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High-density lipoprotein (HDL) is protective against cardiovascular disease. Exercise can increase HDL concentration, and some evidence suggests that this effect occurs more strongly in women than in men. Both HDL and exercise are associated with inflammation. We hypothesized a sex-by-exercise interaction on HDL level, whereby women would benefit from exercise more strongly than men, and tumor necrosis factor alpha and serum soluble tumor necrosis factor receptor-2 would mediate this relationship. This study included 2,957 older adult participants (1,520 women; 41% Black, 59% White; 73.6-years-old) from the Health, Aging, and Body Composition study. Regression models revealed a positive exercise-HDL relationship in women only (sex-by-exercise interaction: β = 0.09, p = .013; exercise on HDL in women: β = 0.07, p = .015), mediated by TNFα (axb = 0.15; CI: 0.01, 0.30), suggesting that exercise may increase HDL levels in women through reduced inflammation. Given that vascular risk contributes to Alzheimer's disease risk, findings have implications for sex differences in AD risk factors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Bernier reports no conflicts. Dr. Sundermann reports no conflicts. Dr. Edland reports no conflicts. Dr. Deters reports no conflicts. Ms. Shepherd reports no conflicts. Dr. Clark reports no conflicts. Dr. Shiroma reports no conflicts. Dr. Banks reports no conflicts.

Biological clocks and other molecular biomarkers of aging are difficult to implement widely in a clinical setting. In this study, we used routinely collected hematological markers to develop an aging clock to predict blood age and determine whether the difference between predicted age and chronologic age (aging gap) is associated with advanced aging in mice. Data from 2,562 mice of both sexes and three strains were drawn from two longitudinal studies of aging. Eight hematological variables and two metabolic indices were collected longitudinally (12,010 observations). Blood age was predicted using a deep neural network. Blood age was significantly correlated with chronological age, and aging gap was positively associated with mortality risk and frailty. Platelets were identified as the strongest age predictor by the deep neural network. An aging clock based on routinely collected blood measures has the potential to provide a practical clinical tool to better understand individual variability in the aging process., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Peripheral risk factors (PRFs) may correlate with dementia plasma biomarkers, potentially reflecting peripheral rather than brain health. This study explores the associations between PRFs and plasma biomarkers glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total-tau, and their role in predicting future dementia., Methods: Data from the Age, Gene/Environment Susceptibility-Reykjavik Study (2002-2015) included 4353 participants mean age of 76.6 years. A subsample of 910 participants tested their association with PRFs and plasma biomarkers' predictive performance. Sociodemographic, clinical, laboratory, sensory, and lifestyle variables (n = 305) were grouped into 34 clusters., Results: Besides age and estimated glomerular filtration rate (eGFR), significant associations were found between plasma biomarkers and clusters related to hemoglobin, red blood cell distribution, and inflammation. Incorporating these clusters into predictive models enhanced precision and sensitivity, though overall prediction improvement was modest (area under the precision-recall curve: GFAP 0.17 to 0.34, NfL 0.20 to 0.38)., Discussion: PRFs are significantly associated with dementia plasma biomarkers; Considering these factors may enhance the predictive accuracy of dementia biomarkers., Highlights: Machine learning identifies key peripheral factors influencing neurodegenerative biomarkers. Hemoglobin and red blood cell distribution cluster associates significantly with biomarker levels. Incorporating diverse peripheral factors modestly enhances incident dementia prediction accuracy in community settings., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This article is a U.S. Government work and is in the public domain in the USA.)

Background: A shift from self-reports to wearable sensors for global physical activity (PA) surveillance has been recommended. The conventional use of a generic cut-point to assess moderate-to-vigorous PA (MVPA) is problematic as these cut-points are often derived from non-representative samples under non-ecological laboratory conditions. This study aimed to develop age- and sex- (age-sex) specific cut-points for MVPA based on population-standardized values as a feasible approach to assess the adherence to PA guidelines and to investigate its associations with all-cause mortality., Methods: A total of 7601 participants (20-85+ years) were drawn from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys (NHANES). Minutes per week of MVPA were assessed with a hip-worn accelerometer. Counts per minute (CPM) were used to define an age-sex specific target intensity, representing the intensity each person should be able to reach based on their age and sex. Age-sex specific MVPA cut-points were defined as any activity above 40% of the target intensity. These population- and free-living-based age-sex specific cut-points overcome many of the limitations of the standard generic cut-point approach. For comparison, we also calculated MVPA with a generic cut-point of 1952 CPM. Both approaches were compared for assessing adherence to PA guidelines and association of MVPA with all-cause mortality (ascertained through December 2015)., Results: Both approaches indicated that 37% of the sample met the 150+ min/week guideline. The generic cut-point approach showed a trend to inactivity with age, which was less pronounced using the age-sex specific cut-points. Overall mortality rates were comparable using generic cut-point (hazard ratio (HR) = 0.61, 95% confidence interval (95%CI): 0.50‒0.73) or age-sex specific cut-points (HR = 0.57, 95%CI: 0.50‒0.66) for the entire sample. The generic cut-point method revealed an age- and sex-related gap in the benefits of achieving 150+ min/week of MVPA, with older adults showing an 18% greater reduction in mortality rates than younger adults, and a larger difference in women than in men. This disparity disappeared when using age-sex specific cut-points., Conclusion: Our findings underscore the value of age-sex specific cut-points for global PA surveillance. MVPA defined with age-sex specific thresholds was associated with all-cause mortality and the dose‒response was similar for all ages and sexes. This aligns with the single recommendation of accumulating 150+ min/week MVPA for all adults, irrespective of age and sex. This study serves as a proof of concept to develop this methodology for PA surveillance over more advanced open-source acceleration metrics and other national and international cohorts., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2025. Production and hosting by Elsevier B.V.)

Objective: Accumulating more steps/day is associated with a lower risk of cancer mortality and composite cancer outcomes. However, less is known about the relationship of steps/day with the risk of multiple site-specific cancers., Methods: This study included >22,000 women from the Women's Health Accelerometry Collaboration Cohort (2011-2022), comprised of women from the Women's Health Study and Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study. Steps/day and step intensity were collected with accelerometry. Incident cancer cases and deaths were adjudicated. Stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of steps/day and step intensity with incident breast, colon, endometrial, lung, and ovarian cancers, a composite of 13 physical activity-related cancers, total invasive cancer, and fatal cancer., Results: On average, women were 73.4 years old, accumulated 4993 steps/day, and had 7.9 years of follow-up. There were small nonsignificant inverse associations with the risks of colon cancer (HR = 0.94, 95% CI: 0.83, 1.05), endometrial cancer (HR = 0.91, 95% CI: 0.82, 1.01), and fatal cancer (HR = 0.95 95% CI: 0.90, 1.00) per 1000 steps/day. More minutes at ≥40 steps/min and a faster peak 10- and 30-min step cadence were associated with a lower risk of endometrial cancer, but findings were attenuated after adjustment for body mass index and steps/day., Conclusions: Among women 62-97 years, there were small nonsignificant inverse associations of colon, endometrial, and fatal cancer with more steps/day. Epidemiologic studies with longer follow-up and updated assessments are needed to further explore these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Current US physical activity (PA) guidelines prescribe moderate to vigorous PA (MVPA) time of at least 150 minutes per week for health. An analogous step-based recommendation has not been issued due to insufficient evidence., Objective: To examine the associations of MVPA time and step counts with all-cause mortality and cardiovascular disease (CVD)., Design, Setting, and Participants: This cohort study analyzed data from an ongoing follow-up study of surviving participants of the Women's Health Study, a randomized clinical trial conducted from 1992 to 2004 in the US to evaluate use of low-dose aspirin and vitamin E for preventing cancer and CVD. Participants were 62 years or older who were free from CVD and cancer, completed annual questionnaires, and agreed to measure their PA with an accelerometer as part of a 2011-2015 ancillary study. Participants were followed up through December 31, 2022., Exposures: Time spent in MVPA and step counts, measured with an accelerometer for 7 consecutive days., Main Outcomes and Measures: The associations of MVPA time and step counts with all-cause mortality and CVD (composite of myocardial infarction, stroke, and CVD mortality) adjusted for confounders. Cox proportional hazards regression models, restricted mean survival time differences, and area under the receiver operating characteristic curve (AUC) were used to evaluate the associations., Results: A total of 14 399 women (mean [SD] age, 71.8 [5.6] years) were included. The median (IQR) MVPA time and step counts were 62 (20-149) minutes per week and 5183 (3691-7001) steps per day, respectively. During a median (IQR) follow-up of 9.0 (8.0-9.9) years, the hazard ratios (HR) per SD for all-cause mortality were 0.82 (95% CI, 0.75-0.90) for MVPA time and 0.74 (95% CI, 0.69-0.80) for step counts. Greater MVPA time and step counts (top 3 quartiles vs bottom quartile) were associated with a longer period free from death: 2.22 (95% CI, 1.58-2.85) months and 2.36 (95% CI, 1.73-2.99) months at 9 years follow-up, respectively. The AUCs for all-cause mortality from MVPA time and step counts were similar: 0.55 (95% CI, 0.52-0.57) for both metrics. Similar associations of these 2 metrics with CVD were observed., Conclusion and Relevance: Results of this study suggest that among females 62 years or older, MVPA time and step counts were qualitatively similar in their associations with all-cause mortality and CVD. Step count-based goals should be considered for future guidelines along with time-based goals, allowing for the accommodation of personal preferences.

