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1.  Weight Change, Body Composition and Risk of Mobility Disability and Mortality in Older Adults:A Population Based Cohort Study 
To examine associations between weight change, body composition, risk of mobility disability and mortality in older adults.
Prospective, longitudinal, population-based cohort.
The Health ABC Study.
Women (n=1044) and men (n=931) aged 70-79.
Weight,lean and fat mass from DXA measured annually over 5 years. Weight was defined as stable (n=664, referent group), 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 subsequent to the weight change period. Associations were analyzed with cox proportional hazards regression adjusted for covariates.
During follow-up, 313 women and 375 men developed mobility disability,322 women and 378 men were deceased. There was no risk of mobility disability or mortality with weight gain. Weight loss and weight cycling were associated with mobility disability in women:hazard ratio (HR)=1.88 (95% confidence interval (CI)=1.40-2.53),HR=1.59 (95% CI=1.11-2.29) and weight loss was associated in men:HR=1.30 (95% CI=1.01-1.69).Weight loss and weight cycling were associated with mortality risk in women:HR=1.47 (95% CI=1.07-2.01), HR=1.62 (95% CI=1.15-2.30) and in men:HR=1.41 (95% CI=1.09-1.83),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 relationships between weight loss and mobility disability in men, and weight loss and mortality in men and women.
Weight cycling and weight loss predict impendingmobility disability and mortality in old age, underscoring the prognostic importance of weight history.
PMCID: PMC4134405  PMID: 25039391
Aging; obesity; physical function; body composition; muscle loss
2.  Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study 
Vascular  2013;22(2):142-148.
The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle–brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P=0.44), but a higher prevalence of ABI 0.9–1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0,9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9–1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53–15.31) and men (3.49, 1.39–8.721. However, ABI 0.9–1.0 was significantly associated with incident clinical PAD (3.33, 1.44–7.70) and incident stroke (2.45, 1.38–4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.
PMCID: PMC4509626  PMID: 23512905
women; sex-specific; peripheral artery disease; epidemiology
3.  Midlife Determinants Associated with Sedentary Behavior in Old Age 
Sedentary behavior is associated with adverse health effects. To prevent sedentary behavior and limit health risks, insights into associated determinants are essential. Sedentary behavior should be viewed as a distinct health behavior, therefore its determinants should be independently identified.
This study examines the prospective associations between a wide-range of midlife determinants and objectively measured sedentary time in old age.
Data from 565 participants (aged 73–92 years) of the AGESII-Reykjavik Study were used. Participants wore an accelerometer (ActiGraph GT3X) on the right hip for 7 consecutive days. On average 31 years earlier (during midlife) demographic, socioeconomic, lifestyle and biomedical factors were collected. Linear regression models were used to examine prospective associations between midlife determinants and sedentary time (<100 counts per minute) in old age.
After adjustment for sex, age, follow-up time, minutes of moderate to vigorous physical activity, BMI, health status, mobility limitation and joint pain in old age, the midlife determinants not being married, primary education, living in a duplex or living in an apartment (vs. villa), being obese and having a heart disease were associated with, respectively, on average 15.3, 12.4, 13.5, 13.3, 21.8, 38.9 sedentary minutes more per day in old age.
This study shows that demographic, socioeconomic and biomedical determinants in midlife were associated with considerably more sedentary time per day in old age. These results can indicate the possibility of predicting sedentariness in old age, which could be used to identify target groups for prevention programs reducing sedentary time in older adults.
PMCID: PMC4061270  PMID: 24389522
Accelerometry; Sedentary Lifestyle; Older Adults; Longitudinal Studies; Socioeconomic Factors; Biomedical Factors
4.  Changes in Daily Activity Patterns with Age among US Men and Women: NHANES 2003–2004 and 2005–2006 
Men achieve more moderate-to-vigorous physical activity (MPVA) than women, yet with advancing age men become more sedentary than women. No study has comprehensively assessed this change in activity pattern. We compare daily and hourly activity patterns by gender and age.
Cross-sectional; Observational
Nationally-representative community sample: NHANES 2003–2004; 2005–2006
Accelerometer data from respondents (n=5,788) aged ≥20 years with 4+ valid days of monitor wear-time, no missing data on valid wear-time minutes, and covariates.
Activity was examined as average counts per minute (CPM) during wear-time, percentage of time spent in non-sedentary activity, and time (minutes) spent in sedentary (<100 counts); light (100–759); MVPA (≥760) intensity levels. Analyses accounted for survey design, adjusted for covariates and were gender specific.
In adjusted models, men spent slightly greater time (~1–2%) in non-sedentary activity than women 20–34y, with levels converging at 35–59y, though a non-significant difference. Women age ≥60 spent significantly greater time (~3–4%) in non-sedentary activity than men, despite similarly achieved average CPM. With increasing age, all non-sedentary activity decreased in men; levels of light-activity remained constant among women (~30%). Older men had fewer CPM at night (~20 CPM), more daytime sedentary minutes (~3), fewer daytime light minutes (~4), and more MVPA minutes (~1) until early evening, than older women.
While gender differences in average CPM reduced with age, differences in non-sedentary activity time emerged as men increased sedentary behavior and reduced MVPA time. Maintained levels of light-intensity activity suggest women continue engaging in common daily activities into older-age more often than men. Findings may help inform the development of behavioral interventions to increase intensity and overall activity levels, particularly among older adults.
