There are few published data demonstrating the co-occurrence of malnutrition and sarcopenia in older adults. In a recent study [20], both entities have been studied in a post-acute care geriatric unit, applying the new ESPEN definition of malnutrition and EWGSOP criteria, assessing the potential clinical relationship between them. The prevalence of malnutrition in this population was 19.3%, and the prevalence of sarcopenia was significantly higher in patients with malnutrition: 82.3 versus 45.1% (p = 0.03), which means that most patients with sarcopenia fulfilled the ESPEN criteria for diagnosis of malnutrition. On the other hand, in the study of Senior et al. [21], sarcopenia was defined with EWGSOP criteria and nutritional

In fact, in hospital settings, malnutrition is approximately 56% in elderly patients [16].

(men).

(if <70 years old) or <22 kg/m2

(women) and <17 kg/m2

or unintentional weight loss

(if >70 years old) or a low fat-free

with two possible options: body mass index (BMI) <18.5 kg/m2

74 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

decrease in muscle mass, strength and/or physical function [17].

either a low BMI <20 kg/m2

the survival [15].

mass index (FFMI) <15 kg/m2

**3.3. Prevalence of malnutrition**

**3.4. Malnutrition-sarcopenia syndrome**

Clinicians should integrate nutrition assessment with sarcopenia screening for optimal evaluation of these two interrelated nutritional issues to help improve patients' clinical outcomes [4].

For sarcopenia screening, a simple clinician tool has been suggested by the EWGSOP [5]. This group has developed an algorithm based on gait speed measurement (a cut-off point of >0.8 m/s identifies risk for sarcopenia) as the easiest and most reliable way to begin sarcopenia screening in clinical practice.

Screening tools for malnutrition are intended for the quick identification of patients at risk of malnutrition, for more in-depth nutritional assessment, or for identifying patients at risk of developing complications or even increased risk of mortality. A variety of malnutrition screening tools are available such as the Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST) [23], the short form of the Mini Nutritional Assessment (SF-MNA) [24] and Nutrition Risk Screening-2002 (NRS-2002) [25]. Based on the evidence presented, the combination of screening and assessing for malnutrition and sarcopenia is recommended to screen for the presence of malnutrition-sarcopenia syndrome in at-risk patient populations, particularly older adults in clinical settings [4].

Clinicians are urged to screen, assess and treat these conditions currently. By examining aspects of both conditions, clinicians can more fully assess their patients' clinical and nutritional status and can design targeted therapies to meet their needs and improve outcomes [4].

Examining patient's nutritional and functional status through screening and assessment for both malnutrition and sarcopenia will enable clinical practitioners to determine the presence of both entities in their patients and to target interventions to prevent and avoid them [4].

#### **5. Nutritional interventions to prevent sarcopenia**

The relationship between muscle mass, strength, physical function and nutritional status has significant clinical implications regarding the therapeutic approaches [26].

Early identification of sarcopenia would be of great clinical relevance because the loss of muscle mass and strength with ageing can be largely reversed by proper exercise programs and nutritional intervention [27]. Of all the therapeutic options available, lifelong improvements in physical activity and diet are probably the most effective public health intervention and the most important treatment option in nursing home residents for this condition, ongoing independence and autonomy in older people. The Society for Sarcopenia, Cachexia and Wasting Disease developed nutritional recommendations for the prevention and management of sarcopenia, which combined exercise with adequate protein and energy intake [28].

On the other hand, adequate caloric intake has to be considered as an essential requisite for any successful therapeutic approach in the institutionalised elderly participants, in terms of prevention and treatment of sarcopenia. Nutrient intake, especially adequate amounts of high-quality protein and amino acids, is the most important anabolic stimulus of skeletal muscle protein synthesis. Epidemiological studies suggest that a low protein intake is associated with sarcopenia. To prevent it, as optimal dietary protein intake, daily 1.0–1.2 g/kg with an optimal repartition over each daily meal or 25–30 g of high-quality protein per meal are recommended. Specifically, the amino acid leucine and meal-induced insulin, both independently stimulate muscle protein synthesis. It has been demonstrated that exercise and amino acid supplementation (3 g of a leucine-enriched balanced essential amino acid mixture twice a day) together may actually be effective in enhancing muscle strength, variables of muscle mass and walking speed in sarcopenic women [29]. Antioxidants and ω 3-polyunsaturated fatty acids may also contribute to the preservation of muscle function. Low 25-hydroxyvitamin D (25(OH)D) serum level in adults is also a potentially modifiable risk factor for sarcopenia [30]. In fact, nutritional interventions combining adequate amounts of vitamin D and proteins are promising strategies to attenuate sarcopenia development [31]. Some studies have shown the effectiveness of other nutritional factors, such as cheese and milk protein and beta-hydroxy-beta-methylbutyrate (HMB), as a potential supplement to improve muscle quality in sarcopenic elderly people [32, 33].

In a recent study [34], Mediterranean dietary pattern (high in olive, low-fat dairy, vegetable, fish, nut and vegetable oil) has demonstrated a favourable role in the prevention of sarcopenia in postmenopausal women, in comparison with a Western pattern (based on high commercial beverage, sugar and dessert, snacks, solid fat, potato, high-fat dairy, legume, organ meat, fast food and sweets). Another study [35] demonstrated that improvements in clinically relevant measures, such as strength and functionality, could be achieved by supplementation with high-quality oral nutritional supplementation.

Other treatments of sarcopenia currently under investigation include testosterone replacement therapy, oestrogens in women, growth hormone and other behavioural and pharmacological strategies. The main limitation of these treatments is the lack of long-term adherence [8].

#### **Author details**

Beatriz Lardiés-Sánchez\* and Alejandro Sanz-París \*Address all correspondence to<EMAIL_ADDRESS>Universitary Hospital Miguel Servet, Zaragoza, Spain

#### **References**

physical activity and diet are probably the most effective public health intervention and the most important treatment option in nursing home residents for this condition, ongoing independence and autonomy in older people. The Society for Sarcopenia, Cachexia and Wasting Disease developed nutritional recommendations for the prevention and management of sarcopenia, which

On the other hand, adequate caloric intake has to be considered as an essential requisite for any successful therapeutic approach in the institutionalised elderly participants, in terms of prevention and treatment of sarcopenia. Nutrient intake, especially adequate amounts of high-quality protein and amino acids, is the most important anabolic stimulus of skeletal muscle protein synthesis. Epidemiological studies suggest that a low protein intake is associated with sarcopenia. To prevent it, as optimal dietary protein intake, daily 1.0–1.2 g/kg with an optimal repartition over each daily meal or 25–30 g of high-quality protein per meal are recommended. Specifically, the amino acid leucine and meal-induced insulin, both independently stimulate muscle protein synthesis. It has been demonstrated that exercise and amino acid supplementation (3 g of a leucine-enriched balanced essential amino acid mixture twice a day) together may actually be effective in enhancing muscle strength, variables of muscle mass and walking speed in sarcopenic women [29]. Antioxidants and ω 3-polyunsaturated fatty acids may also contribute to the preservation of muscle function. Low 25-hydroxyvitamin D (25(OH)D) serum level in adults is also a potentially modifiable risk factor for sarcopenia [30]. In fact, nutritional interventions combining adequate amounts of vitamin D and proteins are promising strategies to attenuate sarcopenia development [31]. Some studies have shown the effectiveness of other nutritional factors, such as cheese and milk protein and beta-hydroxy-beta-methylbutyrate (HMB), as a

potential supplement to improve muscle quality in sarcopenic elderly people [32, 33].

high-quality oral nutritional supplementation.

Beatriz Lardiés-Sánchez\* and Alejandro Sanz-París

\*Address all correspondence to<EMAIL_ADDRESS>Universitary Hospital Miguel Servet, Zaragoza, Spain

**Author details**

In a recent study [34], Mediterranean dietary pattern (high in olive, low-fat dairy, vegetable, fish, nut and vegetable oil) has demonstrated a favourable role in the prevention of sarcopenia in postmenopausal women, in comparison with a Western pattern (based on high commercial beverage, sugar and dessert, snacks, solid fat, potato, high-fat dairy, legume, organ meat, fast food and sweets). Another study [35] demonstrated that improvements in clinically relevant measures, such as strength and functionality, could be achieved by supplementation with

Other treatments of sarcopenia currently under investigation include testosterone replacement therapy, oestrogens in women, growth hormone and other behavioural and pharmacological strategies. The main limitation of these treatments is the lack of long-term adherence [8].

combined exercise with adequate protein and energy intake [28].

76 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

[25] Kondrup J, Rasmussen HH, Hamberg O, Stanga Z, Ad Hoc ESPEN Working Group. Nutritional risk screening (NRS 2002): A new method based on an analysis of controlled clinical trials. Clinical Nutrition. 2003;**22**(3):321-336

[12] Guigoz Y. The Mini Nutritional Assessment (MNA) review of the literature: What does

[13] Söderhamn U, Söderhamn O. Reliability and validity of the nutritional form for the

[14] Cederholm T, Bosaeus I, Barazzoni R, Bauer J, Van Gossum A, Klek S, et al. Diagnostic criteria for malnutrition: An ESPEN Consensus Statement Clinical Nutrition. 2015;**34**(3):

[15] Beck AM. Weight loss, mortality and associated potentially modifiable nutritional risk factors among nursing home residents: A Danish follow-up study. Journal of Nutrition

[16] Pirlich M, Schütz T, Norman K, et al. The German hospital malnutrition study. Clinical

[17] Vivanti A, Ward N, Haines T. Nutritional status and associations with falls, balance, mobility and functionality during hospital admission. Journal of Nutrition Health and

[18] Saka B, Ozkaya H, Karisik E, Akin S, Akpinar TS, Tufan F, et al. Malnutrition and sarcopenia are associated with increased mortality rate in nursing home residents: A prospective study. European Geriatric Medicine. 2016;**7**(3):232-238. DOI: 10.1016/j.

[19] Landi F, Cruz-Jentoft AJ, Liperoti R, Russo A, Giovanni S, Tosato M, et al. Sarcopenia and mortality risk in frail older persons aged 80 years and older: Results from ilSIR-

[20] Sánchez-Rodríguez D, Marco E, Ronquillo-Moreno N, Miralles R, Vázquez-Ibar O, Escalada F. Prevalence of malnutrition and sarcopenia in a post-acute care geriatric unit: Applying the new ESPEN definition and EWGSOP criteria. Clin Nutr. 2016 Sep 9. pii:

[21] Senior HE, Henwood TR, Beller EM, Mitchell GK, Keogh JW. Prevalence and risk factors of sarcopenia among adults living in nursing homes. Maturitas 2015;**82**(4):418-423. DOI:

[22] Norman K, Stobäus N, González MC, Schulzke JD, Pirlich M. Hand grip strength: Outcome predictor and marker of nutritional status. Clinical Nutrition. 2006;**30**(2):135-142

[23] Stratton RJ, Hackston A, Longmore D, Dixon R, Price S, Stroud M, King C, Elia M. Malnutrition in hospital outpatients and inpatients: Prevalence, concurrent validity and ease of use of the "malnutrition universal screening tool" (MUST) for adults. British

[24] Ranhoff AH, Gjoen AU, Mowé M. Screening for malnutrition in elderly acute medical patients: The usefulness of MNA-SF. Journal of Nutrition Health and Aging. 2005;**9**(4):

ENTE study. Age Ageing. 2013;**42**(2):203-209. DOI: 10.1093/ageing/afs194

S0261-5614(16)30233-3. DOI:10.1016/j.clnu.2016.08.024. [Epub ahead of print]

it tell us? Journal of Nutrition Health and Aging. 2006;**10**(6):466-485

elderly (NUFFE). Journal of Advanced Nursing. 2002;**37**(1):28-34

335-340. DOI: 10.1016/j.clnu.2015.03.001

78 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

Health and Aging. 2015;**19**(1):96-101

Nutrition. 2006;**25**(4):563-572

10.1016/j.maturitas.2015.08.006

Journal of Nutrition. 2004;**92**(5):799-808

221-225

Aging. 2011;**15**:388-391

eurger.2015.12.010

### **Sarcopenic Dysphagia as a New Concept**

#### Kotomi Sakai and Kunihiro Sakuma

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.68791

#### **Abstract**

Dysphagia (swallowing difficulties) is a serious problem associated with malnutrition, dehydration, aspiration pneumonia, and death. Its well‐known causes include stroke, neuromuscular disease, and head and neck cancer, and these affect muscles and sensa‐ tion during deglutition. In recent years, dysphagia due to sarcopenia (i.e. "sarcopenic dysphagia") has been reported as a new concept. Sarcopenic dysphagia results from low swallowing and general skeletal muscle mass and strength. The characteristic changes in swallowing muscles occur primarily in oral and pharyngeal muscles along with other associated factors. With a rapidly aging population, the number of older adults with sar‐ copenic dysphagia is expected to increase. Therefore, it is necessary to investigate the pathophysiology and treatment strategies for sarcopenic dysphagia. In this chapter, we summarize previous studies related to sarcopenic dysphagia.

