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Depression is Associated With Sarcopenia Due to Low Muscle Strength: Results From the ELSA-Brasil Study
JAMDA xxx (2018) 1e6
JAMDA journal homepage: www.jamda.com
Original Study
Depression is Associated With Sarcopenia Due to Low Muscle Strength: Results From the ELSA-Brasil Study Claudia Szlejf MD, PhD a, *, Claudia K. Suemoto MD, MSc, PhD a, b, Andre R. Brunoni MD, PhD c, Maria Carmen Viana MD, PhD d, Arlinda B. Moreno PhD e, Sheila M.A. Matos PhD f, Paulo A. Lotufo MD, PhD a, g, Isabela M. Benseñor MD, PhD a, g a
Center for clinical and epidemiological research, Hospital Universitario, University of Sao Paulo, Sao Paulo, Brazil Division of Geriatrics, University of Sao Paulo Medical School, Sao Paulo, Brazil Service of Interdisciplinary Neuromodulation, Laboratory of Neuroscience and National Institute of Biomarkers in Psychiatry, Department and Institute of Psychiatry, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil d Center of Psychiatric Epidemiology (CEPEP), Department of Social Medicine, Postgraduate Program in Public Health, Federal University of Espírito Santo, Vitória, Brazil e Department of Epidemiology and Quantitative Methods in Health, National School of Public Health Sérgio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil f Collective Health Institute, Federal University of Bahia, Salvador, Brazil g Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Brazil b c
a b s t r a c t Keywords: Sarcopenia muscle strength depression older adult
Objectives: To investigate the association of sarcopenia and its defining components with depression in Brazilian middle-aged and older adults. Design: Cross-sectional study. Setting and Participants: This analysis included 5927 participants from the ELSA-Brasil Study second data collection, aged 55 years and older, with complete data for exposure, outcome, and covariates. Measures: Muscle mass was evaluated by bioelectrical impedance analysis and muscle strength by handgrip strength. Sarcopenia was defined according to the Foundation for the National Institutes of Health (FNIH) criteria. Depression was assessed using the Clinical Interview Scheduled Revised (CIS-R). Information on sociodemographic characteristics, lifestyle, and clinical comorbidities were also obtained. Results: The frequencies of sarcopenia, presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass was 1.9%, 18.8%, 20.7%, 4.8%, and 2.9%, respectively. After adjustment for sociodemographic characteristics, clinical conditions, and lifestyle factors, depression was associated with sarcopenia (odds ratio [OR] ¼ 2.23, 95% confidence interval [CI] ¼ 1.11-4.48, P ¼ .024) and low muscle strength (OR ¼ 1.94, 95% CI ¼ 1.20-3.15, P ¼ .007), but it was not associated with presarcopenia, low muscle mass, and low muscle strength without loss of muscle mass. Conclusions: Depression is associated with sarcopenia defined by the FNIH criteria mainly because of its association with weakness. Future studies are needed to clarify the temporal relationship between both conditions. Ó 2018 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
A.R.B. is recipient of a CAPES/Alexander von Humboldt fellowship award for experienced researchers and a consultant of the Neurocare Group GmbH (Munich, Germany). The ELSA-Brasil study was supported by the Brazilian Ministry of Health and CNPq (grants 01060010.00RS, 01060212.00BA, 01060300.00ES, 01060278.00MG, 01060115.00SP, 01060071.00RJ). * Address correspondence to Claudia Szlejf MD, PhD, Centro de pesquisa Clínica e Epidemiológica, Hospital Universitário, Av. Lineu Prestes 2565, 3 andar, CEP 05508000; São Paulo, SP, Brazil. E-mail address: [email protected] (C. Szlejf). https://doi.org/10.1016/j.jamda.2018.09.020 1525-8610/Ó 2018 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
Sarcopenia, defined as the age-related loss of muscle mass and function,1 is a morbid condition that may increase the risk of mortality, hospitalization, falls, and disability in older adults.2 Although the scientific community recognizes the importance of studying sarcopenia and its associated factors, there is no universal operational definition. In the last decade, different consensus panels created algorithms to identify sarcopenia based on the combination of loss of muscle mass, function, and/or strength,1,3,4 although none of them were data-driven criteria validated to predict relevant clinical
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outcomes. Using pooled data from several cohorts, the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project defined clinically relevant measures of low muscle mass and low muscle strength associated with poor physical performance. Based on reduced gait speed, the Consortium determined cutoff points for low appendicular lean mass standardized for body mass index and low grip strength,5 which were further validated with incident mobility impairment and mortality.6 Although the FNIH criteria have been adopted in many studies, in Brazil they were used in only one small study in patients with chronic kidney disease to assess the frequency of sarcopenia.7 Depression, a common psychiatric disorder in late life, decreases quality of life, and increases the risk of mortality, cardiovascular diseases, and disability.8,9 Depression and sarcopenia share common pathophysiological pathways related to neurotrophins, inflammation, and oxidative stress, which are modulated by lifestyle behaviors, such as physical activity, smoking, and nutrition.10 The association between depression and sarcopenia has been investigated by cross-sectional studies, and a meta-analysis demonstrated that sarcopenia was independently associated with depression,11 although studies included in this meta-analysis adopted different definitions of sarcopenia and none used the FNIH definition. In a study with nursing home older adults, depression was not associated with sarcopenia defined by the FNIH criteria12; however, population-based studies exploring this association, using FNIH criteria to define sarcopenia, are missing. Therefore, the aims of this study were to investigate the association of depression with sarcopenia and its defining components (presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass) according to the FNIH criteria in Brazilian middle-aged and older adults participating in the ELSA-Brasil study.