PMCID: PMC4115191  PMID: 24962323
NHANES 2003–2004, 2005–2006; Physical activity; Sedentary behavior; Accelerometer; Patterns of daily activity
5.  Is there a sex difference in accelerometer counts during walking in older adults? 
Accelerometers have emerged as a useful tool for measuring free-living physical activity in epidemiological studies. Validity of activity estimates depends on the assumption that measurements are equivalent for males and females while performing activities of the same intensity. The primary purpose of this study was to compare accelerometer count values in males and females undergoing a standardized 6-min walk test.
The study population was older adults (78.6 ± 4.1 years) from the AGES-Reykjavik Study (N = 319). Participants performed a 6-min walk test at a self-selected fast pace while wearing an ActiGraph GT3X at the hip. Vertical axis counts·s−1 was the primary outcome. Covariates included walking speed, height, weight, BMI, waist circumference, femur length, and step length.
On average, males walked 7.2% faster than females (1.31 vs. 1.22 m·s−1, p < 0.001) and had 32.3% greater vertical axis counts·s−1 (54.6 vs. 39.4 counts·s−1, p < 0.001). Accounting for walking speed reduced the sex difference to 19.2% and accounting for step length further reduced the difference to 13.4% (p < 0.001).
Vertical axis counts·s−1 were disproportionally greater in males even after adjustment for walking speed. This difference could confound free-living activity estimates.
PMCID: PMC3716856  PMID: 23417023
Physical activity; 6-minute walk test; accelerometry; AGES-Reykjavik Study
6.  Moderate Activity and Fitness, Not Sedentary Time, Are Independently Associated with Cardio-Metabolic Risk in U.S. Adults Aged 18–49 
This cross-sectional study is one of the first to examine and compare the independent associations of objectively measured sedentary time, moderate to vigorous physical activity (MVPA) and fitness with cardio-metabolic risk factors. We studied 543 men and women (aged 18–49 years) from the NHANES 2003–2004 survey. Sedentary time and MVPA were measured by accelerometry. Fitness was assessed with a submaximal treadmill test. Cardio-metabolic risk factors included: waist circumference (WC), BMI, blood pressure, fasting glucose, HDL- and non HDL cholesterol, triglycerides (TG), and C-reactive protein (CRP). Sedentary time, MVPA and fitness were used as predictors for the cardio-metabolic outcomes in a multiple regression analysis. Standardized regression coefficients were computed. Results show that sedentary time was associated with HDL-cholesterol (β = −0.080, p = 0.05) and TG (β = 0.080, p = 0.03). These results became non-significant after adjustment for MVPA and fitness. MVPA was associated with WC (β = −0.226), BMI (β = −0.239), TG (β = −0.108) and HDL-cholesterol (β = 0.144) (all p < 0.05). These results remained significant after adjustment for sedentary time and fitness. Fitness was associated with WC (β = −0.287), BMI (β = −0.266), systolic blood pressure (β = −0.159), TG (β = −0.092), and CRP (β = −0.130) (all p < 0.05). After adjustment for sedentary time and MVPA these results remained significant. These differences in relative importance of sedentary time, MVPA and fitness on cardio-metabolic-risk are important in the design of prevention programs. In this population, the strength of the associations between MVPA and fitness with cardio-metabolic markers appeared to be similar; both MVPA and fitness showed independent associations with cardio-metabolic risk factors. In contrast, sedentary time showed no independent associations with cardio-metabolic risk after correction for fitness and MVPA.
PMCID: PMC4377904  PMID: 25711356
accelerometry; exercise; physical activity; physical fitness; sedentary lifestyle; NHANES; adult
7.  Adipose Tissue Density, a Novel Biomarker Predicting Mortality Risk in Older Adults 
Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics.
VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4–13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics.
Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.36–2.80; Health ABC) and 1.88 (1.31–2.69; AGES-Reykjavik) and for SAT density, 1.76 (1.35–2.28; Health ABC) and 1.56 (1.15–2.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.12–2.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.21–2.07), and AGES-Reykjavik, 1.43 (1.07–1.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs.
VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related.
PMCID: PMC3859360  PMID: 23707956
Obesity; Aging; Leptin; Adiponectin.
8.  Soluble Tumor Necrosis Factor Receptors and Heart Failure Risk in Older Adults: The Health, Aging, and Body Composition Study 
Circulation. Heart failure  2013;7(1):5-11.
Tumor necrosis factor (TNF) levels are associated with risk for heart failure (HF). The soluble TNF type-1 (sTNF-R1) and type-2 (sTNF-R2) receptors are elevated in patients with manifest HF, but whether they are associated with risk for incident HF is unclear.
