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1.  Association of change in brain structure to objectively measured physical activity and sedentary behavior in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study 
Behavioural brain research  2015;296:118-124.
Many studies have examined the hypothesis that greater participation in physical activity (PA) is associated with less brain atrophy. Here we examine, in a sub-sample (n = 352, mean age 79.1 years) of the Age, Gene/Environment Susceptibility-Reykjavik Study cohort, the association of the baseline and 5-year change in magnetic resonance imaging (MRI)-derived volumes of gray matter (GM) and white matter (WM) to active and sedentary behavior (SB) measured at the end of the 5-year period by a hip-worn accelerometer for seven consecutive days. More GM (β = 0.11; p = 0.044) and WM (β = 0.11; p = 0.030) at baseline was associated with more total physical activity (TPA). Also, when adjusting for baseline values, the 5-year change in GM (β = 0.14; p = 0.0037) and WM (β = 0.11; p = 0.030) was associated with TPA. The 5-year change in WM was associated with SB (β= −0.11; p = 0.0007). These data suggest that objectively measured PA and SB late in life are associated with current and prior cross-sectional measures of brain atrophy, and that change over time is associated with PA and SB in expected directions.
PMCID: PMC5111543  PMID: 26363425
Physical activity; Sedentary behavior; Brain atrophy; Elderly; MRI
2.  Muscle Quality and Muscle Fat Infiltration in Relation to Incident Mobility Disability and Gait Speed Decline: the Age, Gene/Environment Susceptibility-Reykjavik Study 
Aging is associated with increased risk of reduced mobility. However, data on muscle components in relation to subjective and objective indicators of disability is limited.
Data were from 2,725 participants (43% men) aged 74.8±4.7 years from the AGES-Reykjavik Study. At baseline, maximal isometric thigh strength (dynamometer chair), and midthigh muscle area and muscle fat infiltration were assessed with computed tomography. Usual 6 m gait speed and mobility disability were assessed at baseline and after 5.2±0.3 years. Incident mobility disability was defined as having much difficulty or unable to walk 500 m or climb-up 10 steps. A decrease of ≥0.1 m/s in gait speed was considered clinically relevant.
Greater strength and area were protective for mobility disability risk and gait speed decline. After adjustment for other muscle components, greater strength was independently associated with lower mobility disability risk in women odds ratios (OR) 0.78 (95% CI 0.62, 0.99), and lower decline in gait speed risk among both men OR 0.64 (0.54, 0.76), and women OR 0.72 (0.62, 0.82). Larger muscle area was independently associated with lower mobility disability risk in women OR 0.67 (0.52, 0.87) and lower decline in gait speed risk in men OR 0.74 (0.61, 0.91).
Greater muscle strength and area were independently associated with 15–30% decreased risk of mobility disability in women and gait speed decline in men. Among women, greater muscle strength was also associated with lower risk of gait speed decline. Interventions aimed at maintaining muscle strength and area in old age might delay functional decline.
PMCID: PMC4506318  PMID: 25748031
Epidemiology; Functional performance; Muscle; Imaging; Gait
3.  Variation in population levels of physical activity in European adults according to cross-European studies: a systematic literature review within DEDIPAC 
Physical inactivity is a well-known public health risk that should be monitored at the population level. Physical activity levels are often surveyed across Europe. This systematic literature review aims to provide an overview of all existing cross-European studies that assess physical activity in European adults, describe the variation in population levels according to these studies, and discuss the impact of the assessment methods.
Six literature databases (PubMed, EMBASE, CINAHL, PsycINFO, SportDiscus and OpenGrey) were searched, supplemented with backward- and forward tracking and searching authors’ and experts’ literature databases. Articles were included if they reported on observational studies measuring total physical activity and/or physical activity in leisure time in the general population in two or more European countries. Each record was reviewed, extracted and assessed by two independent researchers and disagreements were resolved by a third researcher. The review protocol of this review is registered in the PROSPERO database under registration number CRD42014010334.
Of the 9,756 unique identified articles, twenty-five were included in this review, reporting on sixteen different studies, including 2 to 35 countries and 321 to 274,740 participants. All but two of the studies used questionnaires to assess physical activity, with the majority of studies using the IPAQ-short questionnaire. The remaining studies used accelerometers. The percentage of participants who either were or were not meeting the physical activity recommendations was the most commonly reported outcome variable, with the percentage of participants meeting the recommendations ranging from 7 % to 96 % across studies and countries.
