Design: Multicenter, single-blind, randomized trial.Setting: 8 centers in the United States.Participants: 1635 community-dwelling adults, aged 70 to 89 years, with functional limitations.Intervention: A structured, moderate-intensity physical activity program incorporating aerobic, resistance, and flexibility activities or a health education program consisting of workshops and stretching exercises.Measurements: Frailty, as defined by the SOF (Study of Osteoporotic Fractures) index, at baseline and 6, 12, and 24 months, and MMD, defined as the inability to walk 400 m, for up to 3.5 years.Results: Over 24 months of follow-up, the risk for frailty (n = 1623) was not statistically significantly different in the physical activity versus the health education group (adjusted prevalence difference, -0.021 [95% CI, -0.049 to 0.007]). Among the 3 criteria of the SOF index, the physical activity intervention was associated with improvement in the inability to rise from a chair (adjusted prevalence difference, -0.050 [CI, -0.081 to -0.020]). Baseline frailty status did not modify the effect of physical activity on reducing incident MMD (P for interaction = 0.91).Limitation: Frailty status was neither an entry criterion nor a randomization stratum.Conclusion: A structured, moderate-intensity physical activity program was not associated with a reduced risk for frailty over 2 years among sedentary, community-dwelling older adults. The beneficial effect of physical activity on the incidence of MMD did not differ between frail and nonfrail participants.Primary Funding Source: National Institute on Aging, National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: Incident disability rates enable the comparison of risk across populations. Understanding these by age, sex, and race is important for planning for the care of older adults and targeting prevention.Methods: We calculated incident disability rates among older adults in the Cardiovascular Health Study, a study of 5,888 older adults aged ≥ 65 years over 6 years of follow-up. Disability was defined in the following two ways: (i) self-report of disability (severe difficulty or inability) in any of six Activities of Daily Living (ADL), and (ii) mobility difficulty (any difficulty walking half a mile or climbing 10 steps). Incident disability rates were calculated as events per 100 person years for age, gender, and race groups.Results: The incidence of ADL disability, and mobility difficulty were 2.7 (2.5-2.8), and 9.8 (9.4-10.3) events per 100 person years. Women, older participants, and blacks had higher rates in both domains.Conclusion: Incidence rates are considerably different based on the domain examined as well as age, race, and gender composition of the population. Prevention efforts should focus on high risk populations and attempt to ameliorate factors that increase risk in these groups. [ABSTRACT FROM AUTHOR]

Background: There are no primary prevention trials of aspirin with relevant geriatric outcomes in elderly people. ASPirin in Reducing Events in the Elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin that will determine whether 5 years of daily 100-mg enteric-coated aspirin extends disability-free and dementia-free life in a healthy elderly population and whether these benefits outweigh the risks.Methods: Set in primary care, this randomized double-blind placebo-controlled trial has a composite primary endpoint of death, incident dementia or persistent physical disability. Participants aged 70+ years (non-minorities) or 65+ years (U.S. minorities) were free of cardiovascular disease, dementia, or physical disability and without a contraindication to, or indication for, aspirin. Baseline data include physical and lifestyle, personal and family medical history, hemoglobin, fasting glucose, creatinine, lipid panel, urinary albumin:creatinine ratio, cognition (3MS, HVLT-R, COWAT, SDMT), mood (CES-D-10), physical function (gait speed, grip strength), Katz activities of daily living and quality of life (SF-12).Results: Recruitment ended in December 2014 with 16,703 Australian and 2,411 U.S. participants, a median age of 74 (range 65-98) years and 56% women. Approximately 55% of the U.S. cohort were from minority groups; 9% of the total cohort. Proportions with hypertension, overweight, and chronic kidney disease were similar to age-matched populations from both countries although lower percentages had diabetes, dyslipidemia, and osteoarthritis.Discussion: Findings from ASPREE will be generalizable to a healthier older population in both countries and will assess whether the broad benefits of daily low-dose aspirin in prolonging independent life outweigh the risks. [ABSTRACT FROM AUTHOR]

Background: Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity.Methods: Using data from the Long Life Family Study, we performed genomewide association analyses on an endophenotype construct, LF1, comprising a linear combination of traits across health domains. LF1 primarily reflected traits from the pulmonary and physical activity domains.Results: We detected a significant association between LF1 and a locus on chromosome 10p15 (p-value = 4.65 × 10-8) and suggestive evidence (p-value < 5 × 10-6) for association on chromosomes 1, 2, 8, 12, 15, 18, and 22. Using data from the Health, Aging and Body Composition Study, we subsequently replicated the association for the 1p13 region near the NBPF6 locus (p-value = 3.65 × 10-4).Conclusions: Our analyses indicate that loci influencing a healthy aging endophenotype construct predominantly comprised of pulmonary and physical function domains may be located on chromosome 1p13 near the NBPF6 locus. Further investigation of this possible locus and other suggestive loci may reveal novel biological pathways that influence healthy aging. [ABSTRACT FROM AUTHOR]

To identify biomarkers of body mass index, body fat, trunk fat, and appendicular lean mass, nontargeted metabolomics was performed in plasma from 319 black men in the Health, Aging and Body Composition study (median age 72 years, median body mass index 26.8 kg/m2). Body mass index was calculated from measured height and weight; percent fat, percent trunk fat, and appendicular lean mass were measured with dual-energy x-ray absorptiometry. Pearson partial correlations between body composition measures and metabolites were adjusted for age, study site, and smoking. Out of 350 metabolites, body mass index, percent fat, percent trunk fat, and appendicular lean mass were significantly correlated with 92, 48, 96, and 43 metabolites at p less than .0014. Metabolites most strongly correlated with body composition included carnitine, a marker of fatty acid oxidation (positively correlated), triacylglycerols (positively correlated), and amino acids including branched-chain amino acids (positively correlated except for acetylglycine and serine). Gaussian Graphical Models of metabolites found that 25 lipid metabolites clustered into a single network. Groups of five amino acids, three plasmalogens, and two carnitines were also observed. Findings confirm prior reports of associations between amino acids, lean mass, and fat mass in addition to associations not previously reported. Future studies should consider whether these metabolites are relevant for metabolic disease processes. [ABSTRACT FROM AUTHOR]

