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Objectives: To examine the associations between cumulative physical activity (PA) and its changes over 3 years and changes over 9 years of follow-up in physical performance in older adults., Design: Longitudinal., Setting: Community-based., Participants: Men and women aged 65 and older from the Invecchiare in Chianti study (N = 782)., Measurements: Physical performance was assessed at baseline and at 3-, 6-, and 9-year follow-up using the Short Physical Performance Battery (SPPB). PA was assessed through an interviewer-administered questionnaire at baseline and 3-year follow-up. Analyses were adjusted for education, body mass index, smoking, alcohol intake, coronary heart disease, stroke, peripheral arterial disease, cancer, lung disease, lower extremity osteoarthritis, depression, and Mini-Mental State Examination., Results: Over 3 years of follow-up, 27.8% of participants were inactive, 52.2% were minimally active, and 20.0% were active, and the PA of 37.2% decreased, there was no change in PA of 50.1% and the PA of 12.7% increased. After adjustment for potential covariates, being mostly active (-1.08, 95% confidence interval (CI) = -1.43 to -0.73) and minimally active (-1.33, 95% CI = -1.53 to -1.12) over 3 years of follow-up was associated with less decline in SPPB score than being mostly inactive (-2.60, 95% CI = -2.92 to -2.27). When analyzing changes, increasing PA (-0.57, 95% CI = -1.01 to -0.12) was associated with less decline in SPPB score over 9 years than decreasing PA (-2.16, 95% CI = -2.42 to -1.89)., Conclusion: Maintaining or increasing PA levels may attenuate age-associated physical performance decline., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

This study aimed to characterize the prevalence of various pain qualities in older adults with chronic nonmalignant pain and determine the association of pain quality to other pain characteristics namely: severity, interference, distribution, and pain-associated conditions. In the population-based MOBILIZE Boston Study, 560 participants aged ≥70 years reported chronic pain in the baseline assessment, which included a home interview and clinic exam. Pain quality was assessed using a modified version of the McGill Pain Questionnaire (MPQ) consisting of 20 descriptors from which 3 categories were derived: cognitive/affective, sensory, and neuropathic. Presence of ≥2 pain-associated conditions was significantly associated with 18 of the 20 pain quality descriptors. Sensory descriptors were endorsed by nearly all older adults with chronic pain (93%), followed by cognitive/affective (83.4%) and neuropathic descriptors (68.6%). Neuropathic descriptors were associated with the greatest number of pain-associated conditions including osteoarthritis of the hand and knee. More than half of participants (59%) endorsed descriptors in all 3 categories and had more severe pain and interference, and multisite or widespread pain than those endorsing 1 or 2 categories. Strong associations were observed between pain quality and measures of pain severity, interference, and distribution (P < 0.0001). Findings from this study indicate that older adults have multiple pain-associated conditions that likely reflect multiple physiological mechanisms for pain. Linking pain qualities with other associated pain characteristics serve to develop a multidimensional approach to geriatric pain assessment. Future research is needed to investigate the physiological mechanisms responsible for the variability in pain qualities endorsed by older adults.