Methods Study Population and Design The present study is a cross-sectional analysis of the ELSA-Brasil second data examination, which was conducted after 4 years of baseline. The ELSA-Brasil is a cohort of active and retired employees from public institutions located in different Brazilian cities, aged between 35 and 74 years at baseline, with the aim to investigate cardiovascular and chronic diseases in Brazilian adults. The study design and cohort profile have been published elsewhere.13,14 The baseline evaluation was conducted between 2008 and 2010 and included 15,105 participants. The second data collection, conducted between 2012 and 2014, reassessed 14,104 individuals that participated in the baseline evaluation, and collected information on sociodemographics, lifestyle factors, mental health, cognitive status, and occupational exposure. Anthropometric measurements, body composition analysis, and laboratory tests were also obtained. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local institutional review boards. All participants signed the informed consent prior to enrollment. For this analysis, we excluded participants (1) younger than 55 years at the time of the second data collection, (2) with self-reported weakness in both hands due to pain or any other condition, and (3) with incomplete data for exposure, outcomes, or covariates. Physical Measurements and Sarcopenia Assessment Anthropometric and body composition evaluations were performed after an overnight fast of 12 hours. Anthropometric assessment included height (in meters), measured with a fixed stadiometer with 0.1 cm accuracy (seca 216, seca Brasil, Cotia-SP, Brazil); weight (in
kilograms), measured with an electronic digital scale (Toledo Brasil Indústria de Balanças Ltda, São Bernardo do Campo-SP, Brazil); and body mass index (BMI), calculated as weight (in kilograms) divided by squared height (in meters). Obesity was defined as BMI 30. Body composition was assessed with a tetrapolar vertical bioelectrical impedance analyzer using 8-point tactile electrodes (Inbody230, InBody Co, Ltd, Seoul, Korea). Bioelectrical impedance analysis is a simple, safe, accessible, and precise method to assess skeletal muscle mass in large studies, with accurate estimates in comparison to dualenergy x-ray absorptiometry.15,16 Appendicular lean mass (in kilograms) was obtained, adding arms and legs lean mass. Appendicular lean mass standardized by BMI (ALMBMI) was calculated by dividing the appendicular lean mass by the BMI. Finally, grip strength was assessed with a Jamar hydraulic hand dynamometer (Sammons Preston, Bolingbrook, IL). Three measures were taken from each side, and the highest of all was considered. Sarcopenia was defined according to FNIH Sarcopenia Project criteria: low muscle mass defined by ALMBMI <0.789 for men and <0.512 for women, and low muscle strength defined as handgrip strength <26 kg for men and <16 kg for women.6 Using the same FNIH cut-off points, we classified participants with low muscle mass and normal muscle strength in presarcopenic. Depression Assessment Depressive symptoms were assessed using a Brazilian version of the Clinical Interview Scheduled Revised (CIS-R).17 This questionnaire is reliable when applied by trained lay interviewers to evaluate mental symptoms and psychiatric disorders.18 At the ELSA-Brasil’s second data examination, 5 sections of the CIS-R were applied: fatigue, concentration and forgetfulness, sleep problems, depression (which assesses depressed mood), and depressive ideas (which assesses low self-esteem, lack of sexual desire, restlessness, slowness, guilt, hopelessness, and suicidal thoughts). Each section presents 2 questions that confirm the presence of the specific symptom in the last month. Additionally, the interviewers applied a section that assess the overall effect in life of positive psychiatric symptoms. The combination of answers yields the diagnoses of depression (mild, moderate, and severe) according to the International Classification of Diseases, 10th Revision (ICD-10). Sociodemographic Characteristics and Clinical Profile Questionnaires addressed sociodemographic characteristics and lifestyle, such as age, sex, self-reported race (white, black, brown, and others), education (high school or lower vs higher education), smoking status (never, former, and current smoker), leisure-time physical activity using the International Physical Activity Questionnaire long form (classifying participants in active, insufficiently active, and inactive),19 and current alcohol use. The evaluated clinical conditions were hypertension (use of anti-hypertensive drug, systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg), diabetes mellitus (self-reported, use of oral hypoglycemic agents or insulin therapy, fasting plasma glucose 126 mg/dL, 2-hour postprandial 75 g glucose test 200 mg/dL, or glycosylated hemoglobin 6.5%), coronary artery disease (previous self-reported myocardial infarction or myocardial revascularization), self-reported previous stroke, and thyroid function status (classified as euthyroidism, overt hypothyroidism, subclinical hypothyroidism, overt hyperthyroidism, and subclinical hyperthyroidism according to thyrotropin and free thyroxine levels, and the use of medications for thyroid function disorders). Data for previous cardiovascular disease and thyroid function were obtained from the baseline evaluation of the ELSA-Brasil study.
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Statistical Analysis All continuous variables were nonnormally distributed and were presented as median and interquartile range, and categorical variables as absolute and relative frequencies. Characteristics of participants according to depression status were compared using the Wilcoxon rank-sum test, chi-square test, and Fisher exact test for continuous variables nonnormally distributed, categorical variables, and categorical variables with small cell counts, respectively. To investigate the association of depression with sarcopenia, presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass, we used simple and adjusted logistic regression models. Multiple models were built as follows: model 1 adjusted by sociodemographic characteristics (age, sex, education, and race) and model 2 adjusted for sociodemographic characteristics, clinical conditions, and lifestyle factors (diabetes mellitus, hypertension, coronary artery disease, previous stroke, thyroid dysfunction, smoking status, alcohol consumption, and leisure-time physical activity). Effect modification of older age (65 years) and sex on the association of depression and sarcopenia was investigated with interaction terms, considering a P value < .10 to stratify the analysis. Additionally, simple and fully adjusted logistic regression models were used to explore the association of each symptom of depression evaluated by the CIS-R with sarcopenia, presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass. Data were analyzed using Stata 14.2 (StataCorp LP, College Station, TX). The alpha-level was set at 0.05.
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14,014 participants in the ELSA-Brasil Study 2nd wave
7248 participants aged 55 years or older
2 participants with reported weakness in both hands: one due to rheumatoid arthritis and the other due to pain. 7246 participants
Missing data on sarcopenia: 831 -
-
Hand-grip test: 333 Bioelectrical impedance analysis: 393 Both: 105
6415 participants
Missing data on the CIS-R score and/or other covariates: 488
5927 participants
Results Fig. 1. Flowchart of study participants.
Among the 14,014 participants in the first follow-up evaluation of the ELSA-Brasil study, we excluded 6766 individuals younger than 55 years, 2 individuals with reported weakness in both hands due to pain and rheumatoid arthritis, and 1319 individuals with incomplete data on sarcopenia parameters, CIS-R scores, or covariates. Therefore, 5927 participants (mean age: 62.7 5.9 years, 54.4% women) were included in this analysis, as seen in Figure 1. Sarcopenia was found in 114 participants (1.9%), 71 women (2.2%) and 43 men (1.6%); 40 were younger than 65 years (1.0%) and 74 were older than 65 years (3.8%). The frequency of presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass was 18.8%, 20.7%, 4.8%, and 2.9%, respectively. Depression was present in 243 participants (4.1%). Table 1 shows participants’ characteristics according to depression status. Participants with depression had higher frequency of sarcopenia, low muscle mass, low muscle strength, lower appendicular lean mass, ALMBMI, and lower grip strength, and higher body mass index. They were also predominantly female and black, with lower education, and with higher frequency of hypertension and physical inactivity. Table 2 shows the association of depression with sarcopenia and its defining components. After adjustment for sociodemographic characteristics, clinical conditions, and lifestyle factors, depression was associated with sarcopenia and low muscle strength, and showed a tendency toward association with low muscle strength without loss of muscle mass. Depression was not associated with presarcopenia and low muscle mass. Older age and sex were not effect modifiers on the association between depression and sarcopenia (interaction term P values ¼ .235 and .936, respectively). When we investigated the association of each symptom of depression evaluated by the CIS-R with sarcopenia and its defining components, impaired concentration and forgetfulness were associated with sarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass after controlling for confounders; sleep problems were associated with sarcopenia and low muscle mass; depressed mood was associated with sarcopenia
and low muscle strength; and depressive ideas with sarcopenia, low muscle strength, and low muscle strength without loss of muscle mass (see Table 3). Discussion In the present study, sarcopenia was found in 1% of middle-aged and almost 4% of older adults of a Brazilian cohort. Our study also showed that middle-aged and older adults with depression have higher odds of sarcopenia as defined by the FNIH criteria after adjustment for sociodemographic characteristics, lifestyle, and clinical conditions. This association was mainly due to low muscle strength. Moreover, depressive key symptoms such as concentration and forgetfulness, depressed mood, and depressive ideas were associated with both sarcopenia and weakness. This study used a large sample to assess the frequency of sarcopenia according to the FNIH criteria, and our findings are compatible with other studies.5,20 The study of Souza et al, conducted in a small sample of Brazilian patients with chronic kidney disease, found a much higher prevalence of sarcopenia (28.7%) defined by the FNIH criteria, and this difference was probably due to the presence of chronic kidney disease.7 Conversely, our study sample was composed of younger and healthier individuals. A meta-analysis of Brazilian studies found that in older adults the pooled prevalence of sarcopenia according to other operational definitions that include low muscle mass and function is around 16%.21 Indeed, the FNIH criteria are more restrictive than other definitions of sarcopenia.22 Cross-sectional studies that investigated the association of depression and sarcopenia assessed by low muscle mass combined with low muscle function and/or poor physical performance are scarce. Sarcopenia defined according to the European Working Group on Sarcopenia in Older People criteria was associated with depressive symptoms in cohorts of community-dwelling older adults in Taiwan
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Table 1 Characteristics of Participants According to Depression (n ¼ 5927)
Sarcopenia Appendicular lean mass, kg, median (IQR) BMI, median (IQR) ALMBMI, median (IQR) Low muscle mass Presarcopenia Grip strength, kg, median (IQR) Low muscle strength Low muscle strength without loss of muscle mass Age, y, median (IQR) Female Race Black Brown White Other Higher education Diabetes mellitus Hypertension Coronary artery disease Stroke Thyroid dysfunction Subclinical hypothyroidism Hypothyroidism Subclinical hyperthyroidism Hyperthyroidism Current or previous smoker Current alcohol use Leisure time physical activity Inactive Insufficiently active Active
Without Depression (n ¼ 5684)
With Depression (n ¼ 243)
P
104 18.96 26.96 0.704 1166 1062 30 264 160 62 3037
(1.83) (15.82-23.06) (24.33-30.11) (0.578-0.854) (20.51) (18.68) (23-38) (4.64) (2.81) (58-66) (53.43)
10 17.22 28.06 0.614 63 53 25 21 11 61 185
.026* <.001y <.001y <.001y .042z .222z <.001y .008* .117* .004y <.001z .032*
788 1408 3237 251 3212 1618 2935 155 90
(13.86) (24.77) (56.95) (4.42) (56.51) (28.47) (51.64) (2.73) (1.58)
49 63 124 7 100 77 148 10 6
(20.16) (25.93) (51.03) (2.88) (41.15) (31.69) (60.91) (4.12) (2.47)
368 541 84 50 2765 3688
(6.47) (9.52) (1.48) (0.88) (48.65) (64.88)
17 18 6 3 129 117
(7.00) (7.41) (2.47) (1.23) (53.09) (48.15)
3321 (58.43) 847 (14.90) 1516 (26.67)
(4.12) (15.44-20.50) (25.00-31.83) (0.524-0.716) (25.93) (21.81) (20-32) (8.64) (4.53) (57-65) (76.13)
<.001z .276z .005z .226* .290* .449*
.175z <.001z <.001*
179 (73.66) 23 (9.47) 41 (16.87)
ALMBMI, appendicular lean mass standardized to BMI; IQR, interquartile range. Values are n (%) unless otherwise noted. *Fisher exact test. y Wilcoxon rank-sum test. z 2 c test.
