Chair-based exercise programs in institutionalized older women: Salivary steroid hormones, disabilities and frailty changes

Journal Pre-proof Chair-based exercise programs in institutionalized older women: Salivary steroid hormones, disabilities and frailty changes

Guilherme Furtado, Humberto Moreira Carvalho, Marisa Loureiro, Miguel Patrício, Matheus Uba-Chupel, Juan C. Colado, Eef Hogervorst, José Pedro Ferreira, Ana Maria Teixeira PII:

S0531-5565(19)30474-7

DOI:

https://doi.org/10.1016/j.exger.2019.110790

Reference:

EXG 110790

To appear in:

Experimental Gerontology

Received date:

14 July 2019

Revised date:

2 November 2019

Accepted date:

20 November 2019

Please cite this article as: G. Furtado, H.M. Carvalho, M. Loureiro, et al., Chair-based exercise programs in institutionalized older women: Salivary steroid hormones, disabilities and frailty changes, Experimental Gerontology(2019), https://doi.org/10.1016/ j.exger.2019.110790

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© 2019 Published by Elsevier.

Journal Pre-proof Chair-based exercise programs in institutionalized older women: salivary steroid hormones, disabilities and frailty changes

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Guilherme Furtado ([email protected]) Humberto Moreira Carvalho ([email protected]) e Marisa Loureiro ([email protected]) e Miguel Patrício ([email protected]) a Matheus Uba-Chupel ([email protected]) d Juan C. Colado ([email protected]) c Eef Hogervorst ([email protected]) a José Pedro Ferreira ([email protected]) a Ana Maria Teixeira ([email protected])

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Research Center for Sport and Physical Activity, CIDAF (UID/PTD/04213/2019), Faculty of Sports Sciences and Physical Education – University of Coimbra, Portugal (FCDEF-UC). b Faculty of Physical Education, Federal University of Santa Catarina, Brazil c School of Sport and Exercise Sciences, Loughborough University, United Kingdom d Research Group in Prevention and Health in Exercise and Sport, University of Valencia (Spain) e Laboratory of Biostatistics and Medical Informatics and IBILI, Faculty of Medicine of the University of Coimbra

Correspondence: Ana Maria Botelho Teixeira (email: [email protected]) President of the International Society for Exercise and Immunology; Faculty of Sport Science and Physical Education, University of Coimbra, Coimbra, Portugal. Research Unit of Physical activity and Sport at Faculty of Sport Sciences and Physical Education – University of Coimbra, Portugal. Address: Estádio Universitário de Coimbra, Pavilhão III, postal code: 3040-156. Contacts: +351 239 802 770, Fax: +351 239 802 779, email: [email protected]

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Journal Pre-proof Abstract Purpose: Many people experience aging-related losses in different physical domains, which leads to a condition often called physical frailty (PF). The aim of this study was to analyse the effects of two different, 28-weeks, class chair-exercise protocols on salivary steroid hormones (SH), PF, and functional disabilities (FD) in frail older women. Methods: A sample of older frail individuals (n = 60, 817.84 years) participated in the study and were divided into three groups: chair elastic-band muscle

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strength exercises (CSE), n=20), chair-multimodal exercise (CME, n =21) and a control non-exercise group (CGne, n = 19). Both exercise programs consisted of 45 minutes of

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supervised chair-based exercise group classes, carried out 3 times/week. CME

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participants performed a progressive training using walking, mobility and body weight resistance exercises. The CSE participants exercised using an elastic-band system of

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progressive exercises. Both CSE and CME followed a circuit training protocol. The

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controls did not change their usual lifestyle. The indicators of PF, FD and SH concentrations were analyzed before and after the intervention. Results: Both exercise

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programs diminished the PF status showing significant time and time versus treatment

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interactions (p<0.01). An increase in the CME group, between baseline and 14-weeks, and in the CSE group, after 28 weeks, for Testosterone concentrations was observed (p<0.01). Dehydroepiandrosterone (DHEA) increased after 28-weeks in the CME group and decreased in the CGne after the same period (p<0.05). Both exercise programs decreased the negative scores of several FD domains, specially fear of falling that showed significant effects with time (p<0.01), and time vs intervention (p<0.05). Conclusion: Both chair-exercise based programs were effective in stimulating positive changes in physical health and in steroid hormone responses, especially in DHEA. The control group did show a negative trend towards an increased PF status and decreased

Journal Pre-proof levels of SH. It is crucial for public health to identify the main factors associated with Functional Disability and Physical Frailty that underlie the development of new methods for complementary therapies, such as the use of low doses of hormonal supplementation combined with long-term exercise interventions.

Keywords: Frail-Older adults, salivary steroids hormones, muscle-strength, multimodal, physical exercise, Functional disability

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1. Introduction

Frailty is a problematic aging expression and represents a growing challenge for

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modern health systems (Tocchi et al., 2014). Linda Fried and colleagues identified the

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phenotype of physical frailty (PF), that is assessed using five criteria capable of classifying the older population into frail, pre-frail and non-frail categories (Fried et al.,

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2001). Nowadays, the recently coined concept of frailty is understood to be

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characterized by a decreased resistance to stressors, an increased risk for adverse biological and behavioral health outcomes, modulating the risk of several types of

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physical and hormonal disorders (Bernabei et al., 2014). Furthermore, the presence of

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hormonal dysfunction has been reported to predict increased FD during the ageing process, and appears to be the link between musculoskeletal health and Physical Frailty (Brinkley et al., 2009). Decline in one or more FD indicators is a primary determinant of quality of life in advanced age, with worse declines in physical abilities being strongly associated with PF, increased caregiver burden, and greater financial costs for public health (Bergman et al., 2013). Increasing physical activity levels (i.e. through regular exercise) emerges as a gold standard preventative action for most dimensions of FD associated with the PF condition, as aspects such as strength, mobility, and

Journal Pre-proof cardiorespiratory fitness are crucial for maintaining the ability to perform daily life tasks (Chou et al., 2012). After the age of 65 years, muscle mass presents a decline rate of approximately 12 to 15% per decade (Chen et al., 2007). Neuromuscular changes in older people, such as the decrease in type II and increase in type I fibbers, contributed to decrease physical activity levels (Peterson et al., 2009), increasing the number of falls (Ensrud et al., 2009). This cascade of physical decline has an intrinsic relationship with negative

steroid

hormones

(SH),

such

as

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changes in the endocrine system. Recent evidence revealed that fluctuations in salivary Cortisol

(COR),

Testosterone

(TT)

and

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Dehydroepiandrosterone (DHEA) may be involved in the vulnerability observed in frail

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subjects, especially in older women (Holanda et al., 2012; Varadhan et al., 2008). While high levels of stress can determine physical and psychological impairment (Clow et al.,

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2010), moderate stress (i.e. provided by regular exercise) with a mild increase in COR

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levels may have a positive effect in coping and in physical performance (Mura et al., 2014). Low TT levels have been associated with a higher risk of PF, anemia, sarcopenia

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and low bone density (Ferrucci et al., 2006) while also, affecting women's exercise