**Keywords:** sarcopenia, deglutition disorders, rehabilitation

#### **1. Introduction**

The term "sarcopenia" was first proposed by Rosenberg [1] to describe age‐related decrease in muscle mass. In 2010, the European Working Group on Sarcopenia in Older People (EWG‐ SOP) proposed the sarcopenia consensus on definition and diagnostic criteria. The EWGSOP defined sarcopenia as a geriatric syndrome characterized by progressive and generalized loss of muscle mass and strength. In addition, they proposed diagnostic criteria for sarcopenia [2]. Subsequently, the International Working Group on Sarcopenia (IWGS) proposed similar definitions [3]. In 2014, the Asian Working Group for Sarcopenia (AWGS) proposed diag‐ nostic criteria based on data on Asian populations [4]. In 2016, sarcopenia was recognized as an independent condition by an ICD‐10‐CM code [5]. Currently, sarcopenia is recognized worldwide.

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Since sarcopenia is characterized by generalized loss of muscle mass and function, it can involve a concomitant reduction in swallowing muscles mass and function. Swallowing is defined as "the function of clearing food and drink through the oral cavity, pharynx, and esopha‐ gus into the stomach at an appropriate rate and speed" by the International Classification of Functioning, Disability and Health [6]. According to medical terminology, "dysphagia" is the symptom (not a disease) characterized by swallowing problems. Dysphagia has been pro‐ posed as a geriatric syndrome such as sarcopenia [7]. In 1992, Veldee and Peth indicated that malnutrition affects swallowing muscles; however, the term "sarcopenia" was not coined [8]. In 2005, Robbins et al. used the term "dysphagia due to sarcopenia" in their study [9]. Since then, studies on dysphagia related to sarcopenia have increased drastically. The term "sarco‐ penic dysphagia" was first used by kuroda in 2012 [10]. Since then, the term "sarcopenic dys‐ phagia" has been used by mainly Japanese researchers [11]. However, this is not a standard medical term. In 2015, Clave and Shaker, worldwide leading researchers in dysphagia, used the term "sarcopenic dysphagia" in a review article [12], wherein sarcopenic dysphagia was introduced as a new concept of dysphagia. To our knowledge, that was the first article that described the term "sarcopenic dysphagia," except those from Japan.

Dysphagia results in serious complications such as aspiration pneumonia, choking, dehydration, malnutrition, and lower quality of life, all of which are potentially lethal. A meta‐analysis on aspiration pneumonia in frail older people revealed that dysphagia is a significant risk factor for aspiration pneumonia [13]. Furthermore, dysphagia negatively affects the nationwide cost of medication because of these complications, readmissions, higher drug intake, and prolonged hospitalization [14, 15]. Therefore, dysphagia is a serious problem that should be prevented and treated.

Many studies have been reported on dysphagia due to neurological diseases such as stroke, Parkinson's disease and other forms of dementia, amyotrophic lateral sclerosis, head and neck cancer, and esophageal cancer. However, articles on sarcopenic dysphagia are few because it is a new concept of dysphagia. We described the number of articles about dysphagia based on years of publication in **Table 1**. We used "aging" or "frail" or "sarcopenia" and "dysphagia"

We set the keywords related to sarcopenia (aging, frail, or sarcopenia) and major causes of dysphagia (stroke, head and neck cancer, or Parkinson's disease) for comparison of research interests. We described the number of articles overall and their years of publication in the last three years. Compared to stroke, Parkinson's disease, and head and neck cancer, articles related to sarcopenic dysphagia are less. The articles were accessed on January 7, 2017.

**Table 1.** Number of articles retrieved for the terms "dysphagia" or "swallowing" and each keyword on PubMed.

or "swallowing" as keywords for retrieving in PubMed. In addition, stroke or Parkinson's disease or head and neck cancer were used as keywords to compare these with the number of articles on dysphagia related to sarcopenia. Since sarcopenia is a geriatric syndrome [2], the number of older adults with sarcopenia would increase with a rapidly aging worldwide population. Similarly, the number of older adults with sarcopenic dysphagia would increase. Thus, it is important to investigate the clinical conditions and treatment strategies for sarco‐ penic dysphagia. In this chapter, we summarize dysphagia related to sarcopenia based on previous studies on mainly healthy or frail subjects or those with sarcopenia.

#### **2. Epidemiology of sarcopenic dysphagia**

#### **2.1. Definition and prevalence**

Since sarcopenia is characterized by generalized loss of muscle mass and function, it can involve a concomitant reduction in swallowing muscles mass and function. Swallowing is defined as "the function of clearing food and drink through the oral cavity, pharynx, and esopha‐ gus into the stomach at an appropriate rate and speed" by the International Classification of Functioning, Disability and Health [6]. According to medical terminology, "dysphagia" is the symptom (not a disease) characterized by swallowing problems. Dysphagia has been pro‐ posed as a geriatric syndrome such as sarcopenia [7]. In 1992, Veldee and Peth indicated that malnutrition affects swallowing muscles; however, the term "sarcopenia" was not coined [8]. In 2005, Robbins et al. used the term "dysphagia due to sarcopenia" in their study [9]. Since then, studies on dysphagia related to sarcopenia have increased drastically. The term "sarco‐ penic dysphagia" was first used by kuroda in 2012 [10]. Since then, the term "sarcopenic dys‐ phagia" has been used by mainly Japanese researchers [11]. However, this is not a standard medical term. In 2015, Clave and Shaker, worldwide leading researchers in dysphagia, used the term "sarcopenic dysphagia" in a review article [12], wherein sarcopenic dysphagia was introduced as a new concept of dysphagia. To our knowledge, that was the first article that

Dysphagia results in serious complications such as aspiration pneumonia, choking, dehydration, malnutrition, and lower quality of life, all of which are potentially lethal. A meta‐analysis on aspiration pneumonia in frail older people revealed that dysphagia is a significant risk factor for aspiration pneumonia [13]. Furthermore, dysphagia negatively affects the nationwide cost of medication because of these complications, readmissions, higher drug intake, and prolonged hospitalization [14, 15]. Therefore, dysphagia is a serious problem that should be prevented and

Many studies have been reported on dysphagia due to neurological diseases such as stroke, Parkinson's disease and other forms of dementia, amyotrophic lateral sclerosis, head and neck cancer, and esophageal cancer. However, articles on sarcopenic dysphagia are few because it is a new concept of dysphagia. We described the number of articles about dysphagia based on years of publication in **Table 1**. We used "aging" or "frail" or "sarcopenia" and "dysphagia"

**Total 2016 2015 2014**

1019 139 141 120

We set the keywords related to sarcopenia (aging, frail, or sarcopenia) and major causes of dysphagia (stroke, head and neck cancer, or Parkinson's disease) for comparison of research interests. We described the number of articles overall and their years of publication in the last three years. Compared to stroke, Parkinson's disease, and head and neck cancer,

**Table 1.** Number of articles retrieved for the terms "dysphagia" or "swallowing" and each keyword on PubMed.

Stroke 1416 159 145 134

Parkinson's disease 472 50 53 46 Aging 305 31 31 30 Frail 75 8 6 8 Sarcopenia 38 13 11 6

articles related to sarcopenic dysphagia are less. The articles were accessed on January 7, 2017.

described the term "sarcopenic dysphagia," except those from Japan.

82 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

treated.

Head and neck cancer

The current definition of sarcopenic dysphagia is "difficulty swallowing due to sarcopenia of general skeletal and swallowing muscles" [7, 12]. Although the diagnostic criteria for sarcopenia are defined by the cutoff value of muscle mass and physical function or muscle strength [2, 16], the diagnostic criteria for sarcopenic dysphagia have not been standardized. However, a few studies have attempted to investigate the prevalence of sarcopenic dyspha‐ gia; these included subjects without diseases directly affecting swallowing function, such as stroke, Parkinson's disease, and head and neck cancer. Maeda and Akagi [17, 18] reported its prevalence as 42.3 and 30%, respectively, in acute older inpatients at admission. In addition, in their prospective observational study [19], 26% of acute older inpatients developed sarco‐ penic dysphagia within 60 days of admission. Their studies mainly included older inpatients with acute internal diseases. For older inpatients, it is easy to develop sarcopenic dysphagia during hospitalization because of rest in bed and anorexia by illness. In our study subjects, from acute hospitals to a rehabilitation hospital [11], 32.2% of older inpatients had sarcopenic dysphagia on admission. Our study included many older inpatients with orthopedic disor‐ ders. These findings suggest that the prevalence of sarcopenic dysphagia is approximately 30–40% in older inpatients. In community‐dwelling older adults, the review article reported that approximately 15% of them had dysphagia [20]. The risk factors of dysphagia included age, history of clinical disease, and physical frailty, including reduced activities of daily liv‐ ing. However, this review did not have sarcopenic dysphagia as an endpoint. Older inpatients are at a higher risk of sarcopenic dysphagia than community‐dwelling older adults. The pre‐ vention, assessment, and intervention for sarcopenic dysphagia are important, especially in older inpatients.

#### **2.2. Etiology**

Several pathophysiological mechanisms are known for sarcopenia in general skeletal mus‐ cles. Sarcopenia is categorized as primary and/or secondary sarcopenia based on etiology [2]. The most prominent cause of primary sarcopenia is aging, while those of secondary sar‐ copenia are inactivity (bed rest, sedentary lifestyle, deconditioning, or zero‐gravity condi‐ tions), malnutrition (inadequate dietary intake), and disease (advanced organ failure such as heart, lung, liver, kidney, brain, inflammatory disease, malignancy, or endocrine disease). Several studies have shown associations of aging, inactivity, malnutrition, and disease with dysphagia [21–23]. The characteristic change in the swallowing mechanism in healthy older adults, because of aging, is referred to as "presbyphagia" [24]. Anatomical and functional changes due to aging render older adults at risk of dysphagia [25, 26]. Though aging causes reduced swallowing function, it does not cause dysphagia. In relation to inactivity, physi‐ cal inactivity can cause sarcopenic dysphagia [19]. In our study in a rehabilitation hospital [11], physical activity level was independently associated with the functional level of oral intake of food and liquid. In addition, the duration of tentative nil per os (NPO) without dysphagia assessment in patients with aspiration pneumonia resulted in reduced swallow‐ ing ability during treatment [27]. Inactivity of swallowing muscles itself can cause disuse of themselves and appendicular skeletal muscles. Aspiration pneumonia in older adults usu‐ ally results in bedrest and NPO for treatment. Although aspiration pneumonia is known to be caused by dysphagia, it can also cause sacropenic dysphagia because of inactivity and malnutrition with its treatment. In relation to nutritional status, mid‐upper arm circumfer‐ ence was associated with swallowing function [10]. In addition, nutritional status was a factor of the prognosis of swallowing ability in older inpatients [19]. In other studies, mal‐ nutrition has been suggested to cause dysphagia [8, 28]. Veldee and Peth [8] postulated that swallowing muscles have moderate‐to‐high percentage of type II fibers because normal swallowing is characterized by rapid contraction of muscles. Furthermore, malnutrition can affect those swallowing muscles because type II fibers are reportedly affected by mal‐ nutrition more easily than type I fibers [29–32]. Malnutrition can be one of the main causes of sarcopenic dysphagia.

