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03/2019 journal articles

PROCEEDINGS OF THE CANADIAN FRAILTY NETWORK WORKSHOP: IDENTIFYING BIOMARKERS OF FRAILTY TO SUPPORT FRAILTY RISK ASSESSMENT, DIAGNOSIS AND PROGNOSIS. TORONTO, JANUARY 15, 2018

J. Muscedere, P.M. Kim, J. Afilalo, C. Balion, V.E. Baracos, D. Bowdish, M. Cesari, J. D. Erusalimsky, T. Fülöp, G. Heckman, S.E. Howlett, R.g. Khadaroo, J.L. Kirkland, L. Rodriguez Mañas, E. Marzetti, G. Paré, P. Raina, K. Rockwood, A. Sinclair, C. Skappak, C. Verschoor, S. Walter, for the Canadian Frailty Network

J Frailty Aging 2019;8(3):106-116

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The Canadian Frailty Network (CFN), a pan-Canadian not-for-profit organization funded by the Government of Canada through the Networks of Centres of Excellence Program, is dedicated to improving the care of older Canadians living with frailty. The CFN has partnered with the Canadian Longitudinal Study on Aging (CLSA) to measure potential frailty biomarkers in biological samples (whole blood, plasma, urine) collected in over 30,000 CLSA participants. CFN hosted a workshop in Toronto on January 15 2018, bringing together experts in the field of biomarkers, aging and frailty. The overall objectives of the workshop were to start building a consensus on potential frailty biomarker domains and identify specific frailty biomarkers to be measured in the CLSA biological samples. The workshop was structured with presentations in the morning to frame the discussions for the afternoon session, which was organized as a free-flowing discussion to benefit from the expertise of the participants. Participants and speakers were from Canada, Italy, Spain, United Kingdom and the United States. Herein we provide pertinent background information, a summary of all the presentations with key figures and tables, and the distillation of the discussions. In addition, moving forward, the principles CFN will use to approach frailty biomarker research and development are outlined. Findings from the workshop are helping CFN and CLSA plan and conduct the analysis of biomarkers in the CLSA samples and which will inform a follow-up data access competition.

CITATION:
J. Muscedere ; P.M. Kim ; J. Afilalo ; C. Balion ; V.E. Baracos ; D. Bowdish ; M. Cesari ; J. D. Erusalimsky ; T. Fülöp ; G. Heckman ; S.E. Howlett ; R.g. Khadaroo ; J.L. Kirkland ; L. Rodriguez Mañas ; E. Marzetti ; G. Paré ; P. Raina ; K. Rockwood ; A. Sinclair ; C. Skappak ; C. Verschoor ; S. Walter ; for the Canadian Frailty Network ; (2019): Proceedings of the Canadian Frailty Network Workshop: Identifying biomarkers of frailty to support frailty risk assessment, diagnosis and prognosis. Toronto, January 15, 2018. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2019.12

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HIGHLIGHTS FROM THE 2019 INTERNATIONAL CONGRESS ON FRAILTY AND SARCOPENIA RESEARCH

M. Maltais, M. Aubertin-Leheudre, C. Dray, R.A. Fielding, Y. Rolland, M. Cesari, B. Vellas

J Frailty Aging 2019;8(3):117-119

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CITATION:
M. Maltais ; M. Aubertin-Leheudre ; C. Dray ; R.A. Fielding ; Y. Rolland ; M. Cesari ; B. Vellas (2019): Highlights from the 2019 International Congress on Frailty and Sarcopenia Research. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2019.13

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DEVELOPMENT OF PHARMACOTHERAPIES FOR THE TREATMENT OF SARCOPENIA

D. Rooks, R. Roubenoff

J Frailty Aging 2019;8(3):120-130

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Sarcopenia, the associated loss of skeletal muscle mass and strength and impaired physical function seen with aging, is a growing, global public health challenge in need of accepted, proven treatments that address the needs of a broad range of older adults. While exercise, primarily resistance training, and increased dietary protein have been shown to delay and even reverse losses in muscle mass, strength and physical function seen with aging, proven treatments that are accessible globally, cost effective and sustainable by patients are needed. While no drug has yet demonstrated the substantial safety and clinical value needed to be the first pharmacological therapy registered for muscle wasting or sarcopenia, the field is active. Several approaches to treating the muscle loss and subsequent functional decline are being studied in a variety of patient populations across every continent. We provide a review of the leading programs and approaches and available findings from recent studies. In addition, we briefly discuss several related issues needed to facilitate the development of a safe and efficacious pharmacotherapeutic that could be used as part of a treatment plan for older men and women with sarcopenia.

