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Background. The Mobility and Vitality Lifestyle Program (MOVE UP) is a behavioral weight-management intervention for improving mobility among community-dwelling older adults. We examined program factors that affect implementation outcomes and participant-level health outcomes. Methods. The MOVE UP program was implemented in the greater Pittsburgh area from January 2015 to June 2019 to improve lower extremity performance in community-dwelling older adults who were overweight or obese. Thirty-two sessions were delivered over 13 months. All sessions were designed to be 1-hour in length, on-site, group-based, and led by trained and supported community health workers (CHWs). Participants completed weekly Lifestyle Logs for self-monitoring of body weight, diet, and physical activity. We evaluated the MOVE UP program using the RE-AIM framework, and collected quantitative data at baseline, 5-, 9-, and 13-months. Multilevel linear regression models assessed the impacts of program factors (site, CHW, and participant characteristics) on implementation outcomes and participant-level health outcomes. Results. Twenty-two CHWs delivered MOVE UP program to 303 participants in 26 cohorts. Participants were similar to the target source population in weight but differed in some demographic characteristics. The program was effective for weight loss and lower extremity function in both intervention and maintenance periods (p s <.01), with an independent effect for Lifestyle Logs submission but not session attendance. Discussion. CHWs were able to deliver a multi-component weight loss intervention effectively in community settings. CHW and site characteristics had independent impacts on participants' adherence. Lifestyle Log submission may be a more potent measure of adherence in weight loss interventions than attendance. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested an association between bone mineral density (BMD) and heart failure (HF) risk that may be racedependent. Methods: We evaluated the relationship between BMD and incident HF in a cohort of older adults, the Health, Aging, and Body Composition (Health ABC) study (n = 2835), and next performed a pooled analysis involving a second older cohort, the Cardiovascular Health Study (n = 1268). Hip BMD was measured by dual-energy X-ray absorptiometry in both cohorts and spine BMD by computed tomography in a subset from Health ABC. Results: In Health ABC, lower BMD at the total hip was associated with higher incident HF in Black women after multivariable adjustment. Similar associations were found for BMD at the femoral neck and spine. In both cohorts, pooled analysis again revealed an association between lower total hip BMD and increased risk of HF in Black women (HR = 1.41 per 0.1-g/cm² decrement [95% CI = 1.23–1.62]), and showed the same to be true for White men (HR = 1.12 [1.03–1.21]). There was a decreased risk of HF in Black men (HR 0.80 [0.70–0.91]), but no relationship in White women. The associations were numerically stronger with HFpEF for Black women and White men, and with HFrEF for Black men. Findings were similar for femoral neck BMD. Sensitivity analyses delaying HF follow-up by 2 years eliminated the association in Black men. Conclusions: Lower BMD was associated with higher risk of HF and especially HFpEF in older Black women and White men, highlighting the need for additional investigation into underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Gerontology and ageing research are increasingly focussing on healthy life span (healthspan), the period of life lived free of serious disease and disability. Late‐life depression (LLD) is believed to impact adversely on physical health. However, no studies have examined its effect on healthspan. This study investigated the effect of LLD and subthreshold depression on disability‐free survival, a widely accepted measure of healthspan. Methods: This prospective cohort study used data from the ASPirin in Reducing Events in the Elderly study. Participants were aged ≥70 years (or ≥65 years for African‐American and Hispanic participants) and free of dementia, physical disability and cardiovascular disease. Depressive symptoms were measured using the 10‐item Centre for Epidemiological Studies Depression Scale (CES‐D‐10). LLD and subthreshold depression were defined as CES‐D‐10 scores ≥8 and 3–7, respectively. Disability‐free survival was defined as survival free of dementia and persistent physical disability. Results: A total of 19,110 participants were followed up for a maximum of 7.3 years. In female participants, LLD was associated with lower disability‐free survival adjusting for sociodemographic and lifestyle factors, medical comorbidities, polypharmacy, physical function and antidepressant use (HR, 1.50; 95% CI, 1.23–1.82). In male participants, LLD was associated with lower disability‐free survival adjusting for sociodemographic and lifestyle factors (HR, 1.30; 95% CI, 1.03–1.64). Subthreshold depression was also associated with lower disability‐free survival in both sexes. Conclusions: LLD may be a common and important risk factor for shortened healthspan. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Body composition assessment by computed tomography (CT) predicts health outcomes in diverse populations. However, its performance in predicting mortality has not been directly compared to dual-energy X-ray absorptiometry (DXA). Additionally, the association between different body compartments and mortality, acknowledging the compositional nature of the human body, is not well studied. Compositional data analysis, which is applied to multivariate proportion-type data set, may help to account for the interrelationships of body compartments by constructing log ratios of components. Here, we determined the associations of baseline CT-based measures of mid-thigh cross-sectional areas versus DXA measures of body composition with all-cause mortality in the Health ABC cohort, using both traditional (individual body compartments) and compositional data analysis (using ratios of body compartments) approaches.Methods: The Health ABC study assessed body composition in 2911 older adults in 1996-1997. We investigated the individual and ratios of (by compositional analysis) body compartments assessed by DXA (lean, fat, and bone masses) and CT (muscle, subcutaneous fat area, intermuscular fat, and bone) on mortality, using Cox proportional hazard models.Results: Lower baseline muscle area by CT (hazard ratio [HR]men = 0.56; 95% confidence interval [95% CI]: 0.48-0.67, HRwomen = 0.60; 95% CI: 0.48-0.74) and fat mass by DXA (HRmen = 0.48; 95% CI: 0.24-0.95) were predictors of mortality in traditional Cox regression analysis. Consistently, compositional data analysis revealed that lower muscle area versus IMF, muscle area versus bone area, and lower fat mass versus lean mass were associated with higher mortality in both sexes.Conclusion: Both CT measure of muscle area and DXA fat mass (either individually or relative to other body compartments) were strong predictors of mortality in both sexes in a community research setting. [ABSTRACT FROM AUTHOR]