Background/objectives Poor appetite in older adults leads to sub-optimal food intake and increases the risk of undernutrition. The impact of poor appetite on food intake in older adults is unknown. The aim of this study was to examine the differences in food intake among older community-dwelling adults with different reported appetite levels. Design Cross-sectional analysis of data from a longitudinal prospective study. Setting Health, aging, and body composition study performed in the USA. Participants 2,597 community-dwelling adults aged 70-79. Measurements A semi-quantitative, interviewer-administered, 108-item food frequency questionnaire designed to estimate dietary intake. Poor appetite was defined as the report of a moderate, poor, or very poor appetite in the past month and was compared with good or very good appetite. Results The mean age of the study sample was 74.5 ± 2.8 years; 48.2% were men, 37.7% were black, and 21.8% reported a poor appetite. After adjustment for total energy intake and potential confounders (including biting/chewing problems), participants with a poor appetite had a significantly lower consumption of protein and dietary fiber, solid foods, protein rich foods, whole grains, fruits, and vegetables, but a higher consumption of dairy foods, fats, oils, sweets, and sodas compared to participants with very good appetite. In addition, they were less likely to report consumption of significant larger portion sizes. Conclusion Older adults reporting a poor appetite showed a different dietary intake pattern compared to those with (very) good appetite. Better understanding of the specific dietary intake pattern related to a poor appetite in older adults can be used for nutrition interventions to enhance food intake, diet variety, and diet quality. [ABSTRACT FROM AUTHOR]

Background Physical activity ( PA) reduces the rate of mobility disability, compared with health education ( HE), in at risk older adults. It is important to understand aspects of performance contributing to this benefit. Objective To evaluate intervention effects on tertiary physical performance outcomes. Design The Lifestyle Interventions and Independence for Elders ( LIFE) was a multi-centered, single-blind randomized trial of older adults. Setting Eight field centers throughout the United States. Participants 1635 adults aged 78.9 ± 5.2 years, 67.2% women at risk for mobility disability (Short Physical Performance Battery [SPPB] <10). Interventions Moderate PA including walking, resistance and balance training compared with HE consisting of topics relevant to older adults. Outcomes Grip strength, SPPB score and its components (balance, 4 m gait speed, and chair-stands), as well as 400 m walking speed. Results Total SPPB score was higher in PA versus HE across all follow-up times (overall P = .04) as was the chair-stand component (overall P < .001). No intervention effects were observed for balance (overall P = .12), 4 m gait speed (overall P = .78), or grip strength (overall P = .62). However, 400 m walking speed was faster in PA versus HE group (overall P =<.001). In separate models, 29% of the rate reduction of major mobility disability in the PA versus HE group was explained by change in SPPB score, while 39% was explained by change in the chair stand component. Conclusion Lower extremity performance ( SPPB) was significantly higher in the PA compared with HE group. Changes in chair-stand score explained a considerable portion of the effect of PA on the reduction of major mobility disability-consistent with the idea that preserving muscle strength/power may be important for the prevention of major mobility disability. [ABSTRACT FROM AUTHOR]

Background: We recently reported that protection against coronary artery disease (CAD) mortality is the major contributor to longer life associated with FOXO3 genotype. The present study examined this relation in more detail.Methods: We performed a 15-year observational study of 3,584 older American men of Japanese ancestry from the Kuakini Honolulu Heart Program cohort and 1,595 White and 1,067 Black elderly individuals from the Health Aging and Body Composition study.Results: Multivariate Cox regression models demonstrated that carriage of the longevity-associated G allele of FOXO3 single nucleotide polymorphisms rs2802292 was a protective factor against CAD mortality in all three populations. In Japanese and Whites, but not in Blacks, the protective effect of the G allele was little changed in models adjusted for other major risk factors. Population-attributable risk (PAR) models found that the nonprotective TT genotype contributed 15%, 9%, and 3% to CAD mortality risk in Japanese, White, and Black Americans, respectively, and was one of the top three contributing factors to CAD mortality. In Japanese, this effect size was comparable with hypertension (15%), but in Whites and Blacks PAR for hypertension was higher (29% and 26%, respectively). G-allele carriers had lower plasma TNF-α than noncarriers, suggesting inflammation as a potential mediating factor for CAD mortality risk.Conclusion: FOXO3 genotype is an important risk factor for CAD mortality in older populations. More research is needed to identify potential mechanisms and targets for intervention. [ABSTRACT FROM AUTHOR]

Background: The healthy aging index (HAI) was developed as a marker of health in multiple systems that can identify individuals who age most successfully.Methods: We calculated an HAI in 934 Framingham Offspring Study participants aged 60 or older at baseline. Heart rate and C-reactive protein (CRP) were added in modified versions of the HAI. Cox proportional hazard models were used to quantify the association of the HAI with mortality, cardiovascular disease (CVD), and cancer. We used fully conditional specification to multiply impute missing values for HAI components, increasing the sample size by 44%.Results: Over 10 years of follow-up, there were 138 deaths, 103 incident cases of CVD, and 138 incident cases of cancer. In models adjusted for age, sex, and behavioral risk factors, the HAI was associated with mortality (hazard ratio [HR] per unit of HAI 1.24, 95% confidence interval [CI] 1.13-1.36) and with CVD (HR 1.27, 95% CI 1.13-1.42), but not with cancer (HR 1.01, 95% CI 0.91-1.11) in observed (non-missing) data. In multivariable models further adjusting for prevalent diseases, results were slightly attenuated. When including heart rate and CRP, a modified HAI gave stronger associations. Results with imputed data are similar to results from complete case analyses.Conclusions: In our large community-based sample, the HAI is a strong predictor of mortality and CVD. Other factors that are strongly associated with mortality, such as heart rate and CRP can improve the ability of the HAI to identify the healthiest older adults. [ABSTRACT FROM AUTHOR]

Background: Prior studies have only considered one measurement of physical performance in its relationship to fractures and mortality. A single measurement is susceptible to large within-person changes over time, and thus, may not capture the true association between physical performance and the outcomes of interest.Methods: Using data from the Study of Osteoporotic Fractures, we followed 7,015 women enrolled prior to age 80 years who had outcome information beyond this age. Trajectories of walking speed (m/s) and chair stand speed (stands/s) were estimated up to the last visit prior to age 80 years using mixed-effects linear regression. Physical performance at age 80 (PF_age80) was assessed at the last visit prior to age 80 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression and multivariate models adjusted for all other covariates.Results: Greatest walking speed decline and chair stand speed decline were both associated with higher risk of hip fracture (HR: 1.28; 95% CI: 1.03, 1.58 and HR: 1.26; 95% CI: 1.03, 1.54, respectively), but not nonspine fractures. Greatest walking speed decline and chair stand speed decline were both associated with a significant 29% (95% CI: 17-42%) and 27% (95% CI: 15-39%) increased risk of mortality, respectively.Conclusions: Greatest declines in walking speed and chair stand speed were both associated with an increased risk of hip fracture and mortality independent of PF_age80 and other important confounders. Both physical performance change and the single physical performance measurement should be considered in the etiology of hip fracture and mortality. [ABSTRACT FROM AUTHOR]