Objective: In this study, we examine how impairments in vision, hearing, touch, and olfaction relate to depression in older adults, considering both individual and multisensory impairments (MSIs)., Study Design: Analysis of cross-sectional data from a longitudinal investigation involving black and white older adults aged 70 to 79 at enrollment., Setting: We studied 1640 black and white participants in the Health ABC study using complete sensory evaluation data from years 3 to 5., Methods: Our MSI assessment utilized data obtained for visual acuity, hearing perception, olfactory performance, and tactile function. We performed multivariable logistic regression analyses to examine the associations between the presence of individual and MSIs and depression which was defined as the presence of antidepressants prescribed for depression, or a Center for Epidemiological Studies Depression Scale score of greater than 10., Results: We observed a possible dose-response relationship between the number of sensory impairments and depression. In adjusted models, when compared to no impairments, vision (odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.09-1.93) and hearing impairments (OR = 1.49, 95% CI: 1.11-1.99) were significantly associated with depression, whereas olfaction (OR = 1.11, 95% CI: 0.83-1.47) and tactile impairments (OR = 1.28, 95% CI: 0.96-1.70) were not. Participants with 3 sensory impairments had a higher rate of depression (OR = 2.05, 95% CI: 1.22-3.54) compared to those without impairments, and this risk increased further for those with 4 sensory impairments (OR = 2.95, 95% CI: 1.48-5.88)., Conclusion: The findings suggest that individuals with MSI represent a high-risk population for depression, warranting close monitoring to screen for depression. The study emphasizes the importance of considering multiple sensory impairments in the context of mental health and supports the early identification and monitoring of depression in this population., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Describing correlates of physical activity (PA) and sedentary behavior (SB) among postmenopausal cancer survivors can help identify risk profiles and can be used to support development of targeted interventions to improve PA and reduce SB in this population., Objective: To describe PA/SB and identify correlates of PA/SB among cancer and cancer-free post-menopausal women., Methods: Women from the Women's Health Study (N = 16,629) and Women's Health Initiative/Objective Physical Activity and Cardiovascular Health Study (N = 6,079) were asked to wear an accelerometer on the hip for 7 days. Multiple mixed-effects linear regression models were used to identify sociodemographic-, health-, and chronic condition-related correlates (independent variables) associated with PA and SB (dependent variables) among women with (n = 2,554) and without (n = 20,154) a history of cancer. All correlates were mutually adjusted for each other., Results: In unadjusted analyses, women with a history of cancer took fewer mean daily steps (4,572 (standard deviation 2557) vs 5,029 (2679) steps/day) and had lower mean moderate-to-vigorous PA (74.9 (45.0) vs. 81.6 (46.7) minutes/day) than cancer-free women. In adjusted analyses, for cancer and cancer-free women, age, diabetes, overweight, and obesity were inversely associated with all metrics of PA (average vector magnitude, time in moderate-to-vigorous PA, step volume, time at ≥40 steps/minutes, and peak 30-minute step cadence). In unadjusted analyses, mean SB was similar for those with and without cancer (529.7 (98.1) vs. 521.7 (101.2) minutes/day). In adjusted analyses, for cancer and cancer-free women, age, diabetes, cardiovascular disease, current smoking, overweight, and obesity were positive correlates of SB, while Black or Hispanic race/ethnicity, weekly/daily alcohol intake, and excellent/very good/good self-rated health were inverse correlates of SB., Conclusion: Several sociodemographic, health, and chronic conditions were correlates of PA/SB for postmenopausal women with and without cancer. Future studies should examine longitudinal relationships to gain insight into potential determinants of PA/SB., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schilsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm., Introduction: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD)., Methods: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients., Results: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men., Conclusions: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Evidence suggests that individuals diagnosed with Parkinson's Disease (PD) spend less time in moderate-to-vigorous intensity physical activity (MVPA) compared to those without PD. However, prior studies primarily included men and did not consider movement across the entire intensity spectrum. To address these gaps, the association of PD status with total volume physical activity and time spent in sedentary, low light-intensity physical activity (LLPA), high light-intensity physical activity (HLPA), and MVPA among older women was examined. This is a cross-sectional analysis of 17,466 ambulatory women enrolled in the Women's Health Study (WHS) with a median (IQR) age of 70 (67-75) years who were asked to wear an accelerometer for 7 days from 2011 to 2015 for the ancillary study. Reported PD status was assessed via annual mail-in questionnaires prior to device wear. Compared to those without PD (n = 16,661), PD (n = 80) was associated with 98,400 fewer vector magnitude (VM) counts per day and with spending an average of 23.2 more minutes per day sedentary and 10.5 more minutes per day in LLPA. Further, PD was associated with spending 6.4 and 27.3 fewer minutes per day in HLPA and MVPA, respectively, compared to women without PD. PD in women is associated with more daily sedentary time and less time spent in health-enhancing physical activity. Prevention strategies to promote physical activity should be emphasized to enhance health and limit progression of disability in women living with PD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Aim: The objective of the current study was to examine whether physical activity and sedentary behavior were associated with appetite among community-dwelling older adults., Methods: Cross-sectional analysis was performed on three cohort studies: the Longitudinal Aging Study Amsterdam (LASA); the Health, Aging and Body Composition Study (HABC Study) and the I'm Still Standing Study (ISS Study); (n = 1173, n = 162, n = 125; age range: 57-99, 85-95, 80-100 years; women: 51%, 56%, 61%, respectively). Physical activity and sedentary behavior were measured using hip-worn (LASA and HABC) and wrist-worn (ISS) accelerometers. Appetite was self-reported. Logistic regression models were fitted by accelerometer placement to explore the association between good appetite and various physical activity metrics (total activity, sedentary behavior, and time spent in different intensities of physical activity)., Results: Among cohorts using hip-worn accelerometers, those having total activity within the highest tertile had more than double the odds of having good appetite compared with those within the lowest tertile (odds ratio [OR] 2.16 (1.15-4.06)). Each additional percent of daily sedentary behavior decreased the odds for having good appetite by 3% (OR 0.97 (0.95-0.996)), while each additional percent of daily light-intensity physical activity increased the odds for having good appetite by 4% (OR 1.02 (1.01-1.06)). No association was found between either physical activity or sedentary behavior and appetite for measurements with the wrist-worn accelerometers., Conclusions: Among community-dwelling older adults, the associations between appetite, accelerometer-assessed physical activity and sedentary behavior differ by accelerometer placement location. This study highlights the importance of careful interpretation of accelerometer data from different body locations and concurrent health outcomes. Geriatr Gerontol Int 2023; 23: 411-417., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background: Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC risk among women in the Women's Health Accelerometry Collaboration (WHAC)., Methods: The WHAC comprised 21,089 postmenopausal women (15,375 from the Women's Health Study [WHS]; 5714 from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study [OPACH]). Women wore an ActiGraph GT3X+ on the hip for ≥4 days and were followed for 7.4 average years to identify physician-adjudicated in situ (n = 94) or invasive (n = 546) BCs. Multivariable stratified Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles of physical activity measures in association with incident BC overall and by cohort. Effect measure modification was examined by age, race/ethnicity, and body mass index (BMI)., Results: In covariate-adjusted models, the highest (vs. lowest) tertiles of VM/15s, TPA, LPA, and MVPA were associated with BC HRs of 0.80 (95% CI, 0.64-0.99), 0.84 (95% CI, 0.69-1.02), 0.89 (95% CI, 0.73-1.08), and 0.81 (95% CI, 0.64-1.01), respectively. Further adjustment for BMI or physical function attenuated these associations. Associations were more pronounced among OPACH than WHS women for VM/15s, MVPA, and TPA; younger than older women for MVPA; and women with BMI ≥30 than <30 kg/m 2 for LPA., Conclusion: Greater levels of accelerometer-assessed PA were associated with lower BC risk. Associations varied by age and obesity and were not independent of BMI or physical function., (© 2023 American Cancer Society.)

Background: Social determinants of health (SDoH) are environmental conditions that influence health outcomes. As olfactory dysfunction (OD) in older individuals is associated with increased morbidity and mortality, we sought to investigate the impact of specific SDoH on olfactory function., Methods: A cross-sectional analysis of the Health, Aging and Body Composition Study, a US population-based epidemiologic cohort study, was performed. Olfactory function was assessed utilizing both a self-report and a psychophysical olfactory test (CC-SIT test). Multivariable logistic regressions were performed to examine associations between specific SDoH with self-reported anosmia (sOD) and objective anosmia (oOD) as assessed by psychophysical testing. Differences in sensitivity and specificity were evaluated with sample tests for equality of proportions., Results: Of 2219 participants, 13% had oOD and 18% had objective hyposmia; only 10% had sOD. Individuals identifying as Black race had higher odds of oOD (odds ratio [OR]:1.41, 95% confidence interval [CI]:1.02-1.95), while females and those reporting family incomes ≥$50,000 had lower odds of oOD (OR: 0.46, CI:0.34-0.62; OR:0.52, CI:0.29-0.93), adjusting for covariates. No specific SDoH was significantly associated with sOD. The sensitivity and specificity of sOD for oOD was 23.1% and 92.0%, respectively. sOD had greater sensitivity in females than males (30.8% vs. 18.8%, p = 0.030), while specificity varied significantly depending on family income (range: 90.0%-94.8%, p = 0.033)., Conclusions: Utilizing a large population-based study, we find disparities in the prevalence and self-recognition of OD among individuals of different gender, race, and income levels. Further effort is needed to evaluate factors propagating these disparities and to raise awareness of OD across all patient populations., (© 2022 ARS-AAOA, LLC.)