CITATION:
D. Rooks ; R. Roubenoff (2019): Development of pharmacotherapies for the treatment of sarcopenia. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2019.11

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SERUM VITAMIN D AND AGE-RELATED MUSCLE LOSS IN AFRO-CARIBBEAN MEN: THE IMPORTANCE OF AGE AND DIABETIC STATUS

J. Hwang, J.M. Zmuda, A.L. Kuipers, C.H. Bunker, A.J. Santanasto, V.W. Wheeler, I. Miljkovic

J Frailty Aging 2019;8(3):131-137

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Background: Prospective studies examining the potential association of vitamin D with age-related muscle loss have shown inconsistent results. Objective: To examine the association between baseline serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and prospective change in lean mass with aging in African ancestry population. We also determined if associations were modulated by age and diabetes mellitus (DM). Design: Prospective observational cohort study. Setting: Data were collected from a random sub-sample of 574 men, participants of the Tobago Bone Health Study (TBHS). Participants: 574 Afro-Caribbean men, aged 43+ years (mean age: 59.1 ± 10.5), who were randomly selected as the participants in both the baseline and the follow-up visits. Measurements: Baseline fasting serum 25(OH)D was measured using liquid chromatography mass spectrometry (LC-MS/MS), and and 1,25(OH)2D was measured using radioimmunosassay (RIA). Changes in dual-energy X-ray absorptiometry (DXA)-measured appendicular lean mass (ALM), and total body lean mass (TBLM) were measured over an average of 6.0 ± 0.5 years. The associations of 25(OH)D and 1,25(OH)2D with ALM and TBLM were assessed by multiple linear regression model after adjusting for potential confounders. Results: When stratifying all men into two groups by age, greater baseline 25(OH)D and 1,25(OH)2D levels were associated with smaller losses of ALM and TBLM in older (age 60+ years) but not in younger (age 43 – 59 years) men. When stratifying by DM status, the associations of 25(OH)D and 1,25(OH)2D with declines in ALM and TBLM were statistically significant only in prediabetic, but not among normal glycemic or diabetic men. Conclusion: Higher endogenous vitamin D concentrations are associated with less lean mass loss with aging among older and prediabetic Afro-Caribbean men independent of potential confounders. Our findings raise a possibility that maintaining high serum vitamin D level might be important for musculoskeletal health in elderly and prediabetic African ancestry men.

CITATION:
J. Hwang ; J.M. Zmuda ; A.L. Kuipers ; C.H. Bunker ; A.J. Santanasto ; V.W. Wheeler ; I. Miljkovic (2018): Serum Vitamin D and Age-related Muscle Loss in Afro-Caribbean Men: The Importance of Age and Diabetic Status. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2018.40

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RELATING THE MNA MOBILITY SINGLE ITEM TO USUAL WALKING SPEED IN HOSPITALIZED AND COMMUNITY-DWELLING GERIATRIC PATIENTS

S. De Breucker, T. Mets, T. Pepersack

J Frailty Aging 2019;8(3):138-140

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Usual walking speed (WS) is a relatively easy and reproducible tool for detecting mobility impairment. For some reasons, however, geriatric patients might not be able to perform walking tests. Therefore, a subjective assessment could be an alternative method to screen for mobility impairment. In the present paper, we explore the use of the mobility item from the Mini Nutritional Assessment-short form (MNA-sf) to assess mobility and its congruence with walking speed in hospitalized and ambulatory patients. We analyzed retrospective data from 357 patients and found a highly significant correlation between WS and the MNA-sf mobility item. After dichotomization of the MNA-sf mobility score (mobility impairment ≤1 and no impairment >1), AUC for ROC curves showed that the mobility item derived from the MNA-sf reflects fairly well the mobility of geriatric hospitalized patients (AUC = 0.773), while it performs better in ambulatory patients (AUC = 0.838).

