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While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer‐derived (activPAL3) 6‐ or 7‐day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid–femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat‐induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter‐daily stability was associated with a higher (worse) cfPWV in those without T2DM (std β = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std β = 0.07, p = 0.002). A higher within‐day variability in faster paced stepping was associated with a lower (worse) heat‐induced skin hyperemia in those with T2DM (std β = −0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro‐ and microvascular health, which may have implications for the prevention of vascular disease. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Nerve conduction studies (NCSs) are widely used to support the clinical diagnosis of neuromuscular disorders. The aims of this study were to obtain reference values for peroneal, tibial, and sural NCSs and to examine the associations with demographic and anthropometric factors. Methods: In 5099 participants (aged 40–79 years) without type 2 diabetes of The Maastricht Study, NCSs of peroneal, tibial, and sural nerves were performed. Values for compound muscle action potential (CMAP) and sensory nerve action potential amplitude, nerve conduction velocity (NCV), and distal latency were acquired. The association of age, sex, body mass index (BMI), and height with NCS values was determined using uni‐ and multivariate linear regression analyses. Results: Detailed reference values are reported per decade for men and women. Significantly lower NCVs and longer distal latencies were observed in all nerves in older and taller individuals as well as in men. In these groups, amplitudes of the tibial and sural nerves were significantly lower, whereas a lower peroneal nerve CMAP was only significantly associated with age. BMI showed a multidirectional association. After correction for anthropometric factors in the multivariate analysis, the association between sex and NCS values was less straightforward. Discussion: These values from a population‐based dataset could be used as a reference for generating normative values. Our findings show the association of NCS values with anthropometric factors. In clinical practice, these factors can be considered when interpreting NCS values. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The retina may provide non‐invasive, scalable biomarkers for monitoring cerebral neurodegeneration. METHODS: We used cross‐sectional data from The Maastricht study (n = 3436; mean age 59.3 years; 48% men; and 21% with type 2 diabetes [the latter oversampled by design]). We evaluated associations of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses with cognitive performance and magnetic resonance imaging indices (global grey and white matter volume, hippocampal volume, whole brain node degree, global efficiency, clustering coefficient, and local efficiency). RESULTS: After adjustment, lower thicknesses of most inner retinal layers were significantly associated with worse cognitive performance, lower grey and white matter volume, lower hippocampal volume, and worse brain white matter network structure assessed from lower whole brain node degree, lower global efficiency, higher clustering coefficient, and higher local efficiency. DISCUSSION: The retina may provide biomarkers that are informative of cerebral neurodegenerative changes in the pathobiology of dementia. [ABSTRACT FROM AUTHOR]

Background: We investigated the association of neighborhood walkability with accelerometer‐measured physical activity (PA) and sedentary behavior (SB) and examined whether objective and subjective measures of walkability resulted in similar findings. Methods: PA and SB from the first 7689 Maastricht Study participants ages 40–75 from 2010 to 2017 were measured using accelerometers for 7 days. Mean daily step count, light‐intensity PA, moderate‐ to vigorous‐ intensity PA (MVPA), and SB were calculated. Objective walkability was measured by the 7‐component Dutch Walkability Index within 500 m Euclidean buffers around residential addresses of participants. Subjective walkability was obtained from the Abbreviated Neighborhood Environment Walkability Scale. Linear regression models analyzed the associations of walkability with PA and SB, controlling for potential confounders. Results: Objective walkability was negatively associated with light intensity PA in the most walkable quartile (b = −14.58, 95% CI = −20.94, −8.23). Compared to participants living in the least walkable neighborhoods, those in the most walkable quartile had statistically significantly higher SB levels (b = 11.64, 95% CI = 4.95, 18.32). For subjective walkability, mean daily step count was significantly higher in the most walkable quartile (b = 509.60, 95% CI = 243.38, 775.81). Higher subjective walkability was positively associated with MVPA (b = 4.40, 95% CI = 2.56, 6.23). Conclusion: Living in a neighborhood with higher objective walkability was associated with lower levels of PA and higher SB levels while higher subjective walkability was associated with higher levels of PA. These results show discordant findings and thus, the effect of walkability on participant PA and SB within our sample is to be determined. [ABSTRACT FROM AUTHOR]