In relation to the disease, the prevalence of sarcopenia is high among chronically ill patients, ranging from 15 to 50% in patients with cancer and 30 to 45% in patients with liver failure [33]. In addition, cachexia is a metabolic syndrome characterized by loss of muscle mass with or without loss of fat mass, which can cause sarcopenia, and is prevalent in 50 to 80% of cases in several types of cancer [34]. Wakabayashi et al. [23] showed that loss of skeletal muscle mass was related to severe dysphagia in patients with cancer. Patients with chronic progressive diseases such as cancer can develop dysphagia more easily than those with other diseases, owing to sarcopenia. In older adults with Alzheimer's disease, decreased skeletal muscle mass resulted in poor swallowing functions [35]. Dysphagia in neurodegen‐ erative disease can be caused by sarcopenia. Decreased general skeletal muscle mass was considered a risk factor for sarcopenic dysphagia in acute older inpatients [19]. Although the detailed pathophysiological mechanism of sarcopenic dysphagia from decreased general skeletal muscle mass is largely unclear, sarcopenic dysphagia can develop during general sarcopenia.

A high prevalence of sarcopenic dysphagia in older inpatients may be because hospitalization causes further inactivity and/or decrease in nutritional status and leads to severe sarcopenia. Almost all these studies revealed the associations between dysphagia and sarcopenia; how‐ ever, these are not causal relationships because of the cross‐sectional design of these studies. Further studies are required to explore causal relationships. We described the possible patho‐ physiological mechanism of sarcopenic dysphagia in **Figure 1**.

**Figure 1.** Possible mechanism of sarcopenic dysphagia. Older adults with presbyphagia can develop generalized sarcopenia due to disease, inactivity, or malnutrition. In the progress of generalized sarcopenia, sarcopenic dysphagia can develop due to decreased tongue, pharyngeal, and/or suprahyoid muscle function involved in swallowing.

#### **3. Pathophysiology of sarcopenic dysphagia**

#### **3.1. Swallowing process**

Several studies have shown associations of aging, inactivity, malnutrition, and disease with dysphagia [21–23]. The characteristic change in the swallowing mechanism in healthy older adults, because of aging, is referred to as "presbyphagia" [24]. Anatomical and functional changes due to aging render older adults at risk of dysphagia [25, 26]. Though aging causes reduced swallowing function, it does not cause dysphagia. In relation to inactivity, physi‐ cal inactivity can cause sarcopenic dysphagia [19]. In our study in a rehabilitation hospital [11], physical activity level was independently associated with the functional level of oral intake of food and liquid. In addition, the duration of tentative nil per os (NPO) without dysphagia assessment in patients with aspiration pneumonia resulted in reduced swallow‐ ing ability during treatment [27]. Inactivity of swallowing muscles itself can cause disuse of themselves and appendicular skeletal muscles. Aspiration pneumonia in older adults usu‐ ally results in bedrest and NPO for treatment. Although aspiration pneumonia is known to be caused by dysphagia, it can also cause sacropenic dysphagia because of inactivity and malnutrition with its treatment. In relation to nutritional status, mid‐upper arm circumfer‐ ence was associated with swallowing function [10]. In addition, nutritional status was a factor of the prognosis of swallowing ability in older inpatients [19]. In other studies, mal‐ nutrition has been suggested to cause dysphagia [8, 28]. Veldee and Peth [8] postulated that swallowing muscles have moderate‐to‐high percentage of type II fibers because normal swallowing is characterized by rapid contraction of muscles. Furthermore, malnutrition can affect those swallowing muscles because type II fibers are reportedly affected by mal‐ nutrition more easily than type I fibers [29–32]. Malnutrition can be one of the main causes

84 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

In relation to the disease, the prevalence of sarcopenia is high among chronically ill patients, ranging from 15 to 50% in patients with cancer and 30 to 45% in patients with liver failure [33]. In addition, cachexia is a metabolic syndrome characterized by loss of muscle mass with or without loss of fat mass, which can cause sarcopenia, and is prevalent in 50 to 80% of cases in several types of cancer [34]. Wakabayashi et al. [23] showed that loss of skeletal muscle mass was related to severe dysphagia in patients with cancer. Patients with chronic progressive diseases such as cancer can develop dysphagia more easily than those with other diseases, owing to sarcopenia. In older adults with Alzheimer's disease, decreased skeletal muscle mass resulted in poor swallowing functions [35]. Dysphagia in neurodegen‐ erative disease can be caused by sarcopenia. Decreased general skeletal muscle mass was considered a risk factor for sarcopenic dysphagia in acute older inpatients [19]. Although the detailed pathophysiological mechanism of sarcopenic dysphagia from decreased general skeletal muscle mass is largely unclear, sarcopenic dysphagia can develop during general

A high prevalence of sarcopenic dysphagia in older inpatients may be because hospitalization causes further inactivity and/or decrease in nutritional status and leads to severe sarcopenia. Almost all these studies revealed the associations between dysphagia and sarcopenia; how‐ ever, these are not causal relationships because of the cross‐sectional design of these studies. Further studies are required to explore causal relationships. We described the possible patho‐

physiological mechanism of sarcopenic dysphagia in **Figure 1**.

of sarcopenic dysphagia.

sarcopenia.

Swallowing is a complex process involving up to 30 striated muscles [12, 36], although swal‐ lowing is a continuous process generally conceptualized as occurring in several discrete phases. The first phase is the "preoral phase" wherein visual and olfactory qualities of food are recognized and they cause salivation, which is needed for bolus preparation [37]. The second phase is the "oral preparatory phase" wherein food is chewed and mixed with saliva to form a bolus that is easily transported to pharynx. The third phase is the "oral transit phase" wherein the tongue begins anterior‐to‐posterior propulsion of the bolus into pharynx. The fourth phase is the "pharyngeal phase" wherein numerous muscles function in a rapid sequence. The last phase is the "esophageal phase" wherein the bolus enters the esophagus and is transported toward the stomach by peristaltic contractions of the esophagus. Through swallowing, appropriate temporal coordination of feeding and breathing is needed to pro‐ vide proper nutrition and to prevent aspiration because the pathways for food and air com‐ municate in the pharynx [38].

#### **3.2. Preoral phase to oral transit phase**

In the preoral phase, cognitive function is related to dysphagia. In patients with congestive heart failure, cognitive dysfunction is a predictor of dysphagia [39]. In addition, sarcopenia has been independently associated with cognitive impairment in meta‐analysis [40]. Thus, cognitive impairment can contribute to development of sarcopenic dysphagia. On transiting from the oral preparatory phase to the pharyngeal phase, several muscles are involved in swallowing, of which the tongue is a major muscle. The previous studies [9, 41] have found that individuals who aspirate have lower tongue strength than those who do not. Thus, tongue strength is a very important factor for swallowing. To our knowledge, Robbins et al. [42] are the first to indicate that tongue strength is affected by sarcopenia. In their study on healthy men, maximal isometric pressures were significantly greater at the tongue blade site in younger subjects, whereas peak swallow pressures remained similar across both young and older subjects. Nicosia et al. [43] also showed the same results in both healthy men and women. However, Robbins and colleagues [44] showed that both maximal isometric pres‐ sures and swallow pressures reduced with aging, and differences between maximal isometric pressures and swallow pressures were greater in younger adults than in older ones. Their studies have suggested diminished reserve of tongue strength in older adults. Buehring et al. [45] showed that both anterior and posterior maximum tongue pressure negatively correlated with age among community‐dwelling individuals aged ≥ 70 years. Furthermore, Utanohara et al. [46] showed that men aged 20–40 years had higher anterior tongue pressure than the women, and anterior tongue pressure started to decrease from the age of 60 years in men and 70 years in women among healthy older adults. Their study indicated that tongue strength in men reduced with age at a faster rate than it did in women. Collectively, anterior and pos‐ terior tongue strength can decrease differently owing to age‐related sarcopenia among men and women. Although a standard value of tongue strength in healthy older adults has not been established yet, Robbins et al. [41] considered tongue strength of <40 kPa as low, and Utanohara et al. [46] showed average tongue strength at 60 years of age was 37.6 ± 8.8 and 31.9 ± 8.9 kPa at 70 years of age. These values can be useful references in the clinical settings and in research. However, in our subjects aged ≥ 65 years [11], malnutrition was independently asso‐ ciated with low anterior tongue strength but not with age. Thus, decreased tongue strength in older adults can occur easily owing to malnutrition than because of aging.

The association between tongue strength and grip strength that represents whole body strength has been reported in several studies. Mendes et al. [47] showed that tongue and grip strength were reduced with increasing age. This study indicated that tongue strength was decreased owing to reduction in general muscle strength. Anterior tongue strength was significantly correlated with grip strength [11, 45, 47, 48]. However, Butler et al. [49] reported that posterior tongue strength, not anterior, was correlated with grip strength. The association between general muscle strength and tongue strength, whether anterior or posterior tongue, is under discussion. In addition to the difference of magnitude of tongue strength, Nicosia et al. [43] showed the difference of timing of tongue pressure generation between older and younger healthy adults. Time taken to reach maximal isometric pressure and swallowing pressure for liquids was longer in the older group than in the younger one. The timing of tongue strength generation may be also important in sarcopenic dysphagia.

Regarding tongue composition, a few studies have reported the distribution of tongue adipose tissue. Miller et al. [50] reported greater muscle tissue and correspondingly less adipose tissue in the posterior tongue than in the anterior tongue, whereas Nashi et al. [51] reported greater adipose tissue in the posterior tongue than in the anterior tongue on autopsy. As tongue muscle composition changed, amyloid deposits were found to be higher in older adults [52]. Owing to few studies on the tongue composition change by sarcopenia, further studies are required.

Regarding the association with appendicular skeletal muscle mass and tongue strength, Buehring et al. [45] showed that tongue strength was not significantly different in indi‐ viduals who did or did not meet skeletal muscle mass criteria for sarcopenia. However, studies in older inpatients [11, 17] found a significant association between appendicular skeletal muscle mass and tongue strength in correlation analyses. In any case, the associa‐ tion between tongue strength and grip strength as one of sarcopenia indices is evident, and decreased tongue strength can be a symptom of sarcopenia and lead to sarcopenic dyspha‐ gia. Not only tongue strength but also tongue thickness was related to general muscle mass. Tamura et al. [53] showed that tongue thickness was significantly associated with mid‐arm muscle area. Not only appendicular skeletal muscle mass but also tongue muscle mass can be affected by sarcopenia.