CITATION:
S. De Breucker ; T. Mets ; T. Pepersack (2019): Relating the MNA mobility single item to usual walking speed in hospitalized and community-dwelling geriatric patients. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2019.14

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DECREASED HANDGRIP STRENGTH IS ASSOCIATED WITH IMPAIRMENTS IN EACH AUTONOMOUS LIVING TASK FOR AGING ADULTS IN THE UNITED STATES

R. McGrath, K. M. Erlandson, B.M. Vincent, K.J. Hackney, S.D. Herrmann, B.C. Clark

J Frailty Aging 2019;8(3):141-145

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Objectives: The primary purpose of this study was to determine the time-varying associations between decreased handgrip strength (HGS) and individual instrumental activities of daily living (IADL) impairments for a nationally-representative sample of aging adults in the United States. Design: Longitudinal-Panel. Setting: Detailed interviews were completed in person and core interviews were typically completed over the telephone. Participants: A total of 15,336 participants aged at least 50 years who participated in the 2006 wave of the Health and Retirement Study were followed biennially for 8-years. Measurements: A hand-held dynamometer assessed HGS and performance in IADLs were self-reported. Results: Every 5-kilogram decrease in HGS was associated with an increased odds ratio for the following IADL impairments: 1.11 (95% confidence interval (CI): 1.09, 1.13) for using a map, 1.10 (CI: 1.07, 1.12) for grocery shopping, 1.09 (CI: 1.05, 1.14) for taking medications, 1.07 (CI: 1.05, 1.09) for preparing hot meals, 1.06 (CI: 1.04, 1.08) for managing money, and 1.05 (CI: 1.02, 1.09) for using a telephone. Conclusions: Decreased HGS was associated with each IADL impairment, and slightly different associations were observed in individual IADL tasks for aging adults in the United States. Our findings suggest that decreased HGS, which is reflective of reduced function of the neuromuscular system, is associated with diminished performance in autonomous living tasks during aging. Losses in HGS may lead to the development of an IADL impairment. Therefore, health-care providers working with aging adults should utilize measures of HGS as a screening tool for identifying future deficits in neuromuscular functioning. Interventions designed to preserve IADLs in aging adults should also include measures of HGS for detecting early changes in IADL capacity, and intervening at the onset of HGS declines may help aging adults retain their ability to live autonomously.

CITATION:
R. McGrath ; K. M. Erlandson ; B.M. Vincent ; K.J. Hackney ; S.D. Herrmann ; B.C. Clark (2018): Decreased Handgrip Strength is Associated With Impairments in Each Autonomous Living Task for Aging Adults in the United States. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2018.47

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ADHERENCE TO A MEDITERRANEAN DIET IS NOT ASSOCIATED WITH RISK OF SARCOPENIC SYMPTOMOLOGY: A CROSS-SECTIONAL ANALYSIS OF OVERWEIGHT AND OBESE OLDER ADULTS IN AUSTRALIA

A. Stanton, J. Buckley, A. Villani

J Frailty Aging 2019;8(3):146-149

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Adherence to a Mediterranean Diet (MedDiet) is inversely associated with sarcopenia. The aim of this study was to examine the association between adherence to a MedDiet and sarcopenic symptomology in obese older adults. For confirmation of sarcopenia, low appendicular skeletal muscle (ASM: males, ≤7.25kg/m2; females, ≤5.5kg/m2) accompanied low handgrip strength (males, ≤30kg; females, ≤20kg) or low physical performance (Short Physical Performance Battery [SPPB]: ≤8; or gait speed: ≤0.8m/sec). Adherence to a MedDiet was determined using the Mediterranean Diet Adherence Screener (MEDAS). Sixty-five older adults were included. Adherence to a MedDiet was not associated with a decreased risk of sarcopenic symptomology (SPPB: OR = 0.20; 95% CI: 0.01-3.1; P = 0.234; Muscle strength: OR = 1.81; 95% CI: 0.32-10.15; P = 0.499; Gait speed: OR = 0.58; 95% CI: 0.13-2.50; P = 0.468). Future research should investigate whether a Mediterranean-style intervention can prevent or improve sarcopenic symptomology, including in non-Mediterranean populations.

