Publications by authors named "Denise K Houston"

101 Publications

Predicting Future Mobility Limitation in Older Adults: A Machine Learning Analysis of Health ABC Study Data.

J Gerontol A Biol Sci Med Sci 2021 Sep 16. Epub 2021 Sep 16.

Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.

Background: Mobility limitation in older adults is common and associated with poor health outcomes and loss of independence. Identification of at-risk individuals remains challenging because of time-consuming clinical assessments and limitations of statistical models for dynamic outcomes over time. Therefore, we aimed to develop machine learning models for predicting future mobility limitation in older adults using repeated measures data.

Methods: We used annual assessments over nine years of follow-up from the Health, Aging, and Body Composition study to model mobility limitation, defined as self-report of any difficulty walking a quarter mile or climbing 10 steps. We considered 46 predictors, including demographics, lifestyle, chronic conditions and physical function. With a split sample approach, we developed mixed models (generalized linear and Binary Mixed Model forest) using: 1) all 46 predictors, 2) a variable selection algorithm, and 3) the top five most important predictors. Age was included in all models. Performance was evaluated using area under the receiver operating curve (AUC) in two internal validation datasets.

Results: AUC ranged from 0.80-0.84 for the models. The most important predictors of mobility limitation were ease of getting up from a chair, gait speed, self-reported health status, body mass index and depression.

Conclusions: Machine learning models using repeated measures had good performance for identifying older adults at-risk of developing mobility limitation. Future studies should evaluate the utility and efficiency of the prediction models as a tool in clinical settings for identifying at-risk older adults who may benefit from interventions aimed to prevent or delay mobility limitation.
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http://dx.doi.org/10.1093/gerona/glab269DOI Listing
September 2021

Measured Versus Estimated Resting Metabolic Rate in Heart Failure With Preserved Ejection Fraction.

Circ Heart Fail 2021 Aug 4;14(8):e007962. Epub 2021 Aug 4.

University of Michigan Frankel Cardiovascular Center, Ann Arbor (T.M.C., T.M.K., D.P., S.L.H.).

Background: Obesity is common in heart failure with preserved ejection fraction (HFpEF), and a hypocaloric diet can improve functional capacity. Malnutrition, sarcopenia, and frailty are also frequently present, and calorie restriction could harm some patients. Resting metabolic rate (RMR) is an essential determinant of caloric needs; however, it is rarely measured in clinical practice. The accuracy of commonly used predictive equations in HFpEF is unknown.

Methods: RMR was measured with indirect calorimetry in 43 patients with HFpEF undergoing right heart catheterization at the University of Michigan, and among 49 participants in the SECRET trial (Study of the Effects of Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction); SECRET patients also had dual-energy X-ray absorptiometry body composition measures. Measured RMR was compared with RMR estimated using the Harris Benedict, Mifflin-St Jeor, World Health Organization, and Academy for Nutrition and Dietetics equations.

Results: All predictive equations overestimated RMR (by >10%, <0.001 for all), with mean (95% CI) differences Harris Benedict equation +250 (186-313), Mifflin-St. Jeor equation +169 (110-229), World Health Organization equation +300 (239-361), and Academy for Nutrition and Dietetics equation +794 (890-697) kcal/day. Results were similar across both patient groups, and the discrepancy between measured and estimated RMR tended to increase with body mass index. In SECRET, measured RMR was closely associated with lean body mass (ρ=0.74; by linear regression adjusted for age and sex: β=27 [95% CI, 18-36] kcal/day per kg, <0.001; r=0.56).

Conclusions: Commonly used predictive equations systematically overestimate measured RMR in patients with HFpEF. Direct measurement of RMR may be needed to effectively tailor dietary guidance in this population. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT00959660.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373809PMC
August 2021

Effects of Exercise and Weight Loss on Proximal Aortic Stiffness in Older Adults With Obesity.

Circulation 2021 Aug 2;144(9):684-693. Epub 2021 Aug 2.

Department of Internal Medicine, Virginia Commonwealth University, Richmond (W.G.H.).

Background: Obesity may accelerate age-related increases in aortic stiffness. Although aerobic exercise training generally has favorable effects on aortic structure and function, exercise alone may not be sufficient to improve aortic stiffness in older adults with obesity. We determined the effects of aerobic exercise training with and without moderate- to high-caloric restriction (CR) on the structure and function of the proximal aorta in 160 older (65-79 years) men and women with obesity (body mass index=30-45 kg/m).

Methods: Participants were randomly assigned to 1 of 3 groups: aerobic exercise training only (treadmill 4 days/week for 30 minutes at 65% to 70% of heart rate reserve; n=56), aerobic exercise training plus moderate CR (n=55), or aerobic exercise training plus more intensive CR (n=49) for 20 weeks. Aortic pulse wave velocity, aortic distensibility, and other measures of aortic structure and function were assessed by cardiovascular magnetic resonance imaging. Pearson correlation coefficients were examined to assess associations between changes in proximal aortic stiffness and changes in fitness, fatness, and other potential confounders.

Results: Weight loss in the aerobic exercise training plus moderate CR (-8.0 kg [95% CI, -9.17 to -6.87]) and aerobic exercise training plus more intensive CR (-8.98 kg [95% CI, -10.23 to -7.73) groups was significantly greater compared with the aerobic exercise training-only group (-1.66 kg [95% CI, -2.94 to -0.38]; <0.017 for both). There were significant treatment effects for descending aorta distensibility (=0.008) and strain (=0.004) and aortic arch pulse wave velocity (=0.01) with the aerobic exercise training plus moderate CR group having a 21% increase in distensibility (=0.016) and an 8% decrease in pulse wave velocity (=0.058). None of the aortic stiffness measures changed significantly in the aerobic exercise training-only or aerobic exercise training plus more intensive CR groups, and there were no significant changes in any other measure of aortic structure or function in these groups. Overall, increases in aortic distensibility were correlated with improvements in body weight and body fat distribution, but these associations were not statistically significant after adjustment for multiple comparisons.