and Turkey,23,24 and in a study with middle-aged and older adults with end-stage renal disease.25 However, other studies that adopted these criteria did not find an association with depression.26,27 Studies that assessed sarcopenia using the Asian Working Group for Sarcopenia criteria also show conflicting results, with a significant association with depressive symptoms among Korean community-dwelling older women after adjustment for confounders,28 but no association could be demonstrated among Japanese older adults who attended a memory clinic.29 To the extent of our knowledge, no study that investigated the association between depression and sarcopenia in community-dwelling individuals used the FNIH criteria to define sarcopenia, although in a study with nursing-home residents sarcopenia defined by the FNIH criteria was not associated with depression.12 In the meta-analysis of Chang et al. that investigated the
association of sarcopenia and depression, studies that measured muscle mass with bioelectrical impedance analysis and studies that incorporated handgrip strength in the diagnosis of sarcopenia tended to show a stronger association, which is in accordance with our findings.11 In our study, the association of depression and depressive symptoms with sarcopenia was mainly driven by weakness and not by low muscle mass. These findings corroborate previous works.30,31 Fukumori et al demonstrated that lower grip strength increased the odds of depressive symptoms at baseline and of incident depressive symptoms after 1 year in a large prospective study with middle-aged and older adults.30 In a longitudinal study with British older adults, lower tertiles of hand-grip strength and muscle weakness defined according to the FNIH criteria were associated with incident depressive
Table 2 Association of Depression With Sarcopenia and Its Defining Components (N ¼ 5927) Crude Analysis
Sarcopenia Presarcopenia Low muscle mass Low muscle strength Low muscle strength without loss of muscle mass
Model 2y
Model 1*
OR (95% CI)
P
OR (95% CI)
P
OR (95% CI)
P
2.30 1.21 1.36 1.94 1.64
.014 .223 .042 .005 .122
2.41 1.14 1.29 2.03 1.70
.012 .413 .099 .004 .103
2.23 1.06 1.19 1.94 1.67
.024 .731 .264 .007 .115
(1.19-4.46) (0.89-1.66) (1.01-1.82) (1.22-3.09) (0.88-3.06)
(1.21-4.78) (0.83-1.57) (0.95-1.75) (1.26-3.28) (0.90-3.20)
(1.11-4.48) (0.77-1.46) (0.88-1.62) (1.20-3.15) (0.88-3.17)
CI, confidence interval; OR, odds ratio. *Logistic regression adjusted for age, sex, race, and education. y Logistic regression adjusted for age, sex, race, education, diabetes mellitus, hypertension, coronary artery disease, stroke, thyroid function status, smoking status, alcohol consumption, and leisure-time physical activity.
CIS-R, Clinical Interview Schedule Revised. Values are odds ratios (95% confidence intervals). *Logistic regression adjusted for age, sex, race, education, diabetes mellitus, hypertension, coronary artery disease, stroke, thyroid function status, smoking status, alcohol consumption, and leisure-time physical activity. y Low self-esteem, lack of sexual desire, restlessness, slowness, hopelessness, and/or suicidal thoughts. z P < .05. x P < .01.
1.60 (1.02-2.51)z 1.51 (0.97-2.35) 1.70 (1.20-2.40)x 1.68 (1.20-2.35)x 1.01 (0.82-1.25) 1.16 (0.94-1.42) 0.93 (0.74-1.16) 1.78 (1.06-2.99)z 1.87 (1.14-3.09)z
1.06 (0.86-1.32)
0.94 (0.67-1.31) 1.45 (0.97-2.18) 0.95 (0.68-1.32) 1.41 (0.95-2.10) 1.18 (0.92-1.53) 1.59 (1.16-2.17)x 1.22 (0.95-1.57) 1.62 (1.20-2.18)x 1.17 (1.02-1.34)z 1.13 (0.94-1.35) 1.25 (1.09-1.42)x 1.28 (1.07-1.52)x 1.10 (0.96-1.27) 1.05 (0.87-1.27) 1.65 (1.12-2.42)z 1.76 (1.11-2.79)z 1.71 (1.18-2.49)x 1.89 (1.21-2.95)x
1.18 (1.03-1.36)z 1.19 (0.99-1.43)
1.21 (0.87-1.70) 1.63 (1.09-2.46)z 1.29 (0.93-1.78) 1.54 (1.04-2.29)z 1.20 (0.92-1.57) 1.69 (1.23-2.32)x 1.27 (0.99-1.64) 1.65 (1.21-2.24)x 1.05 (0.90-1.22) 1.22 (1.01-1.47)z 1.09 (0.95-1.25) 1.33 (1.11-1.59)x 1.03 (0.88-1.20) 1.15 (0.95-1.40) 1.07 (0.93-1.24) 1.26 (1.04-1.52)z 1.17 (0.77-1.78) 1.73 (1.07-2.81)z 1.23 (0.83-1.83) 1.76 (1.10-2.79)z
Fatigue Concentration and forgetfulness Sleep problems Depression (depressed mood) Depressive ideasy
Adjusted* Crude Adjusted* Crude Crude Crude Adjusted* Crude
Adjusted*
Low Muscle Mass Presarcopenia Sarcopenia
Table 3 Association of CIS-R Clusters of Depressive Symptoms With Sarcopenia and Its Defining Components (N ¼ 5927)
Adjusted*
Low Muscle Strength
Low Muscle Strength Without Loss of Muscle Mass
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symptoms only in obese participants.31 Additionally, low muscle mass according to different definitions was not associated with depression in several studies.32e34 A Brazilian cross-sectional study with community-dwelling older adults defined cutoff points for low handgrip strength based on slow gait speed and found values similar to the ones defined by the FNIH and adopted in the present study.35 However, Vasconcelos et al did not find an association between depressive symptoms and muscle weakness, although depressive symptoms were associated with the combination of muscle weakness and slow gait speed.35 Moreover, presarcopenia and low muscle mass were associated with depressive symptoms in some studies in which muscle mass was measured with dual-energy x-ray absorptiometry, and this could explain the difference in findings.28,36 Different pathways may explain the bilateral association between depression and sarcopenia. Neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, known to promote neuronal survival, differentiation, and synaptic potentiation, are produced by both the brain and skeletal muscle, and are associated with mood and muscle regeneration.10 Another possible mechanism is the chronic low-grade inflammation and oxidative stress associated with both sarcopenia and depression.37,38 Besides the common moleculedriven pathways, sarcopenia and depression also share similar lifestyle factors. Physical activity is credited in the slowing down and the prevention of age-related loss of muscle mass, strength, and function,39 as with the prevention and treatment of depressive symptoms. On the other hand, depression may lead to inactivity.40 Therefore, physical inactivity acts as common risk factor for sarcopenia and depression41 and may also mediate the association of both conditions. Nutrition also plays a major role in the prevention of sarcopenia and depression, since an inadequate