Background: HMG-CoA reductase inhibitors (statins) are among the most commonly prescribed classes of medications. Although their cardiovascular benefits and myalgia risks are well documented, their effects on older adults initiating an exercise training program are less understood.Methods: 1,635 sedentary men and women aged 70-89 years with Short Physical Performance Battery (SPPB) score of 9 or below and were able to walk 400 m were randomized to a structured, moderate-intensity physical activity (PA) program consisting of both center-based (twice/wk) and home-based (3-4 times/wk) aerobic, resistance, and flexibility training or to a health education (HE) program combined with upper extremity stretching.Results: Overall, the PA intervention was associated with lower risk of major mobility disability (hazard ratio [HR] = 0.82; 95% confidence interval [CI] = 0.69-0.98). The effect was similar (p value for interaction = .62) in both statin users (PA n = 415, HE n = 412; HR = 0.86, 95% CI = 0.67-1.1) and nonusers (PA n = 402, HE n = 404; HR = 0.78, 95% CI = 0.61-1.01). Attendance was similar for statin users (65%) and nonusers (63%). SPPB at 12 months was slightly greater for PA (8.35±0.10) than for HE (7.94±0.10) in statin users but not in nonusers (PA 8.25±0.10, HE 8.16±0.10), though the interaction effect was not statistically significant. Self-reported PA levels were not different between statin users and nonusers.Conclusions: Although statins have been associated with adverse effects on muscle, data from the LIFE Study show that statin users and nonusers both benefit from PA interventions. Older adults who require statin medications to manage chronic medical conditions and are sedentary will be able to benefit from interventions to increase PA. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the associations between a broad array of cardiorespiratory and noncardiorespiratory impairments and dyspnea in older persons. Design Cross-sectional. Setting Cardiovascular Health Study. Participants Community-dwelling persons (N = 4,413; mean age 72.6, 57.1% female, 4.5% African American, 27.2% 1)), maximal inspiratory pressure (respiratory muscle strength), echocardiography, ankle-brachial index, blood pressure, whole-body muscle mass (bioelectrical impedance), single chair stand (lower extremity function), grip strength, serum hemoglobin and creatinine, Center for Epidemiologic Studies Depression Scale ( CES-D), Mini-Mental State Examination, medication use, and body mass index ( BMI). Results In a multivariable logistic regression model, impairments that had strong associations with moderate to severe dyspnea were FEV1 less than the lower limit of normal (adjusted odds ratio ( aOR) = 2.88, 95% confidence interval ( CI) = 2.37-3.49), left ventricular ejection fraction less than 45% ( aOR = 2.12, 95% CI = 1.43, 3.16), unable to perform a single chair stand ( aOR = 2.10, 95% CI = 1.61-2.73), depressive symptoms ( CES-D score ≥16; aOR = 2.02, 95% CI = 1.26-3.23), and obesity ( BMI ≥30; aOR = 2.07, 95% CI = 1.67-2.55). Impairments with modest but still statistically significant associations with moderate to severe dyspnea included respiratory muscle weakness, diastolic cardiac dysfunction, grip weakness, anxiety symptoms, and use of cardiovascular and psychoactive medications ( aORs = 1.31-1.71). Conclusion In community-dwelling older persons, several cardiorespiratory and noncardiorespiratory impairments were significantly associated with moderate to severe dyspnea, akin to a multifactorial geriatric health condition. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity is a major driver of physical and cognitive impairment, but rates of decline are also related to ageing. We sought to determine trajectories of decline in a large cohort by disease status, and examined their correspondence with biomarkers of ageing processes including growth hormone, sex steroid, inflammation, visceral adiposity and kidney function pathways.Methods: We have followed the 5888 participants in the Cardiovascular Health Study (CHS) for healthy ageing and longevity since 1989-90. Gait speed, grip strength, modified mini-mental status examination (3MSE) and the digit symbol substitution test (DSST) were assessed annually to 1998-99 and again in 2005-06. Insulin-like growth hormone (IGF-1), dehydroepiandrosterone sulphate (DHEAS), interleukin-6 (IL-6), adiponectin and cystatin-C were assessed 3-5 times from stored samples. Health status was updated annually and dichotomized as healthy vs not healthy. Trajectories for each function measure and biomarker were estimated using generalized estimating equations as a function of age and health status using standardized values.Results: Trajectories of functional decline showed strong age acceleration late in life in healthy older men and women as well as in chronically ill older adults. Adiponectin, IL-6 and cystatin-C tracked with functional decline in all domains; cystatin-C was consistently associated with functional declines independent of other biomarkers. DHEAS was independently associated with grip strength and IL-6 with grip strength and gait speed trajectories.Conclusions: Functional decline in late life appears to mark a fundamental ageing process in that it occurred and was accelerated in late life regardless of health status. Cystatin C was most consistently associated with these functional declines. [ABSTRACT FROM AUTHOR]

Objectives To investigate the association between mortality and heritability of a rescaled Fried frailty index, the Scale of Aging Vigor in Epidemiology ( SAVE), to determine its value for genetic analyses. Design Longitudinal, community-based cohort study. Setting The Long Life Family Study ( LLFS) in the United States and Denmark. Participants Long-lived individuals (N = 4,875, including 4,075 genetically related individuals) and their families (N = 551). Measurements The SAVE was administered to 3,599 participants and included weight change, weakness (grip strength), fatigue (questionnaire), physical activity (days walked in prior 2 weeks), and slowness (gait speed); each component was scored 0, 1, or 2 using approximate tertiles, and summed (range 0 (vigorous) to 10 (frail)). Heritability was determined using a variance component-based family analysis using a polygenic model. Association with mortality in the proband generation (N = 1,421) was calculated using Cox proportional hazards mixed-effect models. Results Heritability of the SAVE was 0.23 ( P < .001) overall (n = 3,599), 0.31 ( P < .001) in probands (n = 1,479), and 0.26 ( P < .001) in offspring (n = 2,120). In adjusted models, higher SAVE scores were associated with higher mortality (score 5-6: hazard ratio ( HR) = 2.83, 95% confidence interval ( CI) = 1.46-5.51; score 7-10: HR = 3.40, 95% CI = 1.72-6.71) than lower scores (0-2). Conclusion The SAVE was associated with mortality and was moderately heritable in the LLFS, suggesting a genetic component to age-related vigor and frailty and supporting its use for further genetic analyses. [ABSTRACT FROM AUTHOR]