Background: Life‐course exposure to risk and protective factors impacts brain macro‐ and micro‐structure, which in turn affects cognition. Brain Age Gap (BAG) directly measures brain reserve by comparing an individual's neuroimaging‐based predicted age with their calendar age. Higher BAG implies accelerated brain aging and lower brain reserve. In this study, we comprehensively modeled mutual associations between brain risk and protective factors, reserve, and cognition in a large, middle‐aged population using structural equation modelling (SEM). Method: Cognitive test scores, lifestyle, and 3T MRI data for n = 4881 participants (mean age(±SD) = 59.2(±8.6), 50.1% male) were available from The Maastricht Study, a population‐based cohort study with extensive phenotyping. Whole brain volumes (gray matter (GM), cerebrospinal fluid (CSF), white matter hyperintensity (WMH)), cerebral microbleeds (CMB), and structural white matter connectivity were calculated. Lifestyle factors were combined into the Lifestyle for BRAin health (LIBRA) weighted sum score, with higher score indicating greater dementia risk (Figure 1). Cognition was calculated by averaging z‐scores across three cognitive domains (executive function and attention, memory, information processing speed). BAG was calculated by comparing calendar age to predictions from a neuroimaging‐based multivariable regression model. Paths between LIBRA, BAG and cognitive function were tested using linear regression and SEM, adjusting for confounders. LIBRA was split into tertiles for SEM analysis. Result: CSF, GM, WMH and CMB best predicted BAG (R2 = 0.455, RMSE = 6.44). In regression analysis higher LIBRA scores (greater dementia risk) were associated with higher BAG (standardized regression coefficient ß = 0.127, p<0.001), lower connectivity (ß = ‐0.071, p = 0.002) and worse cognition (ßlinear = ‐0.044, p = 0.017, ßquadratic = ‐0.047, p = 0.018). Higher BAG was associated with lower connectivity (ß = ‐0.418, p<0.001) and worse cognition (ß = ‐0.165, p<0.001). Lower connectivity was associated with worse cognition (ß = 0.086, p<0.001). In mediation analysis (Figure 2), 21% of the total differences between the highest and lowest LIBRA tertile on cognition was mediated by BAG (ßindirect = ‐0.019, p<0.001; ßtotal = ‐0.092, p<0.001), and an additional 4.1% was mediated via connectivity (ßindirect = ‐0.003, p<0.001; ßtotal = ‐0.073, p<0.001). Conclusion: Associations between health‐ and lifestyle‐based risk/protective factors (LIBRA) and cognition is partially explained by maintenance of brain reserve (BAG) and neural reserve (connectivity). Lifestyle interventions promoting brain and neural reserve may help maintain cognitive function into older age. [ABSTRACT FROM AUTHOR]

Aims: There are sex differences in the excess risk of diabetes‐associated cardiovascular disease. However, it is not clear whether these sex differences exist with regard to other complications like mental health aspects. Therefore, we investigated sex differences in the association of prediabetes and type 2 diabetes (T2D) with cognitive function, depression, and quality of life (QoL). Materials and Methods: In a population‐based cross‐sectional cohort study (n = 7639; age 40–75 years, 50% women, 25% T2D), we estimated sex‐specific associations, and differences therein, of prediabetes and T2D (reference: normal glucose metabolism) with measures of cognitive function, depression, and physical and mental QoL. Sex differences were analysed using multiple regression models with interaction terms. Results: In general, T2D, but not prediabetes, was associated with higher odds of cognitive impairment, major depressive disorder, and poorer QoL. The odds ratio (OR) of cognitive impairment associated with T2D was 1.29 (95% CI: 0.96–1.72) for women and 1.39 (1.10–1.75) for men. The OR of major depressive disorder associated with T2D was 1.19 (0.69–2.04) for women and 1.68 (1.02–2.75) for men. The mean difference of the physical QoL score (ranging from 0 to 100, with 100 indicating the best possible QoL) associated with T2D was −2.09 (−2.92 to −1.25) for women and −1.81 (−2.48 to −1.13) for men. The mean difference of the mental QoL score associated with T2D was −0.90 (−1.79 to −0.02) for women and −0.52 (−1.23 to 0.20) for men. There was no clear pattern of sex differences in the associations of either prediabetes or T2D with measures of cognitive function, depression, or QoL. Conclusions: In general, T2D was associated with worse cognitive function, depression, and poorer QoL. The strength of these associations was similar among women and men. [ABSTRACT FROM AUTHOR]

Introduction: Differences in brain network connectivity may reflect the capability of the neurological substrate to compensate for brain damage and preserve cognitive function (cognitive reserve). We examined the associations between white matter connectivity, brain damage markers, and cognition in a population sample of middle‐aged individuals. Methods: A total of 4759 participants from The Maastricht Study (mean age = 59.2, SD = 8.7, 50.2% male) underwent cognitive testing and diffusion magnetic resonance imaging (dMRI), from which brain volume, structural connectivity, and vascular damage were quantified. Multivariable linear regression was used to investigate whether connectivity modified the association between brain damage and cognition, adjusted for demographic and cardiometabolic risk factors. Results: More atrophic and vascular brain damage was associated with worse cognition scores. Increasing connectivity moderated the negative association between damage and cognition (χ2 = 8.64, df = 3, p ≤ 0.001); individuals with high damage but strong connectivity showed normal cognition. Discussion: Findings support the reserve hypothesis by showing that brain connectivity is associated with cognitive resilience. [ABSTRACT FROM AUTHOR]