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trainability (Copeland et al., 2004). Recently, our group found good correlations between several salivary biomarkers (i.e. COR, alpha-amylase, interleukins) and composed and independent components of PF, reinforcing the relevance of using salivary marker (Furtado et al., 2019), since saliva collection is a non-invasive method to collect informative biological materials with many studies showing that salivary COR, DHEA and TT have a satisfactory association with their respective serum markers (Dorn et al., 2007; Papacosta and Nassis, 2011). Synthesized in the brain, DHEA is a SH that shows a reduction (10% to 20%) from peak levels reached in early adulthood to old age, and is implicated in the

Journal Pre-proof disturbance of the musculoskeletal system, neurotransmitter receptors and androgenic activity (Labrie, 2010). Some evidence of exercise-induced DHEA production with subsequent metabolic changes favourable to anabolism in young and older adults is known (Heaney et al., 2013; Kenny et al., 2010). However, there are very few studies that have tested the effect of long-term exercise on DHEA levels in frail elderly (Walsh and Oliver, 2016), despite its proven predictive power of frailty (Baylis et al., 2013). Regarding the TT/COR ratio, Häkkinen and colleagues have proposed the use of this

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ratio as a diagnostic measure to prevent/detect overtraining, as it gives an indication of the anabolic/catabolic balance in response to regular exercise (Häkkinen et al., 2002). In

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adult women, both acute and chronic exercise modulate circulating hormone

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concentrations, however, the response to different types of exercise programs (i.e. endurance and resistance) are different (Copeland et al., 2004).

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Both muscle-strength and multimodal programmes, as recommended by The

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American College of Sport Medicine (ACSM) are considered to be effective in preventing muscle loss by improving cardiorespiratory and muscular resistance (Garber

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et al., 2011), and attenuate or reverse PF (De Labra et al., 2015). Multimodal exercise

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interventions usually include resistance, balance, aerobic, and flexibility training (Baker et al., 2007). Although ACSM classified the evidence level of multimodal exercise as C or reasonable (on a scale ranging from A to D) (Antunes et al., 2006), most recent findings have shown a general health benefit of this type of training in older patients with PF, especially in decreasing falls incidence and in improving physical fitness related to daily tasks autonomy (Lopez et al., 2017). Improvements in maximal oxygen uptake after multimodal exercise programs in frail individuals were also reported (Theou et al., 2011). Classified as level A or strong according to the ACSM, a musclestrength exercise program induces muscles to contract against an external resistance,

Journal Pre-proof improving neuromuscular mechanisms, with the subsequent increase in strength, endurance, muscle mass and tone (Kraemer et al., 2002). In the case of this program, the elastic-band system was used as an external resistance. Elastic-bands appear to be an equitable alternative to traditional strength training devices, allowing individuals to perform a range of ergonomic movements, and adjust the exercise intensity based on the rate of perceived exertion. Current evidence indicates that supervised and controlled trials of muscle strength exercises represent an effective intervention in PF treatment

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(Dedeyne et al., 2017).

In the case of this study, the chair-based exercise protocol has been integrated in

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both the multimodal and muscle strength program (Kevin et al., 2011). This has proven

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to be a suitable and appropriate method of exercise for inactive older adults with poor physical condition (Robinson et al., 2014). It consists of structured exercises performed

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with a chair for support that guarantees the individual's stability during the session,

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providing older people the opportunity to participate in exercise programs, respecting individual limitations, without discouraging reaching beyond their limits (Kevin et al.,

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2011). However, the effect of both chair-exercise long-term programs on the

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modulation of different SH, FD domains and PF indicators still needs to be explored, since there is insufficient evidence to suggest that benefit is plausible. The increase in FD and the occurrence of PF coincides with substantial changes in the endocrine system, and studies show that several of the outcomes associated with aging are similar to those showed in young adults with hormone deficiencies (Copeland et al., 2004). Therefore, the aim of this study was to analyze the effect of two different 28-weeks chair exercise programs (multimodal and muscle-strengthening with elastic bands) on Physical Frailty, Functional Disabilities and Steroid Hormones in institutionalized pre-frail and frail women. Based on previous findings, we hypothesized

Journal Pre-proof that both the chair elastic-band muscle strength (CSE) and the chair multimodal exercises (CME) would be able to decrease disabilities, attenuate Physical Frailty and simultaneously increase the levels of anabolic steroid hormones.

2. Methods This study consisted of a three arms controlled trial chair-based exercise intervention. Participants were institutionalized-dwelling women living in centres of

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health and social support (CHS) in the city of Coimbra, Portugal. The CHS that took part in this study had the same daily routine, including mealtimes, daily activities,

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clinical staff organization and management. All the participants resided in the CHS.

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This study was approved by the University of Coimbra, Faculty of Sport Sciences and Physical Education Ethical Committee (reference number: CE/FCDEF-UC/000202013)

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human research (Braga, 2013).

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respects the Portuguese Resolution (Art.° 4st; Law no. 12/2005, 1st series) on ethics in

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2.1 Criteria for participants selection

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Inclusion criteria: participants had to be 70 years old or more, be frail or prefrail, clinically stable with their drug therapy updated. If a severe comorbidity condition was detected, participation in the intervention was decided by the local medical staff. Exclusion criteria: taking 30 seconds or more to complete the dynamic balance test in, since time-scores above this value indicate severe functional disability (Bischoff et al., 2003); involvement in other structured exercise programs in the last six months; use of medication that significantly impairs attention (i.e. lorazepam, alprazolam, pregabalin); individuals classified with morbid obesity (clinical diagnosed); no controlled medical diagnosed of severe cardiometabolic, respiratory and musculoskeletal disorders (i.e.

Journal Pre-proof amyotrophic lateral sclerosis, muscular dystrophy); presence of mental illness (i.e. schizophrenia, schizoaffective or bipolar disorder); hearing or vision impairments or involvement in hormone therapy. Lastly, the final judgment of the clinical staff was always taken into consideration in order to insert the participant in the study.

2.2 Sample size calculation and allocation Estimation of sample size was performed by comparison of frail outcomes

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between pre- and post-exercise interventions, based on previous studies, that reported high effect size (ES) for the frailty composed score (de Labra et al., 2015). Assuming a

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minimum power of .80 as realistically expected and moderate ES (0.5), the

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recommended sample size for this study were 19 participants per group. Further assuming a dropout rate of 25 to 35% (Picorelli et al., 2014b), the sample size was

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increased to 28 per group, to a total of 84 participants, allocated into three groups. The

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sample size was computed with G*Power 3.1.9.2 (Faul et al., 2007). The final sample analyzed consisted of 60 participants based on a per-protocol analysis for trials (Gupta,

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2011): non-exercising control group (CGne, n=19), chair elastic-band muscle strength

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(CSE, n=20) and chair multimodal exercises (CME, n=21) programmes. The allocation to treatment was randomized (1:1:1) according to Consolidated Standards of Reporting Trials (CONSORT).