Background Few studies have investigated associations of acclerometer-based assessments of physical activity (PA) and sedentary behavior (SB) with incidence of cardiovascular disease (CVD) and its components. This prospective cohort study assessed the associations of accelerometer-measured PA and SB with total CVD, myocardial infarction, and ischemic stroke (IS). Methods and Results The authors included 16 031 women aged 62 years and older, free of CVD, with adherent accelerometer wear (≥10 hours/day for ≥4 days) from the Women's Health Study (mean age, 71.4 years [SD, 5.6 years]). Hip-worn ActiGraph GT3X+ accelerometers measured total volume of PA (total average daily vector magnitude), minutes per day of high-light PA and moderate to vigorous PA (MVPA), and SB. Women reported diagnoses of CVD, which were adjudicated using medical records and death certificates. Hazard ratios (HRs) were estimated for each exposure, and 95% CIs using Cox proportional hazards models were adjusted for accelerometer wear time, age, self-reported general health, postmenopausal hormone therapy, smoking status, and alcohol use. The hypothetical effect of replacing 10 minutes/day of SB or high-light PA with MVPA on CVD incidence was assessed using adjusted isotemporal substitution Cox models. Over a mean of 7.1 years (SD, 1.6 years) of follow-up, 482 total CVD cases, 107 myocardial infarction cases, and 181 IS cases were diagnosed. Compared with the lowest quartiles of total average daily vector magnitude and MVPA (≤60 minutes), women who were in the highest quartiles (>120 minutes of MVPA) had a 43% (95% CI, 24%-58%) and 38% (95% CI, 18%-54%) lower hazard of total CVD, respectively. Estimates were similar for total average daily vector magnitude and MVPA with IS, but PA was not associated with myocardial infarction overall. High-light PA was not associated with any CVD outcomes. Women who spent <7.4 hours sedentary per day had a 33% (95% CI, 11%-49%) lower hazard of total CVD compared with those who spent ≥9.5 hours sedentary. Replacing 10 minutes of SB with MVPA was associated with a 4% lower incidence of total CVD (HR, 0.96 [95% CI, 0.93-0.99]). Conclusions Accelerometer-assessed total PA and MVPA were inversely associated with total CVD and IS incidence, and SB was directly associated with total CVD; high-light PA was not related to CVD.

Background: Volitional physical activity level is predictive of a variety of health outcomes, but has not been examined in patients recently hospitalized for acute decompensated HF (ADHF)., Methods: Ten to 14 days after index hospitalization for ADHF, 93 participants wore a wrist-mounted triaxial accelerometer (ActiGraph GT3X+) to objectively quantify sedentary behavior, light physical activity, and moderate-to-vigorous physical activity. Levels were compared to 2 groups of age-matched NHANES participants: healthy and chronic, stable HF. The relationship between physical activity levels and physical function [Short Physical Performance Battery (SPPB)], HF-specific quality-of-life (QOL) [Kansas City Cardiomyopathy Questionnaire (KCCQ)], and cognition [Montreal Cognitive Assessment (MOCA)] were examined., Results: ADHF participants accumulated a median 1,008 (IQR 896, 1,109) minutes of sedentary time, 88 (57, 139) minutes of light physical activity, and 10 (6, 25) minutes of moderate-to-vigorous physical activity per day. Sedentary time, light physical activity, or moderate-to-vigorous activity did not differ by sex or EF subtype. ADHF participants spent only 9% of awake time nonsedentary, compared to 34% and 27% for healthy adults and adults with chronic, stable HF, respectively. Among ADHF participants, SPPB, KCCQ, and MOCA scores did not differ among quartiles of total physical activity., Conclusions: Older patients recently hospitalized for ADHF have very low levels of physical activity and high levels of sedentary time, both of which may be potential targets for interventions in this high-risk population. Physical activity level was not significantly associated with objectively measured physical function, QOL, or cognition, suggesting that this measure provides independent information regarding the patient experience of living with HF., Trial Registration: NCT02196038, https://clinicaltrials.gov/ct2/show/NCT02196038., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Higher physical activity levels are associated with lower risks of cancer, cardiovascular disease, and diabetes, but associations with many common and less severe health conditions are not known. These conditions impose large health care burdens and reduce quality of life., Objectives: To investigate the association between accelerometer-measured physical activity and the subsequent risk of hospitalization for 25 common reasons for hospitalization and to estimate the proportion of these hospitalizations that might have been prevented if participants had higher levels of physical activity., Design, Setting, and Participants: This prospective cohort study used data from a subset of 81 717 UK Biobank participants aged 42 to 78 years. Participants wore an accelerometer for 1 week (between June 1, 2013, and December 23, 2015) and were followed up over a median (IQR) of 6.8 (6.2-7.3) years; follow-up for the current study ended in 2021 (exact date varied by location)., Exposures: Mean total and intensity-specific accelerometer-measured physical activity., Main Outcomes and Measures: Hospitalization for the most common health conditions. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% CIs for mean accelerometer-measured physical activity (per 1-SD increment) and risks of hospitalization for 25 conditions. Population-attributable risks were used to estimate the proportion of hospitalizations for each condition that might be prevented if participants increased their moderate to vigorous physical activity (MVPA) by 20 minutes per day., Results: Among 81 717 participants, the mean (SD) age at accelerometer assessment was 61.5 (7.9) years; 56.4% were female, and 97.0% self-identified as White. Higher levels of accelerometer-measured physical activity were associated with lower risks of hospitalization for 9 conditions: gallbladder disease (HR per 1 SD, 0.74; 95% CI, 0.69-0.79), urinary tract infections (HR per 1 SD, 0.76; 95% CI, 0.69-0.84), diabetes (HR per 1 SD, 0.79; 95% CI, 0.74-0.84), venous thromboembolism (HR per 1 SD, 0.82; 95% CI, 0.75-0.90), pneumonia (HR per 1 SD, 0.83; 95% CI, 0.77-0.89), ischemic stroke (HR per 1 SD, 0.85; 95% CI, 0.76-0.95), iron deficiency anemia (HR per 1 SD, 0.91; 95% CI, 0.84-0.98), diverticular disease (HR per 1 SD, 0.94; 95% CI, 0.90-0.99), and colon polyps (HR per 1 SD, 0.96; 95% CI, 0.94-0.99). Positive associations were observed between overall physical activity and carpal tunnel syndrome (HR per 1 SD, 1.28; 95% CI, 1.18-1.40), osteoarthritis (HR per 1 SD, 1.15; 95% CI, 1.10-1.19), and inguinal hernia (HR per 1 SD, 1.13; 95% CI, 1.07-1.19), which were primarily induced by light physical activity. Increasing MVPA by 20 minutes per day was associated with reductions in hospitalization ranging from 3.8% (95% CI, 1.8%-5.7%) for colon polyps to 23.0% (95% CI, 17.1%-28.9%) for diabetes., Conclusions and Relevance: In this cohort study of UK Biobank participants, those with higher physical activity levels had lower risks of hospitalization across a broad range of health conditions. These findings suggest that aiming to increase MVPA by 20 minutes per day may be a useful nonpharmaceutical intervention to reduce health care burdens and improve quality of life.

Background: The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes., Methods: White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4-6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength <27 kg and ALM index <7.0 kg/m 2 ), SDOC (grip strength <35.5 kg and gait speed <0.8 m/s) and Modified SDOC (grip strength <35.5 kg and gait speed <1.0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight; estimates were combined across cohorts using random-effects meta-analysis., Results: Mean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I 2 : 0.0%]; SDOC [2.75 (2.28, 3.31), I 2 : 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I 2 : 58.3%]., Conclusions: There was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes 1 . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel 2 ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries., (© 2022. The Author(s).)