Conclusions: In older adults with obesity, combining aerobic exercise with moderate CR leads to greater improvements in proximal aortic stiffness than exercise alone. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT01048736.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405553PMC
August 2021

Association between 25-Hydroxyvitamin D and Metabolic Syndrome in Older Adults: The Health, Aging and Body Composition Study.

Int J Endocrinol 2021 13;2021:6671823. Epub 2021 Mar 13.

For the Health ABC Study, Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Objective: Low 25-hydroxyvitamin D (25[OH]D) levels and metabolic syndrome (MetS) are prevalent among older adults; however, longitudinal studies examining 25(OH)D status and MetS are lacking. We explore the association of 25(OH)D levels with prevalent and incident MetS in white and black older adults. . A total of 1620 white and 1016 black participants aged 70-79 years from the Health ABC cohort with measured 25(OH)D levels and data on MetS and covariates of interest were examined. The association between 25(OH)D levels and prevalent MetS at baseline and incident MetS at 6-year follow-up was examined in whites and blacks separately using logistic regression adjusting for demographics, lifestyle factors, and renal function.

Results: At baseline, 635 (39%) white and 363 (36%) black participants had prevalent MetS. In whites, low 25(OH)D levels were associated with prevalent MetS (adjusted OR (95% CI), 1.85 (1.47, 2.34)) and 1.96 (1.46, 2.63) for 25(OH)D of 20-<30 and <20 vs. ≥30 ng/ml, respectively). The association was attenuated after adjustment for BMI but remained significant. No association was found between 25(OH)D levels and prevalent MetS in blacks. Among those without MetS at baseline (765 whites, 427 blacks), 150 (20%) whites and 87 (20%) blacks had developed MetS at 6-year follow-up. However, 25(OH)D levels were not associated with incident MetS in whites or blacks.

Conclusion: In older adults, low 25(OH)D levels were associated with increased odds of prevalent MetS in whites but not in blacks. No association was observed between 25(OH)D levels and incident MetS in either whites or blacks.
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http://dx.doi.org/10.1155/2021/6671823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981173PMC
March 2021

Effect of dietary protein intake on bone mineral density and fracture incidence in older adults in the Health, Aging, and Body Composition study.

J Gerontol A Biol Sci Med Sci 2021 Mar 3. Epub 2021 Mar 3.

Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.

Background: Dietary recommendations may underestimate the protein older adults need for optimal bone health. This study sought to determine associations of protein intake with bone mineral density (BMD) and fracture among community-dwelling white and black older adults.

Methods: Protein as a percentage of total energy intake (TEI) was assessed with a food frequency questionnaire in 2,160 older adults (73.5±2.8 years; 51.5% women; 35.8% black) in the Health, Aging, and Body Composition prospective cohort. Hip, femoral neck, and whole body BMD was assessed by dual-energy x-ray absorptiometry at baseline and 4 years, and lumbar trabecular, cortical, and integral BMD was assessed by computed tomography at baseline and 5 years. Fragility fractures over 5 years were adjudicated from self-report data collected every 6 months. Associations with tertiles of protein intake were assessed using analysis of covariance for BMD and multivariate Cox regression for fracture, adjusting for confounders.

Results: Participants in the upper protein tertile (≥15% TEI) had 1.8-6.0% higher mean hip and lumbar spine BMD compared to the lower protein tertile (<13% TEI; p<0.05). Protein intake did not affect change in BMD at any site over the follow-up period. Participants in the upper protein tertile had a reduced risk of clinical vertebral fracture over five years of follow-up (Hazard Ratio: 0.36 [95% Confidence Intervals (CI), 0.14, 0.97] vs. lower protein tertile, p=0.04).

Conclusions: Older adults with higher protein intake (≥15% TEI) had higher BMD at the hip, whole body, and lumbar spine, and a lower risk of vertebral fracture.
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http://dx.doi.org/10.1093/gerona/glab068DOI Listing
March 2021

Dietary protein intake and circulating advanced glycation end product/receptor for advanced glycation end product concentrations in the Health, Aging, and Body Composition Study.

Am J Clin Nutr 2020 12;112(6):1558-1565

Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Background: Advanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking.

Objectives: We examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black).

Methods: CML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors.

Results: CML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio.

Conclusions: Higher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.
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http://dx.doi.org/10.1093/ajcn/nqaa241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727487PMC
December 2020

Promoting Active Aging: Lessons Learned in an Implementation Pilot in Primary Care.

J Am Geriatr Soc 2021 02 2;69(2):373-380. Epub 2020 Oct 2.

Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Physical activity (PA) preserves mobility, but few practices screen older adults for mobility impairment or counsel on PA.

Design: "Promoting Active Aging" (PAA) was a mixed-methods randomized-controlled pilot, to test the feasibility and acceptability of a video-based PA counseling tool and implementation into practice of two mobility assessment tools.

Setting: Three primary care practices affiliated with Wake Forest Baptist Health.

Participants: Adults aged 65 years and older who presented for primary care follow-up and were willing and able to answer self-report questions and walk 4 meters (n = 59).

Intervention: Video-based PA counseling intervention versus control video, "Healthy Eating."

Measurements: Potential participants completed mobility assessments: self-report (Mobility Assessment Tool-short form (MAT-sf)) and performance based (4-meter walk test). We assessed PAA's implementation-feasibility, acceptability, and value-via interviews and surveys. Effectiveness was measured via participant attendance at a PA information session.

Results: Of 92 patients approached, 89 (96.7%) agreed to mobility assessment. Eighty-nine completed MAT-sf, and 97.8% (87/89) completed 4-meter walk test. Sixty-seven (75%) met eligibility criteria, and 59 (88%) consented to be randomized either to the PA counseling intervention (Video-PA) or to active control (Video-C). Most participants viewed the walk test positively (51/59; 86.4%). Staff reported that completion of patient surveys, MAT-sf, and videos required significant staff time and support (median = 26 minutes for all), resulting in low acceptability of MAT-sf and the videos. Attendance at a PA information session did not differ by randomization group (Video-PA = 11/29 (37.9%); Video-C = 12/30 (40%); 95% confidence interval for difference in proportion = -0.29 to 0.25).