Background Dietary protein may slow the decline in muscle mass and function with aging, making it a sensible candidate to prevent or modulate disability progression. At present, studies providing reliable estimates of the association between protein intake and physical function, and its interaction with physical activity (PA), in community-dwelling older adults are lacking. Objectives We investigated the longitudinal relation between protein intake and physical function, and the interaction with PA. Methods We undertook a pooled analysis of individual participant data from cohorts in the PROMISS (PRevention Of Malnutrition In Senior Subjects in the European Union) consortium (the Health Aging and Body Composition Study, Quebec Longitudinal Study on Nutrition and Successful Aging, Longitudinal Aging Study Amsterdam, and Newcastle 85+) in which 5725 community-dwelling older adults were followed up to 8.5 y. The relation between protein intake and walking speed was determined using joint models (linear mixed-effects and Cox proportional hazards models) and the relation with mobility limitation was investigated using multistate models. Results Higher protein intake was modestly protective of decline in walking speed in a dose-dependent manner [e.g. protein intake ≥1.2 compared with 0.8 g/kg adjusted body weight (aBW)/d: β = 0.024, 95% CI: 0.009, 0.032 SD/y], with no clear indication of interaction with PA. Participants with protein intake ≥0.8 g/kg aBW/d had also a lower likelihood of incident mobility limitation, which was observed for each level of PA. This association seemed to be dose-dependent for difficulty walking but not for difficulty climbing stairs. No associations between protein intake and other mobility limitations transitions were observed. Conclusions Higher daily protein intake can reduce physical function decline not only in older adults with protein intake below the current RDA of 0.8 g/kg BW/d, but also in those with a protein intake that is already considered sufficient. This dose-dependent association was observed for each level of PA, suggesting no clear synergistic association between protein intake and PA in relation to physical function. [ABSTRACT FROM AUTHOR]

Background/Objectives: Non‐steroidal anti‐inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine‐based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures. Design: Cross‐sectional and longitudinal analyses. Setting: Multicenter, community‐based cohort. Participants: Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements. Exposure: Prescription and over‐the‐counter NSAID use ascertained by self‐report. Measurements: Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin‐to‐creatinine ratio (ACR), kidney injury molecule‐1 (KIM‐1), and interleukin‐18 (IL‐18) were measured in 2,999 participants; alpha‐1 microglobulin (α1m), neutrophil gelatinase‐associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year. Results: Participants had a mean age of 74 years, 51% were female, and 41% African‐American. No eGFR differences were detected between NSAID users (n = 655) and non‐users (n = 2,344) at baseline (72 ml/min/1.73 m2 in both groups). Compared to non‐users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51–0.89) and lower mean urine IL‐18 concentration at baseline (−11%; 95% CI = −4% to −18%), but similar mean KIM‐1 (5%; 95% CI = −5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non‐users did not differ significantly in the rate of eGFR decline (−2.2% vs ‐2.3% per year). Conclusion: Self‐reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption. [ABSTRACT FROM AUTHOR]

Background Lower antioxidant serum concentrations have been linked to declines in lean mass and physical function in older adults. Yet population data on the effect of dietary antioxidants on loss of muscle strength and physical function are lacking. Objective We sought to determine the association of antioxidant intake [vitamin C, vitamin E, and total and individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin)] with annualized change in grip strength and gait speed in adults from the Framingham Offspring study. Methods This prospective cohort study included participants with a valid FFQ at the index examination and up to 2 prior examinations and at ≥2 measures of primary outcomes: grip strength (n  = 2452) and/or gait speed (n  = 2422) measured over 3 subsequent examinations. Annualized change in grip strength (kg/y) and change in gait speed (m/s/y) over the follow-up period were used. Linear regression was used to calculate β coefficients and P values, adjusting for covariates. Results Mean ± SD age of participants was 61 ± 9 y (range: 33–88 y). Median intakes (IQR, mg/d) of vitamin C, vitamin E, and total carotenoid across available examinations were 209.2 (133.1–394.2), 27.1 (7.4–199.0), and 15.3 (10.4–21.3), respectively. The mean follow-up time was ∼12 ± 2 y (range: 4.5–15.4 y). In the sex-combined sample, higher intakes of total carotenoids, lycopene, and lutein + zeaxanthin were associated with increased annualized change in grip strength [ β (SE) per 10-mg higher intake/d, range: 0.0316 (0.0146) to 0.1223 (0.0603) kg/y)]. All antioxidants except for vitamin C were associated with faster gait speed [ β (SE) per 10-mg higher intake/d, range: 0.00008 (0.00004) to 0.0187 (0.0081) m/s/y]. Conclusions Higher antioxidant intake was associated with increase in grip strength and faster gait speed in this cohort of adults. This finding highlights the need for a randomized controlled trial of dietary antioxidants and their effect on muscle strength and physical function. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Our aim was to examine the impacts of baseline fatigue on the effectiveness of a physical activity (PA) intervention to prevent major mobility disability (MMD) and persistent major mobility disability (PMMD) in participants from the Lifestyle Interventions and Independence for Elders (LIFE) study. DESIGN: Prospective cohort of individuals aged 65 years or older undergoing structured PA intervention or health education (HE) for a mean of 2.6 years. SETTING: LIFE was a multicenter eight‐site randomized trial that compared the efficacy of a structured PA intervention with an HE program in reducing the incidence of MMD. PARTICIPANTS: Study participants (N = 1591) at baseline were 78.9 ± 5.2 years of age, with low PA and at risk for mobility impairment. MEASUREMENTS: Self‐reported fatigue was assessed using the modified trait version of the Exercise‐Induced Feelings Inventory, a six‐question scale rating energy levels in the past week. Responses ranged from 0 (none of the time) to 5 (all of the time). Total score was calculated by averaging across questions; baseline fatigue was based on the median split: 2 or higher = more fatigue (N = 856) and lower than 2 = less fatigue (N = 735). Participants performed a usual‐paced 400‐m walk every 6 months. We defined incident MMD as the inability to walk 400‐m at follow‐up visits; PMMD was defined as two consecutive walk failures. Cox proportional hazard models quantified the risk of MMD and PMMD in PA vs HE stratified by baseline fatigue adjusted for covariates. RESULTS: Among those with higher baseline fatigue, PA participants had a 29% and 40% lower risk of MMD and PMMD, respectively, over the trial compared with HE (hazard ratio [HR] for MMD =.71; 95% confidence interval [CI] =.57‐.90; P =.004) and PMMD (HR =.60; 95% CI =.44‐.82; P =.001). For those with lower baseline fatigue, no group differences in MMD (P =.36) or PMMD (P =.82) were found. Results of baseline fatigue by intervention interaction was MMD (P =.18) and PMMD (P =.05). CONCLUSION: A long‐term moderate intensity PA intervention was particularly effective at preserving mobility in older adults with higher levels of baseline fatigue. J Am Geriatr Soc 68:619–624, 2020 [ABSTRACT FROM AUTHOR]