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are currently under clinical development for treating anemia in chronic kidney disease (CKD), but it is important to monitor their cardiovascular safety. Genetic variants can be used as predictors to help inform the potential risk of adverse effects associated with drug treatments. We therefore aimed to use human genetics to help assess the risk of adverse cardiovascular events associated with therapeutically altered EPO levels to help inform clinical trials studying the safety of HIF-PHIs. By performing a genome-wide association meta-analysis of EPO (n = 6,127), we identified a cis-EPO variant (rs1617640) lying in the EPO promoter region. We validated this variant as most likely causal in controlling EPO levels by using genetic and functional approaches, including single-base gene editing. Using this variant as a partial predictor for therapeutic modulation of EPO and large genome-wide association data in Mendelian randomization tests, we found no evidence (at p < 0.05) that genetically predicted long-term rises in endogenous EPO, equivalent to a 2.2-unit increase, increased risk of coronary artery disease (CAD, OR [95% CI] = 1.01 [0.93, 1.07]), myocardial infarction (MI, OR [95% CI] = 0.99 [0.87, 1.15]), or stroke (OR [95% CI] = 0.97 [0.87, 1.07]). We could exclude increased odds of 1.15 for cardiovascular disease for a 2.2-unit EPO increase. A combination of genetic and functional studies provides a powerful approach to investigate the potential therapeutic profile of EPO-increasing therapies for treating anemia in CKD., Competing Interests: Declaration of interests C.E.H. was awarded an MRC iCASE studentship (MR/P016065/1), which was cofunded by GSK and the MRC for the duration of the study. GSK are undertaking clinical development into a novel PHI and have given permission to publish this work alongside an internal review of the manuscript. A.Y.C. is an employee of GSK, is a shareholder of GSK stock, and was involved in the study design, interpretation of the data, and writing of the paper. V.V.P. was an employee of GSK at the time of the study conception and design. He was involved in interpreting the data and writing of the paper and is a shareholder of GSK and Roche Holding AG stocks. D.M.W. was an employee of GSK at the time of the study conception and design and was involved in the interpretation of the data and writing of the paper. H.L.L. and M.A.N. received support from a consulting contract between Data Tecnica International and the National Institute on Aging (NIA), National Institutes of Health (NIH). They were involved in data analysis and review of the manuscript. N.V. is a full-time employee of Regeneron Pharmaceutical Inc. and receives stock options and restricted stock units as compensation. D.D.J. received support from the Center of Human Health and the Environment P30ESO25128 grant. F.I. is an AbbVie employee and receives stocks from AbbVie, which has not been involved in this work at any level., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Poor olfaction is associated with worse functional performance in older adults, but longitudinal evidence is lacking. We investigated poor olfaction in relation to longitudinal changes in physical functioning among community-dwelling older adults., Method: The analysis included 2 319 participants from the Health, Aging and Body Composition study (aged 71-82 years, 47.9% men, and 37.3% Blacks) who completed the Brief Smell Identification Test in 1999-2000. Olfaction was defined as good (test score 11-12), moderate (9-10), or poor (0-8). Physical functioning was assessed up to 4 times over 8 years, using the Short Physical Performance Battery (SPPB) and the Health Aging and Body Composition Physical Performance Battery (HABCPPB). We conducted joint model analyses and reported the differences in annual declines across olfaction groups., Results: During the follow-up, compared to those with good olfaction, older adults with poor olfaction had greater annual declines in both the SPPB score (-0.137, 95% CI: -0.186, -0.088) and all its subscales: standing balance (-0.068, 95% CI: -0.091, -0.044), chair stand (-0.046, 95% CI: -0.070, -0.022), and gait speed (-0.022, 95% CI: -0.042, -0.001). A similar observation was made for the HABCPPB score (difference in annual decline: -0.032, 95% CI: -0.042, -0.021). These findings are robust and cannot be explained by measured confounding from demographics, lifestyle factors, and chronic diseases or by potential biases due to death and loss of follow-up. Similar associations were observed across subgroups of sex, race, and self-reported general health status., Conclusion: This study provides the first epidemiological evidence that poor olfaction predicts a faster decline in physical functioning. Future studies should investigate potential mechanisms., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Higher amounts of physical activity are associated with increased longevity. However, whether different leisure time physical activity types are differentially associated with mortality risk is not established., Objectives: To examine whether participation in equivalent amounts of physical activity (7.5 to <15 metabolic equivalent of task [MET] hours per week) through different activity types is associated with mortality risk and to investigate the shape of the dose-response association., Design, Setting, and Participants: Participants in this cohort were respondents from the National Institutes of Health-AARP Diet and Health Study who completed the follow-up questionnaire between 2004 and 2005. This questionnaire collected data on weekly durations of different types of physical activities. Mortality was ascertained through December 31, 2019., Exposures: MET hours per week spent participating in the following activities: running, cycling, swimming, other aerobic exercise, racquet sports, golf, and walking for exercise., Main Outcomes and Measures: All-cause, cardiovascular, and cancer mortality. Separate multivariable-adjusted Cox proportional hazards regression models were fitted to estimate hazard ratios (HRs) and 95% CIs of mortality for each of the 7 types of leisure time physical activities, as well as the sum of these activities., Results: A total of 272 550 participants (157 415 men [58%]; mean [SD] age at baseline, 70.5 [5.4] years [range, 59-82 years]) provided information on types of leisure time activity, and 118 153 (43%) died during a mean (SD) follow-up of 12.4 (3.9) years. In comparison with those who did not participate in each activity, 7.5 to less than 15 MET hours per week of racquet sports (HR, 0.84; 95% CI, 0.75-0.93) and running (HR, 0.85; 95% CI, 0.78-0.92) were associated with the greatest relative risk reductions for all-cause mortality, followed by walking for exercise (HR, 0.91; 95% CI, 0.89-0.93), other aerobic activity (HR, 0.93; 95% CI, 0.90-0.95), golf (HR, 0.93; 95% CI, 0.90-0.97), swimming (HR, 0.95; 95% CI, 0.92-0.98), and cycling (HR, 0.97; 95% CI, 0.95-0.99). Each activity showed a curvilinear dose-response association with mortality risk; low MET hours per week of physical activity for any given activity type were associated with a large reduction in mortality risk, with diminishing returns for each increment in activity thereafter. Associations were similar for cardiovascular and cancer mortality., Conclusions and Relevance: This cohort study of older individuals found differences between different types of leisure time activities and mortality risk, but there were significant associations between participating in 7.5 to less than 15 MET hours per week of any activity and mortality risk.

Background: Depression is common in Parkinson's disease (PD). It is however unclear when and how depressive symptoms develop and progress in the course of PD development., Objective: To assess how depressive symptoms evolve in PD, using repeated measures., Methods: In 2994 older adults, ages 70-79 years, depressive symptoms were assessed 8 times over 11 years using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). For each PD patient at each time point, we calculated the difference between CESD-10 score and its expected value estimated based on data from individuals without PD, and then realigned the time scale in reference to the year of PD diagnosis. We examined longitudinal changes in CESD-10 scores before and after PD diagnosis using a joint modeling approach to account for competing risks of non-participation and death., Results: A total of 79 PD patients were identified at enrollment or during the follow-up, with repeatedly assessed depressive symptom data up to 9 years before and after PD diagnosis. We found a monotonic trend of increasing CESD-10 score in PD patients throughout the observational period (p = 0.002). The observed scores became higher than expected approximately 7 years before PD diagnosis and significantly different 1 year before PD diagnosis., Conclusions: Increasing depressive symptomatology appears to precede PD diagnosis by a few years., Competing Interests: The authors have declared that no competing interests exist.