CITATION:
A. Stanton ; J. Buckley ; A. Villani (2018): Adherence to a Mediterranean Diet is not associated with risk of sarcopenic symptomology: A cross-sectional analysis of overweight and obese older adults in Australia. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2018.46

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RELATIONSHIP BETWEEN GRIP STRENGTH AND NONALCOHOLIC FATTY LIVER DISEASE IN MEN LIVING WITH HIV REFERRED TO A METABOLIC CLINIC

P. Debroy, J.E. Lake, A. Malagoli, G. Guaraldi, for the Modena HIV Metabolic Cohort Team

J Frailty Aging 2019;8(3):150-153

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This study aimed to assess the relationship between grip strength (GS) and nonalcoholic fatty liver (NAFLD) in treated HIV-infected men. We included 169 HIV-infected men. GS was assessed using a hand-grip dynamometer. NALFD was defined by liver-spleen attenuation ratio <1.1 on computed tomography. Mean (SD) age was 57 (6) years and BMI 24.5 (2.9) kg/m2. NAFLD was diagnosed in 33% of men; sarcopenia was present in 28%. Mean (SD) hand grip strength in the dominant hand was 37.5 (7.6) kg. In multivariate logistic regression, intermediate and low GS were associated with higher risk of NAFLD (OR 3.05; CI 1.27-7.61, p=0.01; OR 2.47; CI 1.01-6.19, p=0.05, respectively). GS has an inverse association with NAFLD prevalence in HIV-infected men. Specific mechanisms through which muscle weakness and NAFLD are related require further exploration but are not accounted for merely by the burden of comorbid illness, HIV disease stage, or ART exposure.

CITATION:
P. Debroy ; J.E. Lake ; A. Malagoli ; G. Guaraldi ; for the Modena HIV Metabolic Cohort Team ; (2018): Relationship between grip strength and nonalcoholic fatty liver disease in men living with HIV referred to a metabolic clinic. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2018.37

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THE GROWTH HORMONE RELEASING HORMONE ANALOGUE, TESAMORELIN, DECREASES MUSCLE FAT AND INCREASES MUSCLE AREA IN ADULTS WITH HIV

S. Adrian, A. Scherzinger, A. Sanyal, J.E. Lake, J. Falutz, M.P. Dubé, T. Stanley, S. Grinspoon, J.-C. Mamputu, C. Marsolais, T.T. Brown, K.M. Erlandson

J Frailty Aging 2019;8(3):154-159

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Background: Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. Objectives: The goals of this exploratory secondary analysis were to determine the effects of tesamorelin on muscle quality (density) and quantity (area). Design: Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. Setting: U.S. and Canadian sites. Participants: People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%).Intervention: Tesamorelin or placebo. Measurements: Computed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm. Results: Tesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p<0.005), and the lean anterolateral/abdominal and rectus muscles (1.39 and 1.78 Hounsfield units; both p<0.005) compared to placebo. Significant increases were also seen in total area of the rectus and psoas muscles (0.44 and 0.46 centimeters2; p<0.005), and in the lean muscle area of all four truncal muscle groups (0.64-1.08 centimeters2; p<0.005). Conclusions: Among those with clinically significant decrease in visceral adipose tissue on treatment, tesamorelin was effective in increasing skeletal muscle area and density. Long term effectiveness of tesamorelin among people with and without HIV, and the impact of these changes in daily life should be further studied.

CITATION:
S. Adrian ; A. Scherzinger ; A. Sanyal ; J.E. Lake ; J. Falutz ; M.P. Dubé ; T. Stanley ; S. Grinspoon ; J.-C. Mamputu ; C. Marsolais ; T.T. Brown ; K.M. Erlandson (2018): The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2018.45

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