Background: To evaluate the discordance in frailty classification between the frailty index (FI) and the physical frailty phenotype (PFP) and identify factors discriminating those with discordant frailty classification from each other and from those for whom the assessments agree.Methods: A prospective observational study of older adults aged 65 and older selected from Medicare eligibility lists in four U.S. communities (n = 5,362). The PFP was measured by the Cardiovascular Health Study PFP. Participants meeting three or more of the five criteria were deemed frail. The FI was calculated as the proportion of deficits in an a priori selected set of 48 measures, and participants were classified as frail if FI is greater than 0.35.Results: The prevalence of frailty was 7.0% by the PFP and 8.3% by the FI. Of the 730 deemed frail by either instrument, only 12% were in agreement, whereas 39% were classified as frail by the PFP, but not the FI, and 48% were classified as frail by the FI, but not the PFP. Participants aged 65-72 years or with greater disease burden were most likely to be characterized as being FI-frail, but not PFP-frail. The associations of frailty with age and mortality were stronger when frailty was measured by the PFP rather than the FI.Conclusions: Despite comparable frailty prevalence between the PFP and the FI, there was substantial discordance in individual-level classification, with highest agreement existing only in the most vulnerable subset. These findings suggest that there are clinically important contexts in which the PFP and the FI cannot be used interchangeably. [ABSTRACT FROM AUTHOR]

Background: Optimization of intentional weight loss in obese older adults, through preferential fat mass reduction, is challenging, as the concomitant lean mass loss may exacerbate sarcopenia. Recent studies have suggested within-day distribution of protein intake plays a role in determining body composition remodeling. Here, we assessed whether changes in within-day protein intake distribution are related to improvements in body composition in overweight/obese older adults during a hypocaloric and exercise intervention. Methods: Thirty-six community-dwelling, overweight-to-obese (BMI 28.0-39.9 kg/m2), sedentary older adults (aged 70.6±6.1 years) were randomized into either physical activity plus successful aging health education (PA+SA; n=15) or physical activity plus weight loss (PA+WL; n=21) programs. Body composition (by CT and DXA) and dietary intake (by three-day food records) were determined at baseline, 6-month, and 12-month follow-up visits. Within-day protein distribution was calculated as the coefficient of variation (CV) of protein ingested per defined time periods (breakfast [5:00−10:59], lunch [11:00−16:59] and dinner [17:00−1:00]). Secondary analysis was performed to determine associations between changes in protein intake distribution and body composition. Results: In both groups, baseline protein intake was skewed towards dinner (PA+SA: 49.1%; PA+WL: 54.1%). The pattern of protein intake changed towards a more even within-day distribution in PA+WL during the intervention period, but it remained unchanged in PA+SA. Transition towards a more even pattern of protein intake was independently associated with a greater decline in BMI (P<0.05) and abdominal subcutaneous fat (P<0.05) in PA+WL. However, changes in protein CV were not associated with changes in body weight in PA+SA. Conclusion: Our results show that mealtime distribution of protein intake throughout the day was associated with improved weight and fat loss under hypocaloric diet combined with physical activity. This finding provides a novel insight into the potential role of within-day protein intake on weight management in obese older people. [ABSTRACT FROM AUTHOR]

The US population aged 90 years or more is growing rapidly, and there are limited data on their health. The Cardiovascular Health Study is a prospective study of black and white adults aged ≥65 years recruited in 2 waves (1989–1990 and 1992–1993) from Medicare eligibility lists in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. We created a synthetic cohort of the 1,889 participants who had reached age 90 years at baseline or during follow-up through July 16, 2015. Participants entered the cohort at 90 years of age, and we evaluated their changes in health after age 90 years (median duration of follow-up, 3 years (interquartile range, 1.3–5)). Measures of health included cardiovascular events, cognitive function, depressive symptoms, prescription medications, self-rated health, and functional status. The mortality rate was high: 19.0 per 100 person-years (95% confidence interval : 17.8, 20.3) in women and 20.9 per 100 person-years (95% confidence interval: 19.2, 22.8) in men. Cognitive function and all measures of functional status declined with age; these changes were similar by sex. When we isolated period effects, we found that medication use increased over time. These estimates can help inform future research and can help health-care systems meet the needs of this growing population. [ABSTRACT FROM AUTHOR]