Background: We examined whether physical activity in early adulthood, late midlife, and old age as well as cumulative physical activity history are associated with changes in physical functioning and mortality in old age., Methods: Data are from participants aged 65 years or older enrolled in the InCHIANTI study who were followed up from 1998-2000 to 2007-2008 (n = 1,149). At baseline, participants recalled their physical activity levels at ages 20-40, 40-60, and in the previous year, and they were categorized as physically inactive, moderately active, and physically active. Physical performance was assessed with the Short Physical Performance Battery and self-reported mobility disability was evaluated at the 3-, 6- and 9-year follow-up. Mortality follow-up was assessed until the end of 2010., Results: Physical inactivity at baseline was associated with greater decline in Short Physical Performance Battery score (mean 9-year change: -2.72, 95% CI: -3.08, -2.35 vs -0.98, 95% -1.57, -0.39) and greater rate of incident mobility disability (hazard ratio 4.66, 95% CI 1.14-19.07) and mortality (hazard ratio 2.18, 95% CI 1.01-4.70) compared to physically active participants at baseline. Being physically active throughout adulthood was associated with smaller decline in physical performance as well as with lower risk of incident mobility disability and premature death compared with those who had been less active during their adult life., Conclusions: Higher cumulative physical activity over the life course was associated with less decline in physical performance and reduced rate of incident mobility disability and mortality in older ages., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Low serum bicarbonate associates with mortality in CKD. This study investigated the associations of bicarbonate and acid-base status with mortality in healthy older individuals., Design, Setting, Participants, & Measurements: We analyzed data from the Health, Aging, and Body Composition Study, a prospective study of well functioning black and white adults ages 70-79 years old from 1997. Participants with arterialized venous blood gas measurements (n=2287) were grouped into <23.0 mEq/L (low), 23.0-27.9 mEq/L (reference group), and ≥28.0 mEq/L (high) bicarbonate categories and according to acid-base status. Survival data were collected through February of 2014. Mortality hazard ratios (HRs; 95% confidence intervals [95% CIs]) in the low and high bicarbonate groups compared with the reference group were determined using Cox models adjusted for demographics, eGFR, albuminuria, chronic obstructive pulmonary disease, smoking, and systemic pH. Similarly adjusted Cox models were performed according to acid-base status., Results: The mean age was 76 years, 51% were women, and 38% were black. Mean pH was 7.41, mean bicarbonate was 25.1 mEq/L, 11% had low bicarbonate, and 10% had high bicarbonate. Mean eGFR was 82.1 ml/min per 1.73 m(2), and 12% had CKD. Over a mean follow-up of 10.3 years, 1326 (58%) participants died. Compared with the reference group, the mortality HRs were 1.24 (95% CI, 1.02 to 1.49) in the low bicarbonate and 1.03 (95% CI, 0.84 to 1.26) in the high bicarbonate categories. Compared with the normal acid-base group, the mortality HRs were 1.17 (95% CI, 0.94 to 1.47) for metabolic acidosis, 1.21 (95% CI, 1.01 to 1.46) for respiratory alkalosis, and 1.35 (95% CI, 1.08 to 1.69) for metabolic alkalosis categories. Respiratory acidosis did not associate with mortality., Conclusions: In generally healthy older individuals, low serum bicarbonate associated with higher mortality independent of systemic pH and potential confounders. This association seemed to be present regardless of whether the cause of low bicarbonate was metabolic acidosis or respiratory alkalosis. Metabolic alkalosis also associated with higher mortality., (Copyright © 2016 by the American Society of Nephrology.)

Background: Studies suggest that in patients with heart failure (HF), high serum erythropoietin is associated with risk of recurrent HF and mortality. Trials of erythropoietin-stimulating agents in persons with kidney disease have also suggested an increased incidence of adverse clinical events. No large studies of which we are aware have evaluated the association of endogenous erythropoietin levels with clinical outcomes in the community-living older adults., Methods and Results: Erythropoietin concentration was measured in 2488 participants aged 70-79 years in the Health, Aging and Body Composition Study. Associations of erythropoietin with incident HF, coronary heart disease, stroke, mortality, and ≥ 30% decline in estimated glomerular filtration rate were examined using Cox proportional hazards and logistic regression over 10.7 years of follow-up. Mean (SD) age was 75 (3) years and median (quartile 1, quartile 3) erythropoietin was 12.3 (9.0, 17.2) mIU/mL. There were 503 incident HF events, and each doubling of serum erythropoietin was associated with a 25% increased risk of incident HF 1.25 (95% confidence interval 1.13, 1.48) after adjusting for demographics, prevalent cardiovascular disease, cardiovascular disease risk factors, kidney function, and serum hemoglobin. There was no interaction of serum erythropoietin with chronic kidney disease or anemia (P > 0.50). There were 330 incident coronary heart disease events, 161 strokes, 1112 deaths, and 698 outcomes of ≥ 30% decline in estimated glomerular filtration rate. Serum erythropoietin was not significantly associated with these outcomes., Conclusions: Higher levels of endogenous erythropoietin are associated with incident HF in older adults. Studies need to elucidate the mechanisms through which endogenous erythropoietin levels associate with specific outcomes., (© 2015 American Heart Association, Inc.)