2.4 Assessments All measures were done by 3 researchers, to diminish differences in data collection procedures. Previously, a data quality assessment was done in the preliminary phase of this study (Teixeira et al., 2016), and reported for each functional fitness and anthropometric indicator through scores of internal consistency reliability (ICR). For the

Journal Pre-proof psychometric rate scales, the Cronbach’s alpha () or Cohen's kappa coefficient (k) were reported. The instructors of the exercise sessions did not take part in the data collection procedures. Precaution was taken to avoid interaction between individuals of the two chair-exercise groups by staggering the classes schedule. All the tests were applied by the research team, who established contact with the participants without reference to the exercise program. The all functional fitness tests were applied by two researchers and the questionnaires were applied by a single investigator in a face to face

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approach.

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2.4.1 Physical Frailty screening

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Assessment of PF was performed based on the five criteria of the Fried protocol. Shrinking was assessed by self-report of unintentional weight loss of four kilograms or

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more in the last six months, validated by medical records over one year for each

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participant; Self-reported exhaustion was evaluated by concordance of two questions (7 and 20) of the CES-D depression scale; Weakness, was analyzed using the handgrip

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strength test and adjusted for gender and body mass index; Slowness, was measured by

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the 4.6 meters walking test, adjusted for gender and stature (ICR = .80); Low levels of physical activity (PA) component were assessed by the International Questionnaire short version (IPAQ-SV, ICR = .78). The prevalence of PF was calculated to generate a frailty total score, as well as the presence of each of the five criteria of the Fried’s model. The positive scoring in one or two criteria classifies the participants as pre-frail, in three to five as frail and non-frail or robust when the subject has none of the five criteria (Fried et al., 2001).

Journal Pre-proof 2.4.2 Steroids hormones quantification Saliva samples were collected in a non-fasted state by passive drool always at the same time in the morning (between 10:00h to 11:30h) to minimize circadian effects. The collection was performed by a resident nurse and one assistant researcher. Individuals salivated without any orofacial movement, for 3 mins, into high-quality polypropylene vials to avoid problems with analytic retention or the introduction of contaminants that could interfere with the immunoassays. The tubes containing the

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saliva samples were then frozen (-20ºC), until the day of the analysis, when they were defrosted and centrifuged in order to obtain a clear sample. The levels of salivary COR,

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DHEA and TT were determined by competitive enzyme-linked immunosorbent assay,

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according to the manufacturer instructions (Salimetrics UK, 2017). The reference values for COR (<0.007 ug/dL, r = .91), TT (1 pg/mL, r = .96) and DHEA (5 pg/mL, r =.86)

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were reported by the manufacturer, in terms of sensitivity and their respective

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correlation with serum samples. The use of whole saliva samples to assess biological markers requires less clinical training and is non-invasive method (compared to the

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collection of blood samples) and is suitable for measuring the endocrinological profile

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linked to physical performance (Papacosta and Nassis, 2011).

2.4.3 Functional disability (FD) assessment The Katz Index of Independent daily life activities (ADL,  = .81) was used to rank adequacy of performance in the biosocial functions and classifies people as dependent or independent (Katz et al., 1970). Subjective fear of falling (FES,  = .88) was measured through the Falls Efficacy Scale (Melo, 2009). Perception of physical changes behaviour (PCB,  = .83) was assessed through the Attitudes to Ageing Questionnaire (Laidlaw et al., 2007). Agility and dynamic balance (ADB) was assessed

Journal Pre-proof through the eight-foot-up and go test (ICR = .80), that measured the time needed for the participant to get up from the chair, walk around either side of the cone, and to sit back down (Rikli and Jones, 2013). The Tandem Stance Balance test (TSB) was used to access static balance (ICR = .76), and consists of the participant maintaining the standing position with eyes opened and one foot in front of the opposite foot for 30 seconds (Cho et al., 2004). FD was evaluated according to a multidimensional construct that integrated self-reported and functional test performance-based measures (Tomey

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and Sowers, 2009), with previous studies showing good correlations between all FD

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domains (Furtado et al., 2019).

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2.4.4 Clinical status

The Mini Nutritional Assessment (MNA, k = .74) was used to evaluate the

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nutritional status and the participants were classed as: a predetermined state of

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malnutrition (scores of < 17 points), malnutrition risk (scores between 17 and 23.5 points) and adequate nutritional status (scores of > 23.5 points) (Loureiro, 2008). All

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participants were provided with similar diets, in terms of caloric intake and nutrients,

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controlled by a local nutritionist and clinical staff and were preserved unaltered during the intervention period. The Charlson Comorbidity Index (CCI, ICR = .94) was used to classify comorbid conditions based on the registry of each individual comorbidity and was combined with age and gender to form a single index (Charlson et al., 1994). Participants with scores equal or above six points were weekly supervised by the local medical staff. Medication use was assessed through medical record over one year for each participant and the prevalence of use, according to the group of action mechanism, was reported. To reduce potential confounding effects, all the participants were encouraged to maintain unchanged diets, medication treatments, and routines across the

Journal Pre-proof 28-weeks of the intervention (which were very similar among participants as they lived under similar conditions).

2.4.5 Biosocial and anthropometric measures. Information on chronological age was collected. Body mass was determined using a portable scale (Seca®, model 770, Germany) with a precision of 0.1 kilograms (ICR = .89). Stature was determined using a portable stadiometer (Seca Body meter®,

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model 208, Germany) with a precision of 0.1 centimeters (ICR = .87). Body mass index (BMI) was calculated according the formula [BMI = weight/height2]. The standardized

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procedures described in previous studies were followed (Lohman et al., 1988).

2.4.6 Intervention programs description

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The exercise programs were conducted by exercise specialists, and consisted of

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structured exercises performed with a chair for support ensuring the individual's security and stability during the session (Anthony et al., 2013). The average height of the subjects was taken into account to determine the dimensions of the chair. The ACSM guidelines for exercise prescription to non-active older adults and guidelines of integrated exercise periodization were respected (Chodzko-Zajko et al., 2009; Garber et al., 2011). In both exercise programs, intensity was indirectly calculated using the Karvonen’s formula to predict target heart rate (HR), with HRmax being calculated using a specific formula for older populations [Target Heart Rate = [(HRmax − resting HR) × %Intensity] + resting HR] (Tanaka et al., 2001). For safety reasons, both CSE and

Journal Pre-proof CME programs were monitored using heart rate monitors (Polar, model RCX5, randomly distributed among participants in each session. Additionally, intensity was measured through the specific rating perceived exertion (RPE) scales for each exercise program. The interventions were offered for 28-weeks, totaling 74 exercise sessions, with two-three sessions per week on nonconsecutive days (separated by 48 hours). A detailed methodologic description was published by our group in the article (Teixeira et

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al., 2016).