Conclusions: Mobility assessment, particularly a 4-meter walk test, was feasible in primary care. Tablet-based assessment (MAT-sf) and video counseling tools, selected to reduce staff effort, instead required significant time to implement. Future work to promote PA should identify effective ways to facilitate adoption of PA in sedentary older adults that do not burden staff.
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http://dx.doi.org/10.1111/jgs.16838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902351PMC
February 2021

Longitudinal partially ordered data analysis for preclinical sarcopenia.

Stat Med 2020 10 11;39(24):3313-3328. Epub 2020 Jul 11.

Department of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Sarcopenia is a geriatric syndrome characterized by significant loss of muscle mass. Based on a commonly used definition of the condition that involves three measurements, different subclinical and clinical states of sarcopenia are formed. These states constitute a partially ordered set (poset). This article focuses on the analysis of longitudinal poset in the context of sarcopenia. We propose an extension of the generalized linear mixed model and a recoding scheme for poset analysis such that two submodels-one for ordered categories and one for nominal categories-that include common random effects can be jointly estimated. The new poset model postulates random effects conceptualized as latent variables that represent an underlying construct of interest, that is, susceptibility to sarcopenia over time. We demonstrate how information can be gleaned from nominal sarcopenic states for strengthening statistical inference on a person's susceptibility to sarcopenia.
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http://dx.doi.org/10.1002/sim.8667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386024PMC
October 2020

A randomized pilot study to evaluate graft versus fistula vascular access strategy in older patients with advanced kidney disease: results of a feasibility study.

Pilot Feasibility Stud 2020 17;6:86. Epub 2020 Jun 17.

Division of Health Services Research, Department of Foundations of Medicine, NYU Long Island School of Medicine, Long Island, NY USA.

Background: Although older adults encompass almost half of patients with advanced chronic kidney disease, it remains unclear which long-term hemodialysis vascular access type, arteriovenous fistula or arteriovenous graft, is optimal with respect to effectiveness and patient satisfaction. Clinical outcomes based on the initial AV access type have not been evaluated in randomized controlled trials. This pilot study tested the feasibility of randomizing older adults with advanced kidney disease to initial arteriovenous fistula versus graft vascular access surgery.

Methods: Patients 65 years or older with pre-dialysis chronic kidney disease or incident end-stage kidney disease and no prior arteriovenous vascular access intervention were randomized in a 1:1 ratio to undergo surgical placement of a fistula or a graft after providing informed consent. Trial feasibility was evaluated as (i) recruitment of ≥ 70% of eligible participants, (ii) ≥ 50 to 70% of participants undergo placement of index arteriovenous access within 90 to 180 days of enrollment, respectively, (iii) ≥ 80% adherence to study-related assessments, and (iv) ≥ 70% of participants who underwent index arteriovenous access placement will have a follow-up duration of ≥ 12 months after index surgery date.

Results: Between September 2018 and October 2019, 81% (44/54) of eligible participants consented and were enrolled in the study; 11 had pre-dialysis chronic kidney disease, and 33 had incident or prevalent end-stage kidney disease. After randomization, 100% (21/21) assigned to arteriovenous fistula surgery and 78% (18/23) assigned to arteriovenous graft surgery underwent index arteriovenous access placement within a median (1st, 3rd quartile) of 5.0 (1.0, 14.0) days and 13.0 (5.0, 44.3) days, respectively, after referral to vascular surgery. The completion rates for study-specific assessments ranged between 40.0 and 88.6%. At median follow-up of 215.0 days, 5 participants expired, 7 completed 12 months of follow-up, and 29 are actively being followed. Assessments of grip strength, functional independence, and vascular access satisfaction were completed by > 85% of patients who reached pre-specified post-operative assessment time point.

Conclusions: Results from this study reveal it is feasible to enroll and randomize older adults with advanced kidney disease to one of two different arteriovenous vascular access placement surgeries. The study can progress with minor protocol adjustments to a multisite clinical trial.

Trial Registration: Clinical Trials ID, NCT03545113.
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http://dx.doi.org/10.1186/s40814-020-00619-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298797PMC
June 2020

Sex-and race-specific associations of protein intake with change in muscle mass and physical function in older adults: the Health, Aging, and Body Composition (Health ABC) Study.

Am J Clin Nutr 2020 07;112(1):84-95

Department of Health Sciences, Faculty of Science, Vrije University Amsterdam, Amsterdam Public Health research institute, Amsterdam, the Netherlands.

Background: Protein intake recommendations advise ≥0.8 g/kg body weight (BW)/d, whereas experts propose a higher intake for older adults (1.0-1.2 g/kg BW/d). It is unknown whether optimal protein intake differs by sex or race.

Objectives: We examined the shape of sex- and race-specific associations of dietary protein intake with 3- and 6-y changes in appendicular lean mass (aLM) and gait speed and also 6-y incidence of mobility limitation in community-dwelling older men and women.

Methods: We used data on men (n = 1163) and women (n = 1237) aged 70-81 y of the Health, Aging, and Body Composition Study. Protein intake was assessed using an FFQ (1998-1999). aLM and gait speed were measured at baseline and at 3 and 6 y. Difficulty walking one-quarter mile or climbing stairs was measured every 6 mo over 6 y. Prospective associations were evaluated with linear and Cox regression models, comparing fit of models with and without spline functions. All analyses were stratified by sex and additionally by race.

Results: Mean ± SD protein intake was 0.94 ± 0.36 g/kg adjusted body weight (aBW)/d in men and 0.95 ± 0.36 g/kg aBW/d in women. There were no strong indications of nonlinear associations. In women, higher protein intake was associated with less aLM loss over 3 y (adjusted B per 0.1 g/kg aBW/d: 39.4; 95% CI: 11.6, 67.2), specifically in black women, but not over 6 y or with gait speed decline. In men, protein intake was not associated with changes in aLM and gait speed. Higher protein intake was associated with a lower risk of mobility limitation in men (adjusted HR per 1.0 g/kg aBW/d: 0.55; 95% CI: 0.34, 0.91) and women (adjusted HR: 0.56; 95% CI: 0.33, 0.94), specifically white women.