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., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of the Study: The purpose of this study was to describe prevalence of technology use among adults ages 65 and older, particularly for those with disability and activity-limiting symptoms and impairments., Design and Methods: Data from the 2011 National Health and Aging Trends Study, a nationally representative sample of community-dwelling Medicare beneficiaries (N = 7,609), were analyzed. Analysis consisted of technology use (use of e-mail/text messages and the internet) by sociodemographic and health characteristics and prevalence ratios for technology usage by disability status., Results: Forty percent of older adults used e-mail or text messaging and 42.7% used the internet. Higher prevalence of technology use was associated with younger age, male sex, white race, higher education level, and being married (all p values <.001). After adjustment for sociodemographic and health characteristics, technology use decreased significantly with greater limitations in physical capacity and greater disability. Vision impairment and memory limitations were also associated with lower likelihood of technology use., Implications: Technology usage in U.S. older adults varied significantly by sociodemographic and health status. Prevalence of technology use differed by the type of disability and activity-limiting impairments. The internet, e-mail, and text messaging might be viable mediums for health promotion and communication, particularly for younger cohorts of older adults and those with certain types of impairment and less severe disability., (© The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Physical activity (PA) may play a role in preserving kidney health. The purpose of this study was to determine if PA and sedentary behavior are associated with incident chronic kidney disease (CKD) and change in kidney function in older adults., Methods: The Health, Aging, and Body Composition study is a prospective cohort of 3075 well-functioning older adults. PA and television watching was measured by self-report, and serum cystatin C was used to estimate glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 ml/min/1.73 m(2). Rapid kidney function decline was defined as an annual loss in eGFR of >3 ml/min/1.73 m(2). Discrete survival analysis was used to determine if baseline PA and television watching were related to 10-year cumulative incidence of CKD and rapid decline in kidney function., Results: Individuals who reported watching television >3 hours/day had a higher risk of incident CKD (HR 1.34; 95% CI, 1.09-1.65) and experiencing a rapid decline in kidney function (HR 1.26; 95% CI, 1.05-1.52) compared with individuals who watched television <2 hours/day. PA was not related to either outcome., Conclusions: High levels of television watching are associated with declining kidney function; the mechanisms that underlie this association need further study.

Background: Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed., Methods: This prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999-2009)., Results: At 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease., Conclusions: Considering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Diabetes among older adults causes many complications, including decreased lower-extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine the following: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship., Research Design and Methods: This study included 983 participants, age 65 years and older from the InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0 to 12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to 5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations., Results and Conclusion: One hundred twenty-six (12.8%) participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β=-0.99; p<0.01), decreased walking speed (β=-0.1m/s; p<0.01), decreased nerve conduction velocity (β=-1.7m/s; p<0.01), and increased neuropathy (β=0.25; p<0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF., (© 2014.)

This study sought to determine the prevalence and impact of pain in a nationally representative sample of older adults in the United States. Data from the 2011 National Health and Aging Trends Study were analyzed. In-person interviews were conducted in 7601 adults ages ≥65 years. The response rate was 71.0% and all analyses were weighted to account for the sampling design. The overall prevalence of bothersome pain in the last month was 52.9%, afflicting 18.7 million older adults in the United States. Pain did not vary across age groups (P = 0.21), and this pattern remained unchanged when accounting for cognitive performance, dementia, proxy responses, and residential care living status. Pain prevalence was higher in women and in older adults with obesity, musculoskeletal conditions, and depressive symptoms (P < 0.001). The majority (74.9%) of older adults with pain endorsed multiple sites of pain. Several measures of physical capacity, including grip strength and lower-extremity physical performance, were associated with pain and multisite pain. For example, self-reported inability to walk 3 blocks was 72% higher in participants with than without pain (adjusted prevalence ratio 1.72 [95% confidence interval 1.56-1.90]). Participants with 1, 2, 3, and ≥4 sites of pain had gait speeds that were 0.01, 0.03, 0.05, and 0.08 meters per second slower, respectively, than older adults without pain, adjusting for disease burden and other potential confounders (P < 0.001). In summary, bothersome pain in the last month was reported by half of the older adult population of the United States in 2011 and was strongly associated with decreased physical function., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Objective: To determine whether anemia is associated with incident dementia in older adults., Methods: We studied 2,552 older adults (mean age 76.1 years; 38.9% black; 51.8% female) participating in the Health, Aging, and Body Composition study and free of dementia at baseline. We defined anemia using WHO criteria (hemoglobin concentration <13 g/dL for men and <12 g/dL for women). Dementia diagnosis was determined by dementia medication use, hospital records, or a change in modified mini-mental state (3MS) score of more than 1.5 SD from mean. Discrete time Cox proportional hazard regression models were used to examine the hazard for developing dementia associated with anemia., Results: Of 2,552 participants, 393 (15.4%) older adults had anemia at baseline [corrected]. Over 11 years of follow-up, 455 (17.8%) participants developed dementia. In the unadjusted model, those with baseline anemia had an increased risk of dementia (23% vs. 17%, hazard ratio = 1.64; 95% confidence interval 1.30, 2.07) compared to those without anemia. The association remained significant after adjusting for demographics, APOE ε4, baseline 3MS score, comorbidities, and renal function. Additional adjustment for other anemia measures (mean corpuscular volume, red cell distribution width), erythropoietin, and C-reactive protein did not appreciably change the results. There was no interaction by sex and race on risk of developing dementia., Conclusion: Among older adults, anemia is associated with an increased risk of developing dementia. Findings suggest that further study of anemia as a risk factor for dementia and a target for intervention for cognitive health is warranted.