Methods and Results
Using Cox proportional hazard models, we examined the association between baseline levels of sTNF-R1 and sTNF-R2 with incident HF risk among 1285 participants of the Health, Aging, and Body Composition Study (age 74.0±2.9 years; 51.4% women; 41.1% black). At baseline, median (interquartile range) of TNF, sTNF-R1, and sTNF R2 levels were 3.14 (2.42-4.06) pg/ml, 1.46 (1.25-1.76) ng/ml, and 3.43 (2.95-4.02) ng/ml, respectively. During a median follow-up of 11.4 (6.9, 11.7) years, 233 (18.1%) participants developed HF. In models controlling for other HF risk factors, TNF (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.02-1.61 per log2 increase), and sTNF-R1 (HR, 1.68; 95%CI, 1.15-2.46 per log2 increase), but not sTNF-R2 (HR, 1.15; 95%CI, 0.80-1.63 per log2 increase), were associated with a higher risk for HF. These associations were consistent across whites and blacks (TNF, sTNF-R1, sTNF-R2, interaction P=0.531, 0.091 and 0.795, respectively), and in both genders (TNF, sTNF-R1, sTNF-R2, interaction P=0.491, 0.672 and 0.999, respectively). TNF-R1 was associated with a higher risk for HF with preserved versus reduced ejection fraction (HR, 1.81; 95%CI, 1.03, 3.18; P=0.038 for preserved vs. HR, 0.90; 95%CI, 0.56, 1.44; P=0.667 for reduced ejection fraction, interaction P=0.05).
In older adults, elevated levels of sTNF-R1 are associated with an increased risk for incident HF. However, addition of TNF-R1 to the previously validated Health ABC HF risk model did not demonstrate material improvement in net discrimination or reclassification.
PMCID: PMC3990649  PMID: 24323631
heart failure; tumor necrosis factor; inflammation
9.  Elevated HbA1c and Fasting Plasma Glucose in Predicting Diabetes Incidence Among Older Adults 
Diabetes Care  2013;36(12):3923-3929.
To determine which measures—impaired fasting glucose (IFG), elevated HbA1c, or both—best predict incident diabetes in older adults.
From the Health, Aging, and Body Composition study, we selected individuals without diabetes, and we defined IFG (100–125 mg/dL) and elevated HbA1c (5.7–6.4%) per American Diabetes Association guidelines. Incident diabetes was based on self-report, use of antihyperglycemic medicines, or HbA1c ≥6.5% during 7 years of follow-up. Logistic regression analyses were adjusted for age, sex, race, site, BMI, smoking, blood pressure, and physical activity. Discrimination and calibration were assessed for models with IFG and with both IFG and elevated HbA1c.
Among 1,690 adults (mean age 76.5, 46% men, 32% black), 183 (10.8%) developed diabetes over 7 years. Adjusted odds ratios of diabetes were 6.2 (95% CI 4.4–8.8) in those with IFG (versus those with fasting plasma glucose [FPG] <100 mg/dL) and 11.3 (7.8–16.4) in those with elevated HbA1c (versus those with HbA1c <5.7%). When FPG and HbA1c were considered together, odds ratios were 3.5 (1.9–6.3) in those with IFG only, 8.0 (4.8–13.2) in those with elevated HbA1c only, and 26.2 (16.3–42.1) in those with both IFG and elevated HbA1c (versus those with normal FPG and HbA1c). Addition of elevated HbA1c to the model with IFG resulted in improved discrimination and calibration.
Older adults with both IFG and elevated HbA1c have a substantially increased odds of developing diabetes over 7 years. Combined screening with FPG and HbA1c may identify older adults at very high risk for diabetes.
PMCID: PMC3836095  PMID: 24135387
10.  Self-reported adherence to the physical activity recommendation and determinants of misperception in older adults 
We aimed to compare self-reported adherence to the physical activity recommendation with accelerometry in older persons and to identify determinants of misperception. The sample included 138 adults aged 65–75 y participating in the Longitudinal Aging Study Amsterdam. Participants completed a lifestyle questionnaire and wore an accelerometer for one week. More than half (56.8%) of the participants reported to adhere to the physical activity recommendation (in 5-minute bouts), however, based on accelerometry this percentage was only 24.6%. Of those who reported to adhere, 65.3% did not do so based on accelerometry. The misperceivers were older (p<0.009), more often female (p=0.007), had a poorer walking performance (p=0.02), reported a lower social support (p=0.04), and tended to have a lower self-efficacy (p=0.09) compared to those who correctly perceived their adherence to the recommendation. These results suggest that misperception of adherence to the physical activity recommendation is highly prevalent among specific subgroups of older persons.
PMCID: PMC3929529  PMID: 23752449
11.  Unhealthy lifestyles do not mediate the relationship between socioeconomic status and incident depressive symptoms; The Health ABC study 
The relationship between low socioeconomic status (SES) and depressive symptoms is well described, also in older persons. Although studies have found associations between low SES and unhealthy lifestyle factors and between unhealthy lifestyle factors and depressive symptoms, not much is known about unhealthy lifestyles as a potential explanation of socioeconomic differences in depressive symptoms in older persons.
To study the independent pathways between SES (education, income, perceived income, and financial assets), lifestyle factors (smoking, alcohol use, body mass index, and physical activity), and incident depressive symptoms (CES-D 10 and reported use of antidepressant medication), we used 9 years of follow-up data (1997–2007) from 2,694 American black and white participants aged 70–79 from the Health, Aging, and Body Composition (Health ABC) study. At baseline, 12.1% of the study population showed prevalent depressive symptoms, use of antidepressant medication, or treatment of depression in the five years prior to baseline. These persons were excluded from the analyses.