This study aims to compare the accelerometer‐measured daily patterns of PA and sedentary behavior among participants with and without prevalent/incident depressive symptoms. We used data from 5582 individuals in The Maastricht Study (59.9 ± 8.6 years, 50.3% women). Daily patterns of sedentary time, light‐intensity physical activity (LiPA), moderate‐to‐vigorous physical activity (MVPA), and sit‐to‐stand transitions were objectively measured at baseline with the activPAL3 activity monitor. Depressive symptoms were assessed using the 9‐item Patient Health Questionnaire, both at baseline and annually (median follow‐up: 5.1 years). General linear models were used to compare patterns of physical activity and sedentary behavior between those with and without prevalent/incident depressive symptoms. Participants with prevalent depressive symptoms had significantly more sedentary time (18.6 min/day) and lower LiPA (26.8 min/day) and MVPA (4.8 min/day) than participants without depressive symptoms. Considering the daily patterns, participants with prevalent depressive symptoms had significantly more sedentary time early in the afternoon (12:00–18:00), early evening (18:00–21:00), and during the night (00:00–03:00), less time in LiPA in all periods between 09:00–21.00 and less MVPA in the morning (09:00:12:00), early afternoon (12:00–15:00), and evening (18:00–21:00), than those without. Similar differences in activity and sedentary behavior patterns between those and without incident depressive symptoms were observed albeit the differences were smaller. Overall, we did not find specific time slots particularly associated with both prevalent and incident depressive symptoms. These findings may indicate that less sedentary time and more intense PA can be important targets for the prevention of depression irrespective of the timing of the day. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic inequalities in the risk for cognitive impairment have been reported, which might partly act through structural brain damage or differential numbers of brain connections (structural connectivity). This study investigated the extent to which the association of early‐life socioeconomic status (SES) with later‐life cognitive performance is mediated by later‐life SES, and whether the association of SES with later‐life cognitive performance can be explained by structural brain damage and connectivity. Method: We used cross‐sectional data from the population‐based Maastricht study (n = 4,839; mean age 59.2±8.7 years, 49.8% women). Early‐life SES was assessed retrospectively by self‐reported poverty and parental education. Later‐life SES included education, occupation, and household income. Participants underwent cognitive testing and 3 T magnetic resonance imaging to measure volumes of white matter hyperintensities, gray matter, white matter, cerebrospinal fluid, and structural connectivity. Multiple linear regression analyses tested the associations between SES, brain markers and cognition. Analyses were adjusted for age, sex, and type 2 diabetes (because of oversampling). Structural equation modeling tested mediation. Result: Higher SES was associated with higher grey matter volume, lower white matter volume, and higher structural connectivity. Structural brain damage and lower structural connectivity were associated with lower overall cognitive performance. Both higher early‐life and later‐life SES were associated with overall higher cognitive performance (B [95% CI] medium versus low early‐life SES = 0.17[0.12;0.23]; B high versus low early‐life SES = 0.26[0.20;0.32]; B medium versus low later‐life SES = 0.46[0.41;0.52]; B high versus low later‐life SES = 0.72[0.67;0.78]). The association of early‐life SES with later‐life cognitive performance was partly mediated by later‐life SES (73.8%). The extent to which the association of SES with cognitive performance could be explained by structural brain damage or connectivity was marginal (up to 5.9%). Conclusion: Though there was an association between early‐life SES and later‐life cognitive performance independent of later‐life SES, a large part of this association could be explained by later‐life SES. Structural brain damage and connectivity marginally explained socioeconomic inequalities in cognitive performance. More research is needed to investigate alternative pathways that explain associations of life‐course SES with later‐life cognition. [ABSTRACT FROM AUTHOR]

Background/Objectives: Homecare staff often take over activities instead of "doing activities with" clients, thereby hampering clients from remaining active in daily life. Training and supporting staff to integrate reablement into their working practices may reduce clients' sedentary behavior and improve their independence. This study evaluated the effectiveness of the "Stay Active at Home" (SAaH) reablement training program for homecare staff on older homecare clients' sedentary behavior. Design Cluster randomized controlled trial (c‐RCT). Setting: Dutch homecare (10 nursing teams comprising a total of 313 staff members). Participants: 264 clients (aged ≥65 years). Intervention: SAaH seeks to equip staff with knowledge, attitude, and skills on reablement, and to provide social and organizational support to implement reablement in homecare practice. SAaH consists of program meetings, practical assignments, and weekly newsletters over a 9‐month period. The control group received no additional training and delivered care as usual. Measurements Sedentary behavior (primary outcome) was measured using tri‐axial wrist‐worn accelerometers. Secondary outcomes included daily functioning (GARS), physical functioning (SPPB), psychological functioning (PHQ‐9), and falls. Data were collected at baseline and at 12 months; data on falls were also collected at 6 months. Intention‐to‐treat analyses using mixed‐effects linear and logistic regression were performed. Results: We found no statistically significant differences between the study groups for sedentary time expressed as daily minutes (adjusted mean difference: β 18.5 (95% confidence interval [CI] −22.4, 59.3), p = 0.374) and as proportion of wake/wear time (β 0.6 [95% CI −1.5, 2.6], p = 0.589) or for most secondary outcomes. Conclusion: Our c‐RCT showed no evidence for the effectiveness of SAaH for all client outcomes. Refining SAaH, by adding components that intervene directly on homecare clients, may optimize the program and require further research. Additional research should explore the effectiveness of SAaH on behavioral determinants of clients and staff and cost‐effectiveness. [ABSTRACT FROM AUTHOR]