The included studies showed substantial variation in the assessment methods, reported outcome variables and, consequently, the presented physical activity levels. Because of this, absolute population levels of physical activity in European adults are currently unknown. However, when ranking countries, Ireland, Italy, Malta, Portugal, and Spain generally appear to be among the less active countries. Objective data of adults across Europe is currently limited. These findings highlight the need for standardisation of the measurement methods, as well as cross-European monitoring of physical activity levels.
Electronic supplementary material
The online version of this article (doi:10.1186/s12966-016-0398-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4924233  PMID: 27350359
Adults; Assessment methods; Europe; Physical Activity; Prevalence; Review
4.  Variation in population levels of sedentary time in European adults according to cross-European studies: a systematic literature review within DEDIPAC 
Sedentary behaviour is increasingly recognized as a public health risk that needs to be monitored at the population level. Across Europe, there is increasing interest in assessing population levels of sedentary time. This systematic literature review aims to provide an overview of all existing cross-European studies that measure sedentary time in adults, to describe the variation in population levels across these studies and to discuss the impact of assessment methods.
Six literature databases (PubMed, EMBASE, CINAHL, PsycINFO, SportDiscus and OpenGrey) were searched, supplemented with backward- and forward tracking and searching authors’ and experts’ literature databases. Articles were included if they reported on observational studies measuring any form of sedentary time in the general population in two or more European countries. Each record was reviewed, extracted and assessed by two independent researchers, and disagreements were resolved by a third researcher. The review protocol of this review is registered in the PROSPERO database under registration number CRD42014010335.
Of the 9,756 unique articles that were identified in the search, twelve articles were eligible for inclusion in this review, reporting on six individual studies and three Eurobarometer surveys. These studies represented 2 to 29 countries, and 321 to 65,790 participants. Eleven studies focused on total sedentary time, while one studied screen time. The majority of studies used questionnaires to assess sedentary time, while two studies used accelerometers. Total sedentary time was reported most frequently and varied from 150 (median) to 620 (mean) minutes per day across studies and countries.
One third of European countries were not included in any of the studies. Objective measures of European adults are currently limited, and most studies used single-item self-reported questions without assessing sedentary behaviour types or domains. Findings varied substantially between studies, meaning that population levels of sedentary time in European adults are currently unknown. In general, people living in northern Europe countries appear to report more sedentary time than southern Europeans. The findings of this review highlight the need for standardisation of the measurement methods and the added value of cross-European surveillance of sedentary behaviour.
Electronic supplementary material
The online version of this article (doi:10.1186/s12966-016-0397-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4924266  PMID: 27350251
Adults; Assessment methods; Europe; Prevalence; Sedentary behaviour; Review
5.  Movement Prediction Using Accelerometers in a Human Population 
Biometrics  2015;72(2):513-524.
We introduce statistical methods for predicting the types of human activity at sub-second resolution using triaxial accelerometry data. The major innovation is that we use labeled activity data from some subjects to predict the activity labels of other subjects. To achieve this, we normalize the data across subjects by matching the standing up and lying down portions of triaxial accelerometry data. This is necessary to account for differences between the variability in the position of the device relative to gravity, which are induced by body shape and size as well as by the ambiguous definition of device placement. We also normalize the data at the device level to ensure that the magnitude of the signal at rest is similar across devices. After normalization we use overlapping movelets (segments of triaxial accelerometry time series) extracted from some of the subjects to predict the movement type of the other subjects. The problem was motivated by and is applied to a laboratory study of 20 older participants who performed different activities while wearing accelerometers at the hip. Prediction results based on other people’s labeled dictionaries of activity performed almost as well as those obtained using their own labeled dictionaries. These findings indicate that prediction of activity types for data collected during natural activities of daily living may actually be possible.
PMCID: PMC4760916  PMID: 26288278
Accelerometer; Activity type; Movelets; Prediction
6.  Physical Activity and Sedentary Behavior in Metabolically Healthy versus Unhealthy Obese and Non-Obese Individuals – The Maastricht Study 
PLoS ONE  2016;11(5):e0154358.