Conclusions: Associations between protein intake and physical outcomes may vary by sex and race. Therefore, it is important to consider sex and race in future studies regarding protein needs in older adults.
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http://dx.doi.org/10.1093/ajcn/nqaa099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326591PMC
July 2020

Machine Learning in Aging: An Example of Developing Prediction Models for Serious Fall Injury in Older Adults.

J Gerontol A Biol Sci Med Sci 2021 03;76(4):647-654

Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Advances in computational algorithms and the availability of large datasets with clinically relevant characteristics provide an opportunity to develop machine learning prediction models to aid in diagnosis, prognosis, and treatment of older adults. Some studies have employed machine learning methods for prediction modeling, but skepticism of these methods remains due to lack of reproducibility and difficulty in understanding the complex algorithms that underlie models. We aim to provide an overview of two common machine learning methods: decision tree and random forest. We focus on these methods because they provide a high degree of interpretability.

Method: We discuss the underlying algorithms of decision tree and random forest methods and present a tutorial for developing prediction models for serious fall injury using data from the Lifestyle Interventions and Independence for Elders (LIFE) study.

Results: Decision tree is a machine learning method that produces a model resembling a flow chart. Random forest consists of a collection of many decision trees whose results are aggregated. In the tutorial example, we discuss evaluation metrics and interpretation for these models. Illustrated using data from the LIFE study, prediction models for serious fall injury were moderate at best (area under the receiver operating curve of 0.54 for decision tree and 0.66 for random forest).

Conclusions: Machine learning methods offer an alternative to traditional approaches for modeling outcomes in aging, but their use should be justified and output should be carefully described. Models should be assessed by clinical experts to ensure compatibility with clinical practice.
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http://dx.doi.org/10.1093/gerona/glaa138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011704PMC
March 2021

Weight Change 2 Years After Termination of the Intensive Lifestyle Intervention in the Look AHEAD Study.

Obesity (Silver Spring) 2020 05;28(5):893-901

Department of Medicine, St. Luke's Roosevelt Hospital Center, Columbia University, New York, New York, USA.

Objective: This study evaluated weight changes after cessation of the 10-year intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study. It was hypothesized that ILI participants would be more likely to gain weight during the 2-year observational period following termination of weight-loss-maintenance counseling than would participants in the diabetes support and education (DSE) control group.

Methods: Look AHEAD was a randomized controlled trial that compared the effects of ILI and DSE on cardiovascular morbidity and mortality in participants with overweight/obesity and type 2 diabetes. Look AHEAD was converted to an observational study in September 2012.

Results: Two years after the end of the intervention (EOI), ILI and DSE participants lost a mean  (SE) of 1.2  (0.2) kg and 1.8  (0.2) kg, respectively (P = 0.003). In addition, 31% of ILI and 23.9% of DSE participants gained ≥ 2% (P < 0.001) of EOI weight, whereas 36.3% and 45.9% of the respective groups lost ≥ 2% of EOI weight (P = 0.001). Two years after the EOI, ILI participants reported greater use of weight-control behaviors than DSE participants.

Conclusions: Both groups lost weight during the 2-year follow-up period, but more ILI than DSE participants gained ≥ 2% of EOI weight. Further understanding is needed of factors that affected long-term weight change in both groups.
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http://dx.doi.org/10.1002/oby.22769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437140PMC
May 2020

AGS and NIA Bench-to Bedside Conference Summary: Osteoporosis and Soft Tissue (Muscle and Fat) Disorders.

J Am Geriatr Soc 2020 01 2;68(1):31-38. Epub 2019 Dec 2.

University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York.

This report summarizes the presentations and recommendations of the eleventh annual American Geriatrics Society and National Institute on Aging research conference, "Osteoporosis and Soft Tissue (Muscle/Fat) Disorders," on March 11-12, 2019, in Bethesda, Maryland. Falls, fractures, and sarcopenia have a major impact on health in older adults, and they are interconnected by known risk factors. The link between osteoporosis, which is common in older adults, and the risk of falls is well known. Sarcopenia, the age-related decline in skeletal muscle mass and function, is also associated with an increased risk of falls and fractures because it reduces strength and leads to functional limitations. In addition to increasing the risk of falls, sarcopenia and osteoporosis can lead to frailty, reduced quality of life, morbidity, and mortality. The conference highlighted the impact of bone and soft tissue disorders on quality of life, morbidity, and mortality in older adults. Presenters described factors that contribute to these disorders; health disparities experienced by various subpopulations; and promising biological, pharmacologic, and behavioral interventions to prevent or treat these disorders. The workshop identified many research gaps and questions along with research recommendations that have the potential to enhance the prospect of healthy aging and improved quality of life for older adults. J Am Geriatr Soc 68:31-38, 2019.
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http://dx.doi.org/10.1111/jgs.16248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316395PMC
January 2020

The Role of Diet on Life and Health Span-Lessons Learned Over the Past 75 Years.

Authors:
Denise K Houston

J Gerontol A Biol Sci Med Sci 2020 07;75(8):1499-1501

Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston - Salem, North Carolina.

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http://dx.doi.org/10.1093/gerona/glz273DOI Listing
July 2020

Effect of Weight Change Following Intentional Weight Loss on Bone Health in Older Adults with Obesity.

Obesity (Silver Spring) 2019 11 4;27(11):1839-1845. Epub 2019 Sep 4.

Department of Health and Exercise Science, Wake Forest University, Winston-Salem, North Carolina, USA.

Objective: This study aimed to examine change in bone mineral density (BMD) and trabecular bone score among older adult weight regainers (WR) and weight maintainers (WM).

Methods: Observational data come from 77 older adults (mean age: 67 [SD 5] years; 69% women; 70% white) with obesity (mean BMI: 33.6 [SD  3.7] kg/m ) who lost weight during an 18-month weight loss intervention. Total body mass and body composition, along with regional (total hip, femoral neck, lumbar spine) BMD and trabecular bone score, were measured at baseline, 18 months, and 30 months. WR (n = 36) and WM (n = 41) categories were defined as a ≥ 5% or < 5% weight gain from 18 to 30 months, respectively.