Objective: This study investigated whether arterial stiffening is a determinant of subtle retinal microvascular changes that precede diabetic retinopathy. Research design and methods: This study used cross‐sectional data from the Maastricht Study, a type 2 diabetes‐enriched population‐based cohort study. We used multivariable linear regression analysis to investigate, in individuals without and with type 2 diabetes, the associations of carotid distensibility coefficient and carotid‐femoral pulse wave velocity with retinal microvascular diameters and flicker light‐induced dilation and adjusted for cardiovascular and lifestyle risk factors. Results: The retinal microvascular diameter study population consisted of N = 2434 participants (51.4% men, mean ± SD age 59.8 ± 8.1 years, and 28.1% type 2 diabetes). No measures of arterial stiffness were significantly associated with microvascular diameters. Greater carotid distensibility coefficient (i.e., lower carotid stiffness) was significantly associated with greater retinal arteriolar flicker light‐induced dilation (per standard deviation, standardized beta [95% CI] 0.06 [0.00; 0.12]) and non‐significantly, but directionally similarly, associated with greater retinal venular flicker light‐induced dilation (0.04 [−0.02; 0.10]). Carotid‐femoral pulse wave velocity (i.e., aortic stiffness) was not associated with retinal microvascular flicker light‐induced dilation. The associations between carotid distensibility coefficient and retinal arteriolar and venular flicker light‐induced dilation were two‐ to threefold stronger in individuals with type 2 diabetes than in those without. Conclusion: In this population‐based study greater carotid, but not aortic, stiffness was associated with worse retinal flicker light‐induced dilation and this association was stronger in individuals with type 2 diabetes. Hence, carotid stiffness may be a determinant of retinal microvascular dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Physical activity may provide a means for the prevention of cardiovascular disease via improving microvascular function. Therefore, this study investigated whether physical activity is associated with skin and retinal microvascular function. Methods: In The Maastricht Study, a population‐based cohort study enriched with type 2 diabetes (n = 1298, 47.3% women, aged 60.2 ± 8.1 years, 29.5% type 2 diabetes), we studied whether accelerometer‐assessed physical activity and sedentary time associate with skin and retinal microvascular function. Associations were studied by linear regression and adjusted for major cardiovascular risk factors. In addition, we investigated whether associations were stronger in type 2 diabetes. Results: In individuals with type 2 diabetes, total physical activity and higher‐intensity physical activity were independently associated with greater heat‐induced skin hyperemia (regression coefficients per hour), respectively, 10 (95% CI: 1; 18) and 36 perfusion units (14; 58). In individuals without type 2 diabetes, total physical activity and higher‐intensity physical activity were not associated with heat‐induced skin hyperemia. No associations with retinal arteriolar %‐dilation were identified. Conclusion: Higher levels of total and higher‐intensity physical activity were associated with greater skin microvascular vasodilation in individuals with, but not in those without, type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Dementia prevention poses one of the biggest challenges to our ageing society (1,2). Next to individual modifiable risk factors, shared environmental risk factors have been linked to dementia risk. Exposure to air pollution has been identified as a new candidate risk factor which on a population level carries more risk than well‐established risk factors such as hypertension and type‐2 diabetes (1). This study aimed to investigate the association between exposure to air pollutants with cognitive functioning and markers of structural brain damage next to and above individual risk factors. Method: Cross‐sectional data from the population‐based cohort (N = 4,154; mean age 59.27±8.54 years, 50.12% women) of The Maastricht Study (3) was used and matched to address‐based data from the Geoscience andHealth Cohort Consortium of average exposure to particulate matter (<2.5mg and <10mg), NO2 and soot over the years 2013‐2018. Cognitive functioning was assessed through a neuropsychological test battery. Standardized volumes of grey matter, white matter, cerebrospinal fluid, and presence of cerebral small vessel disease were derived from 3‐Tesla MRI. Individual risk factors were added as one covariate, using the validated Lifestyle for Brain Health score (4). Binary logistic and multiple linear regression analyses tested the associations between air pollutants and the outcome measures. Likelihood‐ratio tests were performed to compare the extensive models. Result: We found a curvilinear association relating particulate matter exposure in the mid to higher range to lower grey matter and higher cerebrospinal fluid volume, independent of age, sex, education, and LIBRA score. There was no association between air pollutant exposure and cognitive functioning or markers of cerebral small vessel disease. Conclusion: In this population‐based cohort, average to high exposure to particulate matter was related to an increase in markers of brain atrophy, showing important implications for environmental and public health policymaking. [ABSTRACT FROM AUTHOR]

Objectives To compare the relative predictive power of handgrip and leg extension strength in predicting slow walking. Design Report of correlative analysis from two epidemiological cohort studies. Setting Foundation of the National Institutes of Health Sarcopenia Project. Participants Men and women aged 67 to 93 (N = 6,766). Measurements Leg strength, handgrip strength, and gait speed were measured. Strength cutpoints associated with slow gait speed were developed using classification and regression tree analyses and compared using ordinary least squares regression models. Results The cutpoints of lower extremity strength associated with slow gait speed were 154.6 N-m in men and 89.9 N-m in women for isometric leg extension strength and 94.5 N-m in men and 62.3 N-m in women for isokinetic leg extension strength. Weakness defined according to handgrip strength (odds ratios ( OR) = 1.99 to 4.33, c-statistics = 0.53 to 0.67) or leg strength ( ORs = 2.52 to 5.77; c-statistics = 0.61 to 0.66) was strongly related to odds of slow gait speed. Lower extremity strength contributed 1% to 16% of the variance and handgrip strength contributed 3% to 17% of the variance in the prediction of gait speed depending on sex and mode of strength assessment. Conclusion Muscle weakness of the leg extensors and forearm flexors is related to slow gait speed. Leg extension strength is only a slightly better predictor of slow gait speed. Thus, handgrip and leg extension strength appear to be suitable for screening for muscle weakness in older adults. [ABSTRACT FROM AUTHOR]