Both obesity and the metabolic syndrome are associated with increased risk of cardiovascular diseases and type 2 diabetes. Although both frequently occur together in the same individual, obesity and the metabolic syndrome can also develop independently from each other. The (patho)physiology of “metabolically healthy obese” (i.e. obese without metabolic syndrome) and “metabolically unhealthy non-obese” phenotypes (i.e. non-obese with metabolic syndrome) is not fully understood, but physical activity and sedentary behavior may play a role.
To examine objectively measured physical activity and sedentary behavior across four groups: I) “metabolically healthy obese” (MHO); II) “metabolically unhealthy obese” (MUO); III)”metabolically healthy non-obese” (MHNO); and IV) “metabolically unhealthy non-obese” (MUNO).
Data were available from 2,449 men and women aged 40–75 years who participated in The Maastricht Study from 2010 to 2013. Participants were classified into the four groups according to obesity (BMI≥30kg/m2) and metabolic syndrome (ATPIII definition). Daily activity was measured for 7 days with the activPAL physical activity monitor and classified as time spent sitting, standing, and stepping.
In our study population, 562 individuals were obese. 19.4% of the obese individuals and 72.7% of the non-obese individuals was metabolically healthy. After adjustments for age, sex, educational level, smoking, alcohol use, waking time, T2DM, history of CVD and mobility limitation, MHO (n = 107) spent, per day, more time stepping (118.2 versus 105.2 min; p<0.01) and less time sedentary (563.5 versus 593.0 min., p = 0.02) than MUO (n = 440). In parallel, MHNO (n = 1384) spent more time stepping (125.0 versus 115.4 min; p<0.01) and less time sedentary (553.3 versus 576.6 min., p<0.01) than MUNO (n = 518).
Overall, the metabolically healthy groups were less sedentary and more physically active than the metabolically unhealthy groups. Therefore, physical activity and sedentary time may partly explain the presence of the metabolic syndrome in obese as well as non-obese individuals.
PMCID: PMC4854448  PMID: 27138596
7.  Fat Distribution and Mortality: The AGES-Reykjavik Study 
Obesity (Silver Spring, Md.)  2015;23(4):893-897.
This study examined associations of regional fat depots with all-cause mortality over 11 years of follow-up.
Design and Methods
Data were from 2187 men and 2900 women, aged 66–96 years in AGES-Reykjavik Study. Abdominal visceral fat and subcutaneous fat, and thigh intermuscular fat and subcutaneous fat were measured by CT.
In men, every standard deviation (SD) increment in thigh intermuscular fat was related to a significantly greater mortality risk (HR:1.17, 95%CI:1.08–1.26) after adjustment for age, education, smoking, physical activity, alcohol, BMI, type 2 diabetes and coronary heart disease. In women, visceral fat (per SD increment) significantly increased mortality risk (HR:1.13, 95%CI:1.03–1.25) while abdominal subcutaneous fat (per SD increment) was associated with a lower mortality risk (HR:0.70; 95%CI:0.61–0.80). Significant interactions with BMI were found in women indicating that visceral fat was a strong predictor of mortality in obese women while abdominal and thigh subcutaneous fat were associated with a lower mortality risk in normal and overweight women.
Fat distribution is associated with mortality over 11 years of follow-up independent of overall fatness. The divergent mortality risks for visceral fat and subcutaneous fat in women suggest complex relationships between overall fatness and mortality.
PMCID: PMC4758353  PMID: 25755182
Body Fat Distribution; Body Composition; Mortality; Obesity; Aged
8.  Associations of total amount and patterns of sedentary behaviour with type 2 diabetes and the metabolic syndrome: The Maastricht Study 
Diabetologia  2016;59:709-718.
The study investigated cross-sectional associations of total amount and patterns of sedentary behaviour with glucose metabolism status and the metabolic syndrome.
We included 2,497 participants (mean age 60.0 ± 8.1 years, 52% men) from The Maastricht Study who were asked to wear an activPAL accelerometer 24 h/day for 8 consecutive days. We calculated the daily amount of sedentary time, daily number of sedentary breaks and prolonged sedentary bouts (≥30 min), and the average duration of the sedentary bouts. To determine glucose metabolism status, participants underwent an oral glucose tolerance test. Associations of sedentary behaviour variables with glucose metabolism status and the metabolic syndrome were examined using multinomial logistic regression analyses.