Background: Frailty is associated with morbidity and premature mortality among elderly HIV-uninfected adults, but the determinants and consequences of frailty in HIV-infected populations remain unclear. We evaluated the correlates of frailty, and the impact of frailty on mortality in a cohort of aging injection drug users (IDUs)., Methods: Frailty was assessed using standard criteria among HIV-infected and uninfected IDUs in 6-month intervals from 2005 to 2008. Generalized linear mixed-model analyses assessed correlates of frailty. Cox proportional hazards models estimated risk for all-cause mortality., Results: Of 1230 participants at baseline, the median age was 48 years and 29% were HIV-infected; the frailty prevalence was 12.3%. In multivariable analysis of 3,365 frailty measures, HIV-infected IDUs had an increased likelihood of frailty (OR, 1.66; 95% CI, 1.24-2.21) compared to HIV-uninfected IDUs; the association was strongest (OR, 2.37; 95% CI, 1.62-3.48) among HIV-infected IDUs with advanced HIV disease (CD4<350 cells/mm3 and detectable HIV RNA). No significant association was seen with less advanced disease. Sociodemographic factors, comorbidity, depressive symptoms, and prescription drug abuse were also independently associated with frailty. Mortality risk was increased with frailty alone (HR 2.63, 95% CI, 1.23-5.66), HIV infection alone (HR 3.29, 95% CI, 1.85-5.88), and being both HIV-infected and frail (HR, 7.06; 95%CI 3.49-14.3)., Conclusion: Frailty was strongly associated with advanced HIV disease, but IDUs with well-controlled HIV had a similar prevalence to HIV-uninfected IDUs. Frailty was independently associated with mortality, with a marked increase in mortality risk for IDUs with both frailty and HIV infection.

The red cell distribution width (RDW) is a component of the automated complete blood count (CBC) that quantifies heterogeneity in the size of circulating erythrocytes. Higher RDW values reflect greater variation in red blood cell (RBC) volumes and are associated with increased risk for cardiovascular disease (CVD) events. The mechanisms underlying this association are unclear, but RBC deformability might play a role. CBCs were assessed in 293 adults who were clinically examined. RBC deformability (expressed as the elongation index) was measured using a microfluidic slit-flow ektacytometer. Multivariate regression analysis identified a clear threshold effect whereby RDW values above 14.0% were significantly associated with decreased RBC deformability (β = -0.24; p = 0.003). This association was stronger after excluding anemic participants (β = -0.40; p = 0.008). Greater variation in RBC volumes (increased RDW) is associated with decreased RBC deformability, which can impair blood flow through the microcirculation. The resultant hypoxia may help to explain the previously reported increased risk for CVD events associated with elevated RDW.