intake of micronutrients, calories, and proteins increases the risk of both of them.42,43 Similarly, smoking is a common hazard for both conditions.44,45 Other possible explanation is that lower grip strength is associated with poorer quality of life,46 possibly affecting mental health. On the other hand, depression may cause a decline in system physical functioning, leading to weakness. This is the first large study to assess sarcopenia defined by the FNIH criteria and its association with depression in Latin America, adjusting the analysis for relevant confounders, such as sociodemographic characteristics, cardiovascular risk factors, lifestyle factors, and thyroid function status. Nonetheless, our study has several limitations. The cross-sectional design prevents establishing a causal and temporal relationship between depression and sarcopenia. Although we used data from a prospective study, sarcopenia parameters were not measured at baseline, precluding the estimation of sarcopenia incidence and the investigation of the longitudinal association between depression and sarcopenia. Further analysis of upcoming examinations of the cohort may assess the evolution of sarcopenia in participants with depression or viceversa. Another relevant point is that the ELSA-Brasil is not a population-based study, and participants have higher education and higher income compared to the Brazilian population. Nevertheless, the cohort allows the study of associations. Besides, the applicability of the estimates from ELSA-Brasil to Brazilian adults is supported by the similarities in prevalence of behavioral risk factors and chronic conditions evaluated by ELSA-Brasil and by VIGITEL, a telephonebased behavioral risk factor survey, which has representative data for adults living in 27 Brazilian state capitals and the Federal District.47 Also, appendicular lean mass in our study was determined by bioelectrical impedance analysis and not by dual-energy x-ray absorptiometry, the technique to measure muscle mass proposed by the FNIH criteria. Finally, we adjusted the analysis for relevant confounders on the association between depression and sarcopenia, but residual confounding cannot be ruled out. In conclusion, depression is associated with sarcopenia as defined by the FNIH criteria in Brazilian middle-aged and older adults. Further
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longitudinal studies are needed to clarify the temporal relationship between both conditions. References 1. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European working Group on sarcopenia in older people. Age Ageing 2010;39:412e423. 2. Beaudart C, Zaaria M, Pasleau F, et al. Health outcomes of sarcopenia: A systematic review and meta-analysis. PLoS One 2017;12:ed0169548. 3. Fielding RA, Vellas B, Evans WJ, et al. Sarcopenia: An undiagnosed condition in older adults. Current consensus definition: Prevalence, etiology, and consequences. International Working Group on Sarcopenia. J Am Med Dir Assoc 2011;12:249e256. 4. Chen LK, Liu LK, Woo J, et al. Sarcopenia in Asia: Consensus report of the Asian working Group for sarcopenia. J Am Med Dir Assoc 2014;15:95e101. 5. Studenski SA, Peters KW, Alley DE, et al. The FNIH sarcopenia project: Rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci 2014;69:547e558. 6. McLean RR, Shardell MD, Alley DE, et al. Criteria for clinically relevant weakness and low lean mass and their longitudinal association with incident mobility impairment and mortality: The Foundation for the National Institutes of Health (FNIH) sarcopenia project. J Gerontol A Biol Sci Med Sci 2014;69: 576e583. 7. Souza VA, Oliveira D, Barbosa SR, et al. Sarcopenia in patients with chronic kidney disease not yet on dialysis: Analysis of the prevalence and associated factors. PLoS One 2017;12:e0176230. 8. Eurelings LS, van Dalen JW, Ter Riet G, et al. Apathy and depressive symptoms in older people and incident myocardial infarction, stroke, and mortality: A systematic review and meta-analysis of individual participant data. Clin Epidemiol 2018;10:363e379. 9. Schillerstrom JE, Royall DR, Palmer RF. Depression, disability and intermediate pathways: A review of longitudinal studies. J Geriatr Psychiatry Neurol 2008; 21:183e197. 10. Pasco JA, Williams LJ, Jacka FN, et al. Sarcopenia and the common mental disorders: A potential regulatory role for skeletal muscle on brain function? Curr Osteoporos Rep 2015;13:351e357. 11. Chang KV, Hsu TH, Wu WT, et al. Is sarcopenia associated with depression? A systematic review and meta-analysis of observational studies. Age Ageing 2017;46:738e746. 12. Zeng Y, Xiaohy H, Lingling X, et al. The prevalence of sarcopenia in Chinese elderly nursing home residents: A comparison of 4 diagnostic criteria. J Am Med Dir Assoc 2018;19:690e695. 13. Aquino EM, Barreto SM, Bensenor IM, et al. Brazilian longitudinal study of adult health (ELSA-Brasil): Objectives and design. Am J Epidemiol 2012;175: 315e324. 14. Schmidt MI, Duncan BB, Mill JG, et al. Cohort profile: Longitudinal study of adult health (ELSA-Brasil). Int J Epidemiol 2015;44:68e75. 15. Roubenoff R, Baumgartner RN, Harris TB, et al. Application of bioelectrical impedance analysis to elderly populations. J Gerontol A Biol Sci Med Sci 1997; 52:M129eM136. 16. Malavolti M, Mussi C, Poli M, et al. Cross-calibration of eight-polar bioelectrical impedance analysis versus dual-energy X-ray absorptiometry for the assessment of total and appendicular body composition in healthy subjects aged 2182 years. Ann Hum Biol 2003;30:380e391. 17. Nunes MA, Alves MG de M, Chor D, et al. Cross-cultural adaptation of CIS-R (clinical Interview Scheduled Revised version) for the Portuguese in longitudinal study of adult health (ELSA). Rev HCPA 2011;31:487e490. 18. Lewis G, Pelosi AJ, Araya R, Dunn G. Measuring psychiatric disorder in the community: A standardized assessment for use by lay interviewers. Psychol Med 1992;22:465e486. 19. Craig CL, Marshall AL, Sjöström M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003;35: 1381e1395. 20. Cooper R, Bann D, Wloch EG, et al. “Skeletal muscle function deficit” in a nationally representative British birth cohort in early old age. J Gerontol A Biol Sci Med Sci 2015;70:604e607. 21. Diz JB, Leopoldino AA, Moreira BS, et al. Prevalence of sarcopenia in older Brazilians: A systematic review and meta-analysis. Geriatr Gerontol Int 2017; 17:5e16.