Results: Among skeletal indices, only total hip BMD was significantly reduced during the 18-month intervention period in both WRs (-3.9%; 95% CI: -5.8% to -2.0%) and WMs (-2.4%; 95% CI: -4.3% to -0.5%; P = 0.07). After adjustment for relevant baseline covariates and weight change from 0 to 18 months, 30-month change in total hip BMD was -2.6% (95% CI: -4.3% to -0.9%) and -3.9% (95% CI: -5.7% to -2.1%) among WRs and WMs, respectively (P = 0.07).

Conclusions: Loss of hip BMD persists in the year after a weight loss intervention among older adults with obesity, regardless of weight regain status.
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http://dx.doi.org/10.1002/oby.22604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832808PMC
November 2019

Prospective Associations of Diet Quality With Incident Frailty in Older Adults: The Health, Aging, and Body Composition Study.

J Am Geriatr Soc 2019 09 2;67(9):1835-1842. Epub 2019 Jul 2.

Department of Health Sciences, Faculty of Science, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Objective: To examine associations of diet quality indicators with 4-year incidence of frailty in community-dwelling older adults.

Design: Prospective cohort study.

Setting: Health, Aging, and Body Composition Study, United States.

Participants: Community-dwelling men and women, aged 70 to 81 years in 1998 to 1999 (first follow-up, present study's baseline; n = 2154).

Measurements: At first follow-up, dietary intake over the preceding year was assessed with a food frequency questionnaire. Indicators of diet quality include the Healthy Eating Index (categorized as poor, medium, and good), energy intake, and protein intake (a priori adjusted for energy intake using the nutrient residual model). Frailty status was determined using Fried's five-component frailty phenotype and categorized into "robust" (0 components present), "pre-frailty" (1 - 2 components present), or "frail" (3-5 components present). Cox proportional hazards analysis was used to examine associations of the diet quality indicators with 4-year incidence of (1) frailty and (2) pre-frailty or frailty. Competing risk analysis was used to examine associations with frailty by accounting for competing risks of death.

Results: During the 4-year follow-up, 277 of the 2154 participants, robust or pre-frail at baseline, developed frailty, and 629 of the 1020 participants, robust at baseline, developed pre-frailty or frailty. Among the robust and pre-frail, after adjustment for confounders including energy intake, those consuming poor- and medium-quality diets had a higher frailty incidence than those consuming good-quality diets (hazard ratio [HR] = 1.92 [95% confidence interval {CI} = 1.17-3.17] and HR = 1.40 [95% CI = 0.99-1.98], respectively). No associations for energy or protein intake were observed. Competing risk analyses yielded similar results. Among the robust, those with lower vegetable protein intake had a higher "pre-frailty or frailty" incidence (per -10 g/d: HR = 1.20; 95% CI = 1.04-1.39). No other associations were observed.

Conclusion: Poorer overall diet quality and lower vegetable protein intake may increase the risk of becoming frail in old age. We found no association for intakes of energy, total protein, or animal protein. J Am Geriatr Soc 67:1835-1842, 2019.
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http://dx.doi.org/10.1111/jgs.16011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771787PMC
September 2019

A randomized pilot study comparing graft-first to fistula-first strategies in older patients with incident end-stage kidney disease: Clinical rationale and study design.

Contemp Clin Trials Commun 2019 Jun 9;14:100357. Epub 2019 Apr 9.

Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Timely placement of an arteriovenous (AV) vascular access (native AV fistula [AVF] or prosthetic AV graft [AVG]) is necessary to limit the use of tunneled central venous catheters (TCVC) in patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD). National guidelines recommend placement of AVF as the AV access of first choice in all patients to improve patient survival. The benefits of AVF over AVG are less certain in the older adults, as age-related biological changes independently modulate patient outcomes. This manuscript describes the rationale, study design and protocol for a randomized controlled pilot study of the feasibility and effects of AVG-first access placement in older adults with no prior AV access surgery. Fifty patients age ≥65 years, with incident ESKD on HD via TCVC or advanced kidney disease facing imminent HD initiation, and suitable upper extremity vasculature for initial placement of an AVF or AVG, will be randomly assigned to receive either an upper extremity AVG-first (intervention) or AVF-first (comparator) access. The study will establish feasibility of randomizing older adults to the two types of AV access surgery, evaluate relationships between measurements of preoperative physical function and vascular access development, compare vascular access outcomes between groups, and gather longitudinal assessments of upper extremity muscle strength, gait speed, performance of activities of daily living, and patient satisfaction with their vascular access and quality of life. Results will assist with the planning of a larger, multicenter trial assessing patient-centered outcomes.
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http://dx.doi.org/10.1016/j.conctc.2019.100357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475715PMC
June 2019

Dietary protein intake is not associated with 5-y change in mid-thigh muscle cross-sectional area by computed tomography in older adults: the Health, Aging, and Body Composition (Health ABC) Study.

Am J Clin Nutr 2019 03;109(3):535-543

Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, Netherlands.

Background: A higher protein intake is suggested to preserve muscle mass during aging and may therefore reduce the risk of sarcopenia.

Objectives: We explored whether the amount and type (animal or vegetable) of protein intake were associated with 5-y change in mid-thigh muscle cross-sectional area (CSA) in older adults (n = 1561).

Methods: Protein intake was assessed at year 2 by a Block food-frequency questionnaire in participants (aged 70-79 y) of the Health, Aging, and Body Composition (Health ABC) Study, a prospective cohort study. At year 1 and year 6 mid-thigh muscle CSA in square centimeters was measured by computed tomography. Multiple linear regression analysis was used to examine the association between energy-adjusted protein residuals in grams per day (total, animal, and vegetable protein) and muscle CSA at year 6, adjusted for muscle CSA at year 1 and potential confounders including prevalent health conditions, physical activity, and 5-y change in fat mass.

