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The etiology of late-life depression (LLD) is still poorly understood. Microvascular dysfunction (MVD) has been suggested to play a role in the etiology of LLD, but direct evidence of this association is scarce. The aim of this study was to investigate whether direct and indirect markers of early microvascular dysfunction are associated with prevalent and incident LLD in the population-based Maastricht Study cohort. We measured microvascular dysfunction at baseline by use of flicker light-induced retinal vessel dilation response (Dynamic Vessel Analyzer), heat-induced skin hyperemic response (laser- Doppler flowmetry), and plasma markers of endothelial dysfunction (endothelial dysfunction; sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [Von Willebrand Factor]). Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) at baseline and annually over 4 years of follow-up (n=3029; mean age 59.6±8.2 years, 49.5% were women, n=132 and n=251 with prevalent and incident depressive symptoms [PHQ-9≥10]). We used logistic, negative binominal and Cox regression analyses, and adjusted for demographic, cardiovascular, and lifestyle factors. Retinal venular dilatation and plasma markers of endothelial dysfunction were associated with the more prevalent depressive symptoms after full adjustment (PHQ-9 score, RR, 1.05 [1.00-1.11] and RR 1.06 [1.01-1.11], respectively). Retinal venular dilatation was also associated with prevalent depressive symptoms (PHQ-9≥10; odds ratio, 1.42 [1.09-1.84]), after full adjustment. Retinal arteriolar dilatation and plasma markers of endothelial dysfunction were associated with incident depressive symptoms (PHQ-9≥10; HR, 1.23 [1.04-1.46] and HR, 1.19 [1.05-1.35]), after full adjustment. These findings support the concept that microvascular dysfunction in the retina, and plasma markers of endothelial dysfunction is involved in the etiology of LLD and might help in finding additional targets for the prevention and treatment of LLD. [ABSTRACT FROM AUTHOR]

Microvascular dysfunction may be associated with worse cognitive performance. Most previous studies did not adjust for important confounders, evaluated only individual measures of microvascular dysfunction, and showed inconsistent results. We evaluated the association between a comprehensive set of measures of microvascular dysfunction and cognitive performance in the population-based Maastricht Study. We used cross-sectional data including 3011 participants (age 59.5±8.2; 48.9% women; 26.5% type 2 diabetes mellitus [oversampled by design]). Measures of microvascular dysfunction included magnetic resonance imaging features of cerebral small vessel disease, plasma biomarkers of microvascular dysfunction, albuminuria, flicker light-induced retinal arteriolar and venular dilation response and heat-induced skin hyperemia. These measures were summarized into a microvascular dysfunction composite score. Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the sum of the scores on these 3 cognitive domains. The microvascular dysfunction score was associated with a worse cognitive function score (standardized β, -0.087 [95% CI, -0.127 to -0.047]), independent of age, education level, sex, type 2 diabetes mellitus, smoking, alcohol use, hypertension, total/HDL (high-density lipoprotein) cholesterol ratio, triglycerides, lipid-modifying medication, prior cardiovascular disease, depression and plasma biomarkers of low-grade inflammation. The fully adjusted β-coefficient of the association between the microvascular dysfunction score and the cognitive function score was equivalent to 2 (range, 1-3) years of aging for each SD higher microvascular dysfunction score. The microvascular dysfunction score was associated with worse memory and processing speed but not with worse executive function. The present study shows that microvascular dysfunction is associated with worse cognitive performance. [ABSTRACT FROM AUTHOR]