2.4.7 Chair-multimodal exercises

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In order to establish a progressive resistance program aimed to improve the

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walking and mobility competences, a specific CME program was performed with a determined number of exercises, repetitions, sets, rhythm of execution, rest between

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circuits (see table 1 for more details). Each session was conducted using a functional

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circuit training protocol, that consisted in completing one set of each exercise in a full range motion following active rest, such as two minutes of walking around the gym-

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room (Giné-Garriga et al., 2010). During the first 14-weeks of CME, the body weight

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exercises were executed in the set and reach positions. In the last 14-weeks, the increase in exercise intensity was induced by inclusion of more difficult and complex exercises and challenge sequences, increasing walking time and placing obstacles within the walking route (cones, floor markers, arcs) to work handedness, changes in direction, balance and coordination. A low to moderate intensity effort, around 50-75% of HRmax values, was attained as recommended by the ACSM (Nelson et al., 2007). Additionally, intensity was measured through the modified BORG RPE, that consists of an arbitrary scale ranging from 0 to 10 points, with identical intervals and with reference to the quality of effort: (0) nothing at all; (1) very weak; (2) weak; (3) moderate; (4) somewhat

Journal Pre-proof strong; (5-6) strong; (7-9) very strong; (10) very, very strong (almost maximal). Each exercise session lasted 45 minutes and was divided into three parts: 5 minutes of warmup and active stretching body mobilization (RPE 1-3, HRmax = 50-55%); 35 minutes of body weight exercises aimed at improving walking proficiency in a sitting and standing position (RPE 3-5, HRmax = 56-85%) and finally 5 minutes of passive stretching exercises targeted to encourage cool down (RPE 1-2, HRmax = 45-50%). The CGne did not participate in any physical exercise intervention but was encouraged to maintain

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their normal routine, which included a monthly agenda of artistic and cultural activities

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offered by the CHS.

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2.4.8 Chair elastic-band muscle-strength exercises

To create progressive CSE program, specific exercises were performed with a

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determined number of exercises, sets, a cadence of repetitions and others parameters

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(see table 1 for more details). All exercises followed a circuit exercise protocol, that consisted in completing one set of all exercises consecutively performed in a full range

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motion, followed by a rest period (60 -120 seconds). From the 7 intensity levels in the

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Thera Band's elastic band system, we used the first 3 levels during the 28-weeks of the CSE program. Level one (yellow colour) elastic-bands were used during the first 14weeks. In the remaining 14-weeks, the increase in exercise intensity was introduced by changing to the elastic-bands level 2 and 3 (red and green colour). Perception of intensity was measured through the OMINI RPE, that comprises a subjective effort scale ranging from 0 to 10 points, with identical intervals and with reference to the quality of effort: (0) extremely easy; (1-2) easy; (3-5) somewhat easy, (6-7) somewhathard; (8) hard; (9-10) extremely-hard (Robertson et al., 2003). The goal was to keep the intensity of the exercise activities between 1 to 6 in RPE levels. It was expected that the

Journal Pre-proof relationship with the real effort would be 55-80% of maximum heart-rate (Garber et al., 2011). The CSE session was divided into three parts: 5 minutes of warm-up exercises for general body mobilization (RPE 1 to 3, HRmax = 45-55%), 35 minutes of strength exercises in RPE 4 to 6 (HRmax = 56-75%) and finally, 5 minutes of cool-down stage, through easy-walking and static stretching exercises for ´breath´ control, RPE 1 to 2, totaling 45 minutes per session (HRmax = 45-50%).

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[Insert Table 1 about here, please]

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2.4.9 Exercise engagement

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Exercise frequency was calculated individually through the total sum of class participation entries recorded in a checklist. A total of 74 (100%) sessions were offered

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and the values of engagement in different moments were reported as a percentage.

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During the exercise program, when a participant had two consecutive absences, she was contacted to return to the group classes. Based on previous reports, an adherence to the

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exercise program of up to 65% was established as a minimum for each participant to be

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included in the final data analysis (Picorelli et al., 2014b).

2.5 Data analysis

Descriptive data was presented as mean (standard deviation) or frequencies. The normality of continuous variables was assessed with Shapiro-Wilk tests. In the baseline scores, comparisons between groups were analyzed by one-way ANOVA. Repeated measures ANOVA was used to analyse effect of time (3 levels: pre, 14-week, and 28week), and time*group (3 groups) interactions for frailty total score, disability outcomes and hormonal changes over time, followed by Bonferroni post hoc test. Magnitude of

Journal Pre-proof global effect size (ES) was calculated in the baseline and exercise-modulation treatment. ES interpretation of continuous variables (frailty total score, functional disability and sex steroid hormones) were computed using eta-squared (2). Magnitude of ES = 2 ≤ 0.05 corresponds to a small effect, 2 ≤ 0.13 to a medium effect and 2 > 0.14 to a large effect (Cooper and Hedges, 1994). McNemar tests were used to compare categorical variables (frailty independent components) between the two time-points (base-line to 28 weeks) intervention treatment following Cochrane's Q post-hoc test. For

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each comparison, the magnitude of ES reported was Cramer’s Phi coefficient. In case of interpretability, Phi ≤ 0.2 corresponds to a small effect, Phi ≤ 0.6 corresponds to a

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medium effect and Phi > 0.6 to a large effect (Alfred, Rovai and Baker, 2012). All

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statistical tests were performed at the 0.05 level and 95% confidence intervals, and IBM

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SPSS Statistics 21.0 software were used for all computations.

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3 Results

Grouping dynamics and drop-outs are presented in detail in Figure 1. From the

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119 participants initially screened, 35 (29.4%) subjects were excluded because they did

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not meet the inclusion criteria, lost interest after the study intervention was explained or for other non-specified reasons. In the follow-up phase, 22 subjects withdrew their willingness to participate before or immediately after the beginning of the study for different reasons. A total of 3 participants were excluded from the results analyses due to low exercise adherence. None of the drop-outs left the intervention because of injuries or adverse responses to the intervention. A total of 60 participants were analyzed (CME, n = 21; CSE, n = 20 and CGne, n =19) at completion of the 28-weeks’ study.

Journal Pre-proof [Insert figure 1 about here, please]

Characteristics of the total sample, CME, CSE and GCne groups and their respective means and standard deviations at baseline are presented in Table 2. There were no significant differences between groups for their baseline characteristics or dependent variables at the beginning of the study, indicating that all study groups had similar characteristics regarding anthropometry, diet, physical function, cognitive status,

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drugs use, and different disease prevalence (p>0.05). The high incidence of hypertension, rheumatic (or connective tissue disease) and dyslipidemia/metabolic

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syndrome is also a characteristic of the study sample.

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[Insert table 2 about here, please] 3.1 Steroid hormones

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Table 3 shows the changes in the salivary steroid hormone levels after the 28weeks intervention. No effects of time or time vs group were observed in salivary COR

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levels, although the additional statistics indicated a small ES in both pre-post statistics

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(2=.037 and .043, respectively). There were no significant statistical changes in time or time vs group on salivary TT levels after 28-weeks of exercise intervention, but a posthoc analysis with Bonferroni correction showed an increase for the CME group between baseline and 14 weeks for TT concentration and an increase for the CSE group between 14 and 28-weeks (p>0.05). Additionally, time and time vs group treatments in TT levels presented small (2=.009) and medium effects (2=.066), respectively. A significant time (p<.01, 2=.027, small ES) and time by treatment effect (p<.05, 2=.179, large ES) was observed in DHEA levels. Post-hoc comparisons indicated that DHEA levels increased in the CME group after 28-weeks (p=0.01), and decreased in CGne after the

Journal Pre-proof same period (p=0.01). Despite no significant effects of time and time vs treatment were observed for the salivary TT/COR ratio during the interventions (p>0.05), additional results showed a small (2=.009) and medium (2=.066) ES for time and time vs treatment after interventions, respectively.