Method: The Maastricht Study is a population‐based cohort study with extensive phenotyping, enriched for type‐2 diabetes. Cognitive test scores, structural connectivity data, and 3T MRI were available for n=4798 participants (mean age(±SD)=59.2(±8.7), 50.0% male). Images were assessed by Fazekas score (£1 or ≥2), presence of microbleeds and lacunar infarcts in terms of dichotomous measures, and combined into a cSVD score (range 0‐3). Node degree (ND), a measure of the mean interconnectedness of nodes in the structural connectome, was used as connectivity score. A composite cognition score (CS) was taken as the mean score across three cognitive domains (Memory, Information Processing Speed and Executive Function). Multivariable linear regression analyses were used to investigate the interaction effect between ND and cSVD score on CS, adjusted for age, sex, education, and diabetes status. Result: Higher cSVD score was associated with lower CS. ND modified the association between cSVD score and CS in the adjusted model (p for interaction p<0.004). While there were clear cognitive differences across cSVD levels if ND was low, the association between cSVD and cognition was attenuated in a dose‐response fashion with increasing ND (Figure 1). Conclusion: Structural ND provides evidence of an individual’s CR based on white matter organization in the presence of damage from cSVD. Even in participants with the highest cSVD burden, sufficiently high ND score was associated with normal CS. [ABSTRACT FROM AUTHOR]

Objective This study examined associations of regional fat depots with all-cause mortality over 11 years of follow-up. Methods Data were from 2,187 men and 2,900 women, aged 66-96 years in the AGES-Reykjavik Study. Abdominal visceral fat and subcutaneous fat and thigh intermuscular fat and subcutaneous fat were measured by CT. Results 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-weight and overweight women. Conclusions 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. [ABSTRACT FROM AUTHOR]

Objectives To examine associations between weight change, body composition, risk of mobility disability, and mortality in older adults. Design Prospective, longitudinal, population-based cohort. Setting The Health, Aging, and Body Composition Study. Participants Women (n = 1,044) and men (n = 931) aged 70 to 79. Measurements Weight and lean and fat mass from dual-energy X-ray absorptiometry measured annually over 5 years. Weight was defined as stable (n = 664, reference), loss (n = 662), gain (n = 321), or cycling (gain and loss, n = 328) using change of 5% from year to year or from Year 1 to 6. Mobility disability (two consecutive reports of difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 8 years after the weight change period. Associations were analyzed using Cox proportional hazards regression adjusted for covariates. Results During follow-up, 313 women and 375 men developed mobility disability, and 322 women and 378 men died. There was no risk of mobility disability or mortality with weight gain. Weight loss (hazard ratio ( HR) = 1.88, 95% confidence interval ( CI) = 1.40-2.53) and weight cycling ( HR = 1.59, 95% CI = 1.11-2.29) were associated with mobility disability in women, and weight loss was associated with mobility disability in men ( HR = 1.30, 95% CI = 1.01-1.69). Weight loss and weight cycling were associated with mortality risk in women (weight loss: HR = 1.47, 95% CI = 1.07-2.01; weight cycling: HR = 1.62, 95% CI = 1.15-2.30) and in men (weight loss: HR = 1.41, 95% CI = 1.09-1.83; weight cycling: HR = 1.50, 95% CI = 1.08-2.08). Adjustment for lean and fat mass and change in lean and fat mass from Year 1 to 6 attenuated the relationships between weight loss and mobility disability in men and between weight loss and mortality in men and women. Conclusion Weight cycling and weight loss predict impending mobility disability and mortality in old age, underscoring the prognostic importance of weight history. [ABSTRACT FROM AUTHOR]

Objectives To compare daily and hourly activity patterns according to sex and age. Design Cross-sectional, observational. Setting Nationally representative community sample: National Health and Nutrition Examination Survey ( NHANES) 2003-04 and 2005-06. Participants Individuals (n = 5,788) aged 20 and older with 4 or more valid days of monitor wear-time, no missing data on valid wear-time minutes, and covariates. Measurements Activity was examined as average counts per minute ( CPM) during wear-time; percentage of time spent in nonsedentary activity; and time (minutes) spent in sedentary (<100 counts), light (100-759), and moderate to vigorous physical activity ( MVPA (≥760)). Analyses accounted for survey design, adjusted for covariates, and were sex specific. Results In adjusted models, men spent slightly more time (~1-2%) in nonsedentary activity than women aged 20 to 34, with levels converging at age 35 to 59, although the difference was not significant. Women aged 60 and older spent significantly more time (~3-4%) in nonsedentary activity than men, despite similarly achieved average CPM. With increasing age, all nonsedentary activity decreased in men; light activity remained constant in women (~30%). Older men had fewer CPM at night (~20), more daytime sedentary minutes (~3), fewer daytime light physical activity minutes (~4), and more MVPA minutes (~1) until early evening than older women. Conclusion Although sex differences in average CPM declined with age, differences in nonsedentary activity time emerged as men increased sedentary behavior and reduced MVPA time. Maintained levels of light-intensity activity suggest that women continue engaging in common daily activities into older age more than men. Findings may help inform the development of behavioral interventions to increase intensity and overall activity levels, particularly in older adults. [ABSTRACT FROM AUTHOR]