#### **3.3. Pharyngeal phase**

has been independently associated with cognitive impairment in meta‐analysis [40]. Thus, cognitive impairment can contribute to development of sarcopenic dysphagia. On transiting from the oral preparatory phase to the pharyngeal phase, several muscles are involved in swallowing, of which the tongue is a major muscle. The previous studies [9, 41] have found that individuals who aspirate have lower tongue strength than those who do not. Thus, tongue strength is a very important factor for swallowing. To our knowledge, Robbins et al. [42] are the first to indicate that tongue strength is affected by sarcopenia. In their study on healthy men, maximal isometric pressures were significantly greater at the tongue blade site in younger subjects, whereas peak swallow pressures remained similar across both young and older subjects. Nicosia et al. [43] also showed the same results in both healthy men and women. However, Robbins and colleagues [44] showed that both maximal isometric pres‐ sures and swallow pressures reduced with aging, and differences between maximal isometric pressures and swallow pressures were greater in younger adults than in older ones. Their studies have suggested diminished reserve of tongue strength in older adults. Buehring et al. [45] showed that both anterior and posterior maximum tongue pressure negatively correlated with age among community‐dwelling individuals aged ≥ 70 years. Furthermore, Utanohara et al. [46] showed that men aged 20–40 years had higher anterior tongue pressure than the women, and anterior tongue pressure started to decrease from the age of 60 years in men and 70 years in women among healthy older adults. Their study indicated that tongue strength in men reduced with age at a faster rate than it did in women. Collectively, anterior and pos‐ terior tongue strength can decrease differently owing to age‐related sarcopenia among men and women. Although a standard value of tongue strength in healthy older adults has not been established yet, Robbins et al. [41] considered tongue strength of <40 kPa as low, and Utanohara et al. [46] showed average tongue strength at 60 years of age was 37.6 ± 8.8 and 31.9 ± 8.9 kPa at 70 years of age. These values can be useful references in the clinical settings and in research. However, in our subjects aged ≥ 65 years [11], malnutrition was independently asso‐ ciated with low anterior tongue strength but not with age. Thus, decreased tongue strength in

86 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

older adults can occur easily owing to malnutrition than because of aging.

tongue strength generation may be also important in sarcopenic dysphagia.

The association between tongue strength and grip strength that represents whole body strength has been reported in several studies. Mendes et al. [47] showed that tongue and grip strength were reduced with increasing age. This study indicated that tongue strength was decreased owing to reduction in general muscle strength. Anterior tongue strength was significantly correlated with grip strength [11, 45, 47, 48]. However, Butler et al. [49] reported that posterior tongue strength, not anterior, was correlated with grip strength. The association between general muscle strength and tongue strength, whether anterior or posterior tongue, is under discussion. In addition to the difference of magnitude of tongue strength, Nicosia et al. [43] showed the difference of timing of tongue pressure generation between older and younger healthy adults. Time taken to reach maximal isometric pressure and swallowing pressure for liquids was longer in the older group than in the younger one. The timing of

Regarding tongue composition, a few studies have reported the distribution of tongue adipose tissue. Miller et al. [50] reported greater muscle tissue and correspondingly less adipose tissue in the posterior tongue than in the anterior tongue, whereas Nashi et al. [51] reported greater In the pharyngeal phase of swallowing, decreased pharyngeal strength has been shown to be related to aspiration status [54]. The suprahyoid muscles are important muscles respon‐ sible for pharyngeal strength required for swallowing. Feng and colleagues [55] examined the geniohyoid muscle—one of the suprahyoid muscles—using 80 computed tomography scans of the head and neck from healthy older and younger adults and revealed that the geniohyoid muscle atrophies with age in both the midsagittal and anterior coronal planes in men as well as women. In addition, atrophy of the geniohyoid muscle in the midsagittal plane was related to aspiration in men.

The movement of the hyoid bone, which is pulled upward and forward by the suprahyoid muscles, is assessed as an indicator of suprahyoid muscle function in videofluoroscopic swal‐ lowing studies (VFSS). VFSS is considered the gold standard examination for assessment of swallowing function because it is the only objective examination that evaluates the oral, palatal, pharyngeal, and pharyngoesophageal components of deglutition, comprehensively. Decreased range of motion and velocity of movement of the hyoid bone is observed more frequently in healthy older men than in younger men [56, 57]. In another study, the elevation of the hyoid was found to be greater in older adults both with and without dysphagia than in younger adults; however, in contrast to older adults without dysphagia, those with dysphagia were unable to use this strategy during deglutition of larger boluses [58]. In another study, the range of motion of the hyoid bone during swallowing was not significantly different between older and younger adults among both men and women. In contrast, the hyoid‐larynx dis‐ tance at rest was greater in both older men and women than in younger ones, and the change between the hyoid‐larynx distance at rest and at the maximum approximation during swal‐ lowing was greater in older adults than in younger adults (men: mean 1.25 cm in younger men and 1.54 cm in older men; women: 1.07 cm in younger women and 1.19 cm in older women) [59]. The duration of supraglottic closure in VFSS was longer in older healthy adults than in younger healthy adults [60]. In addition, frail older adults showed slower laryngeal closure and upper esophageal sphincter opening and delayed maximal vertical hyoid motion (healthy, 0.310 ± 0.048 s; frail, 0.480 ± 0.055 s) than healthy adults. Tongue bolus propulsion strength measured by means of Newton's second law of motion in the pharyngeal phase in VFSS was 22.16 ± 2.54 mN in healthy older adults; frail older adults exhibited weaker tongue propulsion strength (8.99 ± 1.09 mN), leading to low bolus velocity and less kinetic energy [60]. There have been few studies on kinematic change related to sarcopenic dysphagia based on imaging findings; therefore, further research is warranted to investigate this issue.

In the assessment of dysphagia, jaw‐opening strength was proposed as an indicator of supra‐ hyoid muscle strength [61]. Based on measurement of jaw‐opening strength in healthy adults, Iida et al. [62] suggested that suprahyoid muscle strength decreases with aging in both men and women. Machida et al. [63] demonstrated that low jaw‐opening strength was associated with sarcopenia in older men. Suprahyoid muscle strength may decrease with aging and is further decreased in older men with sarcopenia. Hiramatsu et al. [64] demonstrated that the initiation of saliva swallowing was delayed and the number of saliva swallowings per 30 s decreased after meals in older adults but not in young adults (premeal, mean 7.61 and post‐ meal 7.30 in younger adults [no significant difference]; premeal, mean 5.35 and postmeal, mean 4.65 in older adults [significant difference, *p* < 0.05]). Their study indicated low endur‐ ance of swallowing muscles, including the suprahyoid muscles, in older adults. Low swal‐ lowing endurance can be an important component of sarcopenic dysphagia. Compared to studies on tongue muscles related to sarcopenia, fewer studies have been conducted on the suprahyoid muscles in relation to sarcopenia.

Kendall and Leonard [65] demonstrated that elderly patients with dysphagia of unknown eti‐ ology had delayed and incomplete pharyngeal constriction compared with both younger and age‐matched controls without dysphagia. Leonard et al. [59] investigated spatial displace‐ ment variables in adults with no history of dysphagia and swallowing complaints. In their study, older adults with dysphagia exhibited poorer maximal pharyngeal constriction during swallowing as compared to healthy young controls. Dysfunction of pharyngeal constriction can be an important symptom of sarcopenic dysphagia. Based on the MRI scans of the neck in 60 women, Molfenter et al. [66] demonstrated that pharyngeal muscle thickness decreases and the size of the pharyngeal lumen increases with age. Such a structural change in the phar‐ ynx can result in incomplete pharyngeal constriction.

As for the sensory impairment associated with dysphagia, silent aspiration is a serious prob‐ lem. Silent aspiration refers to aspiration before, during, or after swallowing in the absence of cough or visible signs of choking and distress. In a previous study, 32.5% of frail older adults with impaired safety swallow exhibited silent aspiration [60]. In a study on 76 healthy older adults [67], 83% (63/76) and 28% (21/76) exhibited penetration and silent aspiration, respectively. In addition, 85 and 61% of the subjects who exhibited penetration and aspira‐ tion, respectively, did not elicit a sensorimotor response. In another study with 56 healthy subjects [68], older adults showed a progressive decline in pharyngeal and supraglottic sensi‐ tivity measured using air pulse stimulation; sensory discrimination was 2.07 ± 0.20 mmHg in subjects aged 20–40 years and 2.68 ± 0.63 mmHg in subjects aged 61–90 years. Sarcopenia can lead to sensory decline in the pharynx and larynx and cause silent aspiration.

With regard to the changes in muscle tissue, sarcopenia or fatty degeneration after atrophy of striated muscles was observed to be accompanied by accumulation of macrophages [69, 70]. The numbers of macrophages per striated muscle fiber were 5–6 times greater in the larynx and pharynx than in other parts of the body (e.g. tongue, shoulder, and anus) in old men [71]. This kind of change in muscle tissue can lead to dysfunction of swallowing muscles with age.

#### **3.4. Esophageal phase**

closure and upper esophageal sphincter opening and delayed maximal vertical hyoid motion (healthy, 0.310 ± 0.048 s; frail, 0.480 ± 0.055 s) than healthy adults. Tongue bolus propulsion strength measured by means of Newton's second law of motion in the pharyngeal phase in VFSS was 22.16 ± 2.54 mN in healthy older adults; frail older adults exhibited weaker tongue propulsion strength (8.99 ± 1.09 mN), leading to low bolus velocity and less kinetic energy [60]. There have been few studies on kinematic change related to sarcopenic dysphagia based

on imaging findings; therefore, further research is warranted to investigate this issue.

suprahyoid muscles in relation to sarcopenia.

88 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

ynx can result in incomplete pharyngeal constriction.

In the assessment of dysphagia, jaw‐opening strength was proposed as an indicator of supra‐ hyoid muscle strength [61]. Based on measurement of jaw‐opening strength in healthy adults, Iida et al. [62] suggested that suprahyoid muscle strength decreases with aging in both men and women. Machida et al. [63] demonstrated that low jaw‐opening strength was associated with sarcopenia in older men. Suprahyoid muscle strength may decrease with aging and is further decreased in older men with sarcopenia. Hiramatsu et al. [64] demonstrated that the initiation of saliva swallowing was delayed and the number of saliva swallowings per 30 s decreased after meals in older adults but not in young adults (premeal, mean 7.61 and post‐ meal 7.30 in younger adults [no significant difference]; premeal, mean 5.35 and postmeal, mean 4.65 in older adults [significant difference, *p* < 0.05]). Their study indicated low endur‐ ance of swallowing muscles, including the suprahyoid muscles, in older adults. Low swal‐ lowing endurance can be an important component of sarcopenic dysphagia. Compared to studies on tongue muscles related to sarcopenia, fewer studies have been conducted on the

Kendall and Leonard [65] demonstrated that elderly patients with dysphagia of unknown eti‐ ology had delayed and incomplete pharyngeal constriction compared with both younger and age‐matched controls without dysphagia. Leonard et al. [59] investigated spatial displace‐ ment variables in adults with no history of dysphagia and swallowing complaints. In their study, older adults with dysphagia exhibited poorer maximal pharyngeal constriction during swallowing as compared to healthy young controls. Dysfunction of pharyngeal constriction can be an important symptom of sarcopenic dysphagia. Based on the MRI scans of the neck in 60 women, Molfenter et al. [66] demonstrated that pharyngeal muscle thickness decreases and the size of the pharyngeal lumen increases with age. Such a structural change in the phar‐

As for the sensory impairment associated with dysphagia, silent aspiration is a serious prob‐ lem. Silent aspiration refers to aspiration before, during, or after swallowing in the absence of cough or visible signs of choking and distress. In a previous study, 32.5% of frail older adults with impaired safety swallow exhibited silent aspiration [60]. In a study on 76 healthy older adults [67], 83% (63/76) and 28% (21/76) exhibited penetration and silent aspiration, respectively. In addition, 85 and 61% of the subjects who exhibited penetration and aspira‐ tion, respectively, did not elicit a sensorimotor response. In another study with 56 healthy subjects [68], older adults showed a progressive decline in pharyngeal and supraglottic sensi‐ tivity measured using air pulse stimulation; sensory discrimination was 2.07 ± 0.20 mmHg in subjects aged 20–40 years and 2.68 ± 0.63 mmHg in subjects aged 61–90 years. Sarcopenia can

lead to sensory decline in the pharynx and larynx and cause silent aspiration.

Dysphagia caused by problems associated with the esophageal phase of swallowing is termed "esophageal dysphagia". Esophageal dysphagia can occur due to achalasia, diffuse esopha‐ geal spasm, nonspecific motor disorders, obstructive lesions such as stenosis or neoplasm, or gastroesophageal reflux disease [72]. Esophageal motility disorder with aging is termed "presbyesophagus" [73]. Neuromuscular dysfunction, decreased resting upper esophageal sphincter (UES) pressure, and delayed relaxation of the UES after swallowing are some age‐related changes in swallowing [74, 75]. Sarcopenia can also alter esophageal functions. Sarcopenic esophageal dysphagia may be also important in addition to sarcopenic oropha‐ ryngeal dysphagia.