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[Insert table 3 about here, please]

3.2 Functional disability and PF composed score

Table 4 shows the time-point differences in physical frailty total score and

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functional disability outcomes after 28-weeks of intervention. The PF composed score

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showed significant time (F[df: 1.43; 78.75]=7.385, p<.01) and time vs treatment interactions (F[df: 2.86; 78.75]=6.765, p<.01) with changes with a medium and large

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ES, respectively (2=.118 and 2=.197). No significant differences of time and time vs

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intervention were observed on Katz of ADL (p>.05). However, post-hoc comparison showed differences observed after 14-weeks between CME and CSE (CI: -2.367, -0.022

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and CI: -2.463, -0.037, respectively, p<.05), as reported in Table 3. On the other hand,

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significant effects of time (F[df =1.7, 93.9] = 20.268, p<.01), and time vs intervention (F[df=3.4, 93.9]2.830, p=.03), were observed after 28-weeks on FES, with a large and medium ES, respectively (2=.270 and 2 =.093). Concerning the self-perception of PCB, significant time vs treatment interactions were found (F[df:4, 110]=3.559, p<.01), where the CME group was the only one that did not present significant changes during the entire study (p>0.05). However, improvements in PCB was found for the elasticband CSE group between baseline and 28 weeks (p<.05), and a significant reduction in CGne (p<.05) after 14 weeks was observed, with this level maintained at 28-weeks. There were no significant time vs treatment interactions in TSB for the three groups,

Journal Pre-proof despite changes over time presenting a medium effect on this parameter (F[df: 1.612; 88.684]=7.609, p = 0.003, 2=.115). Post-hoc analysis showed that differences between CME and CGne were only found after 28-weeks of intervention time (p>0.05).

[Insert table 4 about here, please]

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3.3 Incidence of PF independent components Table 5 presents the incidence of each PF independent component of elderly participants, at baseline, 14 and 28 weeks in all groups, as well as the standardized

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changes across the exercise-based intervention. As for the PF components, significant

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positive variations of incidence with a large ES were showed on Low Levels of Physical

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Activity for both CME (p<.001, Phies = 0.40) and CSE (p<.05, Phies >0.50). Post-hoc comparison showed significant statistical differences after 14-weeks for both exercise

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interventions (p>0.01). A statistical significant decrease on Slowness with moderate ES was observed only for the CME group (p = 0.016; Phies = 0.35). A trend towards a

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decreased incidence of Weakness with moderate ES was also found for the CME

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participants (p=0.58; Phies = 0.30). No significant changes in the PF independent components were found for the CGne, however, a trend to an increased incidence of Slowness with a small ES was found (p=0.08, Phies = 0.21). [Insert table 5 about here, please]

3.4 Rate of perceived exertion, HR control and adherence The final minimum, maximum and mean HR achieved at the end of the intervention by the CME group was 65. (9), 97.56 (12 and 77 (8) bpm, respectively. This was equivalent to 57% to 70% of the predicted HRzmax. The final mean of PES

Journal Pre-proof ranged from moderate (3) to somewhat strong (5). For the CSE group, the final minimum, maximum and mean of HR achieved at the end of the intervention was 69 (14), 96 (13) and 85 (11) bpm, respectively. This corresponded to 48% to 74% of the predicted HRmax. The final mean of PES oscillated from “to somewhat easy” (3) to “somewhat strong” (6), according to the participants self-perception. The percentage of the HR zone and PES for both exercise groups reached previously expected values. Regarding data of exercise engagement, the CSE participants attended an average of 58

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sessions (72% of attendance), out of the 74 sessions offered in total. In the CME, the

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participants had a 72% adherence, corresponding to 54 sessions attended.

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4. Discussion

The main findings of the present study indicated that both CME and CSE had

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similar effects in decreasing the incidence of Low Physical Activity Levels in the PF

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components, resulting in a decrease of the PF composed score and in the subjective fear of falling, as well as in improving static and dynamic balance motor skills. Results also

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showed that the CME protocol was more effective in improving perception of physical

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change behavior. Moreover, we showed that the effect of any exercise-treatment when compared to the CGne was beneficial for all variables, probably by maintaining an appropriate balance of the steroid hormone concentrations, since DHEA levels decreased in the CGne and increases in TT and DHEA levels occurred in the CME group over time. According to the literature, the participants adherence to our exercise interventions was considered high (Picorelli et al., 2014a), with only 3 participants engaging insufficiently. The strategy adopted was to carry out the exercise protocols on the centers of social care, minimizing the non-adherence effect due to contextual factors.

Journal Pre-proof In general, the two chair-exercise protocols were effective in promoting improvements in some physical functioning indicators, corroborating findings from previous studies (Anthony et al., 2013). A decrease in fear of falling can be explained by the increased proficiency in the static and dynamic balance tests and also, a possible increased stimulation of type II fibbers, which assist in motor skills such as quickness, fast-decision making (time-reaction) and the proprioception mechanisms (Ishigaki et al., 2014). The subjective perceived improvement of physical changes behaviour only in the

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CSE group corroborated the findings of a similar study (Gothe et al., 2011) which assumed that muscle-strength training is more sensitive to changes in psychological

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domains related to PCB changes, especially in older women (Huberty et al., 2008).

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A key finding of this study was the ability of both chair-exercise programs to clearly demonstrate the positive modulation on PF components, especially in the Levels

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of Physical Activity of PF. This is an interesting result, since the current stand position

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is that populations from all ages may benefit from the effects of systematic exercise, especially when they increase their spontaneous levels of physical activity (Chodzko-

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Zajko et al., 2009). The exercise periodization methodology used for the design of both

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exercise programs, including several strategies to decrease the sitting time and substantially increase the time spent in the standing position proved to be a good strategy (Garber et al., 2011). Another characteristic that differentiates this study from similar ones is the large total time of the intervention, since the current literature review shows that exercise programs with a longer period (≥ 5months), performed 3 times per week, with 30–45 minutes per session, had largely superior results than other shorter exercise interventions (Theou et al., 2011). There are few studies that have examined the long-term effect of exercise on steroid hormone changes in older women (Ennour-Idrissi et al., 2015). In the present

Journal Pre-proof study, the potential mechanisms for exercise-induced increases in DHEA levels could be explained by an increased secretion rate by the adrenal cortex as a result of adrenocorticotropic hormone stimulation, produced by the anterior pituitary gland (Heaney et al., 2013). This study seems to be in accordance with Heaney and colleagues (2013) suggestions, encouraging the maintenance of chronic exercise (specially musclestrength routines) to induce the increase in DHEA levels, particularly in older frail adults who experience psychobiological chronic stress (Corazza et al., 2013).