Background: The joint associations of total and intensity-specific physical activity with obesity in relation to all-cause mortality risk are unclear., Methods: We included 34 492 adults (72% women, median age 62.1 years, 2034 deaths during follow-up) in a harmonised meta-analysis of eight population-based prospective cohort studies with mean follow-up ranging from 6.0 to 14.5 years. Standard body mass index categories were cross-classified with sample tertiles of device-measured total, light-to-vigorous and moderate-to-vigorous physical activity and sedentary time. In five cohorts with waist circumference available, high and low waist circumference was combined with tertiles of moderate-to-vigorous physical activity., Results: There was an inverse dose-response relationship between higher levels of total and intensity-specific physical activity and mortality risk in those who were normal weight and overweight. In individuals with obesity, the inverse dose-response relationship was only observed for total physical activity. Similarly, lower levels of sedentary time were associated with lower mortality risk in normal weight and overweight individuals but there was no association between sedentary time and risk of mortality in those who were obese. Compared with the obese-low total physical activity reference, the HRs were 0.59 (95% CI 0.44 to 0.79) for normal weight-high total activity and 0.67 (95% CI 0.48 to 0.94) for obese-high total activity. In contrast, normal weight-low total physical activity was associated with a higher risk of mortality compared with the obese-low total physical activity reference (1.28; 95% CI 0.99 to 1.67)., Conclusions: Higher levels of physical activity were associated with lower risk of mortality irrespective of weight status. Compared with obesity-low physical activity, there was no survival benefit of being normal weight if physical activity levels were low., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Stress, social isolation, and changes in health behaviors during the COVID-19 pandemic period may have a lasting influence on health. Here, the correlation between current or prior demographic, social and health related characteristics, including psychosocial factors with perceived impact of the COVID-19 pandemic assessed by questionnaire during the early pandemic period is evaluated among 770 participants of the Baltimore Longitudinal Study of Aging. In multinomial logistic regression models participants with higher pre-pandemic personal mastery, a construct related to self-efficacy, were more likely to report "both positive and negative" impact of the pandemic than a solely "negative" impact (OR: 2.17, 95% CI: 1.29-3.65). Higher perceived stress and frequent contact with family prior to the pandemic were also associated with pandemic impact. These observations highlight the relevance of psychosocial factors in the COVID-19 pandemic experience and identify characteristics that may inform interventions in future public health crises., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality., Methods: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models., Findings: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28])., Interpretation: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity., Funding: US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests AEP and CFP received funding for this project from US Centers for Disease Control and Prevention (CDC) Intergovernmental Personnel Act Agreement. BJJ receives grant funding through the British Heart Foundation. MRC and RSV have received grant funding through National Heart Lung and Blood Institute, National Institutes of Health (NIH). I-ML, KPG, and PP receive grant funding through NIH. KRE receives grant funding through NIH, Robert Wood Johnson Foundation, US Department of Transportation, and North Carolina Department of Transportation; receives consulting fees from NIH; and is on the Board of Trustees with the American College of Sports Medicine. DD has received grant funding through German Research Foundation, travel expenses for 10th International Meeting on Ageing, honoraria for being an instructor at Boston University School of Public Health, been an unpaid speaker for German Society of Epidemiology, and been an unpaid member of the Alumni Leadership Council of Boston University School of Public Health. JS receives grant funding through National Institutes on Aging, NIH. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: In older adults, kidney function declines with age. People with advanced kidney diseases may have poor olfaction. However, it is unclear whether poor olfaction is a marker for declining renal function or future risk of chronic kidney disease (CKD). We therefore investigated olfaction in relation to kidney function and risk of CKD., Methods: These secondary data analyses were limited to participants of the year 3 clinical visit of the Health Aging and Body Composition Study. The analytic sample size varied between 1427 to 2531, depending on participant eligibility and data availability for each analysis. Olfaction was tested using the Brief Smell Identification Test (B-SIT), defined as anosmia (score≤6), hyposmia (7-8), moderate (9-10), and good function (10-11) at baseline. We estimated glomerular filter rate (eGFR) at baseline and seven years later using the CKD-EPI creatinine-cystatin C equation, and defined incident CKD as eGFR<60 ml/min/1.73m2 and eGFR decline ≥1 ml/min/1.73m2/year. Further, we identified CKD hospitalization events from hospitalization and death records. We used inverse probability weighting and weighted multivariable regressions to account for censoring in the prospective analyses and used absolute risk regression to account for competing risk of death., Results: At baseline, compared to participants with good olfaction, the multivariable-adjusted mean eGFR was 3.00 ml/min/1.73m2 lower (95% confidence interval (CI): -5.25, -0.75) for those with anosmia and 1.87 lower (95% CI: -3.94, 0.21) for those with hyposmia with a P for linear trend < 0.001. Those with anosmia at baseline was had a significantly lower eGFR seven years later (-5.31, 95% CI: -8.58, -2.04, P for trend = 0.002), but the association was attenuated after further accounting for baseline eGFR (-2.37, 95%CI: -4.91, 0.16, P for linear trend = 0.147). Olfactory function was not associated with incident CKD or CKD hospitalization., Conclusion: In older adults > age 70 years, poor olfaction is associated with lower kidney function, but not future CKD risk. These associations should be further investigated in relatively younger population., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Physical inactivity is a risk factor for premature mortality and several non-communicable diseases. The purpose of this study was to estimate the global burden associated with physical inactivity, and to examine differences by country income and region., Methods: Population-level, prevalence-based population attributable risks (PAR) were calculated for 168 countries to estimate how much disease could be averted if physical inactivity were eliminated. We calculated PARs (percentage of cases attributable to inactivity) for all-cause mortality, cardiovascular disease mortality and non-communicable diseases including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers of the bladder, breast, colon, endometrium, oesophagus, stomach and kidney., Results: Globally, 7.2% and 7.6% of all-cause and cardiovascular disease deaths, respectively, are attributable to physical inactivity. The proportions of non-communicable diseases attributable to physical inactivity range from 1.6% for hypertension to 8.1% for dementia. There was an increasing gradient across income groups; PARs were more than double in high-income compared with low-income countries. However, 69% of total deaths and 74% of cardiovascular disease deaths associated with physical inactivity are occurring in middle-income countries, given their population size. Regional differences were also observed, with the PARs occurring in Latin America/Caribbean and high-income Western and Asia-Pacific countries, and the lowest burden occurring in Oceania and East/Southeast Asia., Conclusion: The global burden associated with physical inactivity is substantial. The relative burden is greatest in high-income countries; however, the greatest number of people (absolute burden) affected by physical inactivity are living in middle-income countries given the size of their populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This paper describes the Women's Health Accelerometry Collaboration, a consortium of two prospective cohort studies of women age 62 years or older, harmonised to explore the association of accelerometer-assessed physical activity and sedentary behaviour with cancer incidence and mortality., Participants: A total of 23 443 women (age mean 73.4, SD 6.8) living in the USA and participating in an observational study were included; 17 061 from the Women's Health Study (WHS) and 6382 from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health (WHI/OPACH) Study., Findings to Date: Accelerometry, cancer outcomes and covariate harmonisation was conducted to align the two cohort studies. Physical activity and sedentary behaviour were measured using similar procedures with an ActiGraph GT3X+ accelerometer, worn at the hip for 1 week, during 2011-2014 for WHS and 2012-2014 for WHI/OPACH. Cancer outcomes were ascertained via ongoing surveillance using physician adjudicated cancer diagnosis. Relevant covariates were measured using questionnaire or physical assessments. Among 23 443 women who wore the accelerometer for at least 10 hours on a single day, 22 868 women wore the accelerometer at least 10 hours/day on ≥4 of 7 days. The analytical sample (n=22 852) averaged 4976 (SD 2669) steps/day and engaged in an average of 80.8 (SD 46.5) min/day of moderate-to-vigorous, 105.5 (SD 33.3) min/day of light high and 182.1 (SD 46.1) min/day of light low physical activity. A mean of 8.7 (SD 1.7) hours/day were spent in sedentary behaviour. Overall, 11.8% of the cohort had a cancer diagnosis (other than non-melanoma skin cancer) at the time of accelerometry measurement. During an average of 5.9 (SD 1.6) years of follow-up, 1378 cancer events among which 414 were fatal have occurred., Future Plans: Using the harmonised cohort, we will access ongoing cancer surveillance to quantify the associations of physical activity and sedentary behaviour with cancer incidence and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aging leads to profound changes in glucose homeostasis, weight, and adiposity, which are considered good predictors of health and survival in humans. Direct evidence that these age-associated metabolic alterations are recapitulated in animal models is lacking, impeding progress to develop and test interventions that delay the onset of metabolic dysfunction and promote healthy aging and longevity. We compared longitudinal trajectories, rates of change, and mortality risks of fasting blood glucose, body weight, and fat mass in mice, nonhuman primates, and humans throughout their lifespans and found similar trajectories of body weight and fat in the three species. In contrast, fasting blood glucose decreased late in life in mice but increased over the lifespan of nonhuman primates and humans. Higher glucose was associated with lower mortality in mice but higher mortality in nonhuman primates and humans, providing a cautionary tale for translating age-associated metabolic changes from mice to humans., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Objective: To examine the joint associations of daily time spent in different intensities of physical activity, sedentary behaviour and sleep with all-cause mortality., Methods: Federated pooled analysis of six prospective cohorts with device-measured time spent in different intensities of physical activity, sedentary behaviour and sleep following a standardised compositional Cox regression analysis., Participants: 130 239 people from general population samples of adults (average age 54 years) from the UK, USA and Sweden., Main Outcome: All-cause mortality (follow-up 4.3-14.5 years)., Results: Studies using wrist and hip accelerometer provided statistically different results (I 2 =92.2%, Q-test p<0.001). There was no association between duration of sleep and all-cause mortality, HR=0.96 (95% CI 0.67 to 1.12). The proportion of time spent in moderate to vigorous physical activity was significantly associated with lower risk of all-cause mortality (HR=0.63 (95% CI 0.55 to 0.71) wrist; HR=0.93 (95% CI 0.87 to 0.98) hip). A significant association for the ratio of time spent in light physical activity and sedentary time was only found in hip accelerometer-based studies (HR=0.5, 95% CI 0.42 to 0.62). In studies based on hip accelerometer, the association between moderate to vigorous physical activity and mortality was modified by the balance of time spent in light physical activity and sedentary time., Conclusion: This federated analysis shows a joint dose-response association between the daily balance of time spent in physical activity of different intensities and sedentary behaviour with all-cause mortality, while sleep duration does not appear to be significant. The strongest association is with time spent in moderate to vigorous physical activity, but it is modified by the balance of time spent in light physical activity relative to sedentary behaviour., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: While physical activity has consistently been associated with decreased mortality rates, it remains unknown if there is a single "ideal" combination of time in physical activities of different intensities and sedentary behavior (SB) associated with the lowest rate. This study examined the associations of combinations of time in moderate-to-vigorous intensity (MVPA), higher-light intensity (HLPA), lower-light intensity activities (LLPA), and SB with mortality rates in older women., Methods: This prospective cohort study included 16,676 older women from throughout the United States enrolled in the Women's Health Study. Women wore accelerometers on their hip from 2011 to 2015 and were followed through 2017 (mean (SD) of 4.3 (1.1) years). Deaths were confirmed with medical records, death certificates, or the National Death Index. Compositional Cox regression models were used., Results: The mean (SD) age was 72 (5.7) years at accelerometer wear; 503 women died. Compared to the least active women (mean, 3 min/day MVPA, 27 min/day HLPA, 162 min/day LLPA, and 701 min/day SB): compositional models showed an inverse L-shaped dose-response association of MVPA replacing other behaviors with mortality rates mortality rates (P = .02); SB relative to LLPA, HLPA, and MVPA was directly associated with mortality rates in a curvilinear dose-response manner (P < .001); replacing 10 min of SB for MVPA (HR (95% CI) = .86 (.73-.98)) or for HLPA (HR (95% CI.94 (.88-1.00)) associated with 14 and 6% lower mortality rates, respectively; a 47% risk reduction (HR [95% CI] = .53 [.42-.64]) was observed among women meeting physical activity guidelines (mean, 36 min/day MVPA, 79 min/day HLPA, 227 min/day LLPA and 549 min/day SB); and similar mortality rate reductions of 43% (HR (95% CI) = .57 (.41-.73)) were observed with increases in HLPA and LLPA without increasing MVPA, e.g., reallocating SB to 90 min/day of HLPA plus 120 min/day of LLPA., Conclusions: There was no "ideal" combination of physical activities of different intensities and SB associated with the lowest mortality rates. Of particular relevance to older women, replacing SB with light intensity activity was associated with lower mortality rates, and "mixing and matching" times in different intensities yielded equivalent mortality risk reductions., (© 2021. The Author(s).)