#### **3.5. The coordination of swallowing with respiration**

Disturbed respiration can cause aspiration in older adults [76]. The expiration‐swallow‐expi‐ ration (EX/EX) pattern is essential to prevent aspiration [77]. However, the probability of the non‐EX/EX respiratory phase pattern has been found to be higher in the middle‐ and old‐age groups than in the young‐age group [78]. In addition, older adults had a longer swallowing apnea duration than younger adults for preventing aspiration [78]. Though the coordina‐ tion of respiration and swallowing is regulated by the central pattern generator center in the brainstem, it can be altered in case of advanced age or disease [79]. This mechanism seems to be related to respiratory function change with age or disease. A few studies showed that respiratory muscle strength was related to sarcopenia [80, 81]. Sarcopenia can affect the safety swallowing respiratory pattern. The relationship between sarcopenic dysphagia and respira‐ tory function should be investigated.

#### **4. Treatment for sarcopenic dysphagia**

A systematic review suggested that interventions such as resistance training, compound exercises (a mix of aerobic, flexibility, and/or balance training), and nutritional interventions (protein supplementation, essential amino acid [EAA, mainly leucine] supplementation, β‐hydroxy β‐methylbutyric acid [HMB; a bioactive metabolite of leucine] supplementation with arginine or alone or fatty acid supplementation) were effective for improvement of gen‐ eralized muscle mass and strength or functions [82]. Among these interventions, supervised resistance exercise or composite exercise programs for at least 3 months and preferably lon‐ ger, EAA (with leucine), and HMB were indicated to be more beneficial for improving mus‐ cle‐related parameters in sarcopenia. In another review, Morley [83] suggested that resistance exercise is the most promising candidate for attenuating sarcopenia. In addition, supplemen‐ tation with essential amino acids, creatine, vitamin D, or testosterone was also indicated to be effective.

With respect to treatment of dysphagia in relation to sarcopenia, the effectiveness of resistance training intervention to improve tongue muscle function has been demonstrated. Robbins et al. [9] used the Iowa Oral Performance Instrument to examine the effect of an 8‐week progressive tongue resistance exercise program consisting of compressing an air‐filled bulb between the tongue and hard palate in 10 healthy older adults aged 70–89 years. The frequency of exercise was 30 times in a single session, three times a day, and 3 days a week. The exercise intensity level in that study was 60% of the maximum pressure in the first week and 80% of the maxi‐ mum pressure in the remaining 7 weeks. In this study, isometric tongue strength (baseline: mean 41 kPa; week 2: 44 kPa [nonsignificant difference]; week 4: 47 kPa [*p* = 0.02 compared to baseline]; week 6: 49 kPa [*p* = 0.01 compared to baseline]), tongue volume (change rate ranges from 2.16 to 10.68% upward), and peak swallowing pressure increased after the intervention. Tongue strength and thickness are decreased in sarcopenia but can have possible reversibility. The method used for measurement of tongue strength is described in **Figure 2**.

The effectiveness of the Shaker Exercise for strengthening the suprahyoid muscles is well‐ known in the field of dysphagia rehabilitation.  Shaker et al. [84] and Easterling [85] examined the effect of this

**Figure 2.** Tongue strength measurement. Compressing an air‐filled bulb between the tongue and the hard palate and displaying the maximum tongue strength at the upper row (JMS, Hiroshima, Japan).

**Figure 3.** Shaker exercise. Lying on a bed and raising the head without lifting the shoulder, while looking at the toes.

exercise in healthy older adults. They showed that the anterior hyoid and larynx as well as the deglutitive anteroposterior UES opening diameter increased after this exercise was performed three times daily for 6 weeks. Wakabayashi et al. [86] demonstrated that dysphagia with aspi‐ ration was independently associated with both malnutrition and low head lifting strength. They suggested head lifting strength as an indicator of the severity of dysphagia in frail older adults. Strengthening the head lifting muscles can be an effective treatment for sarcopenic dysphagia. In recent years, a new method to strengthen the suprahyoid muscles—the Chin Tuck against Resistance (CTAR) exercise—has been developed [87]. This exercise involves squeezing a rubber ball placed between the chin and the manubrium sterni (**Figure 4**). The maximum activation level of the suprahyoid muscles measured using sEMG was significantly greater after this exercise than after both the isometric and isokinetic tasks in the Shaker Exercise; in addition, the CTAR exercise was less strenuous. CTAR was suggested to also be more specific in targeting the suprahyoid muscles than the Shaker exercise [88]. Instead of the rubber ball, a training device named ISO Swallowing Exercise Device (Alternative Speech and Swallowing Solutions, Inc.) was developed in America recently. The CTAR may be more feasible and efficient to improve swallowing function in older adults with sarcopenic dys‐ phagia. The jaw‐opening Exercise was developed as another training regimen for improving suprahyoid muscle strength [89]. This exercise is performed by opening the jaw to the maxi‐ mum extent and maintaining this position for 10 s while feeling a sensation of stretching. This exercise is repeated 5 times with 10 s of rest as 1 set. Two sets of this exercise are needed to be performed daily. After this exercise, the upward movement of the hyoid bone and the open‐ ing of the UES significantly increased in all subjects. In addition, the time for pharynx passage also significantly decreased. In this study, among eight subjects with chronic dysphagia, four had dysphagia due to cerebrovascular disease and the remaining four had dysphagia due to possible sarcopenia. Further studies on interventions for people with sarcopenic dysphagia are warranted in the future.

For the treatment of dysphagia and prevention of aspiration pneumonia, compensatory strat‐ egies are important [7]. Particularly, modification of the consistency of ingested liquids is commonly used as a compensatory strategy. Rofes et al. [60] demonstrated that the preva‐ lence of penetration and aspiration decreased by increasing the viscosity of ingested liquids

**Figure 2.** Tongue strength measurement. Compressing an air‐filled bulb between the tongue and the hard palate and

exercise is the most promising candidate for attenuating sarcopenia. In addition, supplemen‐ tation with essential amino acids, creatine, vitamin D, or testosterone was also indicated to

With respect to treatment of dysphagia in relation to sarcopenia, the effectiveness of resistance training intervention to improve tongue muscle function has been demonstrated. Robbins et al. [9] used the Iowa Oral Performance Instrument to examine the effect of an 8‐week progressive tongue resistance exercise program consisting of compressing an air‐filled bulb between the tongue and hard palate in 10 healthy older adults aged 70–89 years. The frequency of exercise was 30 times in a single session, three times a day, and 3 days a week. The exercise intensity level in that study was 60% of the maximum pressure in the first week and 80% of the maxi‐ mum pressure in the remaining 7 weeks. In this study, isometric tongue strength (baseline: mean 41 kPa; week 2: 44 kPa [nonsignificant difference]; week 4: 47 kPa [*p* = 0.02 compared to baseline]; week 6: 49 kPa [*p* = 0.01 compared to baseline]), tongue volume (change rate ranges from 2.16 to 10.68% upward), and peak swallowing pressure increased after the intervention. Tongue strength and thickness are decreased in sarcopenia but can have possible reversibility.

The method used for measurement of tongue strength is described in **Figure 2**.

The effectiveness of the Shaker Exercise for strengthening the suprahyoid muscles is well‐ known in the field of dysphagia rehabilitation.  Shaker et al. [84] and Easterling [85] examined the effect of this

be effective.

90 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

displaying the maximum tongue strength at the upper row (JMS, Hiroshima, Japan).

**Figure 4.** Chin tuck against resistance exercise. Squeezing a rubber ball placed between the chin and the manubrium sterni. Source: http://www.speechtherapyworks.com.sg/blog/new‐dysphagia‐exercise‐chin‐tuck‐against‐resistance‐alter‐ native‐to‐shaker‐exercise/.

(liquid, nectar, and pudding viscosity) in frail older patients. In contrast, they also found that the prevalence of oral and pharyngeal residue increased with increase in viscosity. Thus, altering the consistency of ingested liquids can be effective for increasing the safety but not the efficiency of swallowing. The appropriate viscosity level should be determined by objec‐ tive examination in older adults with sarcopenic dysphagia.

As treatments for sarcopenic dysphagia, nutritional and physical interventions have been indicated to be effective. Maeda and Akagi [90] describes the case of an 80‐year‐old woman who recovered from sarcopenic dysphagia with aggressive nutritional management and physical therapy in addition to dysphagia therapy. In their nutritional management, the total energy intake increased from 1200 to 1830 kcal/day, and the amount of protein intake increased from 0.84 ideal body weight (IBW)/day to 1.42 g/kg IBW/day. As a result, the oral intake level [91] improved from "nothing by mouth" level to "total oral diet with multiple consistencies, but requiring special preparation or compensations" level. Wakabayashi and Uwano [92] also described the case of a 71‐year‐old man who recovered from sarcopenic dys‐ phagia with aggressive nutritional management and physical therapy in addition to dyspha‐ gia therapy. His energy intake was 986 kcal/day at the time of referral to the department of rehabilitation medicine and was increased to 2200 kcal/day. The oral intake level in this case improved from "nothing by mouth" level to "total oral diet with no restriction" level. In both the cases, physical function and nutritional status also improved with improvement in oral intake level. These cases indicate that nutritional management and physical rehabilitation in addition to dysphagia rehabilitation can be effective in the treatment of sarcopenic dys‐ phagia. Our study [11] investigated the association between tongue strength, grip strength, and nutritional status, suggesting the effectiveness of physical rehabilitation and nutritional therapy in improving tongue strength. Yoshimura et al. [93] demonstrated that nutritional intervention added to resistance training improved muscle mass and activities of daily living more than resistance training alone in older inpatients in a rehabilitation hospital. Therefore, the combination of nutritional intervention and resistance training can also be effective in the treatment of sarcopenic dysphagia. Wakabayashi and Sakuma [94] have proposed that nutritional rehabilitation is useful for the treatment of sarcopenic dysphagia. In this concept, nutrition management, to increase muscle mass and strength, is proposed to be indispens‐ able for rehabilitation. On the other hand, the effectiveness of nutritional intervention in sarcopenic dysphagia is unclear because of the lack of intervention studies and hence, such studies are warranted in future.

In adults aged 60 years or older, with atrophy of the vocal cords or sulcus vocalis with aging, self‐controlled vocal exercise in the sitting position that consists of counting out loud from 1 to 10 while pulling up firmly on both sides of the seat reduced the frequency of hospitalization for aspiration pneumonia (2/199 in the intervention group and 18/216 in the control group) [95]. Subjects in the intervention group exercised for a total of two sets, both in the morning and in the evening for 6 months. The intrinsic laryngeal muscles commonly cause glottal closure insufficiency with aging [96–98]; therefore, sarcopenia can cause atrophy of the vocal cords. Because insufficient glottal closure increases the risk of aspiration [99], atrophy of the vocal cords can lead to aspiration pneumonia in older adults. The vocal exercise mentioned above can be an effective treatment for sarcopenic dysphagia.