Overall, 1,395 (55.9%) participants had normal glucose metabolism, 388 (15.5%) had impaired glucose metabolism and 714 (28.6%) had type 2 diabetes. The odds ratio per additional hour of sedentary time was 1.22 (95% CI 1.13, 1.32) for type 2 diabetes and 1.39 (1.27, 1.53) for the metabolic syndrome. No significant or only weak associations were seen for the number of sedentary breaks, number of prolonged sedentary bouts or average bout duration with either glucose metabolism status or the metabolic syndrome.
An extra hour of sedentary time was associated with a 22% increased odds for type 2 diabetes and a 39% increased odds for the metabolic syndrome. The pattern in which sedentary time was accumulated was weakly associated with the presence of the metabolic syndrome. These results suggest that sedentary behaviour may play a significant role in the development and prevention of type 2 diabetes, although longitudinal studies are needed to confirm our findings.
PMCID: PMC4779127  PMID: 26831300
Accelerometry; Diabetes mellitus type 2; Metabolic syndrome; Sedentary bouts; Sedentary breaks; Sedentary lifestyle; Sedentary time
9.  Psychological and personality factors in type 2 diabetes mellitus, presenting the rationale and exploratory results from The Maastricht Study, a population-based cohort study 
BMC Psychiatry  2016;16:17.
Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly discuss the importance of these findings for clinical research and practice.
We measured psychological distress and depression using the MINI diagnostic interview, the PHQ-9 and GAD-7 questionnaires in the first 864 participants of The Maastricht Study, a large, population-based cohort study. Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex and education level.
Individuals with type 2 diabetes had higher levels of depressive and anxiety symptoms, odds ratios (95 % CI) were 3.15 (1.49; 6.67), 1.73 (0.83–3.60), 1.50 (0.72–3.12), for PHQ-9 ≥ 10, current depressive disorder and GAD-7 ≥ 10, respectively. Type D personality, social inhibition and negative affectivity were more prevalent in type 2 diabetes, odds ratios were 1.95 (1.23–3.10), 1.35 (0.93–1.94) and 1.70 (1.14–2.51), respectively. Individuals with type 2 diabetes were less extraverted, less conscientious, less agreeable and less emotionally stable, and similar in openness to individuals without type 2 diabetes, although effect sizes were small.
Individuals with type 2 diabetes experience more psychological distress and have different personality traits compared to individuals without type 2 diabetes. Future longitudinal analyses within The Maastricht Study will increase our understanding of biological and behavioral mechanisms that link psychological distress to morbidity and mortality in type 2 diabetes.
PMCID: PMC4728860  PMID: 26817600
Type 2 diabetes; Cohort; Design; Exploratory results; Depression; Anxiety; Personality
10.  Predicting Human Movement with Multiple Accelerometers Using Movelets 
The study aims were: 1) to develop transparent algorithms that use short segments of training data for predicting activity types; and 2) to compare prediction performance of proposed algorithms using single accelerometers and multiple accelerometers.
Sixteen participants (age, 80.6 yr (4.8 yr); BMI, 26.1 kg·m−2 (2.5 kg·m−2)) performed fifteen life-style activities in the laboratory, each wearing three accelerometers at the right hip, left and right wrists. Triaxial accelerometry data were collected at 80 Hz using Actigraph GT3X+. Prediction algorithms were developed, which, instead of extracting features, build activity specific dictionaries composed of short signal segments called movelets. Three alternative approaches were proposed to integrate the information from the multiple accelerometers.
With at most several seconds of training data per activity, the prediction accuracy at the second-level temporal resolution was very high for lying, standing, normal/fast walking, and standing up from a chair (the median prediction accuracy ranged from 88.2% to 99.9% based on the single-accelerometer movelet approach). For these activities wrist-worn accelerometers performed almost as well as hip-worn accelerometers (the median difference in accuracy between wrist and hip ranged from −2.7% to 5.8%). Modest improvements in prediction accuracy were achieved by integrating information from multiple accelerometers.
Discussion and conclusions
It is possible to achieve high prediction accuracy at the secondlevel temporal resolution with very limited training data. To increase prediction accuracy from the simultaneous use of multiple accelerometers, a careful selection of integrative approaches is required.
PMCID: PMC4137461  PMID: 25134005
accelerometer; physical activity; signal processing; pattern recognition; time series
11.  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
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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.
18.  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
19.  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
20.  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
21.  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
22.  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
23.  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.
24.  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
25.  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

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