Results: Mean (95% CI) protein intake was 0.90 (0.88, 0.92) g · kg-1 · d-1 and mean (95% CI) 5-y change in muscle CSA was -9.8 (-10.6, -8.9) cm2. No association was observed between energy-adjusted total (β = -0.00; 95% CI: -0.06, 0.06 cm2; P = 0.982), animal (β = -0.00; 95% CI: -0.06, 0.05 cm2; P = 0.923), or plant (β = +0.07; 95% CI: -0.06, 0.21 cm2; P = 0.276) protein intake and muscle CSA at year 6, adjusted for baseline mid-thigh muscle CSA and potential confounders.

Conclusions: This study suggests that a higher total, animal, or vegetable protein intake is not associated with 5-y change in mid-thigh muscle CSA in older adults. This conclusion contradicts some, but not all, previous research. This trial was registered at www.trialregister.nl as NTR6930.
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http://dx.doi.org/10.1093/ajcn/nqy341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408207PMC
March 2019

Long-Term Effects of Randomization to a Weight Loss Intervention in Older Adults: A Pilot Study.

J Nutr Gerontol Geriatr 2019 Jan-Mar;38(1):83-99. Epub 2019 Mar 8.

a Sticht Center on Aging, Wake Forest School of Medicine , Winston-Salem , NC , USA.

Randomized, controlled trials (RCTs) show intentional weight loss improves body composition and physical function in older adults; however, the long-term benefits (and risks) are unknown. We conducted a pilot study to assess the feasibility of recalling prior RCT participants to examine the long-term effects of intentional weight loss on body composition and physical function. A weighted, random sample of 60 older adults who were randomized to caloric restriction plus exercise (CR + EX) or exercise (EX) only in 5 prior RCTs (mean age at randomization, 67.3 years; 69% women, 80% white) were invited to participate. Follow-up was obtained on 89% (42 clinic visits, 10 phone interviews, 1 death) an average of 3.5 years (range, 2.2-5.8 years) after RCT completion. Despite greater weight, fat and lean mass loss during the RCT (mean difference in change (95% CI): -4.19 (-7.52, -0.86), -2.75 (-5.10, -0.40), and -2.32 (-3.69, -0.95) kg, respectively) in those randomized to CR + EX, long-term changes in weight (2.05 (-2.35, 6.45) kg) and body composition (1.80 (-1.56, 5.17) and 0.03 (-2.20, 2.26) kg for fat and lean mass, respectively) from baseline and physical function at long-term follow-up (mean difference in 400-m walk and SPPB (95% CI): 23.2 (-19.3, 65.6) sec and -0.03 (-1.02, 0.96) points, respectively) were similar in CR + EX and EX only. Although improvements in weight and body composition following intentional weight loss may not be sustained long-term, physical function does not appear to be negatively impacted. A larger study is needed to confirm these results.
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http://dx.doi.org/10.1080/21551197.2019.1572570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447460PMC
May 2020

Effect of a hypocaloric, nutritionally complete, higher-protein meal plan on bone density and quality in older adults with obesity: a randomized trial.

Am J Clin Nutr 2019 02;109(2):478-486

Department of Health and Exercise Science, Wake Forest University, Winston-Salem, NC.

Background: Dietary protein and micronutrients are important to the maintenance of bone health and may be an effective countermeasure to weight-loss-associated bone loss.

Objectives: We aimed to determine the effect of a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan on change in bone density and quality as compared with weight stability in older adults using a randomized post-test design. We hypothesized that participants randomly assigned to this meal plan would maintain similar bone density and quality to weight-stable controls, despite significant reductions in body mass.

Methods: Ninety-six older adults (aged 70.3 ± 3.7 y, 74% women, 27% African American) with obesity [body mass index (kg/m2): 35.4 ± 3.3] were randomly assigned to a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan targeting ≥1.0 g protein · kg body weight-1 · d-1 [weight-loss (WL) group; n = 47] or to a weight-stability (WS) group targeting 0.8 g protein · kg body weight-1 · d-1, the current Recommended Dietary Allowance (n = 49). The primary outcome was total hip bone mineral density (BMD), with femoral neck BMD, lumbar spine BMD, and lumbar spine trabecular bone score (TBS) as secondary outcomes, all assessed at baseline and 3 and 6 mo with dual-energy X-ray absorptiometry.

Results: Baseline total hip, femoral neck, and lumbar spine BMDs were 1.016 ± 0.160, 0.941 ± 0.142, and 1.287 ± 0.246 g/cm2, respectively; lumbar TBS was 1.398 ± 0.109. Despite significant weight loss achieved in the WL group (6.6 ± 0.4 kg; 8.6% ± 0.4% of baseline weight), 6-mo regional BMD estimates were similar to those in the WS group (all P > 0.05). Lumbar spine TBS significantly increased at 6 mo in the WL group (mean: 1.421; 95% CI: 1.401, 1.441) compared with the WS group (1.390: 95% CI: 1.370, 1.409; P = 0.02).

Conclusions: Older adults following a hypocaloric, nutritionally complete, higher-protein meal plan maintained similar bone density and quality to weight-stable controls. Our data suggest that adherence to this diet does not produce loss of hip and spine bone density in older adults and may improve bone quality. This trial was registered at clinicaltrials.gov as NCT02730988.
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http://dx.doi.org/10.1093/ajcn/nqy237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367970PMC
February 2019

Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function.

Br J Nutr 2018 11 12;120(10):1159-1170. Epub 2018 Sep 12.

7Center for Public Health Genomics,University of Virginia School of Medicine,Charlottesville,VA 22903,USA.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (P race difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (P race difference=0·56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
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http://dx.doi.org/10.1017/S0007114518002180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263170PMC
November 2018

Vitamin D Status and Exercise Capacity in Older Patients with Heart Failure with Preserved Ejection Fraction.

Am J Med 2018 12 1;131(12):1515.e11-1515.e19. Epub 2018 Aug 1.

USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass.

Background: Older patients with heart failure with preserved ejection fraction have severe exercise intolerance. Vitamin D may play a role in cardiovascular and skeletal muscle function, and may therefore be implicated in exercise intolerance in heart failure with preserved ejection fraction. However, there are few data on vitamin D status and its relationship to exercise capacity in heart failure with preserved ejection fraction patients.