Objectives: To understand which causes of death are higher in black than white community‐dwelling older adults and determine whether differences in baseline risk factors explain racial differences in mortality. Design: Longitudinal cohort study (Health, Aging, and Body Composition Study). Setting: Pittsburgh, Pennsylvania; and Memphis, Tennessee. Participants: Black and white men and women aged 70 to 79 during recruitment (N=3,075; 48% men, 42% black) followed for a median of 13 years. Measurements: A committee of physicians adjudicated cause of death, which was categorized as cardiovascular disease (CVD), stroke, cancer, dementia, pulmonary, infection, kidney, or other causes. Using competing risks regression, we examined whether known risk factors at baseline (demographic characteristics, smoking, body mass index, chronic diseases, physical function, cognition) could explain racial differences in cause‐specific mortality risk. Results: During follow‐up, 1,991 (65%) participants died. Black participants died at higher rates from cancer (hazard ratio (HR)=1.36, 95% confidence interval (CI)=1.14–1.63), kidney disease (HR=2.09, 95% CI=1.16–3.74), stroke (HR=1.31, 95% CI=0.98–1.76); and CVD (HR=1.16, 95% CI=0.98–1.37). Poorer physical and cognitive performance at baseline among black participants explained most of the racial difference in risks of dying from kidney disease, stroke, and CVD but not cancer. When examining types of cancer deaths, black participants died at higher rates from multiple myeloma, pancreatic cancer, and prostate cancer, which baseline risk factors did not explain either. Conclusion: Factors contributing to poorer physical and cognitive performance in similarly aged black men and women could be targets to reduce excess mortality from CVD, stroke, and kidney disease. More work is needed to identify factors contributing to cancer mortality disparities. [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]

Frailty is an age-related clinical syndrome of decreased resilience to stressors. Among numerous assessments of frailty, the frailty phenotype (FP) scale proposed by Fried et al. has been the most widely used. We aimed to develop a continuous frailty scale that could overcome limitations facing the categorical FP scale and to evaluate its construct validity, predictive validity, and measurement properties. Data were from the Cardiovascular Health Study (n = 4,243) and Health and Retirement Study (n = 7,600), both conducted in the United States. Frailty was conceptualized as a continuous construct, assessed by 5 measures used in the FP scale: gait speed, grip strength, exhaustion, physical activity, and weight loss. We used confirmatory factor analysis to investigate the relationship between the 5 indicators and the latent frailty construct. We examined the association of the continuous frailty scale with mortality and disability. The unidimensional model fit the data satisfactorily; similar factor structure was observed across 2 cohorts. Gait speed and weight loss were the strongest and weakest indicators, respectively; grip strength, exhaustion, and physical activity had similar strength in measuring frailty. In each cohort, the continuous frailty scale was strongly associated with mortality and disability and continued to be associated with outcomes among robust and prefrail persons classified by the FP scale. [ABSTRACT FROM AUTHOR]

Background: Protein-energy malnutrition (PEM) is amajor problem in older adults. Whether poor diet quality is an indicator for the longterm development of PEM is unknown. Objective: The aim was to determine whether poor diet quality is associated with the incidence of PEM in community-dwelling older adults. Design:We used data on 2234 US community-dwelling older adults aged 70-79 y of the Health, Aging, and Body Composition (Health ABC) Study. In 1998-1999, dietary intake over the preceding year was measured by using a Block food-frequency questionnaire. Indicators of diet quality include the Healthy Eating Index (HEI), energy intake, and protein intake. Outcomes were determined annually by using measured weight and height and included the following: 1) incident PEM [body mass index (in kg/m²) <20, involuntary weight loss of =5% in the preceding year at any follow-up examination, or both] and 2) incident persistent PEM (having PEM at 2 consecutive follow-up examinations). Associations of indicators of diet quality with 4-y and 3-y incidence of PEM and persistent PEM, respectively, were examined by multivariable Cox regression analyses. Results: The quality of the diet, as assessed with the HEI, was rated as "poor" for 6.4% and as "needs improvement" for 73.0% of the participants. During follow-up, 24.9% of the participants developed PEM and 8.5% developed persistent PEM. A poor HEI score was not associated with incident PEM or persistent PEM. Lower baseline energy intake was associated with a lower incidence of PEM (HR per 100-kcal/d lower intake: 0.98; 95% CI: 0.97, 0.99) and persistent PEM (HR: 0.97; 95% CI: 0.95, 0.99), although lower baseline protein intake was observed to be associated with a higher incidence of persistent PEM (HR per 10-g/d lower intake: 1.15; 95% CI: 1.03, 1.29). Conclusions: These findings do not indicate that a poor diet quality is a risk factor for the long-term development of PEM in communitydwelling older adults, although there is an indication that lower protein intake is associated with higher PEM risk. [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]

Objectives: To examine the relationship between end-of-life (EOL) treatment preferences and recent hospitalization or emergency department (ED) care in the very old. Design: Quarterly telephone follow-up of participants in the EOL in the Very Old cohort. Setting: The EOL in the Very Old Age cohort drew from 1403 participants in the Health, Aging, and Body Composition (Health ABC) study who were alive in year 15 of follow-up. 87.5% ( n = 1227) were successfully recontacted and enrolled. Participants: Preferences for treatment at the EOL and reported hospital and ED use were examined for 1118 participants (18% involving proxy reports) over 6 months, 1021 (16% with proxy reports) over 12 months, and 945 (23% with proxy reports) over 18 months in 6-month intervals. Measurements: Preferences for eight EOL treatments, elicited once each year; hospitalization and ED use reported every six months. Results: Preferences for more aggressive treatment (endorsing ≥5 of 8 options) were not significantly associated with inpatient or ED treatment. Inpatient and ED treatment were not associated with changes in preferences for aggressive EOL treatment over 12 months. Conclusion: Alternative measures that tap attitudes toward routine care, rather than EOL treatment preferences, may be more highly associated with healthcare utilization. [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: Age-related losses of lean mass and shifts to central adiposity are related to functional decline and may predict mortality and/or explain part of the risk of weight loss. To determine how mortality risk is related to shifts in body composition, changes should be considered in the context of overall weight change.Methods: Five-year changes in body composition were assessed with computed tomography (cm2) and dual x-ray absorptiometry (kg) in 869 men and 934 women initially aged 70-79 years. All-cause mortality was monitored for up to 12 years (2002-2003 to September 30, 2014), and risk was assessed using sex-specific Cox models.Results: Both men and women lost weight, visceral fat area, thigh muscle area, lean mass, and fat mass (all p < .01) but gained intermuscular thigh fat area (p < .01). There were 995 deaths. After adjustment for total weight change, demographics, and chronic disease, losing thigh muscle area was associated with higher mortality in both men (1.21, 1.08-1.35) and women (1.18, 1.01-1.37, per 9.0cm2) and was especially strong in normal weight (body mass index < 25kg/m2) individuals and those losing weight. Losing intermuscular thigh fat was protective against mortality only in normal weight (0.66, 0.51-0.86) and weight stable men (0.79, 0.66-0.95, per 3.2cm2). Changes in visceral fat area were not associated with mortality.Conclusions: Older adults with greater loss of thigh muscle than expected for overall weight change had a higher mortality risk compared to those with relative thigh muscle preservation, suggesting that conservation of muscle mass is important for survival in old age. [ABSTRACT FROM AUTHOR]