Over a period of 9 years time, 860 participants (31.9%) developed depressive symptoms. Adjusted hazard ratios for incident depressive symptoms were higher in participants from lower SES groups compared to the highest SES group. The strongest relationships were found for black men. Although unhealthy lifestyle factors were consistently associated with low SES, they were weakly related to incident depressive symptoms. Lifestyle factors did not significantly reduce hazard ratios for depressive symptoms by SES.
In generally healthy persons aged 70–79 years lifestyle factors do not explain the relationship between SES and depressive symptoms. (250)
PMCID: PMC3402597  PMID: 23567402
Health ABC study; Socioeconomic status; Lifestyle factors; Depressive symptoms; Elderly; United States
12.  Genetic Association Study of Adiposity and Melanocortin-4 Receptor (MC4R) Common Variants: Replication and Functional Characterization of Non-Coding Regions 
PLoS ONE  2014;9(5):e96805.
Common genetic variants 3′ of MC4R within two large linkage disequilibrium (LD) blocks spanning 288 kb have been associated with common and rare forms of obesity. This large association region has not been refined and the relevant DNA segments within the association region have not been identified. In this study, we investigated whether common variants in the MC4R gene region were associated with adiposity-related traits in a biracial population-based study. Single nucleotide polymorphisms (SNPs) in the MC4R region were genotyped with a custom array and a genome-wide array and associations between SNPs and five adiposity-related traits were determined using race-stratified linear regression. Previously reported associations between lower BMI and the minor alleles of rs2229616/Val103Ile and rs52820871/Ile251Leu were replicated in white female participants. Among white participants, rs11152221 in a proximal 3′ LD block (closer to MC4R) was significantly associated with multiple adiposity traits, but SNPs in a distal 3′ LD block (farther from MC4R) were not. In a case-control study of severe obesity, rs11152221 was significantly associated. The association results directed our follow-up studies to the proximal LD block downstream of MC4R. By considering nucleotide conservation, the significance of association, and proximity to the MC4R gene, we identified a candidate MC4R regulatory region. This candidate region was sequenced in 20 individuals from a study of severe obesity in an attempt to identify additional variants, and the candidate region was tested for enhancer activity using in vivo enhancer assays in zebrafish and mice. Novel variants were not identified by sequencing and the candidate region did not drive reporter gene expression in zebrafish or mice. The identification of a putative insulator in this region could help to explain the challenges faced in this study and others to link SNPs associated with adiposity to altered MC4R expression.
PMCID: PMC4018404  PMID: 24820477
13.  The Role of Metabolic Syndrome, Adiposity, and Inflammation in Physical Performance in the Health ABC Study 
Metabolic syndrome (MetS) and functional limitation have been linked, but whether and how specific components of MetS and associated factors, such as inflammation, drive this relationship is unknown.
Data are from 2,822 men and women, aged 70–79 years, participating in the Health, Aging, and Body Composition (Health ABC) study and followed for 5 years. Presence of MetS at baseline was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Interleukin-6, C-reactive protein, and body fat mass were measured at baseline. Measures of physical performance, including 400-m walk time, 20-m walking speed, and the Health ABC physical performance battery (PPB) were obtained at baseline and examination years 2, 4, and 6.
A total of 1,036 (37%) individuals met criteria for MetS. MetS was associated with poorer physical performance at baseline. Effect estimates between MetS and gait speed, and components of the Health ABC PPB (standing balance and repeated sit-to-stand performance) were modestly attenuated after adjustment for inflammation. All associations were attenuated to nonsignificance after adding total body fat mass to the model. Longitudinal analyses yielded similar results. Individual MetS component analysis revealed that abdominal obesity explained the largest fraction of the variation in physical performance.
Although inflammatory biomarkers partially accounted for the relationship between MetS and aspects of physical performance, overall findings implicate adiposity as the primary factor explaining poorer physical performance in older adults with MetS.
PMCID: PMC3623483  PMID: 23109678
Metabolic syndrome; Physical function; Inflammation; Obesity.
14.  Objective measurements of daily physical activity patterns and sedentary behaviour in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study 
Age and Ageing  2012;42(2):222-229.
Background: objectively measured population physical activity (PA) data from older persons is lacking. The aim of this study was to describe free-living PA patterns and sedentary behaviours in Icelandic older men and women using accelerometer.
Methods: from April 2009 to June 2010, 579 AGESII-study participants aged 73–98 years wore an accelerometer (Actigraph GT3X) at the right hip for one complete week in the free-living settings.
Results: in all subjects, sedentary time was the largest component of the total wear time, 75%, followed by low-light PA, 21%. Moderate-vigorous PA (MVPA) was <1%. Men had slightly higher average total PA (counts × day−1) than women. The women spent more time in low-light PA but less time in sedentary PA and MVPA compared with men (P < 0.001). In persons <75 years of age, 60% of men and 34% of women had at least one bout ≥10 min of MVPA, which decreased with age, with only 25% of men and 9% of women 85 years and older reaching this.
Conclusion: sedentary time is high in this Icelandic cohort, which has high life-expectancy and is living north of 60° northern latitude.
PMCID: PMC3575120  PMID: 23117467
physical activity; accelerometry; sedentary behaviour; older adults; BMI; AGES-Reykjavik; older people
15.  Educational Attainment and Late Life Telomere Length in the Health, Aging and Body Composition Study 
Brain, behavior, and immunity  2012;27(1):15-21.