Background: Weight loss is common in Parkinson's disease (PD). However, little is known about when it starts, how PD changes as it progresses, and whether there is a differential loss of lean or fat mass. The objective of this study was to examine how body composition changes before and after PD diagnosis., Methods: In the Health, Aging, and Body Composition study (n = 3075; age range, 70-79 years), body composition was assessed using dual-energy x-ray absorptiometry on an annual or biennial basis from year 1 to year 10. For each PD case each year, we calculated the difference between their actual body composition measures and expected values had they not developed PD. Using linear mixed models with crossed random effects, we further examined the trend of change in body composition measures before and after PD diagnosis., Results: A total of 80 PD cases were identified in this cohort. Compared with their expected values, PD cases began to lose total and fat mass about 6-7 years before diagnosis, although the differences were not statistically significant until 3-5 years after diagnosis. The loss was substantial and persistent, with statistically significant trends of loss for total body mass (P = 0.008), fat mass (P = 0.001), and percentage fat (P < 0.001). In comparison, lean mass was stable throughout the follow-up (P = 0.16). Overall, 96% of the body mass loss in PD cases was from the loss of fat mass., Conclusions: In this longitudinal analysis with objective measures of body composition, we found persistent weight loss in PD cases, predominantly in fat mass, starting a few years before diagnosis. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Accelerometers' accuracy for sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) classification depends on accelerometer placement, data processing, activities, and sample characteristics. As intensities differ by age, this study sought to determine intensity cut-points at various wear locations people more than 70 years old. Data from 59 older adults were used for calibration and from 21 independent participants for cross-validation purposes. Participants wore accelerometers on their hip and wrists while performing activities and having their energy expenditure measured with portable calorimetry. ST and MVPA were defined as ≤1.5 metabolic equivalents (METs) and ≥3 METs (1 MET = 2.8 mL/kg/min), respectively. Receiver operator characteristic (ROC) analyses showed fair-to-good accuracy (area under the curve [AUC] = 0.62-0.89). ST cut-points were 7 m g (cross-validation: sensitivity = 0.88, specificity = 0.80) and 1 count/5 s (cross-validation: sensitivity = 0.91, specificity = 0.96) for the hip; 18 m g (cross-validation: sensitivity = 0.86, specificity = 0.86) and 102 counts/5 s (cross-validation: sensitivity = 0.91, specificity = 0.92) for the non-dominant wrist; and 22 m g and 175 counts/5 s (not cross-validated) for the dominant wrist. MVPA cut-points were 14 m g (cross-validation: sensitivity = 0.70, specificity = 0.99) and 54 count/5 s (cross-validation: sensitivity = 1.00, specificity = 0.96) for the hip; 60 m g (cross-validation: sensitivity = 0.83, specificity = 0.99) and 182 counts/5 s (cross-validation: sensitivity = 1.00, specificity = 0.89) for the non-dominant wrist; and 64 m g and 268 counts/5 s (not cross-validated) for the dominant wrist. These cut-points can classify ST and MVPA in older adults from hip- and wrist-worn accelerometers.

Background: Poor olfaction is common in older adults and might signify broader health implications beyond its role in neurodegeneration. We aimed to evaluate the association of poor olfaction and the risk of any, first-ever, and recurrent pneumonia hospitalisation, as well as death due to pneumonia, in a biracial, community-based cohort of older adults., Methods: For this cohort study, we included participants from the Health, Aging and Body Composition study who were followed up with annual clinic or home visits and semi-annual or quarterly telephone interviews. These individuals completed an olfaction test using the Brief Smell Identification Test (B-SIT) in 1999-2000. Olfaction was defined as good (test score 11-12), moderate (9-10), or poor (0-8). Participants were followed up from baseline until the date of pneumonia hospitalisation, death, last contact, or the end of 13 years of follow-up, whichever came first. We excluded participants who had missing B-SIT scores or missing covariate data from our primary analysis. The primary outcome was total and first-ever hospitalisation due to pneumonia., Findings: 2494 participants aged 71-82 years (mean 75·6 years, SD 2·8) were included in our primary analysis; 1207 (48·4%) were men, 1287 (51·6%) were women; 956 (38·3%) were Black, and 1538 (61·7%) were White. During a median of 12·1 years (IQR 7·4-13·0) of follow-up, we identified a total of 801 hospitalisations due to pneumonia from 537 (21·5%) participants. Of these, 357 (66·5%) had their first-ever event during follow-up. After accounting for potential confounding from demographics, lifestyle factors, health-related conditions, and the competing risk of death, participants with poor olfaction had a higher rate of total pneumonia hospitalisations than that of those with good olfaction (intensity ratio [IR] 1·46, 95% CI 1·22-1·75; p<0·0001). Additionally, poor olfaction was associated with a higher rate for first-ever pneumonia hospitalisation (hazard ratio [HR] 1·37, 95% CI 1·06-1·79; p=0·019). Moderate olfaction was not associated with a higher rate of total (IR 1·05, 0·87-1·26; p=0·62) or first-ever pneumonia hospitalisation (HR 0·97, 0·74-1·26; p=0·79). Results were similar across sex or race subgroups., Interpretation: To our knowledge, this study provides the first epidemiological evidence that poor olfaction is associated with a long-term higher risk of pneumonia in older adults. Future studies should independently confirm this observation, investigate potential mechanisms, and understand its implications for the health of older adults., Funding: Michigan State University., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aging is associated with functional and metabolic decline and is a risk factor for all noncommunicable diseases. Even though mice are routinely used for modeling human aging and aging-related conditions, no comprehensive assessment to date has been conducted on normative mouse aging. To address this gap, the Study of Longitudinal Aging in Mice (SLAM) was designed and implemented by the National Institute on Aging (NIA/NIH) as the mouse counterpart to the Baltimore Longitudinal Study of Aging (BLSA). In this manuscript, we describe the premise, study design, methodologies, and technologies currently employed in SLAM. We also discuss current and future study directions. In this large population mouse study, inbred C57BL/6J and outbred UM-HET3 mice of both sexes are longitudinally evaluated for functional, phenotypic, and biological health, and collection of biospecimens is conducted throughout their life span. Within the longitudinal cohorts, a cross-sectional arm of the study has also been implemented for the well-controlled collection of tissues to generate a biorepository. SLAM and studies stemming from SLAM seek to identify and characterize phenotypic and biological predictors of mouse aging and age-associated conditions, examine the degrees of functional and biomolecular variability that occur within inbred and genetically heterogeneous mouse populations with age, and assess whether these changes are consistent with alterations observed in human aging in BLSA. The findings from these studies will be critical for evaluating the utility of mouse models for studying different aspects of aging, both in terms of interpreting prior findings and designing and implementing future studies., (Published by Oxford University Press on behalf of The Gerontological Society of America 2020.)

Physical activity (PA) is associated with greater fatigability in older adults; little is known about magnitude, shape, timing and variability of the entire 24-h rest-activity rhythm (RAR) associated with fatigability. We identified which features of the 24-h RAR pattern were independently and jointly associated with greater perceived physical fatigability (Pittsburgh Fatigability Scale, PFS, 0-50) in older adults ( n = 181, 71.3 ± 6.7 years). RARs were characterized using anti-logistic extended cosine models and 4-h intervals of PA means and standard deviations across days. A K-means clustering algorithm approach identified four profiles of RAR features: "Less Active/Robust", "Earlier Risers", "More Active/Robust" and "Later RAR". Quantile regression tested associations of each RAR feature/profile on median PFS adjusted for age, sex, race, body mass index and depression symptomatology. Later rise times (up mesor; β = 1.38, p = 0.01) and timing of midpoint of activity (acrophase; β = 1.29, p = 0.01) were associated with higher PFS scores. Lower PA between 4 a.m. and 8 a.m. was associated with higher PFS scores (β = -4.50, p = 0.03). "Less Active/Robust" (β = 6.14, p = 0.01) and "Later RAR" (β = 3.53, p = 0.01) patterns were associated with higher PFS scores compared to "Earlier Risers". Greater physical fatigability in older adults was associated with dampened, more variable, and later RARs. This work can guide development of interventions aimed at modifying RARs to reduce fatigability in older adults.