Methods: Plasma 25-hydroxyvitamin D (25[OH]D) and exercise capacity (peak oxygen consumption, [VO], 6-minute walk distance) were measured in 112 older heart failure with preserved ejection fraction patients (mean ± SD age = 70 ± 8 years) and 37 healthy age-matched controls. General linear models were used to compare 25(OH)D between heart failure with preserved ejection fraction patients and healthy controls, and to determine the cross-sectional association between 25(OH)D and exercise capacity. The association between 25(OH)D and left ventricular function was evaluated secondarily in heart failure with preserved ejection fraction patients.

Results: 25(OH)D concentrations were significantly lower in heart failure with preserved ejection fraction vs healthy controls (11.4 ± 0.6 ng/mL vs 19.1 ± 2.1 ng/mL; P = .001, adjusted for age, race, sex, body mass index, season). More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency (<20 ng/mL) and 30% had frank 25(OH)D deficiency (<10 ng/mL). In heart failure with preserved ejection fraction patients, but not healthy controls, 25(OH)D was significantly correlated with peak VO (r = 0.26; P = 0.007) and 6-minute walk distance (r = 0.34; P < .001).

Conclusions: More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency, and 30% were frankly deficient. Lower 25(OH)D was associated with lower peak VO and 6-minute walk distance in heart failure with preserved ejection fraction, suggesting that 25(OH)D insufficiency could contribute to exercise intolerance in this patient population. These findings provide the data and rationale for a future randomized trial designed to test the potential for vitamin D supplementation to improve exercise intolerance in heart failure with preserved ejection fraction.
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http://dx.doi.org/10.1016/j.amjmed.2018.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859938PMC
December 2018

Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium.

Mol Psychiatry 2019 12 9;24(12):1920-1932. Epub 2018 Jul 9.

Department of Clinical Chemistry, Fimlab Laboratories, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.
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http://dx.doi.org/10.1038/s41380-018-0079-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326896PMC
December 2019

Effects of Caloric Restriction on Cardiorespiratory Fitness, Fatigue, and Disability Responses to Aerobic Exercise in Older Adults With Obesity: A Randomized Controlled Trial.

J Gerontol A Biol Sci Med Sci 2019 06;74(7):1084-1090

Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Obesity compounds aging-related declines in cardiorespiratory fitness, with accompanying fatigue and disability. This study determined the effects of two different levels of caloric restriction (CR) during aerobic training on cardiorespiratory fitness, fatigue, physical function, and cardiometabolic risk.

Methods: The INFINITE study was a 20-week randomized trial in 180 older (65-79 years) men and women with obesity (body mass index = 30-45 kg/m2). Participants were randomly assigned to (i) aerobic training (EX; treadmill 4 days/wk for 30 minutes at 65%-70% of heart rate reserve), (ii) EX with moderate (-250 kcal/d) CR (EX + Mod-CR), or (iii) EX with more intensive (-600 kcal/d) CR (EX + High-CR). Cardiorespiratory fitness (peak aerobic capacity, VO2 peak, primary outcome) was determined during a graded exercise test.

Results: One hundred and fifty-five participants returned for 20-week data collection (87% retention). VO2 peak increased by 7.7% with EX, by 13.8% with EX + Mod-CR, and by 16.0% with EX + High-CR, and there was a significant treatment effect (EX + High-CR = 21.5 mL/kg/min, 95% confidence interval = 19.8-23.2; EX + Mod-CR = 21.2 mL/kg/min, 95% confidence interval = 19.4-23.0; EX = 20.1 mL/kg/min, 95% confidence interval = 18.4-21.9). Both CR groups exhibited significantly greater improvement in self-reported fatigue and disability and in glucose control, compared with EX.

Conclusion: Combining aerobic exercise with even moderate CR is more efficacious for improving cardiorespiratory fitness, fatigue and disability, and glucose control than exercise alone and is as effective as higher-dose CR.
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http://dx.doi.org/10.1093/gerona/gly159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580693PMC
June 2019

Low 25-Hydroxyvitamin D Concentrations and Risk of Incident Cognitive Impairment in Black and White Older Adults: The Health ABC Study.

J Nutr Gerontol Geriatr 2018 Jan-Mar;37(1):1-13. Epub 2018 Mar 5.

h MAS for the Health ABC Study, Wake Forest School of Medicine, Sticht Center on Aging , Winston-Salem , North Carolina , USA.

Using data from the Health, Aging, and Body Composition study, we examined whether low 25-hydroxyvitamin D (25[OH]D) concentrations were associated with prevalent or incident cognitive impairment. Serum 25(OH)D concentrations were measured in 2,786 older adults and categorized as <20 ng/mL, 20 to <30 ng/mL, or ≥30 ng/mL. Cognitive impairment was defined as a score >1.5 standard deviations below race and education specific means on either digit symbol substitution test or modified mini-mental state test. Logistic regression determined the odds of cognitive impairment at baseline and year 5 by 25(OH)D category. 25(OH)D concentrations were <30 ng/mL in 57.3% of whites and 84.6% of blacks. After excluding participants with baseline cognitive impairment (n = 340), 13% of whites and 13% of blacks developed cognitive impairment by year 5. In whites, 25(OH)D concentrations <30 ng/mL were not associated with prevalent or incident cognitive impairment. Black participants with 25(OH)D concentrations <20 ng/mL had a higher odds of prevalent, but not incident cognitive impairment (OR (95% CI): 2.05 (1.08-3.91), p = 0.03) compared to participants with 25(OH)D concentrations ≥30 ng/mL. Low 25(OH)D concentrations were associated with twofold higher odds of prevalent cognitive impairment in blacks.
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http://dx.doi.org/10.1080/21551197.2017.1419899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931701PMC
October 2019

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.

Nat Commun 2018 01 17;9(1):260. Epub 2018 Jan 17.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10 at rs8018720 in SEC23A, and P = 1.9×10 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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http://dx.doi.org/10.1038/s41467-017-02662-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772647PMC
January 2018

Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations.

J Clin Endocrinol Metab 2018 04;103(4):1380-1392

Division of Pediatric Endocrinology, Diabetes and Metabolism, Columbia University Medical Center, New York, New York.