Morbidity and mortality are greater among socially disadvantaged racial/ethnic groups and those of lower socioeconomic status (SES). Greater chronic stress exposure in disadvantaged groups may contribute to this by accelerating cellular aging, indexed by shorter age-adjusted telomere length. While studies consistently relate shorter leukocyte telomere length (LTL) to stress, the few studies, mostly from the UK, examining associations of LTL with SES have been mixed. The current study examined associations between educational attainment and LTL among 2,599 high-functioning black and white adults age 70-79 from the Health, Aging and Body Composition Study. Multiple regression analyses tested associations of race/ethnicity, educational attainment and income with LTL, adjusting for potential confounders. Those with only a high school education had significantly shorter mean LTL (4806 basepairs) than those with post-high school education (4926 basepairs; B=125, SE= 47.6, p = .009). A significant interaction of race and education (B = 207.8, SE = 98.7, p = .035) revealed more beneficial effects of post-high school education for blacks than for whites. Smokers had shorter LTL than non-smokers, but the association of education and LTL remained significant when smoking was covaried (B = 119.7, SE = 47.6, p = .012). While higher income was associated with longer LTL, the effect was not significant (p > .10). This study provides the first demonstration of an association between educational attainment and LTL in a US population where higher education appears to have a protective effect against telomere shortening, particularly in blacks.
PMCID: PMC3543785  PMID: 22981835
Socioeconomic status; education; telomere length; race; health disparities
16.  Development of a questionnaire to assess sedentary time in older persons – a comparative study using accelerometry 
BMC Geriatrics  2013;13:80.
There is currently no validated questionnaire available to assess total sedentary time in older adults. Most studies only used TV viewing time as an indicator of sedentary time. The first aim of our study was to investigate the self-reported time spent by older persons on a set of sedentary activities, and to compare this with objective sedentary time measured by accelerometry. The second aim was to determine what set of self-reported sedentary activities should be used to validly rank people’s total sedentary time. Finally we tested the reliability of our newly developed questionnaire using the best performing set of sedentary activities.
The study sample included 83 men and women aged 65–92 y, a random sample of Longitudinal Aging Study Amsterdam participants, who completed a questionnaire including ten sedentary activities and wore an Actigraph GT3X accelerometer for 8 days. Spearman correlation coefficients were calculated to examine the association between self-reported time and objective sedentary time. The test-retest reliability was calculated using the intraclass correlation coefficient (ICC).
Mean total self-reported sedentary time was 10.4 (SD 3.5) h/d and was not significantly different from mean total objective sedentary time (10.2 (1.2) h/d, p = 0.63). Total self-reported sedentary time on an average day (sum of ten activities) correlated moderately (Spearman’s r = 0.35, p < 0.01) with total objective sedentary time. The correlation improved when using the sum of six activities (r = 0.46, p < 0.01), and was much higher than when using TV watching only (r = 0.22, p = 0.05). The test-retest reliability of the sum of six sedentary activities was 0.71 (95% CI 0.57-0.81).
A questionnaire including six sedentary activities was moderately associated with accelerometry-derived sedentary time and can be used to reliably rank sedentary time in older persons.
PMCID: PMC3733654  PMID: 23899190
Sedentary behavior; Accelerometry; Physical activity; Aging
17.  Socioeconomic factors from midlife predict mobility limitation and depressed mood three decades later; Findings from the AGES-Reykjavik Study 
BMC Public Health  2013;13:101.
Taking into account our rapidly ageing population, older people are of particular interest in studying health inequalities. Most studies of older persons only include measures of current socioeconomic status (SES) and do not take into account data from earlier stages of life. In addition, only classic SES measures are used, while alternative measures, such as car ownership and house ownership, might equally well predict health. The present study aims to examine the effect of midlife socioeconomic factors on mobility limitation and depressed mood three decades later.
Data were from 4,809 men and women aged 33–65 years who participated in the Reykjavik Study (1967–1992) and who were re-examined in old age in the Age, Gene/Environment Susceptibility (AGES) -Reykjavik Study (2002–2006).
Education and occupation predicted mobility limitation and depressed mood. Independently, home and car ownership and the availability of housing features predicted mobility limitation. Shortages of food in childhood and lack of a car in midlife predicted depressed mood.
Socioeconomic factors from midlife and from childhood affect mobility limitation and depressed mood in old age. Prevention of health problems in old age should begin as early as midlife.
PMCID: PMC3599346  PMID: 23379351
Socioeconomic status; Mobility limitation; Depressed mood; Midlife; Old age
18.  Racial Differences in Mortality in Older Adults: Factors Beyond Socioeconomic Status 
Little is known about the simultaneous effect of socioeconomic status (SES), psychosocial, and health-related factors on race differences in mortality in older adults.
This study examined the association between race and mortality and the role of SES, health insurance, psychosocial factors, behavioral factors, and health-related factors in explaining these differences.
Data consisted of 2,938 adults participating in the Health, Aging and Body Composition study. Mortality was assessed over 8 years.