We investigated how baseline values and rates of decline in components of sarcopenia and other body composition parameters relate to adverse clinical outcomes using the Health, Aging, and Body Composition Study. 2689 participants aged 70-79 years were studied. Appendicular lean mass, whole body fat mass, and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. Baseline values and 2-3 year conditional changes (independent of baseline) in each characteristic were examined as predictors of mortality, hospital admission, low trauma fracture, and recurrent falls in the subsequent 10-14 years using Cox regression (generalized estimating equations used for recurrent falls) with adjustment for sex, ethnicity, age, and potential confounders. Lower levels and greater declines in all parameters (excluding hip BMD level) were associated (p < 0.05) with increased rates of mortality; fully-adjusted hazard ratios per SD lower gait speed and grip strength were 1.27 (95% CI 1.19, 1.36) and 1.14 (1.07, 1.21), respectively. Risk factors of hospital admission included lower levels and greater declines in gait speed and grip strength, and greater declines in hip BMD. Lower levels and greater declines in fat mass and hip BMD were associated with low trauma fracture. Lower gait speed, higher fat mass, and both lower levels and greater declines in grip strength were related to recurrent falls. Lower baseline levels and greater declines in musculoskeletal parameters were related to adverse outcomes. Interventions to maximize peak levels in earlier life and reduce rates of age-related decline may reduce the burden of disease in this age group.

Background: Literature shows an inverse association of circulating cholesterol level with the risk of Parkinson's disease (PD); this finding has important ramifications, but its interpretation has been debated., Objective: To longitudinally examine how blood total cholesterol changes during the development of PD., Methods: In the Health, Aging and Body Composition study (n = 3,053, 73.6±2.9 years), blood total cholesterol was measured at clinic visit years 1, 2, 4, 6, 8, 10, and 11. We first examined baseline cholesterol in relation to PD risk, adjusting for potential confounders and competing risk of death. Then, by contrasting the observed with expected cholesterol levels, we examined the trajectory of changes in total cholesterol before and after disease diagnosis., Results: Compared to the lowest tertile of baseline total cholesterol, the cumulative incidence ratio of PD and 95% confidence interval was 0.41 (0.20, 0.86) for the second tertile, and 0.69 (0.35, 1.35) for the third tertile. In the analysis that examined change of total cholesterol level before and after PD diagnosis, we found that its level began to decrease in the prodromal stage of PD and became statistically lower than the expected values ∼4 years before disease diagnosis (observed-expected difference, -6.68 mg/dL (95% confidence interval: -13.14, -0.22)). The decreasing trend persisted thereafter; by year-6 post-diagnosis, the difference increased to -13.59 mg/dL (95% confidence interval: -22.12, -5.06), although the linear trend did not reach statistical significance (p = 0.10)., Conclusion: Circulating total cholesterol began to decrease in the prodromal stage of PD, which may in part explain its reported inverse association with PD.

Purpose: Confounding due to poor health is a concern in accelerometer-based studies of physical activity and health, but detailed investigations of this source of bias are lacking., Methods: US adults (n = 4840) from the National Health and Nutrition Examination Survey (2003 to 2006) wore an accelerometer for 1 to 7 d (mean = 5.7 d) and were followed for mortality through 2015. Logistic regression was used to examine odds ratios between poor health (chronic conditions, self-reported health, mobility limitations, frailty) and low physical activity levels; Cox models were used to estimate adjusted hazard ratios (HR) and 95% CI for mortality associations for a 1 h·d increase in moderate-to-vigorous-intensity physical activity (MVPA) using two commonly used cut-points (MVPA760, MVPA2020). Modeling scenarios with shorter and longer follow-up time, increasing adjustment for poor health, by age group, and after excluding early years of follow-up were used to assess bias., Results: Over a mean of 10.1 yr of follow-up, 1165 deaths occurred. Poor health was associated with low MVPA760 levels and increased mortality risk. In fully adjusted MVPA760 models, HR was 26% stronger comparing 0 to 4 yr (HR = 0.46) with 0 to 12 yr of follow-up (HR = 0.62), particularly in older adults (65 yr and older). Increasing statistical adjustment for poor health attenuated MVPA760 associations by 13% to 15%, and exclusion of the first 2 yr of follow-up had limited effects. Comparable results were obtained with the MVPA2020 cut-point., Conclusions: We did not find evidence that confounding by health status resulted in entirely spurious MVPA-mortality associations; however, potential bias was appreciable in modeling scenarios involving shorter follow-up (<6 yr), older adults, and more limited statistical adjustment for poor health. The strength of MVPA-mortality associations in studies reflecting these scenarios should be interpreted cautiously.

Objectives: To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality., Methods: We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.0 to 14.5 years during which 3451 participants died (7.8% mortality rate). Associations between different combinations of moderate-to-vigorous intensity physical activity (MVPA) and sedentary time were analysed at study level using Cox proportional hazards regression analysis and summarised using random effects meta-analysis., Results: Across cohorts, the average time spent sedentary ranged from 8.5 hours/day to 10.5 hours/day and 8 min/day to 35 min/day for MVPA. Compared with the referent group (highest physical activity/lowest sedentary time), the risk of death increased with lower levels of MVPA and greater amounts of sedentary time. Among those in the highest third of MVPA, the risk of death was not statistically different from the referent for those in the middle (16%; 95% CI 0.87% to 1.54%) and highest (40%; 95% CI 0.87% to 2.26%) thirds of sedentary time. Those in the lowest third of MVPA had a greater risk of death in all combinations with sedentary time; 65% (95% CI 1.25% to 2.19%), 65% (95% CI 1.24% to 2.21%) and 263% (95% CI 1.93% to 3.57%), respectively., Conclusion: Higher sedentary time is associated with higher mortality in less active individuals when measured by accelerometry. About 30-40 min of MVPA per day attenuate the association between sedentary time and risk of death, which is lower than previous estimates from self-reported data., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Poor sense of smell in older adults may lead to weight loss, which may further contribute to various adverse health outcomes. However, empirical prospective evidence is lacking. We aimed to longitudinally assess whether poor olfaction is associated with changes in body composition among older adults., Methods: A total of 2,390 participants from the Health ABC Study had their olfaction assessed using the Brief Smell Identification Test in 1999-2000. Based on the test score, olfaction was defined as poor (0-8), moderate (9-10), or good (11-12). Total body mass, lean mass, and fat mass were measured by dual-energy X-ray absorptiometry annually or biennially from 1999 to 2007., Results: At baseline, compared to participants with good olfaction, those with poor olfaction weighed on average 1.67 kg less (95% CI: -2.92, -0.42) in total mass, 0.53 kg less (95% CI: -1.08, 0.02) in lean mass, and 1.14 kg less (95% CI: -1.96, -0.31) in fat mass. In longitudinal analyses, compared to participants with good olfaction, those with poor olfaction had a greater annual decline in both total mass (-234 g, 95% CI: -442, -26) and lean mass (-139 g, 95% CI: -236, -43). They also tended to have a greater annual loss of fat mass (-113 g, 95% CI: -285, 59), but the difference was not statistically significant., Conclusions: Our results indicate poor olfaction is associated with lower body weight and greater weight loss in older adults. It is imperative for future studies to investigate potential underlying mechanisms and associated adverse health consequences., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Musculoskeletal disorders are common among older people. Preventive strategies require understanding of age-related changes in strength, function and body composition, including how they interrelate. We have described, and examined associations between, 9-year changes in these parameters among 2917 Health, Aging and Body Composition Study participants (aged 70-79 years). Appendicular lean mass (ALM), whole body fat mass and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. For each characteristic annualised percentage changes were calculated; measures of conditional change (independent of baseline) were derived and their interrelationships were examined using Pearson correlations; proportion of variance at 9-year follow-up explained by baseline level was estimated; and mean trajectories in relation to age were estimated using linear mixed models. Analyses were stratified by sex. Median [lower quartile, upper quartile] annual percentage declines were grip strength (1.5 [0.0, 2.9]), gait speed (2.0 [0.6, 3.7]), ALM (0.7 [0.1, 1.4]), fat mass (0.4 [- 1.1, 1.9]) and hip BMD (0.5 [0.0, 1.1]). Declines were linear for ALM and accelerated over time for other characteristics. Most conditional change measures were positively correlated, most strongly between ALM, fat mass and hip BMD (r > 0.28). Proportion of variation at follow-up explained by baseline was lower for grip strength and gait speed (39-52%) than other characteristics (69-86%). Strength and function declined more rapidly, and were less correlated between baseline and follow-up, than measures of body composition. Therefore, broader intervention strategies to prevent loss of strength and function in later life are required as those targeting body composition alone may be insufficient.