22. Dam TT, Peters KW, Fragala M, et al. An evidence-based comparison of operational criteria for the presence of sarcopenia. J Gerontol A Biol Sci Med Sci 2014;69:584e590. 23. Hsu YH, Liang CK, Chou MY, et al. Association of cognitive impairment, depressive symptoms and sarcopenia among healthy older men in the veterans retirement community in southern Taiwan: A cross-sectional study. Geriatr Gerontol Int 2014;14(Suppl. 1):102e108. 24. Kilavuz A, Meseri R, Savas S, et al. Association of sarcopenia with depressive symptoms and functional status among ambulatory community-dwelling elderly. Arch Gerontol Geriatr 2018;76:196e201. 25. Kim JK, Choi SR, Choi MJ, et al. Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease. Clin Nutr 2014;33: 64e68. 26. Alexandre T da S, Duarte YA, Santos JL, et al. Prevalence and associated factors of sarcopenia among elderly Brazilian: Findings from the SABE study. J Nutr Health Aging 2014;18:284e290. 27. Ishii S, Chang C, Tanaka T, et al. The association between sarcopenic obesity and depressive symptoms in older Japanese adults. PLoS One 2016;11:e0162898. 28. Lee I, Cho J, Hing H, et al. Sarcopenia is associated with cognitive impairment and depression in elderly Korean women. Iran J Publ Health 2018;47:327e334. 29. Sugimoto T, Ono R, Murata S, et al. Prevalence and associated factors of sarcopenia in elderly subjects with amnestic mild cognitive impairment or Alzheimer disease. Curr Alzheimer Res 2016;13:718e726. 30. Fukumori N, Yamamoto Y, Takegami M, et al. Association between hand-grip strength and depressive symptoms: Locomotive Syndrome and health outcomes in Aizu cohort study (LOHAS). Age Ageing 2015;44:592e598. 31. Hamer M, Batty GD, Kivimaki M. Sarcopenic obesity and risk of new onset depressive symptoms and risk of new onset depressive symptoms in older adults: English longitudinal study of ageing. Int J Obes (Lond) 2015;39: 1717e1720. 32. Lee JS, Aueyung TW, Kwok T, et al. Associated factors and health impact of sarcopenia in older Chinese men and women: A cross-sectional study. Gerontology 2007;53:404e410. 33. Cho Y, Shin SY, Shin MJ. Sarcopenic obesity is associated with lower indicators of psychological health and quality of life in Koreans. Nutr Res 2015;35: 384e392. 34. Byeon CH, Kang KY, Kang SH, et al. Sarcopenia is not associated with depression in Korean adults: Results from the 2010-2011 Korean National health and nutrition examination survey. Korean J Fam Med 2016;37:37e43. 35. Vasconcelos KS, Dias JM, Bastone A de C, et al. Handgrip strength cutoff points to identify mobility limitations in community-dwelling older people and associated factors. J Nutr Health Aging 2016;20:306e315. 36. Kim NH, Kim HS, Eun CR, et al. Depression is associated with sarcopenia, not central obesity, in elderly Korean men. J Am Geriatr Soc 2011;59:2062e2068. 37. Schaap LA, Pluijm SM, Deeg DJ, et al. Higher inflammatory marker levels in older persons: Associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci 2009;64:1183e1189. 38. Berk M, Williams LJ, Jacka FN, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 2013;11:200. 39. Roshanaei-Moghaddam B, Katon WJ, Russo J. The longitudinal effects of depression on physical activity. Gen Hosp Psychiatry 2009;31:306e315. 40. Phu S, Boersma D, Duque G. Exercise and sarcopenia. J Clin Densitom 2015;18: 488e492. 41. Wegner M, Helmich I, Machado S, et al. Effects of exercise on anxiety and depression disorders: Review of meta-analyses and neurobiological mechanisms. CNS Neurol Disord Drug Targets 2014;13:1002e1014. 42. Szlejf C, Rosas-Carrasco O. Nutrition interventions to manage sarcopenia: An appraisal of the existing evidence. Res Rep Med 2018;1:105. 43. Lai JS, Hiles S, Bisquera A, et al. A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults. Am J Clin Nutr 2014;99:181e197. 44. Steffl M, Bohannon RW, Petr M, et al. Relation between cigarette smoking and sarcopenia: Meta-analysis. Physiol Res 2015;64:419e426. 45. Luger TM, Suls J, Vander Weg MW. How robust is the association between smoking and depression in adults? A meta-analysis using linear mixed-effects models. Addict Behav 2014;39:1418e1429. 46. Sayer AA, Syddhall HE, Martin HJ, et al. Is grip strength associated with healthrelated quality of life? Findings from the Hertfordshire cohort study. Age Ageing 2006;35:409e415. 47. Brasil, Ministério da Saúde. Vigitel Brazil 2010: Protective and Risk Factors for Chronic Diseases ny Telephone Survey. Available at: http://bvsms.saude.gov.br/ bvs/publicacoes/vigitel_2010.pdf. Accessed June 13, 2018.
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Original Study
Depression is Associated With Sarcopenia Due to Low Muscle Strength: Results From the ELSA-Brasil Study Claudia Szlejf MD, PhD a, *, Claudia K. Suemoto MD, MSc, PhD a, b, Andre R. Brunoni MD, PhD c, Maria Carmen Viana MD, PhD d, Arlinda B. Moreno PhD e, Sheila M.A. Matos PhD f, Paulo A. Lotufo MD, PhD a, g, Isabela M. Benseñor MD, PhD a, g a
Center for clinical and epidemiological research, Hospital Universitario, University of Sao Paulo, Sao Paulo, Brazil Division of Geriatrics, University of Sao Paulo Medical School, Sao Paulo, Brazil Service of Interdisciplinary Neuromodulation, Laboratory of Neuroscience and National Institute of Biomarkers in Psychiatry, Department and Institute of Psychiatry, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil d Center of Psychiatric Epidemiology (CEPEP), Department of Social Medicine, Postgraduate Program in Public Health, Federal University of Espírito Santo, Vitória, Brazil e Department of Epidemiology and Quantitative Methods in Health, National School of Public Health Sérgio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil f Collective Health Institute, Federal University of Bahia, Salvador, Brazil g Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Brazil b c
a b s t r a c t Keywords: Sarcopenia muscle strength depression older adult
Objectives: To investigate the association of sarcopenia and its defining components with depression in Brazilian middle-aged and older adults. Design: Cross-sectional study. Setting and Participants: This analysis included 5927 participants from the ELSA-Brasil Study second data collection, aged 55 years and older, with complete data for exposure, outcome, and covariates. Measures: Muscle mass was evaluated by bioelectrical impedance analysis and muscle strength by handgrip strength. Sarcopenia was defined according to the Foundation for the National Institutes of Health (FNIH) criteria. Depression was assessed using the Clinical Interview Scheduled Revised (CIS-R). Information on sociodemographic characteristics, lifestyle, and clinical comorbidities were also obtained. Results: The frequencies of sarcopenia, presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass was 1.9%, 18.8%, 20.7%, 4.8%, and 2.9%, respectively. After adjustment for sociodemographic characteristics, clinical conditions, and lifestyle factors, depression was associated with sarcopenia (odds ratio [OR] ¼ 2.23, 95% confidence interval [CI] ¼ 1.11-4.48, P ¼ .024) and low muscle strength (OR ¼ 1.94, 95% CI ¼ 1.20-3.15, P ¼ .007), but it was not associated with presarcopenia, low muscle mass, and low muscle strength without loss of muscle mass. Conclusions: Depression is associated with sarcopenia defined by the FNIH criteria mainly because of its association with weakness. Future studies are needed to clarify the temporal relationship between both conditions. Ó 2018 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
A.R.B. is recipient of a CAPES/Alexander von Humboldt fellowship award for experienced researchers and a consultant of the Neurocare Group GmbH (Munich, Germany). The ELSA-Brasil study was supported by the Brazilian Ministry of Health and CNPq (grants 01060010.00RS, 01060212.00BA, 01060300.00ES, 01060278.00MG, 01060115.00SP, 01060071.00RJ). * Address correspondence to Claudia Szlejf MD, PhD, Centro de pesquisa Clínica e Epidemiológica, Hospital Universitário, Av. Lineu Prestes 2565, 3 andar, CEP 05508000; São Paulo, SP, Brazil. E-mail address: [email protected] (C. Szlejf). https://doi.org/10.1016/j.jamda.2018.09.020 1525-8610/Ó 2018 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
Sarcopenia, defined as the age-related loss of muscle mass and function,1 is a morbid condition that may increase the risk of mortality, hospitalization, falls, and disability in older adults.2 Although the scientific community recognizes the importance of studying sarcopenia and its associated factors, there is no universal operational definition. In the last decade, different consensus panels created algorithms to identify sarcopenia based on the combination of loss of muscle mass, function, and/or strength,1,3,4 although none of them were data-driven criteria validated to predict relevant clinical