SES differences accounted for 60% of the racial differences in all-cause mortality; behavioral factors and self-rated health further reduced the disparity. The racial differences in coronary heart disease mortality were completely explained by SES. Health insurance and behavioral factors accounted for some, but not all, of the race differences in cancer mortality.
Race-related risk factors for mortality may differ by the underlying cause of mortality.
PMCID: PMC3520064  PMID: 22180315
Race; SES; Behavior; Psychosocial; Mortality; Older adults; Aging
19.  Validation of an Armband to Measure Daily Energy Expenditure in Older Adults 
Objective methods to measure daily energy expenditure in studies of aging are needed. We sought to determine the accuracy of total energy expenditure (TEE) and activity energy expenditure (AEE) estimates from the SenseWear Pro armband (SWA) using software versions 6.1 (SWA 6.1) and 5.1 (SWA 5.1) relative to criterion methods in free-living older adults.
Participants (n = 19, mean age 82.0 years) wore a SWA for a mean ± SD 12.5 ± 1.1 days, including while sleeping. During this same period, criterion values for TEE were assessed with doubly labeled water and for resting metabolic rate (RMR) with indirect calorimetry. AEE was calculated as 0.9 TEE – RMR.
For TEE, there was no difference in mean ± SD values from doubly labeled water (2,040 ± 472 kcal/day) versus SWA 6.1 (2,012 ± 497 kcal/day, p = .593) or SWA 5.1 (2,066 ± 474 kcal/day, p = .606); individual values were highly correlated between methods (SWA 6.1 r = .893, p < .001; SWA 5.1 r = .901, p < .001) and demonstrated strong agreement (SWA 6.1 intraclass correlation coefficient = .896; SWA 5.1 intraclass correlation coefficient = .904). For AEE, mean values from SWA 6.1 (427 ± 304 kcal/day) were lower by 26.8% than criterion values (583 ± 242 kcal/day, p = .003), and mean values from SWA 5.1 (475 ± 299 kcal/day) were lower by 18.5% than criterion values (p = .021); however, individual values were highly correlated between methods (SWA 6.1 r = .760, p < .001; SWA 5.1 r = .786, p < .001) and demonstrated moderate agreement (SWA 6.1 intraclass correlation coefficient = .645; SWA 5.1 intraclass correlation coefficient = .720). Bland–Altman plots identified no systematic bias for TEE or AEE.
Acceptable levels of agreement were observed between SWA and criterion measurements of TEE and AEE in older adults.
PMCID: PMC3172563  PMID: 21734231
Accelerometer; Activity monitor; Physical activity; Aged; DLW
20.  Race, Socioeconomic Resources, and Late-Life Mobility and Decline: Findings From the Health, Aging, and Body Composition Study 
This study examines the relationship between race and mobility over 5 years in initially well-functioning older adults and evaluates how a broad set of socioeconomic status indicators affect this relationship.
Data were from 2,969 black and white participants aged 70–79 from the Health, Aging, and Body Composition study. Mobility parameters included self-reported capacity to walk a quarter mile and climb 10 steps and usual gait speed. Incident mobility limitation was defined as reported difficulty walking a quarter mile or climbing 10 steps at two consecutive semiannual assessments. Gait speed decline was defined as a 4% reduction in speed per year.
At baseline, even though all participants were free of mobility limitation, blacks had slower walking speed than their white counterparts, which was not explained by poverty, education, reading level, or income adequacy. After 5 years, accounting for age, site, and baseline mobility, blacks were more likely to develop mobility limitation than whites. Adjusting for prevalent conditions at baseline eliminated this difference in women; controlling for education eliminated this difference in men. No differences in gait speed decline were identified.
Higher rates of mobility loss observed in older blacks relative to older whites appear to be a function of both poorer initial mobility status and existing health conditions particularly for women. Education may also play a role especially for men.
PMCID: PMC3172564  PMID: 21743093
Race disparities—Functional limitations—SES—Disability
21.  Correlates of insulin resistance in older individuals with and without kidney disease 
Nephrology Dialysis Transplantation  2011;26(9):2814-2819.
Background. Chronic kidney disease (CKD) is associated with insulin resistance (IR). Prior studies have found that in individuals with CKD, leptin is associated with fat mass but resistin is not and the associations with adiponectin are conflicting. This suggests that the mechanism and factors associated with IR in CKD may differ.
Methods. Of the 2418 individuals without reported diabetes at baseline, participating in the Health, Aging and Body Composition study, a study in older individuals aged 70–79 years, 15.6% had CKD defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 based on cystatin C. IR was defined as the upper quartile of the homeostasis model assessment. The association of visceral and subcutaneous abdominal fat, percent body fat, muscle fat, lipids, inflammatory markers and adiponectin were tested with logistic regression. Interactions were checked to assess whether the factors associated with IR were different in those with and without CKD.
Results. Individuals with IR had a lower eGFR (80.7 ± 20.9 versus 75.6 ± 19.6, P < 0.001). After multivariable adjustment, eGFR (odds ratio per 10 mL/min/1.73m2 0.92, 95% confidence interval 0.87–0.98) and CKD (1.41, 1.04–1.92) remained independently associated with IR. In individuals with and without CKD, the significant predictors of IR were male sex, black race, higher visceral fat, abdominal subcutaneous fat and triglycerides. In individuals without CKD, IR was associated with lower high-density lipoprotein and current nonsmoking status in multivariate analysis. In contrast, among individuals with CKD, interleukin-6 (IL-6) was independently associated with IR. There was a significant interaction of eGFR with race and IL-6 with a trend for adionectin but no significant interactions with CKD (P > 0.1). In the fully adjusted model, there was a trend for an interaction with adiponectin for eGFR (P = 0.08) and significant for CKD (P = 0.04 ), where adiponectin was associated with IR in those without CKD but not in those with CKD.