Background: The risk of dementia is doubled in depression. However, the underlying etiology remains unclear. Clinical studies suggest that depression is related to brain atrophy and cerebral small vessel disease (cSVD), which are themselves related to cognition. We studied the associations between depression, structural brain markers and cognition in a general population aged between the 40 and 75 years. Method: We used cross‐sectional data from the Maastricht Study (n=7,066; mean age 59.6±8.7 years, 50.1% women), which, by design, oversampled participants with type 2 diabetes (T2D). Major depressive disorder (MDD, n=236) was assessed by the Mini‐International Neuropsychiatric Interview. From a comprehensive neuropsychological battery, we derived standardized sum scores on tests for memory, information processing speed, and executive functioning and attention. Presence of significant overall cognitive impairment was defined as a score <‐.1.5 SD below norms scores for age, gender and education. Volumes of cerebral spinal fluid (CSF), white matter (WM), grey matter (GM) and white matter hyperintensities (WMH), and presence of lacunar infarcts, cerebral microbleeds and total cSVD burden were assessed by 3 Tesla MRI. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning, adjusted for a range of demographic, cardiovascular, and lifestyle risk factors. Result: In fully adjusted models, MDD was associated with lower scores in memory (B=‐0.11(‐0.22;0.00)), information processing speed (B=‐0.24(‐0.32;‐0.15)), executive functioning and attention (B=‐0.23(‐0.32;‐0.14)), and with presence of significant cognitive impairment (OR=2.37(1.77;3.17)). In those with available MRI data (n=4,734), MDD was associated with a lower GM volume only in older participants (p‐interaction=0.023), and with total WMH (B=0.17(0.01;0.34)), periventricular WMH (B=0.18(0.01;0.35)), and total cSVD burden (OR=1.70(1.09;2.65)) in participants without T2D (OR=1.70(1.09;2.65)). Conclusion: This study shows that MDD is associated with cognitive impairment, including worse memory, information processing speed, and executive functioning and attention, independent of major demographical, cardiovascular and lifestyle risk factors. In older participants, MDD is related to a lower GM volume, while in the wider general population without T2D, MDD is related to markers of cSVD burden. Longitudinal studies are needed to examine the role of structural brain damage in the development of cognitive impairment and dementia in depression. [ABSTRACT FROM AUTHOR]

Visceral adipose tissue (VAT) is a key pathogenic fat depot in the metabolic syndrome (MetS), but liver fat (LF) may also play an important role. We evaluated associations of VAT and LF with MetS in normal weight, overweight, and obese men and women (BMI <25, 25-29.9, and ≥30 kg/m2, respectively). This analysis included 2,495 participants from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study with computed tomography measurements for VAT and LF. MetS was defined by ≥3 of the following: larger abdominal circumference, hypertension, elevated triglyceride (TG), low high-density lipoprotein (HDL), impaired fasting glucose (IFG), and microalbuminuria. We estimated the odds of MetS per 1-s.d. increase in VAT and LF, adjusting for key covariates. VAT was associated with an increased odds of MetS in normal weight, overweight, and obese women (odds ratios (OR) = 2.78, 1.63, and 1.43, respectively; all P < 0.01) that diminished in magnitude with increasing BMI (VAT × BMI class interaction P < 0.001). In men, VAT was related to MetS only among the overweight (OR = 1.69, P < 0.01). LF was associated with MetS in the overweight and obese groups in women (OR = 1.38 and 1.45; both P < 0.001) and in men (OR = 1.38, P = 0.01; and OR = 1.27, P = 0.10), but not in the normal weight groups. These BMI-specific relationships persisted when both fat depots were included in the model. VAT and LF were associated with MetS independently of each other, and these relationships were modified by BMI class such that, VAT was the more important depot at lower levels of obesity and LF at higher levels. Importantly, fatty liver may be a novel metabolic risk factor in overweight and obese individuals. [ABSTRACT FROM AUTHOR]