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outcomes. Using pooled data from several cohorts, the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project defined clinically relevant measures of low muscle mass and low muscle strength associated with poor physical performance. Based on reduced gait speed, the Consortium determined cutoff points for low appendicular lean mass standardized for body mass index and low grip strength,5 which were further validated with incident mobility impairment and mortality.6 Although the FNIH criteria have been adopted in many studies, in Brazil they were used in only one small study in patients with chronic kidney disease to assess the frequency of sarcopenia.7 Depression, a common psychiatric disorder in late life, decreases quality of life, and increases the risk of mortality, cardiovascular diseases, and disability.8,9 Depression and sarcopenia share common pathophysiological pathways related to neurotrophins, inflammation, and oxidative stress, which are modulated by lifestyle behaviors, such as physical activity, smoking, and nutrition.10 The association between depression and sarcopenia has been investigated by cross-sectional studies, and a meta-analysis demonstrated that sarcopenia was independently associated with depression,11 although studies included in this meta-analysis adopted different definitions of sarcopenia and none used the FNIH definition. In a study with nursing home older adults, depression was not associated with sarcopenia defined by the FNIH criteria12; however, population-based studies exploring this association, using FNIH criteria to define sarcopenia, are missing. Therefore, the aims of this study were to investigate the association of depression with sarcopenia and its defining components (presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass) according to the FNIH criteria in Brazilian middle-aged and older adults participating in the ELSA-Brasil study.
Methods Study Population and Design The present study is a cross-sectional analysis of the ELSA-Brasil second data examination, which was conducted after 4 years of baseline. The ELSA-Brasil is a cohort of active and retired employees from public institutions located in different Brazilian cities, aged between 35 and 74 years at baseline, with the aim to investigate cardiovascular and chronic diseases in Brazilian adults. The study design and cohort profile have been published elsewhere.13,14 The baseline evaluation was conducted between 2008 and 2010 and included 15,105 participants. The second data collection, conducted between 2012 and 2014, reassessed 14,104 individuals that participated in the baseline evaluation, and collected information on sociodemographics, lifestyle factors, mental health, cognitive status, and occupational exposure. Anthropometric measurements, body composition analysis, and laboratory tests were also obtained. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local institutional review boards. All participants signed the informed consent prior to enrollment. For this analysis, we excluded participants (1) younger than 55 years at the time of the second data collection, (2) with self-reported weakness in both hands due to pain or any other condition, and (3) with incomplete data for exposure, outcomes, or covariates. Physical Measurements and Sarcopenia Assessment Anthropometric and body composition evaluations were performed after an overnight fast of 12 hours. Anthropometric assessment included height (in meters), measured with a fixed stadiometer with 0.1 cm accuracy (seca 216, seca Brasil, Cotia-SP, Brazil); weight (in
kilograms), measured with an electronic digital scale (Toledo Brasil Indústria de Balanças Ltda, São Bernardo do Campo-SP, Brazil); and body mass index (BMI), calculated as weight (in kilograms) divided by squared height (in meters). Obesity was defined as BMI 30. Body composition was assessed with a tetrapolar vertical bioelectrical impedance analyzer using 8-point tactile electrodes (Inbody230, InBody Co, Ltd, Seoul, Korea). Bioelectrical impedance analysis is a simple, safe, accessible, and precise method to assess skeletal muscle mass in large studies, with accurate estimates in comparison to dualenergy x-ray absorptiometry.15,16 Appendicular lean mass (in kilograms) was obtained, adding arms and legs lean mass. Appendicular lean mass standardized by BMI (ALMBMI) was calculated by dividing the appendicular lean mass by the BMI. Finally, grip strength was assessed with a Jamar hydraulic hand dynamometer (Sammons Preston, Bolingbrook, IL). Three measures were taken from each side, and the highest of all was considered. Sarcopenia was defined according to FNIH Sarcopenia Project criteria: low muscle mass defined by ALMBMI <0.789 for men and <0.512 for women, and low muscle strength defined as handgrip strength <26 kg for men and <16 kg for women.6 Using the same FNIH cut-off points, we classified participants with low muscle mass and normal muscle strength in presarcopenic. Depression Assessment Depressive symptoms were assessed using a Brazilian version of the Clinical Interview Scheduled Revised (CIS-R).17 This questionnaire is reliable when applied by trained lay interviewers to evaluate mental symptoms and psychiatric disorders.18 At the ELSA-Brasil’s second data examination, 5 sections of the CIS-R were applied: fatigue, concentration and forgetfulness, sleep problems, depression (which assesses depressed mood), and depressive ideas (which assesses low self-esteem, lack of sexual desire, restlessness, slowness, guilt, hopelessness, and suicidal thoughts). Each section presents 2 questions that confirm the presence of the specific symptom in the last month. Additionally, the interviewers applied a section that assess the overall effect in life of positive psychiatric symptoms. The combination of answers yields the diagnoses of depression (mild, moderate, and severe) according to the International Classification of Diseases, 10th Revision (ICD-10). Sociodemographic Characteristics and Clinical Profile Questionnaires addressed sociodemographic characteristics and lifestyle, such as age, sex, self-reported race (white, black, brown, and others), education (high school or lower vs higher education), smoking status (never, former, and current smoker), leisure-time physical activity using the International Physical Activity Questionnaire long form (classifying participants in active, insufficiently active, and inactive),19 and current alcohol use. The evaluated clinical conditions were hypertension (use of anti-hypertensive drug, systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg), diabetes mellitus (self-reported, use of oral hypoglycemic agents or insulin therapy, fasting plasma glucose 126 mg/dL, 2-hour postprandial 75 g glucose test 200 mg/dL, or glycosylated hemoglobin 6.5%), coronary artery disease (previous self-reported myocardial infarction or myocardial revascularization), self-reported previous stroke, and thyroid function status (classified as euthyroidism, overt hypothyroidism, subclinical hypothyroidism, overt hyperthyroidism, and subclinical hyperthyroidism according to thyrotropin and free thyroxine levels, and the use of medications for thyroid function disorders). Data for previous cardiovascular disease and thyroid function were obtained from the baseline evaluation of the ELSA-Brasil study.
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Statistical Analysis All continuous variables were nonnormally distributed and were presented as median and interquartile range, and categorical variables as absolute and relative frequencies. Characteristics of participants according to depression status were compared using the Wilcoxon rank-sum test, chi-square test, and Fisher exact test for continuous variables nonnormally distributed, categorical variables, and categorical variables with small cell counts, respectively. To investigate the association of depression with sarcopenia, presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass, we used simple and adjusted logistic regression models. Multiple models were built as follows: model 1 adjusted by sociodemographic characteristics (age, sex, education, and race) and model 2 adjusted for sociodemographic characteristics, clinical conditions, and lifestyle factors (diabetes mellitus, hypertension, coronary artery disease, previous stroke, thyroid dysfunction, smoking status, alcohol consumption, and leisure-time physical activity). Effect modification of older age (65 years) and sex on the association of depression and sarcopenia was investigated with interaction terms, considering a P value < .10 to stratify the analysis. Additionally, simple and fully adjusted logistic regression models were used to explore the association of each symptom of depression evaluated by the CIS-R with sarcopenia, presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass. Data were analyzed using Stata 14.2 (StataCorp LP, College Station, TX). The alpha-level was set at 0.05.