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Additionally, increases in DHEA with a simultaneously slight increase in TT levels, show the effectiveness of exercise as an adjuvant therapy able to promote benefits in the

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musculoskeletal and nervous system in frail older adults (Arlt and Hewison, 2004).

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Small increases in TT concentrations obtained by the CME participants seem to have promoted muscle strength and endurance in our sample (Table 3). Although,

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higher increases were reported in other studies, in these, most of the participants were

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middle-aged and men (Hayes et al., 2015; Nair et al., 2006). In another study the effects in similar hormones were more prominent when the participants were involved in high-

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intensity exercise programs (Ennour-Idrissi et al., 2015). In samples similar to ours,

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several factors such as age-related hormonal decline, changes in body composition (specially decline of muscle mass), low mineral density and disturbances in the neuroendocrine system have been shown as concurrent factors in blunting the response to exercise in older females (Copeland et al., 2002). On the other hand, the response observed in COR and in the TT/COR ratio, corroborates numerous previous studies, since changes in COR levels and consequently variations in the ratios are more perceptible in studies involving acute exercise (Heaney et al., 2014), which was not the case of our study. However, an increase in COR would be expected if both exercise programs had been predominantly continuous aerobic

Journal Pre-proof exercise routines, since this type of exercise program does not only promote an increase COR secretion by the adrenal gland (Mura et al., 2014), it can also promote an increase in adrenal gland volume itself (Kjaer, 1998). In frail older adults, for example, a slight increase in COR levels at non-pathological levels may bring benefits to improve neuroendocrine functions. However, these results warrant caution in interpreting, taking into account the diurnal variation of cortisol in the morning (Sudheimer et al., 2014). In general, it appears that older women retain the ability to stimulate an increase in

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circulating levels of some anabolic hormones via exercise modulation (Wu et al., 2010). Similar results were observed in our study, although the frail subjects appeared to have

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lower hormonal concentrations when compared to the non-frail for all the salivary

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markers assessed (p>0.05).

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4.1 – Limitations

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This study displays some particular characteristics and limitations. The sample size was relatively small, however, significant differences were found after the exercise

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programs in all variables, including in the SH. The multi-comorbidity and subsequently

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polypharmacy use are peculiar characteristics of our study sample. Statins, for example, are a commonly prescribed medicine to reduce cardiovascular disease risk in this type of population. Recent studies show that this pharmacological substance attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients, promoting strong sideblinding effects (Mikus et al., 2013). Statins could also affect TT and DHEA production, since cholesterol is a precursor for these hormones and thus blunt the exercise effects.

Journal Pre-proof 4.1 – Practical applications and future directions Our results support the importance of the implementation of specific physical exercise programs designed especially for frail older women, who seem to suffer, to a greater extent, from the consequences of declining sex steroid hormones. It is crucial for public health to identify the main factors associated with FD and PF that underlie the development of new methods for complementary therapies, such as the use of low doses of hormonal supplementation (i.e. hormone-replacement therapy) combined with long-

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term exercise interventions. Future interventions should attempt to included samples of

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institutionalized frail-older men since that would allow generalization for both genders.

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5. Conclusion

In conclusion, both exercise interventions used in this study produced significant

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benefits in order to diminish the physical frail condition, decreased functional disability

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and also, stimulated satisfactory hormonal responses. In this sense, the results of the current study suggest that chair-based moderate multicomponent exercises and elastic-

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band muscle-strength exercise programs could be used to increase physical activity

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levels, gait speed and muscle-strength, diminishing the incidence of PF condition.

Acknowledgments

We would like to thank the CHS that accepted to participate in this study. Thanks to the post-graduated degree students that volunteer for data collection.

Authors contributors Guilherme Furtado organized acquisition of data and writing of the paper; Marisa Loureiro, Miguel Patrício e Humberto Carvalho assisted the statistical analysis. Matheus Uba Chupel helped in the acquisition of data and made the biochemical

Journal Pre-proof analysis. Eef Hogervorst supported the interpretation of data and reviewed the paper critically. Juan C. Colado collaborated in the design of the CSE program. Ana Maria Teixeira and José Ferreira coordinated the research study protocol.

Funding FEDER funds through COMPETE and national funds through FCT-Portuguese Foundation for Science and Technology in the framework of project PTDC/DTPDES/0154/2012. Guilherme Furtado and Matheus Uba Chupel, CAPES/CNPQ –

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Ministry of Education, Brazil (BEX: 11929/13-8 and and 13642/13-8, respectively).

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Ana Teixeira and José Ferreira are registered at CIDAF (UID/PTD/04213/2016).

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Picorelli, A.M.A., Pereira, D.S., Felício, D.C., Dos Anjos, D.M., Pereira, D.A.G., Dias, R.C., Assis, M.G., Pereira, L.S.M., 2014a. Adherence of older women with

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strength training and aerobic exercise. Clinical interventions in aging 9, 323–31. https://doi.org/10.2147/CIA.S54644 Picorelli, A.M.A., Pereira, L.S.M., Pereira, D.S., Felício, D., Sherrington, C., 2014b. Adherence to exercise programs for older people is influenced by program characteristics and personal factors: a systematic review. Journal of physiotherapy 60, 151–6. https://doi.org/10.1016/j.jphys.2014.06.012 Rikli, R., Jones, C., 2013. Senior Fitness Test Manual. Human Kinetics Publishers., Champaing. Robertson, R.J., Goss, F.L., Rutkowski, J., Lenz, B., Dixon, C., Timmer, J., Frazee, K., Dube, J., Andreacci, J., 2003. Concurrent validation of the OMNI perceived exertion scale for resistance exercise. Medicine and science in sports and exercise

Journal Pre-proof 35, 333–41. https://doi.org/10.1249/01.MSS.0000048831.15016.2A Robinson, K.R., Leighton, P., Logan, P., Gordon, A.L., Anthony, K., Harwood, R.H., Gladman, J.R.F., Masud, T., 2014. Developing the principles of chair based exercise for older people: a modified Delphi study. BMC geriatrics 14, 65. https://doi.org/10.1186/1471-2318-14-65 Salimetrics UK, 2017. Salimetrics: Saliva Collection, Saliva EIA kits, Saliva Testing, & Salivary Bioscience Research [WWW Document]. Salivary Analyts. URL https://www.salimetrics.com/ (accessed 5.28.17).