Aim The Mobility and Independent Living in Elders Study ( MILES) was established in 2012 to estimate the prevalence, incidence, and risk factors for disability and age-related disease in rural older Indians. Here we describe the main goals of MILES, the essential elements of its design and examinations, and the initial findings from the baseline visit. Methods A random sample of 562 men and women aged ≥60 years was enrolled from the Medchal region in Telangana State. Baseline examination consisted of two separate clinical visits, and included measurements of blood pressure, anthropometry, physical function, peripheral artery disease, cognitive function, bone and muscle quality, knee osteoarthritis, carotid intima-media thickness, and blood biomarkers. A comprehensive interview was carried out for demographics, disability and disease history. Annual follow-up visits are ongoing to collect information on incident disability and disease. Results The median age of participants was 66 years (range 60-92 years); median body mass index 21.7 kg/m2, median gait speed 0.67 m/s and 55% self-reported their health status as fair or poor. Conclusions These findings suggest a more frail population in the MILES cohort compared with older adults in USA cohorts. MILES will provide estimates of burden of disease, and disability and risk factors in older adults. Findings will be used to identify potential interventions to prevent disability in this rural Indian population. Geriatr Gerontol Int 2017; 17: 31-40. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to (i) evaluate previous observations that the association of blood pressure (BP) with outcomes varies by gait speed and (ii) evaluate the association of subsequent changes in BP and cardiovascular risk.Methods: Participants included 2,669 adults aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) study. Gait speed was dichotomized at ≥1.0 m/s over a 20-m test at baseline. BP was measured at baseline, and changes in BP over 5 years were evaluated using (i) population-based trajectory models and (ii) intraindividual mean and slope.Results: Over a mean of 10 years, there were 1,366 deaths, 336 first myocardial infarctions, and 295 first strokes. There was a differential pattern of association between baseline systolic BP and diastolic BP and outcomes among brisk and moderate speed walkers. For example, the association between higher diastolic BP and mortality was in the protective direction for moderate speed walkers (hazard ratio = 0.75; 95% confidence interval: 0.63, 0.91) per 10 mmHg higher, whereas it was null in brisk walkers (hazard ratio = 1.05; 95% confidence interval: 0.98, 1.11), p value for interaction .01. The 5-year population-based trajectories did not add important information beyond baseline BP. Individual slopes in both systolic BP and diastolic BP did not appear to have important associations with the outcomes.Conclusions: In this study, we found that the overall level of BP was associated with myocardial infarction, stroke, and death, and this association differed by baseline gait speed, whereas changes in BP were not associated with these outcomes. [ABSTRACT FROM AUTHOR]

Background: Few cohort studies have examined longitudinal associations between age-related changes in cognition and physical performance. Further, whether these associations differ for men versus women or can be attributed to differences in physical activity (PA) is unknown.Methods: Participants were 2,876 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 52% female; 39% black) studied over a 9-year period. Usual gait speed, self-reported PA, and two cognitive measures-Digit Symbol Substitution Test (DSST) and Mini-Modified Mental State examination (3MS)-were assessed years 0 (ie, baseline), 4, and 9.Results: Early decline between years 0 and 4 in gait speed predicted later decline between years 4 and 9 in performance on the 3MS (β = 0.10, p = .004) and on the DSST (β = 0.16, p < .001). In contrast, the associations between early decline in cognition and later decline in gait speed were weaker and were non-significant after correcting for multiple comparisons (β = 0.08, p = .019 for 3MS and β = .06, p = .051 for DSST). All associations were similar for women and men and were unaltered when accounting for PA levels.Conclusions: The results indicate declining gait speed as a precursor to declining cognitive functioning, and suggest a weaker reciprocal process among older women and men. [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]

Objective to examine whether psychomotor speed predicts individual and combined disorders in cognition, mobility and mood and if white matter hyperintensities explain these associations. Design and setting longitudinal; Cardiovascular Health Study. Subjects 5,888 participants (57.6% women, 15.7% black, 75.1 (5.5), mean years (SD)). Methods psychomotor speed (Digit Symbol Substitution Test (DSST)) and small vessel disease (white matter hyperintensities (WMH)) were measured in 1992-94. Global cognition (Modified Mini-Mental State (3MS) examination), mobility (gait speed (GS)) and mood (Center for Epidemiologic Studies Depression (CES-D) scale) were measured annually over 5 years and classified as clinical, subclinical or no disorders based on established values (3MS: 80 and 85 points; GS: 0.6 and 1.0 m/s; CES-D: 10 and 5 points). Analyses were adjusted for demographics, baseline status, education, diabetes, hypertension, ankle--arm index. Results among those with no disorder in cognition, mobility and mood (N = 619) in 1992-94, being in the lowest DSST quartile compared to the highest was associated with nearly twice the odds of developing 1+ clinical or subclinical disorders (N = 413) during follow-up. Associations were stronger for incident clinical disorders in cognition (OR: 8.44, p < 0.01) or mobility (OR: 9.09, p < 0.05) than for mood (OR: 1.88, p < 0.10). Results were similar after adjustment for WMH. Conclusions slower psychomotor speed may serve as a biomarker of risk of clinical disorders of cognition, mobility and mood. While in part attributable to vascular brain disease, other potentially modifiable contributors may be present. Further studying the causes of psychomotor slowing with ageing might provide novel insights into age-related brain disorders. [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]