Objective: To assess whether selenium and carboxymethyl-lysine (CML), two biomarkers of oxidative stress, are independent predictors of anemia in older community-dwelling adults., Methods: Plasma levels of selenium, CML, folate, vitamin B12, and testosterone and markers of iron status and inflammation were measured at baseline in 1036 adults at least 65 y old in the Invecchiare in Chianti Study, a population-based cohort study of aging in Tuscany, Italy, and examined in relation to prevalent anemia and incident anemia over 6 y of follow-up., Results: At enrollment, 11.6% of participants were anemic. Of 472 participants who were non-anemic at enrollment, 72 (15.3%) developed anemia within 6 y of follow-up. At enrollment, plasma CML in the highest quartile (>425 ng/mL) and plasma selenium in the lowest quartile (<66.6 μg/L) predicted incident anemia (hazard ratio 1.67, 95% confidence interval 1.07-2.59, P = 0.02; hazard ratio 1.55, 95% confidence interval 1.01-2.38, P = 0.05, respectively) in a multivariate Cox proportional hazards model that adjusted for age, education, body mass index, cognition, inflammation, red blood cell distribution width, ferritin, vitamin B12, testosterone, and chronic diseases., Conclusion: Elevated plasma CML and low plasma selenium are long-term independent predictors of anemia in older community-dwelling adults. These findings support the idea that oxidative stress contributes to the development of anemia., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: the rate of performance decline may influence the risk of disability or death., Methods: for 4,182 Cardiovascular Health Study participants, we used multinomial Poisson log-linear models to assess the contribution of physical performance in 1998-99, and the rate of performance change between 1992-93 and 1998-99, to the risk of death or disability in 2005-06 in three domains: mobility, upper-extremity function (UEF) and activities of daily living (ADL). We evaluated performance in finger-tapping, grip strength, stride length, gait speed and chair stands separately and together for each outcome, adjusting for age, gender, race and years of disability in that outcome between 1992-93 and 1998-99., Results: participants' age averaged 79.4 in 1998-99; 1,901 died over 7 years. Compared with the lowest change quintile in stride length, the highest quintile had a 1.32 relative risk (RR) of ADL disability (95% CI: 1.16 -1.96) and a 1.27 RR of death (95% CI: 1.07 -1.51). The highest change quintile for grip strength increased the risk of ADL disability by 35% (95% CI: 1.13 -1.61) and death by 31% (95% CI: 1.16 -1.49), compared with the lowest quintile. The annual change in stride length and grip strength also predicted disability in mobility and UEF., Conclusion: performance trajectories independently predict death and disability.

The aim of this study was to assess the kidney function of an older community-dwelling population at baseline and appraise its evolution after 3 years of follow-up in terms of chronic kidney disease (CKD) stage progression, magnitude of glomerular filtration rate (GFR) changes, and value of serum creatinine. This was a prospective population-based study of 676 Italian participants, aged 65 years and older. GFR was estimated using the Cockcroft-Gault equation and the Modification of Diet in Renal Disease Study equation. Using the Cockcroft-Gault equation. A total of 33% of participants had criteria of CKD (GFR < 60 mL/min) at baseline; among them, the majority remained stable, 10% improved, and 7% progressed to more severe CKD stages at follow-up. Loss of GFR in participants with GFR < 60 mL/min was significantly lower (1.4 mL/min per year) than in participants with GFR ≥ 60 mL/min (3.3 mL/min per year) at baseline. Most participants classified with CKD stage 2 (GFR 60-89 mL/min) or stage 3 (GFR 30-59 mL/min) at baseline did not change stage, whereas 55% of people with CKD stage 1 (GFR > 90 mL/min) at baseline worsened to stage 2 and 10% worsened to stage 3. An abnormal high level of serum creatinine at baseline did not help to predict who might worsen at follow-up. Older people with CKD displayed a low progression of renal disease and therefore are at higher risk for co-morbidities related to CKD than for progression to end-stage renal disease.