Purpose: This cross-sectional study examined the mutual independent associations of sedentary behavior, lower intensity physical activity (LPA) and higher intensity physical activity (HPA) (an approximation of moderate to vigorous physical activity with cardiorespiratory fitness (CRF). Methods: Two thousand twenty-four participants were included from The Maastricht Study (mean ± SD age, 59.7 ± 8.1 yr; 49.6% men). With the activPAL3 activity monitor, we assessed sedentary time (ST), sedentary pattern variables (number of sedentary breaks, average sedentary bout duration, and number of prolonged sedentary bouts [≥30 min]), LPA, and HPA. CRF was calculated as maximum power output per kilogram body mass (Wmax⋅kg-1) estimated from a submaximal cycle ergometer test. Linear regression analyses and isotemporal substitution analyses were used to examine associations of ST, sedentary pattern variables, and HPA with CRF. Analyses were stratified by sex. Results: One hour of ST per day was associated with a lower Wmax⋅kg-1: Bmen = -0.03 (95% confidence interval [CI], -0.05 to -0.01) and Bwomen = -0.02 (95% CI, -0.04 to 0.00), independent of HPA. No statistically significant associations between sedentary patterns variables and CRF were observed. LPA was associated with a higher Wmax⋅kg-1: Bmen = 0.12 (95% CI, 0.07-0.17) and Bwomen = 0.12 (95% CI, 0.07-0.18). HPA was associated with a higher Wmax⋅kg-1: Bmen = 0.48 (95% CI, 0.38-0.58) and Bwomen = 0.27 (95% CI, 0.18-0.36). Replacing ST with LPA (Bmen, 0.08; 95% CI, 0.03-0.14; Bwomen, 0.10; 95% CI, 0.05-0.16) or with HPA (Bmen, 0.49; 95% CI, 0.39-0.59; Bwomen = 0.28; 95% CI, 0.19-0.36), but not with standing was associated with higher CRF. Conclusions: Modest associations between sedentary behavior and CRF were observed. Replacing ST with LPA was associated with higher CRF, which could be of particular importance for individuals who cannot engage in HPA. Nonetheless, replacing ST with HPA was associated with greatest estimated change in CRF. [ABSTRACT FROM AUTHOR]

Arterial stiffening, as characterized by an increase in carotid-femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid-femoral pulse-wave velocity (sβ 0.10; 95% confidence interval, 0.03-0.17 and 0.10; 0.04-0.16, respectively) and central pulse pressure (sβ 0.08; 95% confidence interval 0.01-0.15 and 0.07; 0.01-0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid-femoral pulse-wave velocity were more pronounced in individuals with type 2 diabetes mellitus (P-interaction<0.10). These results support the hypothesis that accumulation of advanced glycation end products is involved in arterial stiffening and may explain part of the increased risk of cardiovascular disease in individuals with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Purpose: Sedentary behavior is an emerging independent health risk factor. The accuracy of measuring sedentary time using accelerometers may depend on the wear location. This study in older adults evaluated the accuracy of various hip- and wrist-worn ActiGraph accelerometer cutoff points to define sedentary time using the activPAL as the reference method. Methods: Data from 62 adults (mean age, 78.4 yr) of the Aging Research Evaluating Accelerometry study were used. Participants simultaneously wore an activPAL accelerometer on the thigh and ActiGraph accelerometers on the hip, dominant, and nondominant wrist for 7 d in a free-living environment. Using the activPAL as the reference criteria, we compared classification of sedentary time to hip-worn and wrist-worn ActiGraph accelerometers over a range of cutoff points for both 60-s and 15-s epochs. Results: The optimal cutoff point for the hip vertical axis was <22 counts per minute with an area under the curve (AUC) of 0.85; the optimal hip vector magnitude cutoff point was <174 counts per minute with an AUC of 0.89. For the dominant wrist, the optimal vector magnitude cutoff point to define sedentary time was <2303 counts per minute (AUC, 0.86) and for the nondominant wrist <1853 counts per minute (AUC, 0.86). The optimal 15-s cutoff points resulted in lower agreements compared with activPAL. Conclusions: Hip- and wrist-worn ActiGraph data may be used to define sedentary time with a moderate to high accuracy when compared with activPAL. The observed optimal cutoff point for hip vertical axis <22 counts per minute is substantially lower than the standard <100 counts per minute. It is unknown how these optimal cutoff points perform in different populations. Results on an individual basis should therefore be interpreted with caution. [ABSTRACT FROM AUTHOR]

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.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 was 3.14 (2.42-4.06), 1.46 (1.25-1.76), 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 sexes (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 versus 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 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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Validation of accelerometer wear and nonwear time classification algorithm," by L. Choi and colleagues in the 2011 issue.