Objectives To evaluate the effect of structured physical activity on respiratory outcomes in community-dwelling elderly adults with mobility limitations. Design Multicenter, randomized trial of physical activity vs health education, with respiratory variables prespecified as tertiary outcomes over an intervention period of 24-42 months. Physical activity included walking (goal of 150 min/week) and strength, flexibility, and balance training. Health education included workshops on topics relevant to older adults and upper extremity stretching exercises. Setting Lifestyle Interventions and Independence in Elders ( LIFE) Study. Participants Community-dwelling persons aged 70-89 with Short Physical Performance Battery scores less than 10 (N = 1,635). Measurements Dyspnea severity (defined as moderate to severe according to a Borg index >2 immediately after a 400-m walk), forced expiratory volume in 1 second ( FEV1) (

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: Although the "anti-aging hormone" klotho is associated with sarcopenia in mice, the relationship between klotho and muscle strength in older adults is not well known.Methods: Plasma klotho concentrations were measured in 2,734 older adults, aged 71-80 years, who participated in the Health, Aging and Body Composition Study, a prospective observational cohort study conducted in Memphis, TN and Pittsburgh, PA. Knee extension strength was measured using isokinetic dynamometry at baseline and follow-up 2 and 4 years later. Knee extension strength was normalized for weight.Results: At baseline, participants in the highest tertile of plasma klotho had higher knee extension strength (β = .72, standard error [SE] = .018, p < .0001) compared with those in the lowest tertile in a multivariable linear regression model adjusting for age, sex, race, smoking, study site, C-reactive protein, interleukin-6, and diabetes. Participants in the highest tertile of plasma klotho at baseline had less of a decline in knee strength over 4 years of follow-up (β = -.025, SE = .011, p = .02) compared with those in the lowest tertile in a multivariable linear regression model adjusting for the same covariates above.Conclusions: Plasma klotho concentrations were an independent predictor of changes in knee strength over time in older adults. Further studies are needed to identify the biological mechanisms by which circulating klotho could modify skeletal muscle strength. [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]

Background: Despite wide-spread use of antihypertensives in older adults, the literature is unclear about their association with incident recurrent falls over time.Methods: Health, Aging and Body Composition study participants (n = 2,948) who were well functioning at baseline (1997) were followed to Year 7 (2004). The main outcome was recurrent falls (≥2) in the ensuing 12 months. Antihypertensive use was examined as: (a) any versus none, (b) long- versus short-term (≥2 vs <2 years), and by (c) summated standardized daily dose (SDD; 1 = maximum recommended daily dose for one antihypertensive), and (d) subclass.Results: Controlling for potential demographic, health status/behavior and access to care confounders, we found no increase in risk of recurrent falls in antihypertensive users compared to nonusers (adjusted odds ratio [AOR] = 1.13; 95% CI = 0.88-1.46), or those taking higher SDDs or for longer durations. Only those using a loop diuretic were found to have a modest increased risk of recurrent falls (AOR = 1.50; 95% CI = 1.11-2.03).Conclusions: Antihypertensive use overall was not statistically significantly associated with recurrent falls after adjusting for important confounders. Loop diuretic use may be associated with recurrent falls and needs further study. [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]

Background: Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults.Methods: The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m(2) and usual gait-speed of 1.2 ± 0.2 m/s. Fatigability was defined using rating of perceived exertion (6-20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using (31)P magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax (mM ATP/s) and oxidative capacity of the quadriceps (ATPmax·Quadriceps volume) were calculated. Peak aerobic capacity (VO2peak) was measured using a modified Balke protocol.Results: ATPmax·Quadriceps volume was associated with VO2peak and was 162.61mM ATP·mL/s lower (p = .03) in those with high (rating of perceived exertion ≥10) versus low (rating of perceived exertion ≤9) fatigability. Participants with high fatigability required a significantly higher proportion of VO2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11-1.01, p = .05).Conclusions: Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction is a prominent hallmark of many sensory neuropathies. The purpose of this study was to assess the influence of mitochondrial DNA sequence variation on peripheral nerve function in the population-based Health, Aging, and Body Composition Study.Methods: We investigated the role of common mitochondrial DNA variation (n = 1,580) and complete mitochondrial DNA sequences (n = 138) on peroneal motor nerve conduction velocity and amplitude, average vibration detection threshold, and monofilament sensitivity.Results: Nominal associations among common mitochondrial DNA variants and haplogroups were identified but were not statistically significant after adjustment for multiple comparisons. Sequence-based approaches were used to identify aggregate variant associations across the 16S rRNA (weighted-sum, p = 2E-05 and variable threshold, p = 9E-06) for nerve conduction velocity. Several of these rare 16S variants occurred at or near sites with earlier disease associations and are also in close proximity to the peptidyl transferase center, which is the catalytic center of the 16S rRNA CONCLUSIONS: These results suggest that sequence variation related to mitochondrial protein synthesis/assembly is associated with peripheral nerve function and may provide insight into targets for intervention or new clinical strategies to preserve nerve function in late life. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at specific mtDNA sites lead to inherited mitochondrial diseases with neurological, sensory, and movement impairments. Here we test the hypothesis that heteroplasmy levels in elderly adults are associated with impaired function resembling mild forms of mitochondrial disease.Methods: We examined platelet mtDNA heteroplasmy at 20 disease-causing sites for associations with neurosensory and mobility function among 137 participants from the community-based Health, Aging, and Body Composition Study.Results: Elevated mtDNA heteroplasmy at four mtDNA sites in complex I and tRNA genes was nominally associated with reduced cognition, vision, hearing, and mobility: m.10158T>C with Modified Mini-Mental State Examination score (p = .009); m.11778G>A with contrast sensitivity (p = .02); m.7445A>G with high-frequency hearing (p = .047); and m.5703G>A with 400 m walking speed (p = .007).Conclusions: These results indicate that increased mtDNA heteroplasmy at disease-causing sites is associated with neurosensory and mobility function in older persons. We propose the novel use of mtDNA heteroplasmy as a simple, noninvasive predictor of age-related neurologic, sensory, and movement impairments. [ABSTRACT FROM AUTHOR]