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in Institutionalized Elders. Frontiers in Public Health 4, 133. https://doi.org/10.3389/fpubh.2016.00133 Theou, O., Stathokostas, L., Roland, K.P., Jakobi, J.M., Patterson, C., Vandervoort, A.A., Jones, G.R., 2011. The effectiveness of exercise interventions for the management of frailty: a systematic review. Journal of aging research 2011, 569194. https://doi.org/10.4061/2011/569194 Tocchi, C., Dixon, J., Naylor, M., Jeon, S., McCorkle, R., 2014. Development of a frailty measure for older adults: the frailty index for elders. Journal of nursing measurement 22, 223–40. Tomey, K.M., Sowers, M.R., 2009. Assessment of Physical Functioning: A Conceptual Model Encompassing Environmental Factors and Individual Compensation

Journal Pre-proof Strategies. Physical Therapy 89, 705–714. https://doi.org/10.2522/ptj.20080213 Varadhan, R., Walston, J., Cappola, A.R., Carlson, M.C., Wand, G.S., Fried, L.P., 2008. Higher levels and blunted diurnal variation of cortisol in frail older women. J Gerontol A Biol Sci Med Sci 63, 190–195. https://doi.org/10.1093/gerona/63.2.190 Walsh, N.P., Oliver, S.J., 2016. Exercise, immune function and respiratory infection: An update on the influence of training and environmental stress. Immunology and cell biology 94, 132–9. https://doi.org/10.1038/icb.2015.99 Wu, I.-C.C., Lin, X.-Z.Z., Liu, P.-F.F., Tsai, W.-L.L., Shiesh, S.-C.C., 2010. Low serum

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Figure 1 – Flow chart of the study design according CONSORT statement and sample enrolment during the 28-weeks.

Table 1. Example of single session of both chair multimodal and elastic-band muscle strength exercise program

Chair multimodal exercise program

Total time: 45 minutes

Phase 1 – warming-up: body mobilization and dynamic flexibility exercises

5 minutes reps 10

Cadence 1:2

2-3 2-3 2-3 2-3 2-3 2-3 2-3 2-3 2-3

10-20 10-20 10-20 10-20 10-20 10-20 10-20 10-20 10-20

1:2 1:2 1:2 1:2 1:2 1:2 1:2 1:2 1:2

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1

10

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Notes: RPE = rating perceived exertion scales (B = Borg and O = OMINI).

20-30” 20-30” 20-30” 20-30” 20-30” 20-30” 20-30” 20-30” 60-120”

3-5 3-5 3-5 3-5 3-5 3-5 3-5 3-5 3-5

10”

---

1-2

Total time: 45 minutes

Phase 1 – warming-up body mobilization and dynamic flexibility exercises

Phase 2 – workout Muscle-strengthening exercises 1. Front squat (stand and/or chair) 2. Chair unilateral hip flexion 3. Chair Bench over Row (with flexion) 4. Chest Press (stand and/or chair) 5. Standing (or chair) reverse fly 6. Chair spine twist extension arm (oblique's) 7. Shoulder Press/twist arm front position 8. Chair (or stand) frontal total raiser 9. Biceps arm curl (stand and/or chair) 10. Chair Overhead Triceps extension Phase 3 – cool-down body mobilization and static flexibility exercises Sequence of body mobilization and static flexibility exercises

RPE-B 1-3

5 minutes

Chair elastic-band Resistance Exercises

Sequence of specific joint and full body mobilization exercises

Rest 20”

35 minutes

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Phase 2 – workout Improve-walking/mobility skill exercises 1. Walk around the gym-room during 2-3 minutes. 2. Chair-based sit and reach + easy skipping 3. Chair-based sit and reach + arms coordinator 4. Chair-based leg extension and overhead reach 5. Coordinator, balance, quickness, agility integrated exercise 6. Chair-based skipping + standing rear leg extension 7. Chair-based middle skipping + arms coordinator 8. Chair-based power skipping 9. Walk around the gym-room during 2-3 minutes. Phase 3 – cool-down body mobilization and static flexibility exercises Sequence of specific joint and full body mobilization exercises

sets 2

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Sequence of specific joint and full body mobilization exercises

5 minutes sets 2

reps 6

Cadence 1:1

2-3 2-3 2-3 2-3 2-3 2-3 2-3 2-3 2-3 2-3

10-15 10-15 10-15 10-15 10-15 10-15 10-15 10-15 10-15 10-15

2:2 2:2 2:2 2:2 2:2 2:2 2:2 2:2 2:2 2:2

1

10

---

Rest 20”

RPE-O 1-3

30-45” 30-45” 30-45” 30-45” 30-45” 30-45” 30-45” 30-45” 30-45” 60-120”

4-6 4-6 4-6 4-6 4-6 4-6 4-6 4-6 4-6 4-6

35 minutes

5 minutes 10”

1-2

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Table 2. Characteristics of total sample, experimental and control groups at baseline Chair multimodal exercises (n=21)

Chair Elastic-band exercises (n=20)

Control group nonexercising (n=19)

M±SD

M±SD

M±SD

M±SD

Chronological age (years)

81.62 (7.91)

80.14 (8.19)

81.00 (4.79)

80.93 (10.01)

Stature (meters)

1.51 (0.07)

1.52 (0.61)

1.51 (0.08)

1.51 (0.80)

64.86 (14.06)

63.24 (8.5)

62.03 (17.76)

64.99(14.89)

Body mass index (kg·m )

28.19 (5.71)

26.53 (3.65)

28.35 (7.16)

28.44 (6.06)

Charlson comorbidity index (0-10 points)

7.93 (2.13)

7.55 (1.92)

7.78 (1.98)

8,67 (2.53)

Systolic Blood pressure (mmHg)

126.09 (17.24)

124.05 (15.01)

131.22 (19.37)

122.93 (17.39)

Diastolic Blood pressure (mmHg)

64.85 (11.08)

64.86 (8.07)

67.67 (13.99)

65.87 (10.60)

Mini nutritional assessment (0-30 points)

23.94 (2.66)

23.18(2.75)

24.52 (2.32)

24.36 (2.83)

Physical Frailty index (0-5 points)

2.28 (1.32)

2.35 (1.42)

2.38 (1.72)

2.37 (1.19)

Mini-mental state exam (0-30 points)

20.04 (5.57)

21.42 (5.1)

19.28 (5.53)

21.08 (5.5)

Medication use (units per day)

6.75 (2.34)

7.05 (1.98)

6.95 (3.05)

6.30 (0.95)

73%

75%

74%

54%

48%

52%

61%

60%

59%

39%

41%

38%

31%

28%

33%

78%

Rheumatic or connective tissue disease

48%

Dyslipidemia/metabolic syndrome

64%

Heart failure

37%

Diagnosed mental illness

28%

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Hypertension

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Body mass (Kilograms)

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Total Sample (n=60)

Variables

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Notes: ** p≤0.01; * p≤0.05; M±SD = mean (standard and deviation); The p-values correspond to comparisons between the three groups and were computed with one-way ANOVA one-way or Kruskal-Wallis, depending the assumption (normality) of variable.