The protective mechanisms by which some obese individuals escape the detrimental metabolic consequences of obesity are not understood. This study examined differences in body fat distribution and adipocytokines in obese older persons with and without metabolic syndrome. Additionally, we examined whether adipocytokines mediate the association between body fat distribution and metabolic syndrome. Data were from 729 obese men and women (BMI ≥30 kg/m2), aged 70-79 participating in the Health, Aging and Body Composition (Health ABC) study. Thirty-one percent of these obese men and women did not have metabolic syndrome. Obese persons with metabolic syndrome had significantly more abdominal visceral fat (men: P = 0.04; women: P < 0.01) and less thigh subcutaneous fat (men: P = 0.09; women: P < 0.01) than those without metabolic syndrome. Additionally, those with metabolic syndrome had significantly higher levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) than individuals without metabolic syndrome. Per standard deviation higher in visceral fat, the likelihood of metabolic syndrome significantly increased in women (odds ratio (OR): 2.16, 95% confidence interval (CI): 1.59-2.94). In contrast, the likelihood of metabolic syndrome decreased in both men (OR: 0.56, 95% CI: 0.39-0.80) and women (OR: 0.49, 95% CI: 0.34-0.69) with each standard deviation higher in thigh subcutaneous fat. These associations were partly mediated by adipocytokines; the association between thigh subcutaneous fat and metabolic syndrome was no longer significant in men. In summary, metabolically healthy obese older persons had a more favorable fat distribution, characterized by lower visceral fat and greater thigh subcutaneous fat and a more favorable inflammatory profile compared to their metabolically unhealthy obese counterparts. [ABSTRACT FROM AUTHOR]

To examine the association between hospitalization and annual changes in body composition and strength in older adults. Cohort study. Clinic examinations in Pittsburgh, Pennsylvania, or Memphis, Tennessee. Well-functioning adults aged 70 to 79 who participated in the Health, Aging and Body Composition Study. Hospitalizations were reported at annual clinic visits and in semiannual phone interviews. In the event of death or reported hospitalization, hospitalizations were adjudicated according to medical record review. Dual X-ray absorptiometry (DXA) assessments of total, lean, and fat mass were conducted in six annual examinations, and measures of knee extensor strength were conducted in two annual examinations. DXA assessments followed 2,309 hospitalizations. In men and women, hospitalization in the previous year was associated with greater declines in total mass (−0.76 and −0.81 kg, respectively), fat mass (−0.41 and −0.54 kg), and lean mass (−0.33 and −0.25 kg) ( P<.001 for all) than in nonhospitalized participants, after adjustment for demographics and baseline values. Hospitalization was associated with strength declines in men (−4.02 Nm, P=.046) but not in women. Relationships were similar after adjusting for health behaviors and chronic conditions, although the association between hospitalization and strength was attenuated. Associations increased with number of days hospitalized; hospitalizations totaling 8 days or more in the previous year were associated with significantly greater loss of total, lean, and fat mass and loss of strength in both sexes than in nonhospitalized participants. Hospitalization is associated with significant changes in body composition and strength in older persons. These effects appear particularly important in persons hospitalized for 8 or more days per year. [ABSTRACT FROM AUTHOR]

Objectives Adipose tissue-derived inflammation may contribute to metabolic alterations and eventually to the metabolic syndrome (MetS). The purpose of this study was to: (1) examine the role of adipocytokines in the association between obesity and the MetS and (2) to determine whether the association is different in obese and non-obese persons. Design Cross-sectional population-based InCHIANTI study. Subjects A total of 944 community-dwelling adults aged 65 years and older living in Tuscany, Italy. Measurements Obesity was defined as body mass index ≥30 kg/m2 and MetS as ≥3 of the ATP-III criteria. Circulating levels of C-reactive protein, interleukin (IL)-6, IL-1 receptor antagonist (IL-1ra), IL-18, tumour necrosis factor (TNF)-α R1, adiponectin, resistin and leptin were measured. Additionally, insulin resistance was determined using the homeostasis model assessment (HOMA-IR). Results The prevalence of the MetS was 32%. Both overall and abdominal obesity were significantly associated with the MetS after adjusting for inflammatory cytokines, adipokines and lifestyle factors. After adjusting for multiple confounders and HOMA-IR, IL-1ra, TNF-α R1 and adiponectin ( P < 0·05) remained significantly associated with the MetS. Having multiple cytokines in the highest tertile increased the likelihood of having the MetS in both obese ( P for trend 0·002) and non-obese persons ( P for trend 0·001) independent of insulin resistance. Conclusions Non-obese and obese individuals who develop an intense pro-inflammatory state may be more prone to develop the MetS than those with lower levels of inflammation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the association between physical fitness, assessed according to ability and time to complete a 400-m walk, on changes in body composition and muscle strength over a 7-year period. DESIGN: Prospective observational cohort study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand nine hundred forty-nine black and white men and women aged 70 to 79 participating in the Health, Aging and Body Composition Study. MEASUREMENTS: Body composition (fat and bone-free lean mass) was assessed using dual-energy X-ray absorptiometry in Years 1 to 6 and 8. Knee extension strength was measured using isokinetic dynamometry and grip strength using isometric dynamometry in Years 1, 2, 4, 6, and 8. RESULTS: Less fit people weighed more and had a higher total percentage of fat and a lower total percentage of lean mass than very fit men and women at baseline ( P<.001). Additionally, the least fit lost significantly more weight, fat mass, and lean mass over time than the very fit (all P<.01). Very fit people had the highest grip strength and knee extensor strength at baseline and follow-up; decline in muscle strength was similar in every fitness group. CONCLUSION: Low fitness in old age was associated with greater weight loss and loss of lean mass than with high fitness. Despite having lower muscle strength, the rate of decline in the least fit persons was similar to that in the most fit. In clinical practice, a long-distance walk test as a measure of fitness might be useful to identify people at risk for these adverse health outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate the prospective relationship between alcohol consumption and incident mobility limitation. DESIGN: Cohort study. SETTING: The Health Aging and Body Composition study, conducted in Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Three thousand sixty-one adults aged 70 to 79 without mobility disability at baseline. MEASUREMENTS: Incidence of mobility limitation, defined as self-report at two consecutive semiannual interviews of any difficulty walking one-quarter of a mile or climbing stairs, and incidence of mobility disability, defined as severe difficulty or inability to perform these tasks at two consecutive reports. Alcohol intake, lifestyle-related variables, diseases, and health status indicators were assessed at baseline. RESULTS: During a follow-up time of 6.5 years, participants consuming moderate levels of alcohol had the lowest incidence of mobility limitation (total: 6.4 per 100 person-years (person-years); men: 6.4 per 100 person-years; women: 7.3 per 100 person-years) and mobility disability (total: 2.7 per 100 person-years; men: 2.5 per 100 person-years; women: 2.9 per 100 person-years). Adjusting for demographic characteristics, moderate alcohol intake was associated with lower risk of mobility limitation (hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.55–0.89) and mobility disability (HR=0.66, 95% CI=0.45–0.95) than never or occasional consumption. Additional adjustment for lifestyle-related variables substantially reduced the strength of the associations (HR=0.85, 95% CI=0.66–1.08 and HR=0.81, 95% CI=0.56–1.18, respectively). Adjustment for diseases and health status indicators did not affect the strength of the associations, suggesting that lifestyle is most important in confounding this relationship. CONCLUSION: Lifestyle-related characteristics mainly accounted for the association between moderate alcohol intake and lower risk of functional decline over time. These findings do not support a direct causal effect of alcohol intake on physical function. [ABSTRACT FROM AUTHOR]