(liquid, nectar, and pudding viscosity) in frail older patients. In contrast, they also found that the prevalence of oral and pharyngeal residue increased with increase in viscosity. Thus, altering the consistency of ingested liquids can be effective for increasing the safety but not the efficiency of swallowing. The appropriate viscosity level should be determined by objec‐

**Figure 4.** Chin tuck against resistance exercise. Squeezing a rubber ball placed between the chin and the manubrium sterni. Source: http://www.speechtherapyworks.com.sg/blog/new‐dysphagia‐exercise‐chin‐tuck‐against‐resistance‐alter‐

As treatments for sarcopenic dysphagia, nutritional and physical interventions have been indicated to be effective. Maeda and Akagi [90] describes the case of an 80‐year‐old woman who recovered from sarcopenic dysphagia with aggressive nutritional management and physical therapy in addition to dysphagia therapy. In their nutritional management, the total energy intake increased from 1200 to 1830 kcal/day, and the amount of protein intake increased from 0.84 ideal body weight (IBW)/day to 1.42 g/kg IBW/day. As a result, the oral intake level [91] improved from "nothing by mouth" level to "total oral diet with multiple consistencies, but requiring special preparation or compensations" level. Wakabayashi and Uwano [92] also described the case of a 71‐year‐old man who recovered from sarcopenic dys‐ phagia with aggressive nutritional management and physical therapy in addition to dyspha‐ gia therapy. His energy intake was 986 kcal/day at the time of referral to the department of rehabilitation medicine and was increased to 2200 kcal/day. The oral intake level in this case improved from "nothing by mouth" level to "total oral diet with no restriction" level. In both the cases, physical function and nutritional status also improved with improvement in oral intake level. These cases indicate that nutritional management and physical rehabilitation

tive examination in older adults with sarcopenic dysphagia.

92 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

native‐to‐shaker‐exercise/.

As decrease in pharyngeal and supraglottic sensitivity was indicated in older adults with sarcopenic dysphagia, sensory stimulation may be an effective treatment. Ortega et al. [100] demonstrated the effectiveness of two sensory stimulation techniques. One was the chemical sensory stimulation with a natural TRPV1 agonist solution (natural capsaicinoids 1 × 10−5 M). In this study, capsaicin solution was obtained from an alimentary sauce containing 185.5 μg/g of capsaicinoid. Subjects consumed 10 mL of tomato juice mixed with the capsaicinoid sauce three times per day before each meal, 5 days per week for 2 weeks. The other technique was electrical stimulation in the thyrohyoid position using the Intelect VitalStim device (Chattanooga Group, Hixson, TN, USA), consisting of the application, at rest, of 80 Hz of trans‐ cutaneous electrical stimulus (biphasic, 700μs). Subjects received this therapy for 1 h per day, 5 days a week for 2 weeks. Aspiration was significantly reduced in the group that received a natural TRPV1 agonist solution (TRPV1 group; 38.46% vs. TSES group; 0%) and the prev‐ alence of penetration decreased significantly in the group receiving electrical stimulation (TSES group; 87.5 vs. TRPV1 group; 25%). In addition, the time for laryngeal vestibule closure was significantly shortened in responder patients in the group receiving electrical stimulation (TSES group; 480 ± 167 ms vs. TRPV1 group; 295 ± 189.9 ms). Because the cause of dysphagia in the subjects in this study was aging (39.5%), or a combination of aging with previous stroke or neurodegenerative diseases, the effectiveness of these techniques for older adults with sar‐ copenic dysphagia should be examined.

In rehabilitation for sarcopenic dysphagia, risk management for aspiration pneumonia is also important. Frail older patients with oropharyngeal dysphagia have poorer oral health, higher oral bacterial load, and a higher prevalence of oral colonization by respiratory pathogens than healthy older adults [101]. Since these can be potential risk factors of aspiration pneumonia, oral care is important as a risk management strategy in the treatment of sarcopenic dysphagia.

The Dysphagia Working Group from the European Society for Swallowing Disorders and the European Union Geriatric Medicine Society has proposed that oropharyngeal dysphagia is a multifactorial geriatric syndrome [7] and is treatable only with a multidimensional approach. Further research is required to identify the components of this multidimensional approach.

#### **5. Conclusions**

Sarcopenic dysphagia is a swallowing disorder caused by sarcopenia of the swallowing mus‐ cles, including the general skeletal muscle. Its prevalence seems to be high, particularly in older adults after acute disease. Because sarcopenic dysphagia is caused mainly by inactivity and malnutrition, it is preventable and treatable in most cases. Among published articles on dysphagia, there have been few studies on sarcopenic dysphagia. With an increasing aging population, sarcopenic dysphagia has become an important public health issue. For adequate prevention, diagnosis, and treatment, further studies on the pathophysiology of and interven‐ tion for sarcopenic dysphagia are warranted in future.

#### **Author details**

Kotomi Sakai1,2\* and Kunihiro Sakuma3

\*Address all correspondence to<EMAIL_ADDRESS>
1 Department of Rehabilitation, Setagaya Memorial Hospital, Tokyo, Japan

2 Department of Dysphagia Rehabilitation, Nihon University School of Dentistry, Tokyo, Japan

3 Institute for Liberal Arts, Environment and Society, Tokyo Institute of Technology, Tokyo, Japan

#### **References**

European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age and Ageing. 2010;**39**:412‐423

In rehabilitation for sarcopenic dysphagia, risk management for aspiration pneumonia is also important. Frail older patients with oropharyngeal dysphagia have poorer oral health, higher oral bacterial load, and a higher prevalence of oral colonization by respiratory pathogens than healthy older adults [101]. Since these can be potential risk factors of aspiration pneumonia, oral care is important as a risk management strategy in the treatment of sarcopenic dysphagia. The Dysphagia Working Group from the European Society for Swallowing Disorders and the European Union Geriatric Medicine Society has proposed that oropharyngeal dysphagia is a multifactorial geriatric syndrome [7] and is treatable only with a multidimensional approach. Further research is required to identify the components of this multidimensional approach.

Sarcopenic dysphagia is a swallowing disorder caused by sarcopenia of the swallowing mus‐ cles, including the general skeletal muscle. Its prevalence seems to be high, particularly in older adults after acute disease. Because sarcopenic dysphagia is caused mainly by inactivity and malnutrition, it is preventable and treatable in most cases. Among published articles on dysphagia, there have been few studies on sarcopenic dysphagia. With an increasing aging population, sarcopenic dysphagia has become an important public health issue. For adequate prevention, diagnosis, and treatment, further studies on the pathophysiology of and interven‐

tion for sarcopenic dysphagia are warranted in future.

94 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

\*Address all correspondence to<EMAIL_ADDRESS>
1 Department of Rehabilitation, Setagaya Memorial Hospital, Tokyo, Japan

2 Department of Dysphagia Rehabilitation, Nihon University School of Dentistry, Tokyo,

3 Institute for Liberal Arts, Environment and Society, Tokyo Institute of Technology, Tokyo,

[1] Rosenberg IH. Sarcopenia: Origins and clinical relevance. The Journal of Nutrition.

[2] Cruz‐Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M. Sarcopenia:

Kotomi Sakai1,2\* and Kunihiro Sakuma3

**5. Conclusions**

**Author details**

Japan

Japan

**References**

1997;**127**:990‐991

[30] Sieck GC, Lewis MI, Blanco CE. Effects of undernutrition on diaphragm fiber size, SDH activity, and fatigue resistance. Journal of Applied Physiology. 1989;**66**:2196‐2205

[15] Altman KW, Yu GP, Schaefer SD. Consequence of dysphagia in the hospitalized patient: Impact on prognosis and hospital resources. Archives of Otolaryngology—‐Head &

[16] Chen LK, Lee WJ, Peng LN, Liu LK, Arai H, Akishita M. Recent advances in sarcopenia research in Asia: 2016 update from the Asian Working Group for Sarcopenia. Journal of

[17] Maeda K, Akagi J. Decreased tongue pressure is associated with sarcopenia and sarco‐

[18] Maeda K, Akagi J. Sarcopenia is an independent risk factor of dysphagia in hospitalized

[19] Maeda K, Takaki M, Akagi J. Decreased skeletal muscle mass and risk factors of sarcope‐ nic dysphagia: A prospective observational cohort study. The Journals of Gerontology

[20] Madhavan A, LaGorio LA, Crary MA, Dahl WJ, Carnaby GD. Prevalence of and risk fac‐ tors for dysphagia in the community dwelling elderly: A systematic review. The Journal

[21] Wakabayashi H, Matsushima M. Dysphagia assessed by the 10‐item eating assessment tool is associated with nutritional status and activities of daily living in elderly individu‐ als requiring long‐term care. The Journal of Nutrition, Health & Aging. 2016; 20:22‐27

[22] Aslam M, Vaezi MF. Dysphagia in the elderly. Gastroenterology & Hepatology. 2013;

[23] Wakabayashi H, Matsushima M, Uwano R, Watanabe N, Oritsu H, Shimizu Y. Skeletal muscle mass is associated with severe dysphagia in cancer patients. Journal of Cachexia,

[24] Robbins J, Hamilton JW, Lof GL, Kempster GB. Oropharyngeal swallowing in normal

[25] Humbert IA, Robbins J. Dysphagia in the elderly. Physical Medicine and Rehabilitation

[26] Ney DM, Weiss JM, Kind AJ, Robbins J. Senescent swallowing: Impact, strategies, and interventions. Nutrition in Clinical Practice: Official Publication of the American Society

[27] Maeda K, Koga T, Akagi J. Tentative nil per os leads to poor outcomes in older adults with aspiration pneumonia. Clinical Nutrition (Edinburgh, Scotland). 2016;**35**:1147‐1152

[28] Hudson HM, Daubert CR, Mills RH. The interdependency of protein‐energy malnutri‐

[29] Lewis MI, Sieck GC. Effect of acute nutritional deprivation on diaphragm structure and

Series A, Biological Sciences and Medical Sciences. 2016. [Epub ahead of print]

the American Medical Directors Association. 2016;**17**:767.e1‐767.e7

older people. Geriatrics & Gerontology International. 2015;**4**:515‐21

penic dysphagia in the elderly. Dysphagia. 2015;**30**:80‐87

of Nutrition, Health & Aging. 2016;**20**:806‐815

Sarcopenia and Muscle. 2015;**6**:351‐357

Clinics of North America. 2008;**19**:853‐866

adults of different ages. Gastroenterology. 1992;**103**:823‐829

for Parenteral and Enteral Nutrition. 2009;**24**:395‐413

tion, aging, and dysphagia. Dysphagia. 2000;**15**:31‐38

function. Journal of Applied Physiology. 1990;**68**:1938‐1944

**9**:784‐795

Neck Surgery. 2010;**136**:784‐789

96 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

older adults. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences. 2013;**68**:853‐860

[56] Logemann JA, Pauloski BR, Rademaker AW, Colangelo LA, Kahrilas PJ, Smith CH. Temporal and biomechanical characteristics of oropharyngeal swallow in younger and older men. Journal of Speech, Language, and Hearing Research. 2000;**43**:1264‐1274

[43] Nicosia MA, Hind JA, Roecker EB, Carnes M, Doyle J, Dengel GA, Robbins J. Age effects on the temporal evolution of isometric and swallowing pressure. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences. 2000;**55**:M634‐M640

[44] Robbins J, Humpal NS, Banaszynski K, Hind J, Rogus‐Pulia N. Age‐related differ‐ ences in pressures generated during isometric presses and swallows by healthy adults.

[45] Buehring B, Hind J, Fidler E, Krueger D, Binkley N, Robbins J. Tongue strength is associated with jumping mechanography performance and handgrip strength but not with classic functional tests in older adults. Journal of the American Geriatrics Society.

[46] Utanohara Y, Hayashi R, Yoshikawa M, Yoshida M, Tsuga K, Akagawa Y. Standard val‐ ues of maximum tongue pressure taken using newly developed disposable tongue pres‐

[47] Mendes AE, Nascimento L, Mansur LL, Callegaro D, Jacob Filho W. Tongue forces and handgrip strength in normal individuals: Association with swallowing. Clinics (Sao

[48] Crow HC, Ship JA. Tongue strength and endurance in different aged individuals. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences. 1996;

[49] Butler SG, Stuart A, Leng X, Wilhelm E, Rees C, Williamson J, Kritchevsky SB. The relationship of aspiration status with tongue and handgrip strength in healthy older adults. The Journals of Gerontology Series A, Biological Sciences and Medical sciences.