Conclusions. In mainly Stage 3 CKD, kidney function is associated with IR; except for adiponectin, the correlates of IR are similar in those with and without CKD.
PMCID: PMC3203409  PMID: 21248294
chronic kidney disease; cystatin C; insulin resistance; subcutaneous fat
22.  Does the Amount of Fat Mass Predict Age-Related Loss of Lean Mass, Muscle Strength, and Muscle Quality in Older Adults? 
An excessive amount of adipose tissue may contribute to sarcopenia and may be one mechanism underlying accelerated loss of muscle mass and strength with aging. We therefore examined the association of baseline total body fat with changes in leg lean mass, muscle strength, and muscle quality over 7 years of follow-up and whether this link was explained by adipocytokines and insulin resistance.
Data were from 2,307 men and women, aged 70–79 years, participating in the Health, Aging, and Body Composition study. Total fat mass was acquired from dual energy X-ray absorptiometry. Leg lean mass was assessed by dual energy X-ray absorptiometry in Years 1, 2, 3, 4, 5, 6, and 8. Knee extension strength was measured by isokinetic dynamometer in Years 1, 2, 4, 6, and 8. Muscle quality was calculated as muscle strength divided by leg lean mass.
Every SD greater fat mass was related to 1.3 kg more leg lean mass at baseline in men and 1.5 kg in women (p < .01). Greater fat mass was also associated with a greater decline in leg lean mass in both men and women (0.02 kg/year, p < .01), which was not explained by higher levels of adipocytokines and insulin resistance. Larger fat mass was related to significantly greater muscle strength but significantly lower muscle quality at baseline (p < .01). No significant differences in decline of muscle strength and quality were found.
High fatness was associated with lower muscle quality, and it predicts accelerated loss of lean mass. Prevention of greater fatness in old age may decrease the loss of lean mass and maintain muscle quality and thereby reducing disability and mobility impairments.
PMCID: PMC3184893  PMID: 21572082
Adipose tissue; Muscle mass; Muscle strength; Obesity; Aging
23.  A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone–Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation 
Coviello, Andrea D. | Haring, Robin | Wellons, Melissa | Vaidya, Dhananjay | Lehtimäki, Terho | Keildson, Sarah | Lunetta, Kathryn L. | He, Chunyan | Fornage, Myriam | Lagou, Vasiliki | Mangino, Massimo | Onland-Moret, N. Charlotte | Chen, Brian | Eriksson, Joel | Garcia, Melissa | Liu, Yong Mei | Koster, Annemarie | Lohman, Kurt | Lyytikäinen, Leo-Pekka | Petersen, Ann-Kristin | Prescott, Jennifer | Stolk, Lisette | Vandenput, Liesbeth | Wood, Andrew R. | Zhuang, Wei Vivian | Ruokonen, Aimo | Hartikainen, Anna-Liisa | Pouta, Anneli | Bandinelli, Stefania | Biffar, Reiner | Brabant, Georg | Cox, David G. | Chen, Yuhui | Cummings, Steven | Ferrucci, Luigi | Gunter, Marc J. | Hankinson, Susan E. | Martikainen, Hannu | Hofman, Albert | Homuth, Georg | Illig, Thomas | Jansson, John-Olov | Johnson, Andrew D. | Karasik, David | Karlsson, Magnus | Kettunen, Johannes | Kiel, Douglas P. | Kraft, Peter | Liu, Jingmin | Ljunggren, Östen | Lorentzon, Mattias | Maggio, Marcello | Markus, Marcello R. P. | Mellström, Dan | Miljkovic, Iva | Mirel, Daniel | Nelson, Sarah | Morin Papunen, Laure | Peeters, Petra H. M. | Prokopenko, Inga | Raffel, Leslie | Reincke, Martin | Reiner, Alex P. | Rexrode, Kathryn | Rivadeneira, Fernando | Schwartz, Stephen M. | Siscovick, David | Soranzo, Nicole | Stöckl, Doris | Tworoger, Shelley | Uitterlinden, André G. | van Gils, Carla H. | Vasan, Ramachandran S. | Wichmann, H.-Erich | Zhai, Guangju | Bhasin, Shalender | Bidlingmaier, Martin | Chanock, Stephen J. | De Vivo, Immaculata | Harris, Tamara B. | Hunter, David J. | Kähönen, Mika | Liu, Simin | Ouyang, Pamela | Spector, Tim D. | van der Schouw, Yvonne T. | Viikari, Jorma | Wallaschofski, Henri | McCarthy, Mark I. | Frayling, Timothy M. | Murray, Anna | Franks, Steve | Järvelin, Marjo-Riitta | de Jong, Frank H. | Raitakari, Olli | Teumer, Alexander | Ohlsson, Claes | Murabito, Joanne M. | Perry, John R. B.