Background: Best-practice early interventions to increase physical activity (PA) in children with overweight and obesity should be both feasible and evidence based. Walking is a basic human movement pattern that is practical, cost-effective, and does not require complex movement skills. However, there is still a need to investigate how much walking-as a proportion of total PA level-is performed by children who are overweight and obese in order to determine its utility as a public health strategy., Objective: This study aimed to (1) investigate the proportion of overall PA indicators that are explained by step-based metrics and (2) study step accumulation patterns relative to achievement of public health recommendations in children who are overweight and obese., Methods: A total of 105 overweight and obese children (mean 10.1 years of age [SD 1.1]; 43 girls) wore hip-worn accelerometers for 7 days. PA volumes were derived using the daily average of counts per 15 seconds, categorized using standard cut points for light-moderate-vigorous PA (LMVPA) and moderate-to-vigorous PA (MVPA). Derived step-based metrics included volume (steps/day), time in cadence bands, and peak 1-minute, 30-minute, and 60-minute cadences., Results: Steps per day explained 66%, 40%, and 74% of variance for counts per 15 seconds, LMVPA, and MVPA, respectively. The variance explained was increased up to 80%, 92%, and 77% by including specific cadence bands and peak cadences. Children meeting the World Health Organization recommendation of 60 minutes per day of MVPA spent less time at zero cadence and more time in cadence bands representing sporadic movement to brisk walking (ie, 20-119 steps/min) than their less-active peers., Conclusions: Step-based metrics, including steps per day and various cadence-based metrics, seem to capture a large proportion of PA for children who are overweight and obese. Given the availability of pedometers, step-based metrics could be useful in discriminating between those children who do or do not achieve MVPA recommendations., Trial Registration: ClinicalTrials.gov NCT02295072; https://clinicaltrials.gov/ct2/show/NCT02295072., (©Jairo H Migueles, Cristina Cadenas-Sanchez, Elroy J Aguiar, Pablo Molina-Garcia, Patricio Solis-Urra, Jose Mora-Gonzalez, Eduardo García-Mármol, Eric J Shiroma, Idoia Labayen, Palma Chillón, Marie Löf, Catrine Tudor-Locke, Francisco B Ortega. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 28.04.2020.)

Importance: It is unclear whether the number of steps per day and the intensity of stepping are associated with lower mortality., Objective: Describe the dose-response relationship between step count and intensity and mortality., Design, Setting, and Participants: Representative sample of US adults aged at least 40 years in the National Health and Nutrition Examination Survey who wore an accelerometer for up to 7 days ( from 2003-2006). Mortality was ascertained through December 2015., Exposures: Accelerometer-measured number of steps per day and 3 step intensity measures (extended bout cadence, peak 30-minute cadence, and peak 1-minute cadence [steps/min]). Accelerometer data were based on measurements obtained during a 7-day period at baseline., Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular disease (CVD) and cancer mortality. Hazard ratios (HRs), mortality rates, and 95% CIs were estimated using cubic splines and quartile classifications adjusting for age; sex; race/ethnicity; education; diet; smoking status; body mass index; self-reported health; mobility limitations; and diagnoses of diabetes, stroke, heart disease, heart failure, cancer, chronic bronchitis, and emphysema., Results: A total of 4840 participants (mean age, 56.8 years; 2435 [54%] women; 1732 [36%] individuals with obesity) wore accelerometers for a mean of 5.7 days for a mean of 14.4 hours per day. The mean number of steps per day was 9124. There were 1165 deaths over a mean 10.1 years of follow-up, including 406 CVD and 283 cancer deaths. The unadjusted incidence density for all-cause mortality was 76.7 per 1000 person-years (419 deaths) for the 655 individuals who took less than 4000 steps per day; 21.4 per 1000 person-years (488 deaths) for the 1727 individuals who took 4000 to 7999 steps per day; 6.9 per 1000 person-years (176 deaths) for the 1539 individuals who took 8000 to 11 999 steps per day; and 4.8 per 1000 person-years (82 deaths) for the 919 individuals who took at least 12 000 steps per day. Compared with taking 4000 steps per day, taking 8000 steps per day was associated with significantly lower all-cause mortality (HR, 0.49 [95% CI, 0.44-0.55]), as was taking 12 000 steps per day (HR, 0.35 [95% CI, 0.28-0.45]). Unadjusted incidence density for all-cause mortality by peak 30 cadence was 32.9 per 1000 person-years (406 deaths) for the 1080 individuals who took 18.5 to 56.0 steps per minute; 12.6 per 1000 person-years (207 deaths) for the 1153 individuals who took 56.1 to 69.2 steps per minute; 6.8 per 1000 person-years (124 deaths) for the 1074 individuals who took 69.3 to 82.8 steps per minute; and 5.3 per 1000 person-years (108 deaths) for the 1037 individuals who took 82.9 to 149.5 steps per minute. Greater step intensity was not significantly associated with lower mortality after adjustment for total steps per day (eg, highest vs lowest quartile of peak 30 cadence: HR, 0.90 [95% CI, 0.65-1.27]; P value for trend = .34)., Conclusions and Relevance: Based on a representative sample of US adults, a greater number of daily steps was significantly associated with lower all-cause mortality. There was no significant association between step intensity and mortality after adjusting for total steps per day.

Purpose: To determine whether recommended amounts of leisure-time physical activity (ie, 7.5-15 metabolic equivalent task [MET] hours/week) are associated with lower cancer risk, describe the shape of the dose-response relationship, and explore associations with moderate- and vigorous-intensity physical activity., Methods: Data from 9 prospective cohorts with self-reported leisure-time physical activity and follow-up for cancer incidence were pooled. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% CIs of the relationships between physical activity with incidence of 15 types of cancer. Dose-response relationships were modeled with restricted cubic spline functions that compared 7.5, 15.0, 22.5, and 30.0 MET hours/week to no leisure-time physical activity, and statistically significant associations were determined using tests for trend ( P < .05) and 95% CIs (< 1.0)., Results: A total of 755,459 participants (median age, 62 years [range, 32-91 years]; 53% female) were followed for 10.1 years, and 50,620 incident cancers accrued. Engagement in recommended amounts of activity (7.5-15 MET hours/week) was associated with a statistically significant lower risk of 7 of the 15 cancer types studied, including colon (8%-14% lower risk in men), breast (6%-10% lower risk), endometrial (10%-18% lower risk), kidney (11%-17% lower risk), myeloma (14%-19% lower risk), liver (18%-27% lower risk), and non-Hodgkin lymphoma (11%-18% lower risk in women). The dose response was linear in shape for half of the associations and nonlinear for the others. Results for moderate- and vigorous-intensity leisure-time physical activity were mixed. Adjustment for body mass index eliminated the association with endometrial cancer but had limited effect on other cancer types., Conclusion: Health care providers, fitness professionals, and public health practitioners should encourage adults to adopt and maintain physical activity at recommended levels to lower risks of multiple cancers.

Background: Poor olfaction is a prodromal symptom of Parkinson's disease (PD); however, self-reported sense of smell is often dismissed as unreliable., Objective: To assess self-reported and objectively assessed sense of smell, independently and jointly, in relation to future risk for PD., Methods: We conducted a prospective analysis using data from 2,424 participants, ages 71-82 at baseline, from the Health, Aging, and Body Composition study. Exposures were self-reported poor sense of smell or taste and the objectively measured 12-item Brief Smell Identification Test score. The outcome was incident PD, analyzed using Cox proportional hazard models adjusted for age, sex, race, and cognitive function., Results: After approximately 10 years of follow-up, both self-reported and objectively tested poor sense of smell were independently associated with a higher risk of developing PD: the hazard ratios (95% confidence interval) were 2.8 (1.3, 5.9) and 4.0 (2.1, 7.5), respectively. When analyzed jointly, compared with participants who reported and tested normal, the hazard ratio was 2.2 (1.0, 4.6) for those reported poor sense of smell but tested normal, 3.6 (1.9, 6.9) for reported normal but tested poor, and 7.8 (3.2, 19.4) for both reported and tested poor. We did not find significant interactions between self-reported and objectively tested sense of smell in predicting PD risk., Conclusion: This study provides preliminary evidence that self-reported poor sense of smell or taste should not be simply dismissed as useless in predicting risk of PD. Future studies should confirm our finding and evaluate whether structured questionnaires may further improve the predictability.

Large epidemiological studies that use accelerometers for physical behavior and sleep assessment differ in the location of the accelerometer attachment and the signal aggregation metric chosen. This study aimed to assess the comparability of acceleration metrics between commonly-used body-attachment locations for 24 hours, waking and sleeping hours, and to test comparability of PA cut points between dominant and non-dominant wrist. Forty-five young adults (23 women, 18-41 years) were included and GT3X + accelerometers (ActiGraph, Pensacola, FL, USA) were placed on their right hip, dominant, and non-dominant wrist for 7 days. We derived Euclidean Norm Minus One g (ENMO), Low-pass filtered ENMO (LFENMO), Mean Amplitude Deviation (MAD) and ActiGraph activity counts over 5-second epochs from the raw accelerations. Metric values were compared using a correlation analysis, and by plotting the differences by time of the day. Cut points for the dominant wrist were derived using Lin's concordance correlation coefficient optimization in a grid of possible thresholds, using the non-dominant wrist estimates as reference. They were cross-validated in a separate sample (N = 36, 10 women, 22-30 years). Shared variances between pairs of acceleration metrics varied across sites and metric pairs (range in r 2 : 0.19-0.97, all p < 0.01), suggesting that some sites and metrics are associated, and others are not. We observed higher metric values in dominant vs. non-dominant wrist, thus, we developed cut points for dominant wrist based on ENMO to classify sedentary time (<50 mg), light PA (50-110 mg), moderate PA (110-440 mg) and vigorous PA (≥440 mg). Our findings suggest differences between dominant and non-dominant wrist, and we proposed new cut points to attenuate these differences. ENMO and LFENMO were the most similar metrics, and they showed good comparability with MAD. However, counts were not comparable with ENMO, LFENMO and MAD.