3
14,014 participants in the ELSA-Brasil Study 2nd wave
7248 participants aged 55 years or older
2 participants with reported weakness in both hands: one due to rheumatoid arthritis and the other due to pain. 7246 participants
Missing data on sarcopenia: 831 -
-
Hand-grip test: 333 Bioelectrical impedance analysis: 393 Both: 105
6415 participants
Missing data on the CIS-R score and/or other covariates: 488
5927 participants
Results Fig. 1. Flowchart of study participants.
Among the 14,014 participants in the first follow-up evaluation of the ELSA-Brasil study, we excluded 6766 individuals younger than 55 years, 2 individuals with reported weakness in both hands due to pain and rheumatoid arthritis, and 1319 individuals with incomplete data on sarcopenia parameters, CIS-R scores, or covariates. Therefore, 5927 participants (mean age: 62.7 5.9 years, 54.4% women) were included in this analysis, as seen in Figure 1. Sarcopenia was found in 114 participants (1.9%), 71 women (2.2%) and 43 men (1.6%); 40 were younger than 65 years (1.0%) and 74 were older than 65 years (3.8%). The frequency of presarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass was 18.8%, 20.7%, 4.8%, and 2.9%, respectively. Depression was present in 243 participants (4.1%). Table 1 shows participants’ characteristics according to depression status. Participants with depression had higher frequency of sarcopenia, low muscle mass, low muscle strength, lower appendicular lean mass, ALMBMI, and lower grip strength, and higher body mass index. They were also predominantly female and black, with lower education, and with higher frequency of hypertension and physical inactivity. Table 2 shows the association of depression with sarcopenia and its defining components. After adjustment for sociodemographic characteristics, clinical conditions, and lifestyle factors, depression was associated with sarcopenia and low muscle strength, and showed a tendency toward association with low muscle strength without loss of muscle mass. Depression was not associated with presarcopenia and low muscle mass. Older age and sex were not effect modifiers on the association between depression and sarcopenia (interaction term P values ¼ .235 and .936, respectively). When we investigated the association of each symptom of depression evaluated by the CIS-R with sarcopenia and its defining components, impaired concentration and forgetfulness were associated with sarcopenia, low muscle mass, low muscle strength, and low muscle strength without loss of muscle mass after controlling for confounders; sleep problems were associated with sarcopenia and low muscle mass; depressed mood was associated with sarcopenia
and low muscle strength; and depressive ideas with sarcopenia, low muscle strength, and low muscle strength without loss of muscle mass (see Table 3). Discussion In the present study, sarcopenia was found in 1% of middle-aged and almost 4% of older adults of a Brazilian cohort. Our study also showed that middle-aged and older adults with depression have higher odds of sarcopenia as defined by the FNIH criteria after adjustment for sociodemographic characteristics, lifestyle, and clinical conditions. This association was mainly due to low muscle strength. Moreover, depressive key symptoms such as concentration and forgetfulness, depressed mood, and depressive ideas were associated with both sarcopenia and weakness. This study used a large sample to assess the frequency of sarcopenia according to the FNIH criteria, and our findings are compatible with other studies.5,20 The study of Souza et al, conducted in a small sample of Brazilian patients with chronic kidney disease, found a much higher prevalence of sarcopenia (28.7%) defined by the FNIH criteria, and this difference was probably due to the presence of chronic kidney disease.7 Conversely, our study sample was composed of younger and healthier individuals. A meta-analysis of Brazilian studies found that in older adults the pooled prevalence of sarcopenia according to other operational definitions that include low muscle mass and function is around 16%.21 Indeed, the FNIH criteria are more restrictive than other definitions of sarcopenia.22 Cross-sectional studies that investigated the association of depression and sarcopenia assessed by low muscle mass combined with low muscle function and/or poor physical performance are scarce. Sarcopenia defined according to the European Working Group on Sarcopenia in Older People criteria was associated with depressive symptoms in cohorts of community-dwelling older adults in Taiwan
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Table 1 Characteristics of Participants According to Depression (n ¼ 5927)
Sarcopenia Appendicular lean mass, kg, median (IQR) BMI, median (IQR) ALMBMI, median (IQR) Low muscle mass Presarcopenia Grip strength, kg, median (IQR) Low muscle strength Low muscle strength without loss of muscle mass Age, y, median (IQR) Female Race Black Brown White Other Higher education Diabetes mellitus Hypertension Coronary artery disease Stroke Thyroid dysfunction Subclinical hypothyroidism Hypothyroidism Subclinical hyperthyroidism Hyperthyroidism Current or previous smoker Current alcohol use Leisure time physical activity Inactive Insufficiently active Active
Without Depression (n ¼ 5684)
With Depression (n ¼ 243)
P
104 18.96 26.96 0.704 1166 1062 30 264 160 62 3037
(1.83) (15.82-23.06) (24.33-30.11) (0.578-0.854) (20.51) (18.68) (23-38) (4.64) (2.81) (58-66) (53.43)
10 17.22 28.06 0.614 63 53 25 21 11 61 185
.026* <.001y <.001y <.001y .042z .222z <.001y .008* .117* .004y <.001z .032*
788 1408 3237 251 3212 1618 2935 155 90
(13.86) (24.77) (56.95) (4.42) (56.51) (28.47) (51.64) (2.73) (1.58)
49 63 124 7 100 77 148 10 6
(20.16) (25.93) (51.03) (2.88) (41.15) (31.69) (60.91) (4.12) (2.47)
368 541 84 50 2765 3688
(6.47) (9.52) (1.48) (0.88) (48.65) (64.88)
17 18 6 3 129 117
(7.00) (7.41) (2.47) (1.23) (53.09) (48.15)
3321 (58.43) 847 (14.90) 1516 (26.67)
(4.12) (15.44-20.50) (25.00-31.83) (0.524-0.716) (25.93) (21.81) (20-32) (8.64) (4.53) (57-65) (76.13)
<.001z .276z .005z .226* .290* .449*
.175z <.001z <.001*
179 (73.66) 23 (9.47) 41 (16.87)
ALMBMI, appendicular lean mass standardized to BMI; IQR, interquartile range. Values are n (%) unless otherwise noted. *Fisher exact test. y Wilcoxon rank-sum test. z 2 c test.