PLoS Genetics  2012;8(7):e1002805.
Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8×10−106), PRMT6 (rs17496332, 1p13.3, p = 1.4×10−11), GCKR (rs780093, 2p23.3, p = 2.2×10−16), ZBTB10 (rs440837, 8q21.13, p = 3.4×10−09), JMJD1C (rs7910927, 10q21.3, p = 6.1×10−35), SLCO1B1 (rs4149056, 12p12.1, p = 1.9×10−08), NR2F2 (rs8023580, 15q26.2, p = 8.3×10−12), ZNF652 (rs2411984, 17q21.32, p = 3.5×10−14), TDGF3 (rs1573036, Xq22.3, p = 4.1×10−14), LHCGR (rs10454142, 2p16.3, p = 1.3×10−07), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7×10−08), and UGT2B15 (rs293428, 4q13.2, p = 5.5×10−06). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5×10−08, women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
Author Summary
Sex hormone-binding globulin (SHBG) is the key protein responsible for binding and transporting the sex steroid hormones, testosterone and estradiol, in the circulatory system. SHBG regulates their bioavailability and therefore their effects in the body. SHBG has been linked to chronic diseases including type 2 diabetes and to hormone-sensitive cancers such as breast and prostate cancer. SHBG concentrations are approximately 50% heritable in family studies, suggesting SHBG concentrations are under significant genetic control; yet, little is known about the specific genes that influence SHBG. We conducted a large study of the association of SHBG concentrations with markers in the human genome in ∼22,000 white men and women to determine which loci influence SHBG concentrations. Genes near the identified genomic markers in addition to the SHBG protein coding gene included PRMT6, GCKR, ZBTB10, JMJD1C, SLCO1B1, NR2F2, ZNF652, TDGF3, LHCGR, BAIAP2L1, and UGT2B15. These genes represent a wide range of biologic pathways that may relate to SHBG function and sex steroid hormone biology, including liver function, lipid metabolism, carbohydrate metabolism and type 2 diabetes, and the development and progression of sex steroid hormone-responsive cancers.
PMCID: PMC3400553  PMID: 22829776
24.  Association of Sedentary Time with Mortality Independent of Moderate to Vigorous Physical Activity 
PLoS ONE  2012;7(6):e37696.
Sedentary behavior has emerged as a novel health risk factor independent of moderate to vigorous physical activity (MVPA). Previous studies have shown self-reported sedentary time to be associated with mortality; however, no studies have investigated the effect of objectively measured sedentary time on mortality independent of MVPA. The objective our study was to examine the association between objectively measured sedentary time and all-cause mortality.
7-day accelerometry data of 1906 participants aged 50 and over from the U.S. nationally representative National Health and Nutrition Examination Survey (NHANES) 2003–2004 were analyzed. All-cause mortality was assessed from the date of examination through December 31, 2006.
Over an average follow-up of 2.8 years, there were 145 deaths reported. In a model adjusted for sociodemographic factors, lifestyle factors, multiple morbidities, mobility limitation, and MVPA, participants in third quartile (hazard ratio (HR):4.05; 95%CI:1.55–10.60) and fourth quartile (HR:5.94; 95%CI: 2.49–14.15) of having higher percent sedentary time had a significantly increased risk of death compared to those in the lowest quartile.
Our study suggests that sedentary behavior is a risk factor for mortality independent of MVPA. Further investigation, including studies with longer follow-up, is needed to address the health consequences of sedentary behavior.
PMCID: PMC3374810  PMID: 22719846
25.  Lung Function and Risk for Heart Failure Among Older Adults 
The American journal of medicine  2011;124(4):334-341.
The impact of abnormal spirometric findings on risk for incident heart failure among older adults without clinically apparent lung disease is not well elucidated.
We evaluated the association of baseline lung function with incident heart failure, defined as first hospitalization for heart failure, in 2125 participants of the community-based Health, Aging, and Body Composition Study (age, 73.6±2.9 years; 50.5% men; 62.3% white; 37.7% black) without prevalent lung disease or heart failure. Abnormal lung function was defined either as forced vital capacity (FVC) or forced expiratory volume in 1st second (FEV1) to FVC ratio below lower limit of normal. Percent predicted FVC and FEV1 were also assessed as continuous variables.
During follow-up (median, 9.4years), heart failure developed in 68 of 350 (19.4%) participants with abnormal baseline lung function, as compared to 172 of 1775 (9.7%) participants with normal lung function (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.74-3.07; P<.001). This increased risk persisted after adjusting for previously identified heart failure risk factors in the Health ABC Study, body mass index, incident coronary heart disease, and inflammatory markers (HR, 1.83; 95% CI, 1.33-2.50; P<.001). Percent predicted (%) FVC and FEV1 had a linear association with heart failure risk (HR, 1.21; 95%CI, 1.11-1.32 and 1.18; 95%CI, 1.10-1.26, per 10% lower %FVC and %FEV1, respectively; both P<.001 in fully adjusted models). Findings were consistent in sex and race subgroups, and for heart failure with preserved or reduced ejection fraction.
Abnormal spirometric findings in older adults without clinical lung disease are associated with increased heart failure risk.
PMCID: PMC3073738  PMID: 21435424
Elderly; Epidemiology; Heart Failure; Pulmonary Function Test

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