[50] Miller JL, Watkin KL, Chen MF. Muscle, adipose, and connective tissue variations in intrinsic musculature of the adult human tongue. Journal of Speech, Language, and

[51] Nashi N, Kang S, Barkdull GC, Lucas J, Davidson TM. Lingual fat at autopsy. The

[52] Yamaguchi A, Nasu M, Esaki Y, Shimada H, Yoshiki S. Amyloid deposits in the aged tongue: A postmortem study of 107 individuals over 60 years of age. Journal of Oral

[53] Tamura F, Kikutani T, Tohara T, Yoshida M, Yaegaki K. Tongue thickness relates to

[54] Butler SG, Stuart A, Wilhelm E, Rees C, Williamson J, Kritchevsky S. The effects of aspi‐ ration status, liquid type, and bolus volume on pharyngeal peak pressure in healthy

[55] Feng X, Todd T, Lintzenich CR, Ding J, Carr JJ, Ge Y, Browne JD, Kritchevsky SB, Butler SG. Aging‐related geniohyoid muscle atrophy is related to aspiration status in healthy

nutritional status in the elderly. Dysphagia. 2012;**27**:556‐561

sure measurement device. Dysphagia. 2008;**23**:286‐290

Dysphagia. 2016;**31**:90‐96

98 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

Paulo, Brazil). 2015;**70**:41‐45

Hearing Research. 2002;**45**:51‐65

Laryngoscope. 2007;**117**:1467‐1473

older adults. Dysphagia. 2011;**26**:225‐231

Pathology. 1982;**11**:237‐244

2013;**61**:418‐422

**51**:M247‐M250

2011;**66**:452‐458

[82] Cruz‐Jentoft AJ, Landi F, Schneider SM, Zuniga C, Arai H, Boirie Y, Chen LK, Fielding RA, Martin FC, Michel JP, Sieber C, Stout JR, Studenski SA, Vellas B, Woo J, Zamboni M, Cederholm T. Prevalence of and interventions for sarcopenia in ageing adults: A sys‐ tematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age and Ageing. 2014;**6**:748‐759

[69] Gumucio J, Flood M, Harning J, Phan A, Roche S, Lynch E, Bedi A, Mendias C. T lym‐ phocytes are not required for the development of fatty degeneration after rotator cuff

[70] Siriett V, Salerno MS, Berry C, Nicholas G, Bower R, Kambadur R, Sharma M. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Molecular Therapy: The

[71] Rhee S, Yamamoto M, Kitamura K, Masaaki K, Katori Y, Murakami G, Abe SI. Macrophage density in pharyngeal and laryngeal muscles greatly exceeds that in other striated mus‐ cles: An immunohistochemical study using elderly human cadavers. Anatomy & Cell

[72] Greenslade J, Wyman A. Investigation of dysphagia. Surgery (Oxford). 2006;**24**:89‐92

[73] DeVault KR. Presbyesophagus: A reappraisal. Current Gastroenterology Reports. 2002;

[74] Fulp SR, Dalton CB, Castell JA, Castell DO. Aging‐related alterations in human upper esophageal sphincter function. The American Journal of Gastroenterology. 1990;**85**:

[75] van Herwaarden MA, Katz PO, Matthew Gideon R, Barrett J, Castell JA, Achem S, Castell DO. Are manometric parameters of the upper esophageal sphincter and pharynx

[76] Nilsson H, Ekberg O, Bulow M, Hindfelt B. Assessment of respiration during video fluo‐

[77] Preiksaitis HG, Mills CA. Coordination of breathing and swallowing: Effects of bolus consistency and presentation in normal adults. Journal of Applied Physiology. 1996;

[78] Wang CM, Chen JY, Chuang CC, Tseng WC, Wong AM, Pei YC. Aging‐related changes in swallowing, and in the coordination of swallowing and respiration determined by novel non‐invasive measurement techniques. Geriatrics & Gerontology International.

[79] Shaker R, Li Q, Ren J, Townsend WF, Dodds WJ, Martin BJ, Kern MK, Rynders A. Coordination of deglutition and phases of respiration: Effect of aging, tachypnea, bolus volume, and chronic obstructive pulmonary disease. The American Journal of Physio‐

[80] Izawa KP, Watanabe S, Oka K, Kasahara Y, Morio Y, Hiraki K, Hirano Y, Omori Y, Suzuki N, Kida K, Suzuki K, Akashi YJ. Respiratory muscle strength in relation to sarcopenia in elderly cardiac patients. Aging Clinical and Experimental Research. 2016; 28:1143‐1148

[81] Elliott JE, Greising SM, Mantilla CB, Sieck GC. Functional impact of sarcopenia in respi‐

ratory muscles. Respiratory Physiology & Neurobiology. 2016;**226**:137‐146

affected by age and gender? Dysphagia. 2003;**18**:211‐217

roscopy of dysphagic patients. Academic Radiology. 1997;**4**:503‐507

Journal of the American Society of Gene Therapy. 2007;**15**:1463‐1470

tear. Bone & Joint Research. 2014;**3**:262‐272

100 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

Biology. 2016;**49**:177‐183

**4**:193‐199

1569‐1572

**81**:1707‐1714

2015;**6**:736‐744

logy. 1992;**263**:G750‐G755

### **Rehabilitation in Sarcopenic Elderly**

Raoul Saggini, Simona Maria Carmignano, Lucia Cosenza, Tommaso Palermo and Rosa Grazia Bellomo

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.69638

#### **Abstract**

[94] Wakabayashi H, Sakuma K. Rehabilitation nutrition for sarcopenia with disability: A combination of both rehabilitation and nutrition care management. Journal of Cachexia,

[95] Fujimaki Y, Tsunoda K, Kobayashi R, Tonghyo C, Tanaka F, Kuroda H, Numata T, Ishii T, Kuroda R, Masuda S, Hashimoto S, Misawa H, Shindo N, Mori T, Mori H, Uchiyama N, Kamei Y, Tanaka M, Hamaya H, Funatsuki S, Usui S, Ito I, Hamada K, Shindo A, Tokumaru Y, Morita Y, Ueha R, Nito T, Kikuta S, Sekimoto S, Kondo K, Sakamoto T, Itoh K, Yamasoba T, Matsumoto S. Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: A random‐

[96] Malmgren LT, Fisher PJ, Bookman LM, Uno T. Age‐related changes in muscle fiber types in the human thyroarytenoid muscle: An immunohistochemical and stereologi‐ cal study using confocal laser scanning microscopy. Otolaryngology – head and neck surgery. Official Journal of American Academy of Otolaryngology‐Head and Neck

[97] Malmgren LT, Jones CE, Bookman LM. Muscle fiber and satellite cell apoptosis in the aging human thyroarytenoid muscle: A stereological study with confocal laser scanning microscopy. Otolaryngology – head and neck surgery. Official Journal of American

[98] Martins RH, Benito Pessin AB, Nassib DJ, Branco A, Rodrigues SA, Matheus SM. Aging voice and the laryngeal muscle atrophy. The Laryngoscope. 2015;**125**:2518‐2521 [99] Giraldez‐Rodriguez LA, Johns M, 3rd. Glottal insufficiency with aspiration risk in dys‐

[100] Ortega O, Rofes L, Martin A, Arreola V, Lopez I, Clave P. A Comparative study between two sensory stimulation strategies after two weeks treatment on older patients with

[101] Ortega O, Sakwinska O, Combremont S, Berger B, Sauser J, Parra C, Zarcero S, Nart J, Carrion S, Clave P. High prevalence of colonization of oral cavity by respiratory patho‐ gens in frail older patients with oropharyngeal dysphagia. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society.

ized controlled trial. Clinical Rehabilitation. 2016. [Epub ahead of print]

Academy of Otolaryngology‐Head and Neck Surgery. 2001;**125**:34‐39

phagia. Otolaryngologic Clinics of North America. 2013;**46**:1113‐1121

oropharyngeal dysphagia. Dysphagia. 2016;**31**:706‐716

Sarcopenia and Muscle. 2014;**5**:269‐277

102 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

Surgery. 1999;**121**:441‐451

2015;**27**:1804‐1816

Sarcopenia is a complex problem and an important emerging field in rehabilitation of the elderly. In 2010, the European working group on sarcopenia in older people (EWGSOP) described sarcopenia as a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength, associated with a risk of adverse outcomes such as physical disability, poor quality of life and death. This field of rehabilitation has been defined as 'evaluative, diagnostic and therapeutic interventions whose purpose is to restore functional ability or enhance residual functional capability in elderly people with disabling impairments'. With growing numbers of frail older people, there is an increasing need for appropriate geriatric rehabilitation services. Definitely, sarcopenia needs a specific rehabilitation program to improve muscular mass and strength that must be integrated with a global approach with the aim to recover postural assessment, amplify sensory‐motor systems, in order to gain the necessary information for proper motor planning, to reduce risk of falls. Several physical agents in medicine permit to treat sarcopenia, like vibrations or electrical stimulation. The aim of this chapter is to give an overview about rehabilitative medicine for sarcopenia, highlighting the state of the art, presenting the most significative clinical researches and giving some inputs to set a rehabilitation protocol.

**Keywords:** sarcopenia, physical energies, complex sensory‐motor rehabilitation program, vibrations, electrical stimulation

#### **1. Introduction**

Sarcopenia (from the Greek sarx 'flesh' and penia 'loss') is a term used for the first time by Rosenberg to describe the age‐related decrease in muscle mass. In fact, aging is associated with a progressive decline in muscle mass that can lead to a decrease in muscle quality and strength.

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

In 2010, the European working group on sarcopenia in older people (EWGSOP) described sarcopenia as a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength, associated with a risk of adverse outcomes such as physical disability, poor quality of life and death [1]. The reduction in muscle mass is associated with longer hospitalisation, increased need for rehabilitation care after hospital discharge, infective complications, prolonged duration of mechanical ventilation and higher mortality. There are several approaches to treat sarcopenia and it was demonstrated that, regardless of the type of intervention, treatment improves the quality of life preventing falls, disability and loss of independence among elderly patients [2]. Among interventions, resistance training has been shown to be the most effective to reduce the effects of sarcopenia, this because it induces skeletal muscle hypertrophy and enhances muscle strength; unfortunately, resistance training is not always feasible in sarcopenic elderly people [2]. Therefore, in these cases, physical therapies come to the rescue, i.e. vibrations or electrical stimulations. Particularly, it is possible to use focal vibrations, which excite the afferents coming from the neuromuscular spindle, leading to the activation of the proprioceptive sensory system. Electrical stimulation too is an alternative, even more effective than exercise alone, in strengthening muscles in sarcopenic patients [3]. These alternative approaches to exercise offered a safe addition to a traditional, high‐intensity volitional strengthening program with the aim to implement muscular mass and strength. It is also a necessary adequate sensory‐motor and functional recovery program to reach an acceptable walking ability. The ability to walk is the key to any human movement, despite the fact the human movements are not limited to bipedal locomotion; bipedal locomotion is a fundamental part of daily life and is a prominent target of public health physical activity guidelines [4]. In order to get a better walking performance and a postural global improvement, two integrate procedures may be used: normalisation of the foot‐ground reaction to control vertical and shear forces on the foot during the stance phase; second one is the microgravitary environment that determines the sensory‐motor and functional recovery of the posture during walking activity in combination to the development of proprioceptive information from periphery to the cortical central system [4]. Definitely, sarcopenia needs a specific rehabilitation program to improve muscular mass and strength that must be integrated with a global approach with the aim to recovery postural assessment, amplify sensory‐motor systems, in order to gain the necessary information for proper motor planning, to reduce risk of falls.

#### **2. Background**

Aging, as mentioned, is characterised by a progressive loss of skeletal muscle mass and strength, thus leading to the loss of functional capacity. In sarcopenia, the loss of skeletal muscle mass must be due to a chronic disruption in the balance between muscle protein synthesis and degradation.

In active and healthy elderly patients, the mechanism underlying the loss of muscle mass does not seem to be bound to a disorder of protein metabolism in the basal state (fasting). Rather, it was proposed that muscle in the elderly presents a deficiency in the ability to regulate protein synthesis in response to an anabolic stimulus, such as physical activity or food intake [1].