Background: Blood pressure (BP)-lowering effects of structured exercise are well-established. Effects of 24-hour movement behaviors captured in free-living settings have received less attention. This cross-sectional study investigated associations between a 24-hour behavior composition comprising 6 parts (sleeping, sedentary behavior, standing, slow walking, fast walking, and combined exercise-like activity [eg, running and cycling]) and systolic BP (SBP) and diastolic BP (DBP)., Methods: Data from thigh-worn accelerometers and BP measurements were collected from 6 cohorts in the Prospective Physical Activity, Sitting and Sleep consortium (ProPASS) (n=14 761; mean±SD, 54.2±9.6 years). Individual participant analysis using compositional data analysis was conducted with adjustments for relevant harmonized covariates. Based on the average sample composition, reallocation plots examined estimated BP reductions through behavioral replacement; the theoretical benefits of optimal (ie, clinically meaningful improvement in SBP [2 mm Hg] or DBP [1 mm Hg]) and minimal (ie, 5-minute reallocation) behavioral replacements were identified., Results: The average 24-hour composition consisted of sleeping (7.13±1.19 hours), sedentary behavior (10.7±1.9 hours), standing (3.2±1.1 hours), slow walking (1.6±0.6 hours), fast walking (1.1±0.5 hours), and exercise-like activity (16.0±16.3 minutes). More time spent exercising or sleeping, relative to other behaviors, was associated with lower BP. An additional 5 minutes of exercise-like activity was associated with estimated reductions of -0.68 mm Hg (95% CI, -0.15, -1.21) SBP and -0.54 mm Hg (95% CI, -0.19, 0.89) DBP. Clinically meaningful improvements in SBP and DBP were estimated after 20 to 27 minutes and 10 to 15 minutes of reallocation of time in other behaviors into additional exercise. Although more time spent being sedentary was adversely associated with SBP and DBP, there was minimal impact of standing or walking., Conclusions: Study findings reiterate the importance of exercise for BP control, suggesting that small additional amounts of exercise are associated with lower BP in a free-living setting.

Purpose: Vigorous intermittent lifestyle physical activity (VILPA) are bursts of incidental vigorous activity that occur during day-to-day activities outside of the exercise-domain. VILPA has shown promise in lowering risk of mortality and chronic disease. However, there is an absence of an empirically derived definition. Using physiological and effort-based metrics commonly used to define vigorous intensity, we investigated the minimum time needed to elicit physiological and perceived exertion responses to standardised activities of daily living., Methods: Seventy adults (Age = 58.0 ± 9.6y; 35 female) completed 9 VILPA activities of daily living in a randomised order, that included: fast walking, fast incline walking, stair climbing, stationary cycling, and carrying external weight equal to 5% and 10% of body weight. Metabolic rate (by continuous indirect calorimetry), heart rate (telemetry) and perceived effort (Borg Scale) were measured during exercise. Time to reach VILPA was assessed using %VO 2 max, %HRmax, and rating of perceived exertion thresholds., Results: The mean time to elicit VILPA ranged from 65-95 seconds (mean ± sd = 76.7 ± 3.8 seconds) for %VO 2 max, 68 to 105 seconds (mean ± sd = 82.8 ± 6.8 seconds) for %HRmax, and 20 to 60 seconds (mean ± sd = 44.6 ± 6.7 seconds) for rating of perceived exertion. For each of the three indices, there was no difference in the time to elicit VILPA responses by sex or age (p > 0.08), and times were also consistent between activities of daily living tasks. For example, for females and males, the average time to elicit vigorous responses while walking on a flat surface was 85.8 (±16.9) and 80 (±13.9) seconds, respectively, and for stair climbing while carrying 10% of body weight the duration was 78.4 (±17.6) and 76.9 (±17.7) seconds., Conclusions: When participants undertook activities of daily living, VILPA elicited a physiological response at an average of 77-83 seconds for %VO 2 max and %HRmax, and 45 seconds for perceived exertion. The absence of a difference in the time to reach VILPA between sex and age suggests that a consistent behavioural VILPA translation can be used in interventions and population-based studies designed to assess the health effects of incidental physical activity., Competing Interests: Conflict of Interest and Funding Source: The authors have no conflicts to disclose. Funding for this study came from the National Health and Medical Research Council Ideas Grant (APP 1180812)., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Purpose: The study aims were 1) to develop transparent algorithms that use short segments of training data for predicting activity types and 2) to compare the prediction performance of the proposed algorithms using single accelerometers and multiple accelerometers., Methods: Sixteen participants (age, 80.6 yr (4.8 yr); body mass index, 26.1 kg·m (2.5 kg·m)) performed 15 lifestyle activities in the laboratory, each wearing three accelerometers at the right hip and 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., Results: 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% on the basis of 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 second-level 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.