Background & Aims: Red cell distribution width (RDW), a measure of heterogeneity in the size of circulating erythrocytes, is associated with some chronic diseases and predicts mortality. Although oxidative damage and inflammation have been theorized to affect RDW, the relationships of antioxidants and inflammation with RDW have not been well characterized. The aims were to determine whether total serum carotenoids, α-tocopherol, selenium, protein carbonyls, and interleukin-6 (IL-6) are associated with RDW and predict RDW over time., Methods: RDW was measured at baseline, 12 months, and 24 months follow-up in 786 moderately to severely disabled community-dwelling women, aged ≥65 years, in the Women's Health and Aging Study I in Baltimore, Maryland., Results: Selenium was significantly associated with RDW at baseline and predicted RDW over two years' follow-up in separate multivariate mixed-effects models that adjusted for other covariates. As expected, the addition of IL-6 to the models attenuated the association of serum selenium with RDW, as low antioxidant levels are known to upregulate IL-6. Total carotenoids were associated with RDW at baseline and one year follow-up. Protein carbonyls and α-tocopherol were not significantly associated with RDW., Conclusion: Serum selenium is an independent predictor of RDW and may potentially mediate effects on RDW through IL-6., (Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In patients with overt inflammatory diseases, up-regulated hepcidin impairs iron absorption and macrophage release, causing anemia. Whether the mild proinflammatory state of aging is associated with increased hepcidin is unknown. We characterized the relationships between urinary hepcidin, iron status, anemia, and inflammation in 582 patients 65 years or older participating in the InCHIANTI (Invecchiare in Chianti, "Aging in the Chianti Area") study, a population-based study of aging in Tuscany, Italy. Compared with nonanemic persons, urinary hepcidin (nanograms/milligram of urinary creatinine) was significantly lower in iron deficiency and inflammation anemia compared with no anemia or other anemia types. Urinary hepcidin was positively correlated with log(ferritin) and negatively correlated with the soluble transferrin receptor/log(ferritin) ratio but not correlated with markers of inflammation: interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha, and C-reactive protein (CRP). Lower iron was significantly correlated with higher IL-6 and CRP. Adjusting for confounders, IL-6 and CRP remained significantly associated with serum iron, with no evidence that such a relationship was accounted for by variability in urinary hepcidin. In conclusion, elevated proinflammatory markers were associated with anemia and low iron status, but not with higher urinary hepcidin. Future studies should test whether hepcidin production becomes up-regulated only in situations of overt inflammation.

Background: Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear., Methods: Seven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed., Results: Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.11-1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12-1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07-1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07-1.18). Furthermore, the RDW-mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21-1.44)., Conclusions: RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.

Objectives: To investigate the characteristics of older adults who develop high interleukin-6 (IL-6) levels at 3-year follow-up., Design: Population-based study of adults living in Tuscany, Italy., Setting: Community., Participants: Adults aged 65 and older and were selected for this study. Of 1,155 baseline participants aged 65 and older, 741 had IL-6 measurements at baseline and 3-year follow-up., Measurements: The uppermost quartile of IL-6 was used as the threshold for defining high IL-6 (> or =4.18 pg/mL). Serum IL-6 levels were assessed using enzyme immunoassay., Results: Of the 581 participants with IL-6 levels less than 4.18 pg/mL at baseline, 106 (18.2%) had developed high IL-6 at follow-up. Although women had lower IL-6 levels at baseline than men, the risk of developing high IL-6 did not differ according to sex. High adiposity, defined as a body mass index of 30.0 kg/m(2) or higher (odds ratio (OR)=2.63, 95% confidence interval (CI)=1.40-4.96), and large waist circumference, defined as 102 cm or greater for men and 88 cm or greater for women (OR=2.05, 95% CI=1.24-3.40), were significant predictors of developing high IL-6 at follow-up. Other significant predictors were presence of three or more chronic diseases (OR=3.66, 95% CI=1.54-8.70), higher baseline IL-6 (OR=1.82, 95% CI=1.39-2.38) and higher white blood cell count (OR=1.24, 95% CI=1.06-1.45). Faster walking speed associated with decreased risk of progressing to elevated IL-6 (OR=0.83, 95% CI=0.74-0.92)., Conclusion: Older age, greater adiposity, slower walking speed, higher disease burden, and higher white blood cell count were associated with greater risk of IL-6 elevation over a 3-year period. Future research should target older adults with these characteristics to prevent progression to a proinflammatory state.

In this study, the authors aimed to determine whether higher activity energy expenditure, assessed by using doubly labeled water, was associated with a reduced decline in mobility limitation among 248 older community-dwelling US adults aged 70-82 years enrolled in 1998-1999. Activity energy expenditure was calculated as total energy expenditure (assessed over 2 weeks by using doubly labeled water) minus resting metabolic rate (measured with indirect calorimetry), with adjustment for the thermic effect of food. Across sex-specific tertiles of activity energy expenditure, men in the lowest activity group experienced twice the rate of mobility limitation as men in the highest activity group (41% (n = 18) vs. 18% (n = 8)). Conversely, women in the lowest and highest activity groups exhibited similarly high rates of mobility limitation (40% (n = 16) vs. 38% (n = 15)). After adjustment for potential confounders, men with higher activity energy expenditure levels continued to show reduced risk of mobility limitation (per standard deviation (284 kcal/day): hazard ratio = 0.61, 95% confidence interval: 0.41, 0.92). Women showed no association (per standard deviation (226 kcal/day): hazard ratio = 1.34, 95% confidence interval: 0.98, 1.85). Greater energy expenditure from any and all physical activity was significantly associated with reduced risk of developing mobility limitation among men, but not among women.