Objectives To ascertain whether older adults with extensive disease but relative vigor (adapters) shorten the period at the end of life in which they live with morbidity (compress morbidity). Design Prospective, community-based cohort study in four U.S. cities. Setting Cardiovascular Health Study. Participants Individuals aged 65 and older. Measurements Participants were categorized into three groups according to extent of disease (assessed noninvasively), vigor, and frailty (expected agers (n = 3,528, extent of disease similar to vigor and frailty-reference group), adapters (n = 882, higher disease but vigorous), and prematurely frail (n = 855, lower disease but frail)) and compared according to years of able life ( YAL), years of self-reported healthy life ( YHL), and mortality using multivariable regression and survival analysis. Results After adjustment, adapters had 0.97 (95% confidence interval ( CI) = 0.60-1.33) more YAL and 0.54 (95% CI = 0.19-0.90) more YHL than expected agers, and those who were prematurely frail had −0.99 (95% CI = −1.36 to −0.62) fewer YAL and −0.53 (95% CI = −0.89 to −0.17) fewer YHL than expected agers. Adapters had 0.9 more and prematurely frail had 1.5 fewer years of total life than expected agers ( P < .001). Adapters spent 55% of their remaining life able and healthy, those who were prematurely frail spent 37%, and of expected agers spent 47% ( P < .001). Conclusion Despite similar levels of disease burden, older adults who were more vigorous appeared to compress morbidity and live longer. Older adults with higher frailty lengthened morbidity and had greater mortality. Adaptive factors may compress morbidity and decrease mortality. [ABSTRACT FROM AUTHOR]

Background: Depression and disability are closely linked. Less is known regarding clinical and subclinical depressive symptoms over time and risk of disability and mortality.Methods: Responses to the Center for Epidemiologic Studies Short Depression scale (CES-D10) were assessed over a 4-year period in men (n = 1032) and women (n = 1070) aged 70-79 years initially free from disability. Depressive symptom trajectories were defined with group-based models. Disability (2 consecutive reports of severe difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 9 subsequent years. Hazard ratios (HRs) were estimated using Cox proportional hazards adjusted for covariates.Results: Three trajectories were identified: persistently nondepressed (54% of men, 54% of women, mean baseline CES-D10: 1.16 and 1.46), mildly depressed and increasing (40% of men, 38% of women, mean baseline CES-D10: 3.60 and 4.35), and depressed and increasing (6% of men, 8% of women, mean baseline CES-D10: 7.44 and 9.61). Disability and mortality rates per 1,000 person years were 41.4 and 60.3 in men and 45.8 and 41.9 in women. Relative to nondepressed, men in the mildly depressed (HR = 1.45, 95% confidence interval [CI] 1.11-1.89) and depressed trajectories (HR = 2.12, 95% CI 1.33-3.38) had increased disability; women in the depressed trajectory had increased disability (HR = 2.02, 95% CI 1.37-2.96). Men in the mildly depressed (HR = 1.24, 95% CI 1.01-1.52) and depressed trajectories (HR = 1.63, 95% CI 1.10-2.41) had elevated mortality risk; women exhibited no mortality risk.Conclusions: Trajectories of depressive symptoms without recovery may predict disability and mortality in apparently healthy older populations, thus underscoring the importance of monitoring depressive symptoms in geriatric care. [ABSTRACT FROM AUTHOR]

Background: Inflammation, slow gait, and depression individually are associated with mortality, yet little is known about the trajectories of these measures, their interrelationships, or their collective impact on mortality.Methods: Longitudinal latent class analysis was used to evaluate trajectories of depression (Center for Epidemiologic Studies Depression ≥ 10), slow gait (<1.0 m/s), and elevated inflammation (interleukin 6 > 3.2 pg/mL) using data from the Health Aging and Body Composition Study. Logistic regression was used to identify their associations with mortality.Results: For each outcome, low-probability (n inflammation = 1,656, n slow gait = 1,471, n depression = 1,458), increasing-probability (n inflammation = 847, n slow gait = 880, n depression = 1,062), and consistently high-probability (n inflammation = 572, n slow gait = 724, n depression = 555) trajectories were identified, with 22% of all participants classified as having increasing or consistently high-probability trajectories on inflammation, slow gait, and depression (meaning probability of impairment on each outcome increased from low to moderate/high or remained high over 10 years). Trajectories of slow gait were associated with inflammation (r = .40, p < .001) and depression (r = .49, p < .001). Although worsening trajectories of inflammation were independently associated with mortality (p < .001), the association between worsening trajectories of slow gait and mortality was only present in participants with worsening depression trajectories (p < .01). Participants with increasing/consistently high trajectories of depression and consistently high trajectories of inflammation and slow gait (n = 247) have an adjusted-morality rate of 85.2%, greater than all other classification permutations.Conclusions: Comprehensive assessment of older adults is warranted for the development of treatment strategies targeting a high-mortality risk phenotype consisting of inflammation, depression, and slow gait speed. [ABSTRACT FROM AUTHOR]

Background: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function.Methods: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking ¼ - ½ mile or climbing 10 steps within 3 years.Results: Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to ≥ 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10% to 1% in men, and from 15% to 1% in women, while mobility difficulty trended from 47% to 4% in men and 40% to 6% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve.Conclusion: In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality. [ABSTRACT FROM AUTHOR]

One method by which to identify fundamental biological processes that may contribute to age-related disease and disability, instead of disease-specific processes, is to construct endophenotypes comprising linear combinations of physiological measures. Applying factor analyses methods to phenotypic data (2006-2009) on 28 traits representing 5 domains (cognitive, cardiovascular, metabolic, physical, and pulmonary) from 4,472 US and Danish individuals in 574 pedigrees from the Long Life Family Study (United States and Denmark), we constructed endophenotypes and assessed their relationship with mortality. The most dominant endophenotype primarily reflected the physical activity and pulmonary domains, was heritable, was significantly associated with mortality, and attenuated the association of age with mortality by 24.1%. Using data (1997-1998) on 1,794 Health, Aging and Body Composition Study participants from Memphis, Tennessee, and Pittsburgh, Pennsylvania, we obtained strikingly similar endophenotypes and relationships to mortality. We also reproduced the endophenotype constructs, especially the dominant physical activity and pulmonary endophenotype, within demographic subpopulations of these 2 cohorts. Thus, this endophenotype construct may represent an underlying phenotype related to aging. Additional genetic studies of this endophenotype may help identify genetic variants or networks that contribute to the aging process. [ABSTRACT FROM AUTHOR]