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Table 3. Comparison of salivary steroid hormone levels between baseline, 14 and 28 week time-points of exercise intervention Salivary hormones

Interacti on effects

Baseline M(SD)

14-weeks M(SD)

28-weeks M(SD)

0.23 (0.10) 0.23 (0.13) 0.25 (0.13)

0.26 (0.09) 0.26 (0.11) 0.26 (0.14)

0.36 (0.64) 0.21 (0.12) 0.27 (0.17)

55.62 (25.75)

63.02 (24.86)

67.49 (37.43)

Time

61.49 (23.64)

63.15 (24.46)

70.58 (42.07)

Time x Group

53.93 (27.11)

50.66 (19.04)

52.68 (28.34)

27.53(29. 13) 39.60(32. 63) 46.99(44. 14)

37.96(33. 96) 49.59(42. 99) 38.14(30. 99)

F test

p valu e

2 Effe ct size

Practic al relevan ce

Cortisol

CGne Dehydroepiandroste rone CME CSE CGne Testosterone/cortiso l ratio CME

2.06 9 1.20 3

.131

.037

.344

.043

.509

.750

.009

1.94 0

.136

.066

1.52 8 6.00 9

.000

.027

.036

.179

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CSE

Time x Group

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Testosterone CME

Time

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CGne

47.69(54. 53) 49.26(35. 23) 29.71(14. 25)

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CSE

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CME

Time Time x Group

small effect small effect

small effect mediu m effect

small effect large effect

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0.0061 0.0045 0.0081 1.12 .330 .023 small Time (0.0059) (0.0018) (0.0121) 2 effect CSE 0.0036 0.0046 0.0064 1.23 .302 .050 small Time x Group (0.0025) (0.0029) (0.0132) 3 effect CGne 0.0054 0.0051 0.0055 (0.0030) (0.0023) (0.0024) Notes: ** p≤0.01; * p≤0.05; 2 = Eta Square effect size (> 0.02 = small effect, > 0.13 = medium effect and > 0.26 = large effect; M(SD) = mean (standard deviation). The p-values correspond to comparisons between the three groups and were computed with following Bonferroni post-hoc test, respectively.

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Table 4. Comparison of frailty composed score and functional disability outcomes between baseline, 14 and 28 weeks of intervention moments 14weeks M(SD)

28weeks M(SD)

2.24 (1.49) 2.39 (1.46) 2.87 (1.19)

1.13 (1.12) 2.06 (1.11) 3.2 (1.32)

1.04 (1.16) 1.56 (0.86) 3.27 (1.33)

0.88 (1.51) 1.54 (1.29) 1.73 (1.87)

0.75 (1.15) 1.94 (1.82) 1.93 (1.71)

1.25 (1.78) 1.11 (1.49) 1.87 (1.64)

59.08 (26.66) 38.17 (21.31) 45.73 (28.73)

24.63 (16.87) 23.28 (13.84) 38.8 (19.96)

2

Interaction effects

F test

p value

Time

7.385

.003

.118

Time x Group

6.765

<.001

.197

Time

.289

.750

.005

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Groups

Baseline M(SD)

1.787

.136

.061

Time

20.268

<.001

.270

Time x Group

2.830

.036

.093

2.589

.080

.045

Time x Group

3.559

.009

.115

Time

7.609

.002

.122

Time x Group

2.078

.104

.070

Effect size

Practical relevance

CME CSE CGne

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Physical frailty composed score (0-5 points)

CME CSE CGne

CSE CGne

CGne

29.88 (5.39) 26.83 (5.36) 25.2 (6.22)

27.88 (5.47) 27.67 (3.82) 21.33 (5.56)

28.42 (5.61) 30.5 (4.62) 21.87 (5.08)

2.38 (6.02) 2.83 (6.91) 3.36 (4.91)

6.63 (9.24) 5.6 (6.57) 2.54 (1.93)

10.3 (11.65) 8.46 (6.47) 3.31 (4.36)

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CSE

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Physical changes behavior CME

32.08 (15.43) 18.11 (16.3) 39.67 (20.87)

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CME

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Falls efficacy scale (10-100 points)

Time x Group

small effect medium effect

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Katz index of ADL (1-6 points)

medium effect large effect

Time

large effect medium effect

small effect medium effect

Tandem static balance test (per time, seconds) CME CSE CGne

medium effect medium effect

Note: M(SD) = mean (standard deviation); CME = chair-multimodal exercise, CSE = chair muscle-strength exercise, CGne = control group non-exercise; values of significance (p<0.05) are highlighted in bold; Global effect size (partial eta square) 2 > 0.01 = small effect, 2 > 0.06 = medium effect and 2 > 0.14 = large effect.

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Table 5. Absolute and relative count for physical frailty independent components between baseline, 14 and 28 week time-points of the intervention

Ph i ES

Pract ical relev ance

Chair elastic band strength exercises (n = 20) 1428Base week wee line s ks N(% N(%) N( ) %)

12 (80 %)

13 (86. 7%)

<0. 01

small

12 (66.7 %)

15 (83.3 %)

11 (61. 1%)

8 (53.3 %)

11 (73. 3%)

12 (80 %)

0.2 1

small

12 (66.7 %)

11 (61.1 %)

9 (50 %)

10 (66.7 %)

12 (80 %)

11 (73. 3%)

0.0 8

small

7 (38.9 %)

7 (38.9 %)

4 (26.7 %)

4 (26. 7%)

4 (26. 7%)

<0. 01

small

8 (53.3 %)

9 (60 %)

9 (60 %)

0.0 8

na small

11 (61.1 %)

Pract ical relev ance

0. 04

small

17 (70.8 %)

Pract ical relev ance

12 (50% )*

11 (45. 8%)

0.3 1

medi um

small

11 (45.8 %)

4 (16.7 %)*

4 (16. 7%)

0.3 5

medi um

0. 19

small

7 (29.2 %)

7 (29.2 %)

7 (29. 2%)

<0. 01

small

-p

0. 15

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5 (27. 8%)

Ph i ES

2 (11.1 %)

1 (5.6 %)

0. 13

small

3 (12.5 %)

3 (12.5 %)

3 (12. 5%)

<0. 01

small

2 (11.1 %)**

2 (11. 1%)

0. 40

medi um

11 (45.8 %)

1 (4.2 %)**

0 (0% )

>0. 50

large

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2 (11.1 %)

P hi E S

Chair-multimodal exercises (n = 21) 1428Base week wee line s ks N(% N(% N( ) ) %)

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13 (86.7 %)

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Weakne ss (hand grip test, Kilos) Slowne ss (4.6 walk test, per time) Exhaust ion (selfreported questio n) Non intentio nal Weight loss (Medica l record) Low Physica l activity levels (shortform questio nnaire)

Control group non exercising (n =19) 1428Base wee wee line ks ks N(% N( N( ) %) %)

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Physica l Frailty compo nents

Notes: ** p≤0.01; * p≤0.05; ES = Effect size of Cramer’s Phi coefficient (> 0.1 = small effect, > 0.3 = medium effect and > 0.5 = large effect; M(SD) = mean (standard deviation). The p-values correspond to comparisons between the three groups and were computed with McNemar test following Cochrane's Q post-hoc test; Non-intentional weight loss = validated by medical records over one year for each participant.

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Highlights (for review)

Multimodal and elastic-band muscle strength chair-exercises programs can effective to increase levels of salivary Dehydroepiandrosterone and testosterone;



Both exercise programs was able to improve physical functioning and attenuate the physical frailty status.



We recommend that social health care centers integrate both types of exercise training programs since that presents well-established safety, effectiveness and promote good adherence for this population.

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Figure 1