A growing body of evidence has consistently shown a correlation between obesity and chronic subclinical inflammation. It is unclear whether the size of specific adipose depots is more closely associated with concentrations of inflammatory markers than overall adiposity. This study investigated the relationship between inflammatory markers and computerized tomography-derived abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat in older white and black adults. Data were from 2,651 black and white men and women aged 70–79 years participating in the Health, Aging, and Body Composition (Health ABC) study. Inflammatory markers, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) were obtained from serum samples. Abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat were quantified on computerized tomography images. Linear regression analysis was used to evaluate the cross-sectional relationship between specific adipose depots and inflammatory markers in four race/gender groups. As expected, blacks have less visceral fat than whites and women less visceral fat than men. However, abdominal visceral adiposity was most consistently associated with significantly higher IL-6 and CRP concentrations in all race/gender groups (P < 0.05), even after controlling for general adiposity. Thigh intermuscular fat had an inconsistent but significant association with inflammation, and there was a trend toward lower inflammatory marker concentration with increasing thigh subcutaneous fat in white and black women. Despite the previously established differences in abdominal fat distribution across gender and race, visceral fat remained a significant predictor of inflammatory marker concentration across all four subgroups examined.Obesity (2009) 17 5, 1062–1069. doi:10.1038/oby.2008.627 [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine joint associations of physical activity and adiposity measures (body mass index (BMI), waist circumference, percentage body fat) with incident mobility limitation. DESIGN: Prospective observational cohort study. SETTING: Memphis, Tennessee and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand nine hundred and eighty-two black and white men and women aged 70 to 79 participating in the Health, Aging and Body Composition (Health ABC) study. MEASUREMENTS: Mobility limitation was defined as reported difficulty walking one-quarter of a mile or climbing 10 steps during two consecutive semiannual assessments over 6.5 years. Three measures of adiposity were included in this study: BMI, total percentage body fat, and waist circumference. Physical activity was assessed using a modified leisure-time physical activity questionnaire. RESULTS: Forty-six percent of the cohort developed mobility limitation. White and black men with a high BMI (≥30 kg/m2), high total percentage body fat (>31.3%), or high waist circumference (≥102 cm) had an approximately 60%, 40%, and 40%, respectively, higher risk of incident mobility limitation than those with low adiposity. In women, high adiposity was also associated with a significantly higher mobility limitation risk than in those with low adiposity. Low physical activity (lowest quartile) was associated with a 70% higher risk of mobility limitation in all groups. Persons with high adiposity and low physical activity were at particularly high risk of mobility limitation. People with high adiposity who were physically active had an equally high risk of mobility limitation as inactive people with low adiposity. CONCLUSION: High adiposity and low self-reported physical activity predicted the onset of mobility limitation in well-functioning older persons. Preventing weight gain in old age and promoting physical activity in obese and non-obese older persons may therefore be effective strategies to prevent mobility loss and future disability. [ABSTRACT FROM AUTHOR]

The article provides information on a study which examined the association between lifestyle factors and incident mobility limitation in obese and non-obese older adults. The authors examined data from men and women participating in the Health, Aging and Body Composition study in Pittsburgh, Pennsylvania. Four lifestyle factors were analyzed, which include smoking, alcohol intake, physical activity and diet.