Context: Vitamin D inadequacy is common in the adult population of the United States. Although the genetic determinants underlying vitamin D inadequacy have been studied in people of European ancestry, less is known about populations with Hispanic or African ancestry.

Objective: The Trans-Ethnic Evaluation of Vitamin D (TRANSCEN-D) genomewide association study (GWAS) consortium was assembled to replicate genetic associations with 25-hydroxyvitamin D [25(OH)D] concentrations from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) meta-analyses of European ancestry and to identify genetic variants related to vitamin D concentrations in African and Hispanic ancestries.

Design: Ancestry-specific (Hispanic and African) and transethnic (Hispanic, African, and European) meta-analyses were performed with Meta-Analysis Helper software (METAL).

Patients Or Other Participants: In total, 8541 African American and 3485 Hispanic American (from North America) participants from 12 cohorts and 16,124 European participants from SUNLIGHT were included in the study.

Main Outcome Measures: Blood concentrations of 25(OH)D were measured for all participants.

Results: Ancestry-specific analyses in African and Hispanic Americans replicated single nucleotide polymorphisms (SNPs) in GC (2 and 4 SNPs, respectively). An SNP (rs79666294) near the KIF4B gene was identified in the African American cohort. Transethnic evaluation replicated GC and DHCR7 region SNPs. Additionally, the transethnic analyses revealed SNPs rs719700 and rs1410656 near the ANO6/ARID2 and HTR2A genes, respectively.

Conclusions: Ancestry-specific and transethnic GWASs of 25(OH)D confirmed findings in GC and DHCR7 for African and Hispanic American samples and revealed findings near KIF4B, ANO6/ARID2, and HTR2A. The biological mechanisms that link these regions with 25(OH)D metabolism warrant further investigation.
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http://dx.doi.org/10.1210/jc.2017-01802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276579PMC
April 2018

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

PLoS One 2017 13;12(12):e0186456. Epub 2017 Dec 13.

Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America.

Background: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences.

Objective: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption.

Design: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts.

Results: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA.

Conclusions: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186456PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728559PMC
January 2018

Physical Function Following a Long-Term Lifestyle Intervention Among Middle Aged and Older Adults With Type 2 Diabetes: The Look AHEAD Study.

J Gerontol A Biol Sci Med Sci 2018 10;73(11):1552-1559

University of Alabama at Birmingham School of Medicine.

Background: Lifestyle interventions have been shown to improve physical function over the short term; however, whether these benefits are sustainable is unknown. The long-term effects of an intensive lifestyle intervention (ILI) on physical function were assessed using a randomized post-test design in the Look AHEAD trial.

Methods: Overweight and obese (body mass index ≥ 25 kg/m2) middle-aged and older adults (aged 45-76 years at enrollment) with type 2 diabetes enrolled in Look AHEAD, a trial evaluating an ILI designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance-based physical function including a 4- and 400-m walk, lower extremity physical performance (expanded Short Physical Performance Battery, SPPBexp), and grip strength approximately 11 years postrandomization and 1.5 years after the intervention was stopped (n = 3,783).

Results: Individuals randomized to ILI had lower odds of slow gait speed (<0.8 m/s) compared to those randomized to DSE (adjusted OR [95% CI]: 0.84 [0.71 to 0.99]). Individuals randomized to ILI also had faster gait speed over 4- and 400-m (adjusted mean difference [95% CI]: 0.019 [0.007 to 0.031] m/s, p = .002, and 0.023 [0.012 to 0.034] m/sec, p < .0001, respectively) and higher SPPBexp scores (0.037 [0.011 to 0.063], p = .005) compared to those randomized to DSE. The intervention effect was slightly larger for SPPBexp scores among older versus younger participants (0.081 [0.038 to 0.124] vs 0.013 [-0.021 to 0.047], p = .01).

Conclusions: An intensive lifestyle intervention has modest but significant long-term benefits on physical function in overweight and obese middle-aged and older adults with type 2 diabetes.

Clinicaltrials.gov Identifier: NCT00017953.
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http://dx.doi.org/10.1093/gerona/glx204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175031PMC
October 2018

Association of Vitamin K Status Combined With Vitamin D Status and Lower-Extremity Function: A Prospective Analysis of Two Knee Osteoarthritis Cohorts.

Arthritis Care Res (Hoboken) 2018 08 29;70(8):1150-1159. Epub 2018 May 29.

Tufts University, Boston, Massachusetts.

Objective: Vitamins K and D are important for the function of vitamin K-dependent proteins in joint tissues. It is unclear whether these nutrients are mutually important to functional outcomes related to knee osteoarthritis (OA). We evaluated the association of vitamin K and D sufficiency with lower-extremity function in the Health, Aging and Body Composition knee OA substudy (Health ABC) and conducted a replication analysis in an independent cohort, the Osteoarthritis Initiative (OAI).

Methods: In Health ABC (60% female, mean ± SD age 75 ± 3 years) baseline nutrient status was measured using circulating vitamin K and 25-hydroxyvitamin D (25[OH]D). Lower-extremity function was assessed using the Short Physical Performance Battery (SPPB) and usual 20-meter gait speed. In the OAI (58% female, mean ± SD age 61 ± 9 years), baseline nutrient intake was estimated by food frequency questionnaire. Lower-extremity function was assessed using usual 20-meter gait speed and chair stand completion time. Multivariate mixed models were used to evaluate the association of vitamin K and D status and intake with lower-extremity function over 4-5 years.

Results: Health ABC participants with sufficient plasma vitamin K (≥1.0 nmoles/liter) and serum 25(OH)D (≥50 nmoles/liter) generally had better SPPB scores and faster usual gait speed over followup (P ≤ 0.002). In the OAI, sufficient vitamin K and vitamin D intake combined was associated with overall faster usual gait speed and chair stand completion time over followup (P ≤ 0.029).

Conclusion: Sufficient vitamin K status combined with sufficient vitamin D status was associated with better lower-extremity function in 2 knee OA cohorts. These findings merit confirmation in vitamin K and D co-supplementation trials.
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http://dx.doi.org/10.1002/acr.23451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904020PMC
August 2018
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