Objectives To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function Design Cross-sectional analysis of the Cardiovascular Health Study (1998-1999). Setting Community. Participants Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5). Measurements Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test ( TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand) Results Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = −0.30, 95% confidence interval ( CI) = −0.37 to −0.24) and physical (mean score difference = −0.32, 95% CI = −0.38 to −0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: −0.16, 95% CI = −0.24 to −0.08 vs −0.13, 95% CI = −0.20 to −0.06; physical function: −0.15, 95% CI = −0.22 to −0.08 vs −0.12, 95% CI = −0.18 to −0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function. Conclusion Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication. [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 examine body mass index ( BMI) trajectories with change in lean mass and physical function in old age. Design Prospective cohort study. Setting Health, Aging and Body Composition Study. Participants Black and white men (n = 482) and women (n = 516) aged 73.1 ± 2.7 and initially free of disability. Measurements A group-based trajectory model was used to determine BMI trajectories, the path a person's BMI followed over 9 years. Lean mass, gait speed, grip strength, and knee extension strength were assessed at baseline and after 9 years, and relative changes were calculated. Multivariable linear regression was used to determine associations between trajectories and relative change in lean mass and physical function. Results Four BMI trajectories were identified for men and four for women. Although all demonstrated a decline in BMI, the rate of decline differed according to trajectory for women only. Men in Trajectory 4 (mean BMI at baseline 33.9 ± 2.3 kg/m2) declined more than those in Trajectory 1 (mean BMI at baseline 22.9 ± 1.6 kg/m2) in gait speed (−9.91%, 95% confidence interval ( CI) = −15.15% to −4.67%) and leg strength (−8.63%, 95% CI = −15.62% to −1.64%). Women in Trajectory 4 (mean BMI at baseline 34.9 ± 3.0 kg/m2) had greater losses than those in Trajectory 1 (mean BMI at baseline 20.5 ± 1.6 kg/m2) in lean mass in the arms (−3.19%, 95% CI = −6.16% to −0.23%). No other associations were observed. Conclusion Obese men had the highest risk of decline in physical function despite similar weight loss between trajectories, whereas overweight and obese women who lost the most weight had the greatest risk of lean mass loss. The weight at which a person enters old age is informative for predicting loss in lean mass and physical function, illustrating the importance of monitoring weight. [ABSTRACT FROM AUTHOR]

Objectives To examine the prospective relationship between self-reported physical activity and aerobic fitness in the Health, Aging, and Body Composition Study (Health ABC) using the Long Distance Corridor Walk ( LDCW). Design Cohort study with 7 years of follow-up. Setting Two U.S. clinical sites. Participants Community-dwelling older adults enrolled in Health ABC (N = 3,075, aged 70-79, 52% female, 42% black) with no self-reported difficulty walking one-quarter of a mile or climbing 10 steps. Measurements Participants were classified based on a physical activity questionnaire as being inactive (≤1,000 kcal/wk exercise activity, ≤2,719 kcal/wk total physical activity), lifestyle active (≤1,000 kcal/wk exercise activity, >2,719 kcal/wk total physical activity), or exercisers (≥1,000 kcal/wk exercise activity). The LDCW, an endurance walking test (400 m), was administered at Years 1 (baseline), 2, 4, 6, and 8 to assess aerobic fitness. Results At baseline, LDCW completion times (adjusted for age and sex) were 351.8 seconds (95% confidence interval ( CI) = 346.9-356.8 seconds) for the inactive group, 335.9 seconds (95% CI = 332.7-339.1 seconds) for the lifestyle active group, and 307.7 seconds (95% CI = 303.2-312.3 seconds) for the exerciser group ( P < .001). From baseline to Year 8, the inactive group slowed 36.1 seconds (95% CI = 28.4-43.8 seconds), the lifestyle active group slowed 38.1 seconds (95% CI = 33.6-42.4 seconds), and the exerciser group slowed 40.8 seconds (95% CI = 35.2-46.5 seconds), and did not differ significantly between groups. In linear mixed-effects models, the rate of change in LDCW time did not differ between the groups, although exercisers consistently had the fastest completion times ( P < .001 for all pairwise comparisons). Conclusion Decline in LDCW time occurred regardless of baseline activity, although exercisers maintained higher aerobic fitness, which may delay reaching a critically low threshold of aerobic fitness at which independence is impaired. [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 examine the association between multiple measures of visual impairment ( VI) and incident mobility limitations in older adults. Design Prospective observational cohort study. Setting Memphis, Tennessee, and Pittsburgh, Pennsylvania. Participants Health, Aging and Body Composition study participants aged 70 to 79 without mobility limitations at the Year 3 visit (N = 1,862). Measurements Vision was measured at the Year 3 visit, and VI was defined as distance visual acuity ( VA) worse than 20/40, contrast sensitivity ( CS) less than 1.55 log Contrast, and stereoacuity ( SA) greater than 85 arcsec. Incident persistent walking and stair climbing limitation was defined as two consecutive 6-month reports of any difficulty walking one-quarter of a mile or walking up 10 steps after 1, 3, and 5 years of follow-up. Results At Year 3 (baseline for these analyses), 7.4% had impaired VA, 27.2% had impaired CS, and 29.2% had impaired SA. At all follow-up times, the incidence of walking and stair climbing limitations was higher in participants with VA, CS, or SA impairment. After 5 years, impaired CS and SA were independently associated with greater risk of walking limitation (hazard ratio ( HR) CS = 1.3, 95% confidence interval ( CI) = 1.1-1.7; HRSA = 1.3, 95% CI = 1.1-1.6) and stair climbing limitation ( HRCS = 1.4, 95% CI = 1.1-1.8; HRSA = 1.3, 95% CI=1.1-1.7). Having impaired CS and SA was associated with greater risk of mobility limitations ( HRwalking limitations = 2.0, 95% CI = 1.6-2.5; HRstair limitation = 2.1, 95% CI = 1.6-2.8). Conclusion Multiple aspects of VI may contribute to mobility limitations in older adults. Addressing more than one component of vision may be needed to reduce the effect of vision impairment on functional decline. [ABSTRACT FROM AUTHOR]