and Turkey,23,24 and in a study with middle-aged and older adults with end-stage renal disease.25 However, other studies that adopted these criteria did not find an association with depression.26,27 Studies that assessed sarcopenia using the Asian Working Group for Sarcopenia criteria also show conflicting results, with a significant association with depressive symptoms among Korean community-dwelling older women after adjustment for confounders,28 but no association could be demonstrated among Japanese older adults who attended a memory clinic.29 To the extent of our knowledge, no study that investigated the association between depression and sarcopenia in community-dwelling individuals used the FNIH criteria to define sarcopenia, although in a study with nursing-home residents sarcopenia defined by the FNIH criteria was not associated with depression.12 In the meta-analysis of Chang et al. that investigated the
association of sarcopenia and depression, studies that measured muscle mass with bioelectrical impedance analysis and studies that incorporated handgrip strength in the diagnosis of sarcopenia tended to show a stronger association, which is in accordance with our findings.11 In our study, the association of depression and depressive symptoms with sarcopenia was mainly driven by weakness and not by low muscle mass. These findings corroborate previous works.30,31 Fukumori et al demonstrated that lower grip strength increased the odds of depressive symptoms at baseline and of incident depressive symptoms after 1 year in a large prospective study with middle-aged and older adults.30 In a longitudinal study with British older adults, lower tertiles of hand-grip strength and muscle weakness defined according to the FNIH criteria were associated with incident depressive
Table 2 Association of Depression With Sarcopenia and Its Defining Components (N ¼ 5927) Crude Analysis
Sarcopenia Presarcopenia Low muscle mass Low muscle strength Low muscle strength without loss of muscle mass
Model 2y
Model 1*
OR (95% CI)
P
OR (95% CI)
P
OR (95% CI)
P
2.30 1.21 1.36 1.94 1.64
.014 .223 .042 .005 .122
2.41 1.14 1.29 2.03 1.70
.012 .413 .099 .004 .103
2.23 1.06 1.19 1.94 1.67
.024 .731 .264 .007 .115
(1.19-4.46) (0.89-1.66) (1.01-1.82) (1.22-3.09) (0.88-3.06)
(1.21-4.78) (0.83-1.57) (0.95-1.75) (1.26-3.28) (0.90-3.20)
(1.11-4.48) (0.77-1.46) (0.88-1.62) (1.20-3.15) (0.88-3.17)
CI, confidence interval; OR, odds ratio. *Logistic regression adjusted for age, sex, race, and education. y Logistic regression adjusted for age, sex, race, education, diabetes mellitus, hypertension, coronary artery disease, stroke, thyroid function status, smoking status, alcohol consumption, and leisure-time physical activity.
CIS-R, Clinical Interview Schedule Revised. Values are odds ratios (95% confidence intervals). *Logistic regression adjusted for age, sex, race, education, diabetes mellitus, hypertension, coronary artery disease, stroke, thyroid function status, smoking status, alcohol consumption, and leisure-time physical activity. y Low self-esteem, lack of sexual desire, restlessness, slowness, hopelessness, and/or suicidal thoughts. z P < .05. x P < .01.
1.60 (1.02-2.51)z 1.51 (0.97-2.35) 1.70 (1.20-2.40)x 1.68 (1.20-2.35)x 1.01 (0.82-1.25) 1.16 (0.94-1.42) 0.93 (0.74-1.16) 1.78 (1.06-2.99)z 1.87 (1.14-3.09)z
1.06 (0.86-1.32)
0.94 (0.67-1.31) 1.45 (0.97-2.18) 0.95 (0.68-1.32) 1.41 (0.95-2.10) 1.18 (0.92-1.53) 1.59 (1.16-2.17)x 1.22 (0.95-1.57) 1.62 (1.20-2.18)x 1.17 (1.02-1.34)z 1.13 (0.94-1.35) 1.25 (1.09-1.42)x 1.28 (1.07-1.52)x 1.10 (0.96-1.27) 1.05 (0.87-1.27) 1.65 (1.12-2.42)z 1.76 (1.11-2.79)z 1.71 (1.18-2.49)x 1.89 (1.21-2.95)x
1.18 (1.03-1.36)z 1.19 (0.99-1.43)
1.21 (0.87-1.70) 1.63 (1.09-2.46)z 1.29 (0.93-1.78) 1.54 (1.04-2.29)z 1.20 (0.92-1.57) 1.69 (1.23-2.32)x 1.27 (0.99-1.64) 1.65 (1.21-2.24)x 1.05 (0.90-1.22) 1.22 (1.01-1.47)z 1.09 (0.95-1.25) 1.33 (1.11-1.59)x 1.03 (0.88-1.20) 1.15 (0.95-1.40) 1.07 (0.93-1.24) 1.26 (1.04-1.52)z 1.17 (0.77-1.78) 1.73 (1.07-2.81)z 1.23 (0.83-1.83) 1.76 (1.10-2.79)z
Fatigue Concentration and forgetfulness Sleep problems Depression (depressed mood) Depressive ideasy
Adjusted* Crude Adjusted* Crude Crude Crude Adjusted* Crude
Adjusted*
Low Muscle Mass Presarcopenia Sarcopenia
Table 3 Association of CIS-R Clusters of Depressive Symptoms With Sarcopenia and Its Defining Components (N ¼ 5927)
Adjusted*
Low Muscle Strength
Low Muscle Strength Without Loss of Muscle Mass
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5
symptoms only in obese participants.31 Additionally, low muscle mass according to different definitions was not associated with depression in several studies.32e34 A Brazilian cross-sectional study with community-dwelling older adults defined cutoff points for low handgrip strength based on slow gait speed and found values similar to the ones defined by the FNIH and adopted in the present study.35 However, Vasconcelos et al did not find an association between depressive symptoms and muscle weakness, although depressive symptoms were associated with the combination of muscle weakness and slow gait speed.35 Moreover, presarcopenia and low muscle mass were associated with depressive symptoms in some studies in which muscle mass was measured with dual-energy x-ray absorptiometry, and this could explain the difference in findings.28,36 Different pathways may explain the bilateral association between depression and sarcopenia. Neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, known to promote neuronal survival, differentiation, and synaptic potentiation, are produced by both the brain and skeletal muscle, and are associated with mood and muscle regeneration.10 Another possible mechanism is the chronic low-grade inflammation and oxidative stress associated with both sarcopenia and depression.37,38 Besides the common moleculedriven pathways, sarcopenia and depression also share similar lifestyle factors. Physical activity is credited in the slowing down and the prevention of age-related loss of muscle mass, strength, and function,39 as with the prevention and treatment of depressive symptoms. On the other hand, depression may lead to inactivity.40 Therefore, physical inactivity acts as common risk factor for sarcopenia and depression41 and may also mediate the association of both conditions. Nutrition also plays a major role in the prevention of sarcopenia and depression, since an inadequate intake of micronutrients, calories, and proteins increases the risk of both of them.42,43 Similarly, smoking is a common hazard for both conditions.44,45 Other possible explanation is that lower grip strength is associated with poorer quality of life,46 possibly affecting mental health. On the other hand, depression may cause a decline in system physical functioning, leading to weakness. This is the first large study to assess sarcopenia defined by the FNIH criteria and its association with depression in Latin America, adjusting the analysis for relevant confounders, such as sociodemographic characteristics, cardiovascular risk factors, lifestyle factors, and thyroid function status. Nonetheless, our study has several limitations. The cross-sectional design prevents establishing a causal and temporal relationship between depression and sarcopenia. Although we used data from a prospective study, sarcopenia parameters were not measured at baseline, precluding the estimation of sarcopenia incidence and the investigation of the longitudinal association between depression and sarcopenia. Further analysis of upcoming examinations of the cohort may assess the evolution of sarcopenia in participants with depression or viceversa. Another relevant point is that the ELSA-Brasil is not a population-based study, and participants have higher education and higher income compared to the Brazilian population. Nevertheless, the cohort allows the study of associations. Besides, the applicability of the estimates from ELSA-Brasil to Brazilian adults is supported by the similarities in prevalence of behavioral risk factors and chronic conditions evaluated by ELSA-Brasil and by VIGITEL, a telephonebased behavioral risk factor survey, which has representative data for adults living in 27 Brazilian state capitals and the Federal District.47 Also, appendicular lean mass in our study was determined by bioelectrical impedance analysis and not by dual-energy x-ray absorptiometry, the technique to measure muscle mass proposed by the FNIH criteria. Finally, we adjusted the analysis for relevant confounders on the association between depression and sarcopenia, but residual confounding cannot be ruled out. In conclusion, depression is associated with sarcopenia as defined by the FNIH criteria in Brazilian middle-aged and older adults. Further
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