Objectives To test the hypothesis that men and women with low bone mineral density ( BMD) and sarcopenia have a higher risk of fracture than those with only one or neither conditions. Design The Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures in women are prospective observational studies with a mean follow up of 9 (2000-2012) and 8 years (1997-2009), respectively. Setting U.S. clinical centers. Participants Men (n = 5,544; mean age 73.7) and women (n = 1,114; mean age 77.6) aged 65 and older, able to walk without assistance, and without bilateral hip replacement. Measurements Sarcopenia was defined as low appendicular lean mass plus slowness or weakness and low BMD according to the World Health Organization definition of a T-score less than -1.0. Participants were classified as having normal BMD and no sarcopenia (3,367 men, 308 women), sarcopenia only (79 men, 48 women), low BMD only (1,986 men, 626 women), and low BMD and sarcopenia (112 men, 132 women). Results Men with low BMD and sarcopenia (hazard ratio ( HR)=3.79, 95% confidence interval ( CI)=2.65-5.41) and men with low BMD only ( HR=1.67, 95% CI=1.45-1.93) but not men with sarcopenia only ( HR=1.14, 95% CI=0.62-2.09) had greater risk of fracture than men with normal BMD and no sarcopenia. Women with low BMD and sarcopenia ( HR=2.27, 95% CI=1.37-3.76) and women with low BMD alone ( HR=2.62, 95% CI=1.74-3.95), but not women with only sarcopenia, had greater risk of fracture than women with normal BMD and no sarcopenia. Conclusion Men with low BMD and sarcopenia are at especially high risk of fracture. Sarcopenia alone did not increase fracture risk in either group. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to evaluate cross-sectional and longitudinal associations between ankle-brachial index (ABI) and indicators of cognitive function. Design Randomized clinical trial (Lifestyle Interventions and Independence for Elders Trial). Setting Eight US academic centers. Participants A total of 1601 adults ages 70–89 years, sedentary, without dementia, and with functional limitations. Measurements Baseline ABI and interviewer- and computer-administered cognitive function assessments were obtained. These assessments were used to compare a physical activity intervention with a health education control. Cognitive function was reassessed 24 months later (interviewer-administered) and 18 or 30 months later (computer-administered) and central adjudication was used to classify individuals as having mild cognitive impairment, probable dementia, or neither. Results Lower ABI had a modest independent association with poorer cognitive functioning at baseline (partial r = 0.09; P < .001). Although lower baseline ABI was not associated with overall changes in cognitive function test scores, it was associated with higher odds for 2-year progression to a composite of either mild cognitive impairment or probable dementia (odds ratio 2.60 per unit lower ABI; 95% confidence interval 1.06–6.37). Across 2 years, changes in ABI were not associated with changes in cognitive function. Conclusion In an older cohort sedentary individuals with dementia and with functional limitations, lower baseline ABI was independently correlated with cognitive function and associated with greater 2-year risk for progression to mild cognitive impairment or probable dementia. [ABSTRACT FROM AUTHOR]

Objectives To determine the association between hearing impairment (HI) and risk and duration of hospitalization in community-dwelling older adults in the United States. Design Prospective observational study. Setting Health, Aging and Body Composition Study. Participants Well-functioning community-dwelling white and black Medicare beneficiaries aged 70 to 79 at study enrollment in 1997-98 were followed for a median of 12 years. Measurements Incidence, annual rate, and duration of hospitalization were the primary outcomes. Hearing was defined as the pure-tone average (PTA) of hearing thresholds in decibels re: hearing level (dB HL) at octave frequencies from 0.5 to 4.0 kHz. Mild HI was defined as a PTA from 25 to 40 dB HL, and moderate or greater HI was defined as a PTA greater than 40 dB HL. Results Of the 2,148 participants included in the analysis, 1,801 (83.5%) experienced one or more hospitalizations, with 7,007 adjudicated hospitalization events occurring during the study period. Eight hundred eighty-two (41.1%) participants had normal hearing, 818 (38.1%) had mild HI, and 448 (20.9%) had moderate or greater HI. After adjusting for demographic characteristics and cardiovascular comorbidities, persons with mild HI experienced a 16% (hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.04-1.29) greater risk of incident hospitalization and a 17% (incidence rate ratio (IRR) = 1.17, 95% CI = 1.04-1.32) greater annual rate of hospitalization, and those with moderate or greater HI experienced a 21% (HR = 1.21, 95% CI = 1.06-1.38) greater risk of incident hospitalization and a 19% (IRR = 1.19, 95% CI = 1.04-1.38) greater annual rate of hospitalization than persons with normal hearing. There was no significant association between HI and mean duration of hospitalization. Conclusion Hearing-impaired older adults experience a greater incidence and annual rate of hospitalization than those with normal hearing. Investigating whether rehabilitative therapies could affect the risk of hospitalization in older adults requires further study. [ABSTRACT FROM AUTHOR]

Objectives To determine whether changes in insulin-like growth factor ( IGF) protein levels are greater in participants with type 2 diabetes mellitus or worsening glycemia than in normoglycemic individuals over a 9-year follow-up period. Design Retrospective analysis of a cohort study. Setting Participants were recruited from North Carolina, California, Maryland, and Pennsylvania. Participants Cardiovascular Health Study All Stars participants, a cohort study of community-dwelling adults aged 65 and older (N = 897). Measurements Plasma IGF-I, IGF binding protein ( IGFBP)-1, and IGFBP-3 levels were assessed and American Diabetes Association cut-points for impaired glucose tolerance ( IGT), impaired fasting glucose ( IFG), and diabetes mellitus were used to classify participants at baseline (1996-97) and follow-up (2005-06). Results At baseline, mean age was 76.3 ± 3.6, and 18.5% had diabetes mellitus. Participants with IFG alone and IGT plus IFG had higher IGF-I levels and lower IGFBP-1 levels than those with normoglycemia or diabetes mellitus. The greatest percentage change in IGF levels occurred in those who had diabetes mellitus at baseline (9-year changes: −9.3% for IGF-I, 59.7% for IGFBP-1, −13.4% for IGFBP-3), the smallest in individuals who remained normoglycemic at follow-up (9-year changes: −3.7% for IGF-I, 25.6% for IGFBP-1, −6.4% for IGFBP-3), and intermediate in those who were normoglycemic but developed IFG at follow-up. Conclusion Degrees of glycemic impairment are associated with varying degrees of change in IGF protein levels. The changes observed in the diabetes mellitus group have been previously shown to be associated with heart failure, cancer, and noncancer mortality. [ABSTRACT FROM AUTHOR]