Objectives To examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults. Design Longitudinal cohort study. Setting Health, Aging and Body Composition (Health ABC) Study. Participants Two thousand five participants aged 70-79 at baseline with medication and gait speed data at 1998-99, 1999-2000, 2001-02, and 2002-03. Measurements The independent variables were any statin use and their standardized daily doses (low, moderate, high) and lipophilicity. The primary outcome measure was decline in gait speed of 0.1 m/s or more in the following year of statin use. Multivariable generalized estimating equations were used, adjusting for demographic characteristics, health-related behaviors, health status, and access to health care. Results Statin use increased from 16.2% in 1998-99 to 25.6% in 2002-03. The overall proportions of those with decline in gait speed of 0.1 m/s or more increased from 22.2% in 1998 to 23.9% in 2003. Statin use was not associated with decline in gait speed of 0.1 m/s or more (adjusted odds ratio ( AOR) = 0.90, 95% confidence interval ( CI) = 0.77-1.06). Similar nonsignificant trends were also seen with the use of hydrophilic or lipophilic statins. Users of low-dose statins were found to have a 22% lower risk of decline in gait speed than nonusers ( AOR = 0.78, 95% CI = 0.61-0.99), which was mainly driven by the results from 1999-2000 follow-up. Conclusion These results suggest that statin use did not increase decline in gait speed in community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Objectives To assess the relationship between sensorimotor nerve function and incident mobility disability over 10 years. Design Prospective cohort study with longitudinal analysis. Setting Two U. S. clinical sites. Participants Population-based sample of community-dwelling older adults with no mobility disability at 2000/01 examination (N = 1,680; mean age ± SD 76.5 ± 2.9, body mass index 27.1 ± 4.6; 50.2% female, 36.6% black, 10.7% with diabetes mellitus). Measurements Motor nerve conduction amplitude (poor <1 mV) and velocity (poor <40 m/s) were measured on the deep peroneal nerve. Sensory nerve function was measured using 10- and 1.4-g monofilaments and vibration detection threshold at the toe. Lower extremity symptoms included numbness or tingling and aching or burning pain. Incident mobility disability assessed semiannually over 8.5 years (interquartile range 4.5-9.6 years) was defined as two consecutive self-reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. Results Nerve impairments were detected in 55% of participants, and 30% developed mobility disability. Worse motor amplitude ( HR = 1.29 per SD, 95% CI = 1.16-1.44), vibration detection threshold ( HR = 1.13 per SD, 95% CI = 1.04-1.23), symptoms ( HR = 1.65, 95% CI = 1.26-2.17), two motor impairments ( HR = 2.10, 95% CI = 1.43-3.09), two sensory impairments ( HR = 1.91, 95% CI = 1.37-2.68), and three or more nerve impairments ( HR = 2.33, 95% CI = 1.54-3.53) predicted incident mobility disability after adjustment. Quadriceps strength mediated relationships between certain nerve impairments and mobility disability, although most remained significant. Conclusion Poor sensorimotor nerve function independently predicted mobility disability. Future work should investigate modifiable risk factors and interventions such as strength training for preventing disability and improving function in older adults with poor nerve function. [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 examine associations between weight change, body composition, risk of mobility disability, and mortality in older adults. Design Prospective, longitudinal, population-based cohort. Setting The Health, Aging, and Body Composition Study. Participants Women (n = 1,044) and men (n = 931) aged 70 to 79. Measurements Weight and lean and fat mass from dual-energy X-ray absorptiometry measured annually over 5 years. Weight was defined as stable (n = 664, reference), loss (n = 662), gain (n = 321), or cycling (gain and loss, n = 328) using change of 5% from year to year or from Year 1 to 6. Mobility disability (two consecutive reports of difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 8 years after the weight change period. Associations were analyzed using Cox proportional hazards regression adjusted for covariates. Results During follow-up, 313 women and 375 men developed mobility disability, and 322 women and 378 men died. There was no risk of mobility disability or mortality with weight gain. Weight loss (hazard ratio ( HR) = 1.88, 95% confidence interval ( CI) = 1.40-2.53) and weight cycling ( HR = 1.59, 95% CI = 1.11-2.29) were associated with mobility disability in women, and weight loss was associated with mobility disability in men ( HR = 1.30, 95% CI = 1.01-1.69). Weight loss and weight cycling were associated with mortality risk in women (weight loss: HR = 1.47, 95% CI = 1.07-2.01; weight cycling: HR = 1.62, 95% CI = 1.15-2.30) and in men (weight loss: HR = 1.41, 95% CI = 1.09-1.83; weight cycling: HR = 1.50, 95% CI = 1.08-2.08). Adjustment for lean and fat mass and change in lean and fat mass from Year 1 to 6 attenuated the relationships between weight loss and mobility disability in men and between weight loss and mortality in men and women. Conclusion Weight cycling and weight loss predict impending mobility disability and mortality in old age, underscoring the prognostic importance of weight history. [ABSTRACT FROM AUTHOR]