Mildly low haemoglobin concentration is associated with increased mortality in older adults. However, this relationship has not been well characterized in racial/ethnic minorities. Therefore, this study determined the haemoglobin threshold below which risk of death is significantly increased in older non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Data on 4089 participants of the 1988-94 US National Health and Nutrition Examination Survey who were > or =65 years of age were analyzed with mortality follow-up through December 31, 2000. Mean haemoglobin in non-Hispanic whites (n = 2686) and Mexican Americans (n = 663) was 140 g/l, while in non-Hispanic blacks (n = 740) the mean was 10 g/l lower. A total of 1944 (47.5%) participants died. Among non-Hispanic whites and Mexican Americans, age- and sex-adjusted models showed that the haemoglobin thresholds below which mortality risk was significantly increased were 4 and 2 g/l respectively, above the World Health Organization (WHO) cut-off points for anaemia. In contrast, the threshold for non-Hispanic blacks was 7 g/l below the WHO criteria. Similar threshold effects were observed when analyzing haemoglobin in categories and adjusting for multiple confounders. In conclusion, the haemoglobin threshold below which mortality rises significantly is a full g/dl lower in non-Hispanic blacks than in non-Hispanic whites and Mexican Americans.

Anemia is a common, multifactorial condition among older adults. The World Health Organization (WHO) definition of anemia (hemoglobin concentration <12 g/dL in women and <13 g/dL in men) is most often used in epidemiologic studies of older adults. More than 10% of community-dwelling adults age 65 years and older has WHO-defined anemia. After age 50 years, prevalence of anemia increases with advancing age and exceeds 20% in those 85 years and older. In nursing homes, anemia is present in 48% to 63% of residents. Incidence of anemia in older adults is not well characterized. Among older adults with anemia, approximately one third have evidence of iron, folate, and/or vitamin B(12) deficiency, another third have renal insufficiency and/or chronic inflammation, and the remaining third have anemia that is unexplained. Several studies demonstrate that anemia is associated with poorer survival in older adults. This review details the distribution and consequences of anemia in older adults and identifies future epidemiologic research needs.

Anemia is more common among older blacks than older whites. However, it is unclear whether anemia predicts adverse events similarly in both races. Data on 1018 black and 1583 white adults aged 71 to 82 years were analyzed. Anemia, as defined by World Health Organization (WHO) criteria, was used to predict mortality over 6 years and incidence of mobility disability over 4 years. In proportional hazards models of mortality in whites, the age-adjusted hazard ratio (HR) for anemia in men was 1.96 (95% confidence interval [CI]: 1.35, 2.83) and in women was 2.86 (95% CI: 1.69, 4.82). In contrast, anemia was not associated with mortality in black men (HR = 1.15 [95% CI: 0.77, 1.72]) or women (HR = 1.39 [95% CI: 0.91, 2.14]). Higher mortality rate was observed only in black men with hemoglobin values more than 20 g/L (2.0 g/dL) below the WHO cutoff, whereas mortality rates were elevated in white men with hemoglobin values 1 to 10, 11 to 20, and more than 20 g/L below the WHO cutoff. In conclusion, anemia was significantly associated with increased risk of death and mobility disability in community-dwelling older whites. Conversely, older blacks classified as anemic by WHO criteria were not at risk for adverse events, indicating that alternative criteria are warranted.

Background: Very few studies have examined how disability develops among older Mexican Americans. To determine how disability develops, we explored the Disablement Process model, which posits that impairment, measured by muscle strength, leads to functional limitations, which lead to disability, which ultimately is associated with health-related quality of life (HRQOL)., Methods: A structural equation model approach was used (AMOS 4) with data collected on 622 Mexican Americans aged 71 or older residing in the Southwest., Results: Our results show preliminary support for the Disablement Process model. Impairment is significantly associated with functional limitation (beta =.36, z value = 7.2), which is significantly associated with disability (beta = -.53, z value = 16.1). Finally, disability is significantly related to both physical and mental components of HRQOL (beta = -.69, z value = 23.4; beta = -.26, z value = 6.5, respectively)., Conclusions: Muscle strength as a measure of impairment and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) score as a measure of HRQOL are important factors in understanding disability in older Mexican Americans.