Objectives To determine whether elderly people with different patterns of magnetic resonance imaging ( MRI) findings have different long-term outcomes. Design Longitudinal cohort study. Setting Cardiovascular Health Study. Participants Individuals aged 65 and older were recruited (N = 5,888); 3,660 of these underwent MRI, and 3,230 without a stroke before MRI were included in these analyses. Measurements Cluster analysis of brain MRI findings was previously used to define five clusters: normal, atrophy, simple infract, leukoaraiosis, and complex infarct. Participants were subsequently classified as healthy if they rated their health as excellent, very good, or good and as able if they did not report any limitations in activities of daily living ( ADLs). Mean years of life (YoL), years of healthy life ( YHL), and years of able life ( YAL) were calculated over 16 years after the MRI and compared between clusters using unadjusted and adjusted regression analyses. Results Mean age of participants was 75.0. With 16 years of follow-up, mean YoL was 11.3; YHL, 8.0; and YAL, 8.4. Outcomes differed significantly between clusters. With or without adjustments, outcomes were all significantly better in the normal than complex infarct cluster. The three remaining clusters had intermediate results, significantly different from the normal and complex infarct clusters but not usually from one another. Over 16 years of follow-up, participants in the complex infarct cluster (n = 368) spent the largest percentage of their 8.4 years alive being sick (38%) and not able (38%). Conclusion Findings on MRI scans in elderly adults are associated not only with long-term survival, but also with long-term self-rated health and limitation in ADLs. The combination of infarcts and leukoaraiosis carried the worst prognosis, presumably reflecting small vessel disease. [ABSTRACT FROM AUTHOR]

Objectives To determine the contribution of gradations of subclinical vascular disease ( SVD) to the likelihood of longer survival and to determine what allows some individuals with SVD to live longer. Design Cohort study. Setting Cardiovascular Health Study. Participants Individuals born between June 30, 1918, and June 30, 1921 (N = 2,082; aged 70-75 at baseline (1992-93)). Measurements A SVD index was scored as 0 for no abnormalities, 1 for mild abnormalities, and 2 for severe abnormalities on ankle-arm index, electrocardiogram, and common carotid intima-media thickness measured at baseline. Survival groups were categorized as 80 and younger, 81 to 84, 85 to 89, and 90 and older. Results A 1-point lower SVD score was associated with 1.22 greater odds (95% confidence interval = 1.14-1.31) of longer survival, independent of potential confounders. This association was unchanged after adjustment for intermediate incident cardiovascular events. There was suggestion of an interaction between kidney function, smoking, and C-reactive protein and SVD; the association between SVD and longer survival appeared to be modestly greater in persons with poor kidney function, inflammation, or a history of smoking. Conclusion A lower burden of SVD is associated with longer survival, independent of intermediate cardiovascular events. Abstinence from smoking, better kidney function, and lower inflammation may attenuate the effects of higher SVD and promote longer survival. [ABSTRACT FROM AUTHOR]

In a prospective cohort of nondisabled adults aged 65 years or more in the Established Populations for Epidemiologic Studies of the Elderly (1981–1987 and 1985–1992), we used a competing risk approach to predict the 5-year risk of severe, persistent activities-of-daily-living (ADLs) disability, defined as dependence in ≥3 ADLs for 2 consecutive annual interviews or for 1 interview followed by death in the subsequent year. During 5 years, 6.8% developed severe, persistent ADL dependence, and 14.6% died without severe, persistent ADL dependence in the derivation cohort (n = 8,301); the corresponding percentages were 6.8% and 15.8% in the validation cohort (n = 4,177). A model based on age, current employment, visual impairment, self-rated health, diabetes mellitus, history of stroke or brain hemorrhage, cognitive function, and self-reported physical function showed good calibration. Discrimination, assessed by C statistics, for <70, 70–74, 75–79, and ≥80 years, was 0.75, 0.74, 0.65, and 0.66 in the derivation cohort and 0.70, 0.72, 0.70, and 0.65 in the validation cohort, respectively. In conclusion, a simple risk score based on routinely available clinical information can predict severe, persistent disability in 5 years. Future studies should examine whether physical performance measures can further improve prediction in the oldest old. [ABSTRACT FROM PUBLISHER]

The authors hypothesized that the absence of cross-sectional associations of body mass index (BMI; weight (kg)/height (m)2) with peripheral arterial disease (PAD) in prior studies may reflect lower weight among persons who smoke or have poor health status. They conducted an observational study among 5,419 noninstitutionalized residents of 4 US communities aged ≥65 years at baseline (1989–1990 or 1992–1993). Ankle brachial index was measured, and participants reported their history of PAD procedures. Participants were followed longitudinally for adjudicated incident PAD events. At baseline, mean BMI was 26.6 (standard deviation, 4.6), and 776 participants (14%) had prevalent PAD. During 13.2 (median) years of follow-up through June 30, 2007, 276 incident PAD events occurred. In cross-sectional analysis, each 5-unit increase in BMI was inversely associated with PAD (prevalence ratio (PR) = 0.92, 95% confidence interval (CI): 0.85, 1.00). However, among persons in good health who had never smoked, the direction of association was opposite (PR = 1.20, 95% CI: 0.94, 1.52). Similar results were observed between BMI calculated using weight at age 50 years and PAD prevalence (PR = 1.30, 95% CI: 1.11, 1.51) and between BMI at baseline and incident PAD events occurring during follow-up (hazard ratio = 1.32, 95% CI: 1.00, 1.76) among never smokers in good health. Greater BMI is associated with PAD in older persons who remain healthy and have never smoked. Normal weight maintenance may decrease PAD incidence and associated comorbidity in older age. [ABSTRACT FROM PUBLISHER]

OBJECTIVES: To determine the relative effect of five chronic conditions on four representative universal health outcomes. DESIGN: Cross-sectional. SETTING: Cardiovascular Health Study. PARTICIPANTS: Five thousand two hundred and ninety-eight community-living participants aged 65 and older. MEASUREMENTS: Multiple regression and Cox models were used to determine the effect of heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, depression, and cognitive impairment on self-rated health, 12 basic and instrumental activities of daily living (ADLs and IADLs), six-item symptom burden scale, and death. RESULTS: Each condition adversely affected self-rated health ( P<.001) and ADLs and IADLs ( P<.001). For example, persons with HF performed 0.70±0.08 fewer ADLs and IADLs than those without; persons with depression and persons with cognitive impairment performed 0.59±0.04 and 0.58±0.06 fewer activities, respectively, than those without these conditions. Depression, HF, COPD, and osteoarthritis were associated with 1.18±0.04, 0.40±0.08, 0.40±0.05, and 0.57±0.03 more symptoms, respectively, in individuals with these conditions than in those without. HF (hazard ratio (HR)=2.84, 95% confidence interval (CI)=1.97-4.10), COPD (2.62, 95% CI=1.94-3.53), cognitive impairment (2.05, 95% CI=1.47-2.85), and depression (1.47, 95% CI=1.08-2.01) were each associated with death within 2 years. Several paired combinations of conditions had synergistic effects on ADLs and IADLs. For example, individuals with HF plus depression performed 2.0 fewer activities than persons with neither condition, versus the 1.3 fewer activities expected from adding the effects of the two conditions together. CONCLUSION: Universal health outcomes may provide a common metric for measuring the effects of multiple conditions and their treatments. The varying effects of the conditions across universal outcomes could inform care priorities. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the risks of coronary heart disease (CHD) and total mortality among adults with subclinical hypothyroidism. The study included 55,287 adults in the U.S., Europe, Australia, Brazil and Japan, who were followed up from 1972 to 2007. Of the total study participants, 3,450 developed subclinical hypothyroidism, while 51,837 had euthyroidism. Study authors found that increased thyroid-stimulating hormone (TSH) concentration increased the risk of CHD and CHD-related mortality. They concluded that patients with subclinical hypothyroidism have higher risk of CHD.

OBJECTIVES: To determine the relative importance of geriatric impairments (in muscle strength, physical capacity, cognition, vision, hearing, and psychological status) and chronic diseases in predicting subsequent functional disability in longitudinal analyses. DESIGN: Longitudinal data from the Cardiovascular Health Study were analyzed. Multivariable Cox hazards regression modeling was used to analyze associations between time-dependent predictors and onset of disability in activities of daily living (ADLs) and mobility. SETTING: Four communities across the United States (Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Allegheny County, PA). PARTICIPANTS: Five thousand eight hundred eighty-eight elderly persons. MEASUREMENTS: Data were collected annually through in-person examinations. RESULTS: ADL disability developed in 15% of participants and mobility disability in 30%. A single multivariable model was developed that included demographics, marital status, body mass index, and number of impairments and diseases. The hazard ratios (HRs) of having one, two, and three or more geriatric impairments (vs none) for the outcome of ADL disability were 2.12 (95% confidence interval (CI)=1.63–2.75), 4.25 (95% CI=3.30–5.48), and 7.87 (95% CI=6.10–10.17), respectively, and for having one, two, and three or more chronic diseases were 1.75 (95% CI=1.41–2.19), 2.45 (95% CI=1.95–3.07), and 3.26 (95% CI=2.53–4.19), respectively. Similarly, the HRs of having one, two, and three or more impairments for the outcome of mobility disability were 1.48 (95% CI=1.27–1.73), 2.08 (95% CI=1.77–2.45), and 3.70 (95% CI=3.09–4.42), respectively, and for having one, two, and three or more diseases were 2.06 (95% CI=1.76–2.40), 2.80 (95% CI=2.36–3.31), and 4.20 (95% CI=3.44–5.14), respectively. CONCLUSION: Number of geriatric impairments was more strongly associated than number of chronic diseases with subsequent ADL disability and nearly as strongly associated with the subsequent mobility disability. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to social network size and cranial magnetic resonance imaging findings in older adults.

The article reports on the study that examines the slop of annual decline in estimated glomerular filtration rate (eGFR) using both serum creatinine and cystatin rates in the American older people. The study, conducted by Internal Medicine Dena E. Rifkin and colleagues, reveals that the association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, and prevalent coronary heart disease. It also suggests that rapid decline in eGFR is associated with an increased risk of cardiovascular and all-acute cause mortality in older adults.

Background. Inflammatory biomarkers have shown consistent associations with disability and frailty in older adults. Statin medications may reduce the incidence the frailty because of their anti-inflammatory effects. This study examines associations between current use, duration, and potency of statin medications and incident frailty in initially nonfrail women 65 years old or older. Methods. The authors conducted a prospective analysis of data from the Women's Health Initiative Observational Study (WHI-OS) conducted at 40 clinical centers in the United States. Eligible women were nonfrail and 65-79 years old at baseline 01 = 25,378). Current statin use at baseline was ascertained through direct inspection of medicine containers during clinic visits. Frailty was ascertained through self-reported indicators and physical measurements at baseline and 3-year clinic contacts. Components of frailty included self-reported low physical function, exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models were used to adjust for covariates predicting incident frailty. Results. Among the 25,378 eligible women, 3453 (13.6%) developed frailty by the 3-year follow-up contact. Current statin use had no association with incident frailty (multivariate-adjusted odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.85-1.16). Duration and potency of statin use were also not significantly associated with incident frailty. Among low potency statin users, longer duration of use was associated with reduced risk of frailty (p for trend = .02). A similar pattern of results was observed when frailty was studied in the absence of intervening, incident cardiovascular events. Conclusions. Overall, incidence of frailty was similar in current statin users and nonusers. [ABSTRACT FROM AUTHOR]

The article discusses the effect of Cystatin C on successful aging. A study was conducted to determine the relation between kidney function and aging success for a six-year follow-upcardiovascular health study in the United States. The level of Cystatin C of the Two thousand one hundred forty participants have been observed. The result of the study showed that even if the patient possess a relatively normal kidney function, the presence of cystatin C in a higher level, the greater unsuccessful aging it entails.

OBJECTIVES: To determine whether weight categories predict subsequent mortality and morbidity in older adults. DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population-based cohort of older adults. SETTING: Data were provided by community-dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania. PARTICIPANTS: Five thousand eight hundred eighty-eight adults aged 65 and older at baseline. MEASUREMENTS: The age- and sex-specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65 were estimated. RESULTS: Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than being normal weight, whereas being overweight or obese was rarely associated with worse outcomes than being normal weight and was sometimes associated with significantly better outcomes. CONCLUSION: Similar to middle-aged populations, older adults are likely to be or to become overweight or obese, but higher weight is not associated with worse health in this age group. Thus, the number of older adults at a “healthy” weight may be much higher than currently believed. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess whether chronic kidney disease (CKD) is independently associated with incident physical-function limitation. DESIGN: Prospective cohort study. SETTING: Two sites: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand one hundred thirty-five men and women aged 70 to 79 without functional limitation at baseline from the Health, Aging and Body Composition Study. MEASUREMENTS: Functional limitation was defined as difficulty in walking one-quarter of a mile or climbing 10 steps on two consecutive reports 6 months apart (in the same function). Kidney function was measured using serum cystatin C. Estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula (<60 versus ≥60 mL/min per 1.73 m2), was a secondary predictor. Muscle strength, lean body mass according to dual energy x-ray absorptiometry, comorbidity, medication use, and inflammatory markers were evaluated as covariates. RESULTS: Persons in the highest (≥1.13 mg/L) quartile of cystatin C experienced a significantly higher risk of developing functional limitation than those in the lowest (<0.86 mg/L) quartile (hazard ratio (HR)=1.70, 95% confidence interval (CI)=1.40–2.07). The association between the fourth cystatin C quartile and functional limitation remained after adjustment for demographics, lean body mass, comorbidity, muscle strength, and gait speed (HR=1.41, 95% CI=1.13–1.75), although the association was attenuated after adjustment for markers of inflammation (HR=1.15, 95% CI=0.90–1.46). Similar results were found for eGFR less than 60 mL/min per 1.73 m2, although the association with functional limitation remained after adjustment for inflammatory markers (HR=1.30, 95% CI=1.08–1.56). CONCLUSION: CKD is associated with the development of functional impairment independent of comorbidity, body composition, and tests of strength and physical performance. The mechanism may be related to a heightened inflammatory state in CKD. [ABSTRACT FROM AUTHOR]

To investigate the association between different types of physical activity behavior and incident mobility limitation in older men and women and to examine whether muscle parameters mediate these associations.Cohort study with 4.5-year follow-up.Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. A random sample of white Medicare beneficiaries and all age-eligible blacks.Three thousand seventy-five black and white men and women aged 70 to 79 with no self-reported difficulty walking one-quarter of a mile or climbing 10 steps, enrolled in the Health, Aging and Body Composition (Health ABC) Study.Participants were classified as exercisers (reporting≥1,000 kcal/wk of exercise activity), lifestyle active (reporting<1,000 kcal/wk of exercise activity and≥2,719 kcal/wk of total physical activity), or inactive (reporting<1,000 kcal/wk of exercise activity and<2,719 kcal/wk of total physical activity). The study outcome, incident mobility limitation, was defined as two consecutive, semiannual self-reports of any difficulty walking one quarter of a mile or climbing 10 steps. Thigh muscle area, thigh muscle attenuation (a marker of fat infiltration in muscle), appendicular lean soft tissue mass, and isokinetic knee extensor strength were examined as potential mediators.Over 4.5 years, 34.3% of men and 47.4% of women developed mobility limitation. Inactive persons had twice the risk of incident mobility limitation as exercisers (hazard ratio (HR)=2.08, 95% confidence interval (CI)=1.60−2.70, for men, HR=1.98, 95% CI=1.51−2.60, for women). Lifestyle-active men and women had an intermediate risk (HR=1.47 and 1.44, respectively). For the lifestyle active and inactive, absence of walking activity conferred an additional risk of mobility limitation. Muscle parameters did not mediate the relationship between physical activity and mobility limitation, except for knee extensor strength in men.Exercise and an active lifestyle that includes walking protect against mobility loss in older men and women. Activity effects on muscle parameters do not explain this association. [ABSTRACT FROM AUTHOR]

To compare two sarcopenia definitions and examine the relationship between them and lower extrem-ity function and other health related factors using data from the baseline examination of the Health Aging and Body Composition (Health ABC) Study. Observational cohort study. Two U.S. communities in Memphis, Tennessee, and Pittsburgh, Pennsylvania. Participants were aged 70 to 79 (N=2,984, 52% women, 41% black). Participants were assessed using dual energy x-ray absorptiometry and were classified as sarcopenic using two different approaches to adjust lean mass for body size: appendicular lean mass divided by height-squared (aLM/ht2) and appendicular lean mass adjusted for height and body fat mass (residuals). These methods differed substantially in the classification of individuals as being sarcopenic, especially those who were more obese. The former method was highly correlated with body mass index and identified fewer overweight or obese individuals as sarcopenic. In both men and women, none of the obese group would be considered sarcopenic using the aLM/ht2 method, compared with 11.5% of men and 21.0% of women using the residuals method. In men, both classifications of sarcopenia were associated with smoking, poorer health, lower activity, and impaired lower extremity function. Fewer associations with health factors were noted in women, but the classification based on both height and fat mass was more strongly associated with lower extremity functional limitations (odds ratio (OR)=0.9, 95% confidence interval (CI)=0.7–1.2 for low kg/ht2; OR=1.9, 95% CI=1.4–2.5 for lean mass adjusted for height and fat mass). These findings suggest that fat mass should be considered in estimating prevalence of sarcopenia in women and in overweight or obese individuals. [ABSTRACT FROM AUTHOR]

Presents information on a study which assessed the prevalence and the factors associated with undiagnosed type 2 diabetes among the aged in the United States. Methodology; Results of the study; Conclusions.

OBJECTIVES: To describe gait variability at usual and fast walking speeds in community-dwelling older adults and to describe the effects of increasing gait speed on gait variability. DESIGN: Cross-sectional, descriptive study. SETTING: The Cardiovascular Health Study at the University of Pittsburgh. PARTICIPANTS: Ninety-five community-living older adults, 54 women and 41 men, age 65 and older (mean age ± standard deviation 79.4 ± 3.37). MEASUREMENTS: Gait measured at participant's usual and fast walking speed collected using an instrumented walkway. Step-length and step-width variability were determined using the coefficient of variation. CONCLUSIONS: Step-length and step-width variability have opposite associations with gait speed in older adults. Improvement in step-length and step-width variability with attempted acceleration might be a key factor to examine in future studies of disability risk and therapeutic interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The Health ABC Long Distance Corridor Walk (LDCW) was designed to extend the testing range of self-paced walking tests of fitness for older adults by including a warm-up and timing performance over 400 meters. This study compares performance on the LDCW and 6-minute walk to determine whether the LDCW encourages greater participant effort. DESIGN: Subjects were administered the LDCW and 6-minute walk during a single visit. Test order alternated between subjects, and a 15-minute rest was given between tests. SETTING: The Baltimore Veterans Affairs Medical Center. PARTICIPANTS: Twenty volunteers age 70 to 78. MEASUREMENTS: The LDCW, consisting of a 2-minute warm-up walk followed by a 400-meter walk and a 6-minute walk test were administered using a 20-meter long course in an unobstructed hallway. Heart rate (HR) and blood pressure (BP) were recorded at rest and before and after all walks. RESULTS: All 20 subjects walked a faster pace over 400 meters than for 6 minutes, in which the mean distance covered was 402 meters. From paired t-tests, walking speed was faster (mean difference = 0.23 m/sec; P < .001), and ending HR (mean difference = 7.6 bpm; P < .001) and systolic BP (mean difference = 8.3 mmHg; P = .024) were greater for the 400-meter walk than for the 6-minute walk. Results were independent of test order and subject fitness level. CONCLUSIONS: Providing a warm-up walk and using a target distance instead of time encouraged subjects to work closer to their maximum capacity. This low-cost alternative to treadmill testing can be used in research and clinical settings to assess fitness and help identify early functional decline in older adults. [ABSTRACT FROM AUTHOR]

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke, but the absolute rate of stroke varies widely depending on coexistent vascular disease. We assessed the stroke rate and predictive value of two published schemes for stroke risk stratification in a population-derived cohort of 259 elderly people with nonvalvular AF followed for a median of 5.3 years. The rate of ischemic stroke was 2.8% per year (95% confidence interval [CI] 1.9, 3.9). Thirty-one percent were predicted to be at low risk, and their stroke rate was 1.7% per year (95% CI 0.6, 3.8). Many people with AF in this population-derived cohort had relatively low rates of stroke. Further studies to reliably stratify stroke risk in patients with AF are needed. [ABSTRACT FROM AUTHOR]