According to epidemiological data in literature, the prevalence of sarcopenia in people ranging in ages from 60 to 70 turns out to be 5–13%, while in patients over 80, it varies between 11 and 50% [2]. In 2000, the number of people worldwide over the age of 60 years was estimated at 600 million, a value that is forecast to rise to 1.2 billion in 2025 and 2 billion in 2050 [5]. Making an approximate estimate about the prevalence, people with sarcopenia nowadays are more than 50 million that should increase to over 200 million in the next 40 years.

In 2010, the European working group on sarcopenia in older people (EWGSOP) described sarcopenia as a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength, associated with a risk of adverse outcomes such as physical disability, poor quality of life and death [1]. The reduction in muscle mass is associated with longer hospitalisation, increased need for rehabilitation care after hospital discharge, infective complications, prolonged duration of mechanical ventilation and higher mortality. There are several approaches to treat sarcopenia and it was demonstrated that, regardless of the type of intervention, treatment improves the quality of life preventing falls, disability and loss of independence among elderly patients [2]. Among interventions, resistance training has been shown to be the most effective to reduce the effects of sarcopenia, this because it induces skeletal muscle hypertrophy and enhances muscle strength; unfortunately, resistance training is not always feasible in sarcopenic elderly people [2]. Therefore, in these cases, physical therapies come to the rescue, i.e. vibrations or electrical stimulations. Particularly, it is possible to use focal vibrations, which excite the afferents coming from the neuromuscular spindle, leading to the activation of the proprioceptive sensory system. Electrical stimulation too is an alternative, even more effective than exercise alone, in strengthening muscles in sarcopenic patients [3]. These alternative approaches to exercise offered a safe addition to a traditional, high‐intensity volitional strengthening program with the aim to implement muscular mass and strength. It is also a necessary adequate sensory‐motor and functional recovery program to reach an acceptable walking ability. The ability to walk is the key to any human movement, despite the fact the human movements are not limited to bipedal locomotion; bipedal locomotion is a fundamental part of daily life and is a prominent target of public health physical activity guidelines [4]. In order to get a better walking performance and a postural global improvement, two integrate procedures may be used: normalisation of the foot‐ground reaction to control vertical and shear forces on the foot during the stance phase; second one is the microgravitary environment that determines the sensory‐motor and functional recovery of the posture during walking activity in combination to the development of proprioceptive information from periphery to the cortical central system [4]. Definitely, sarcopenia needs a specific rehabilitation program to improve muscular mass and strength that must be integrated with a global approach with the aim to recovery postural assessment, amplify sensory‐motor systems, in order to gain the necessary

104 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

information for proper motor planning, to reduce risk of falls.

Aging, as mentioned, is characterised by a progressive loss of skeletal muscle mass and strength, thus leading to the loss of functional capacity. In sarcopenia, the loss of skeletal muscle mass must be due to a chronic disruption in the balance between muscle protein syn-

In active and healthy elderly patients, the mechanism underlying the loss of muscle mass does not seem to be bound to a disorder of protein metabolism in the basal state (fasting). Rather, it was proposed that muscle in the elderly presents a deficiency in the ability to regulate protein synthesis in response to an anabolic stimulus, such as physical activity or food intake [1].

**2. Background**

thesis and degradation.

The impact of sarcopenia in elderly affects multiple aspects; in fact, its influence can be seen in terms of morbidity [6], disability [7], increasing in costs related to health care [8] and mortality [9].

The underlying causes of sarcopenia and frailty are multifactorial. Although the progressive loss of muscle mass that occurs with aging is well‐known for many years, but it is only with the latest techniques and prospective‐longitudinal studies that changes related to aging in muscle composition have begun to be described [10].

Several reviews have highlighted cellular and molecular mechanisms underlying the weakness and muscle atrophy related to aging [11]. It has been seen that the loss of muscle strength and mass are the consequence of a progressive atrophy due to a loss of individual muscle fibres associated to a reduction of some motor units; this implies fat and other non‐contractile tissue (i.e. fibrous tissue) infiltrations which involves a reduction of 'muscle quality' [1].

Therefore, changes in musculoskeletal age are initially neuromuscular and subsequently others several factors intervene (**Figure 1**) such as neural transmission, protein synthesis and

**Figure 1.** Factors that affect the muscle maintenance and/or the onset of sarcopenia. + positive influence, − negative influence. GH growth hormone, IGF‐1 insulin‐like growth factor 1, HGF: hepatocyte growth factor, FGF: fibroblast growth factor.

degradation, muscle architecture, composition of muscle fibres, increasing in production of reactive oxygen species, apoptosis of muscle cells, alteration in excitation‐contraction coupling and metabolism [11].

In generic terms, sarcopenia is the age‐associated loss of skeletal muscle mass and function; this decline is progressive and generalised with the possible risk of adverse outcomes such as physical disability, poor quality of life and even death [12, 13]. The causes are multifactorial and can include disuse, changing endocrine function, chronic diseases, inflammation, insulin resistance and nutritional deficiencies. The pathogenic mechanisms underlying sarcopenia are different from acute muscular atrophy resulting from disuse, cachexia, denervation or other conditions.

In order to make the diagnosis of sarcopenia, the European working group on sarcopenia in older people (EWGSOP) recommends verifying the simultaneous presence of both low muscle mass and reduction in muscle function (understood as strength or performance). Thus, the diagnosis requires the satisfaction of the criterion 1 in combination of criterion 2 or criterion 3 (**Table 1**).

The reason why are necessary at least two criteria for the diagnosis is that the force does not depend only on the muscle mass and also the relationship between strength and mass is not linear [14]. In fact, alterations in muscle quality have a central role in the loss of strength in elderly. Hughes et al. [15] showed that only a variation of 5% in strength depends on muscle mass. Muscle weakness may lead to reduced function, decreased physical activity and immobility, thus leading to secondary muscular 'ex non usu' atrophy. Consequently, diminished muscle mass is the result, but also the cause of age‐related loss of strength. This is due to increased levels of pro‐inflammatory cytokines and to a damage of type 2 muscle fibres. Furthermore, the growth in muscle mass is not directly related to an increment in strength, which may be increased even in the absence of a visible variation of muscle mass [16].  Therefore, defining sarcopenia only in terms of loss of muscle mass is too simplistic and may be of limited clinical value. Precisely for this reason, some authors argue that the term dynapenia would be preferable to describe the loss of strength and function associated with aging [17]. However, 'sarcopenia' is a term so widely spread that replacing it could generate more confusion.

Sarcopenia staging, which reflects the severity degree of the disease, is a concept that can be of assistance in clinical management of the condition; specifically, the EWGSOP suggests a division into 'pre‐sarcopenia', 'sarcopenia' and 'severe sarcopenia' (**Table 2**). 'Pre‐sarcopenia' stage is characterised by low muscle mass without influencing on muscle strength or physical

**Table 1.** EWGSOP diagnostic criteria.

**Diagnosis is based on documentation of criterion 1 plus criterion 2 or 3**

**1. Low muscle mass**

**2. Low muscle strength**

**3. Low physical performance**

**Table 2.** EWGSOP stages of sarcopenia.

degradation, muscle architecture, composition of muscle fibres, increasing in production of reactive oxygen species, apoptosis of muscle cells, alteration in excitation‐contraction cou-

In generic terms, sarcopenia is the age‐associated loss of skeletal muscle mass and function; this decline is progressive and generalised with the possible risk of adverse outcomes such as physical disability, poor quality of life and even death [12, 13]. The causes are multifactorial and can include disuse, changing endocrine function, chronic diseases, inflammation, insulin resistance and nutritional deficiencies. The pathogenic mechanisms underlying sarcopenia are different from acute muscular atrophy resulting from disuse, cachexia, denervation or other conditions. In order to make the diagnosis of sarcopenia, the European working group on sarcopenia in older people (EWGSOP) recommends verifying the simultaneous presence of both low muscle mass and reduction in muscle function (understood as strength or performance). Thus, the diagnosis requires the satisfaction of the criterion 1 in combination of criterion 2 or criterion 3

The reason why are necessary at least two criteria for the diagnosis is that the force does not depend only on the muscle mass and also the relationship between strength and mass is not linear [14]. In fact, alterations in muscle quality have a central role in the loss of strength in elderly. Hughes et al. [15] showed that only a variation of 5% in strength depends on muscle mass. Muscle weakness may lead to reduced function, decreased physical activity and immobility, thus leading to secondary muscular 'ex non usu' atrophy. Consequently, diminished muscle mass is the result, but also the cause of age‐related loss of strength. This is due to increased levels of pro‐inflammatory cytokines and to a damage of type 2 muscle fibres. Furthermore, the growth in muscle mass is not directly related to an increment in strength, which may be increased even in the absence of a visible variation of muscle mass [16].  Therefore, defining sarcopenia only in terms of loss of muscle mass is too simplistic and may be of limited clinical value. Precisely for this reason, some authors argue that the term dynapenia would be preferable to describe the loss of strength and function associated with aging [17]. However, 'sarcopenia' is a term so widely

Sarcopenia staging, which reflects the severity degree of the disease, is a concept that can be of assistance in clinical management of the condition; specifically, the EWGSOP suggests a division into 'pre‐sarcopenia', 'sarcopenia' and 'severe sarcopenia' (**Table 2**). 'Pre‐sarcopenia' stage is characterised by low muscle mass without influencing on muscle strength or physical

spread that replacing it could generate more confusion.

**Diagnosis is based on documentation of criterion 1 plus criterion 2 or 3**

pling and metabolism [11].

106 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

(**Table 1**).

**1. Low muscle mass 2. Low muscle strength 3. Low physical performance**

**Table 1.** EWGSOP diagnostic criteria.

performance; this phase can only be identified by techniques that measure muscle mass accurately (see later). Concerning to standard populations, 'sarcopenia' stage is characterised by low muscle mass with low muscle strength or low physical performance. The last stage, when the three criteria (low muscle mass, low muscle strength and low physical performance) are present concomitantly, is defined as 'severe sarcopenia'. Recognising different stages of sarcopenia is essential to choose the most appropriate treatment and setting, thus enabling the achievement of therapeutic goals. Staging also allows to program scientific research focused on a particular stage or to evaluate any changes over time [18].

Generally, all the syndromes associated with prominent muscle loss are described as sarcopenia. Only research on the etiopathological mechanisms of age‐related sarcopenia can lead to distinction from secondary forms, so the most appropriate therapy for each of them can be chosen such as cachexia, frailty and sarcopenic obesity.

The parameters of sarcopenia are muscle mass and function. The measurable variables are mass, strength and physical performance; for diagnostic and research purposes, it is important to identify the best diagnostic test that is able to measure them accurately. It is also important to recognise changes by repeating the same measures over time in the same individuals [18].

Only a few clinical trials are underway to evaluate the potential for sarcopenia treatments compared to the great impact that reduced mobility and functionality have on the quality of life of older people. The absence of standardised primary outcomes is a major challenge for the design of such studies. For intervention trials, EWGSOP presently recommends three primary outcome variables: muscle mass, muscle strength and physical performance (**Table 3**). Further studies could lead to the finding of outcomes currently considered secondary, but which may play a central role in the diagnostic and prognostic phase of this clinical condition.

Among methods of evaluation computed tomography (CT) and magnetic resonance imaging (MRI) can distinguish fat from other soft tissues of the body, thus representing validate methods for estimating muscle mass for research scope. The high costs and risks related to exposure to radiation (TC), limit their use in clinical practice. Dual energy X‐ray absorptiometry (DEXA) distinguishes adipose tissue, bone mineral mass and lean body mass. It can be used both in research and in clinical practice and exposes patients to a smaller quantity of radiations. However, the access to this method is limited for severely obese individuals; furthermore, the equipment is not portable, which limits its use in epidemiological studies on a large scale.

Bioimpedance analysis (BIA) is a test that is not expensive, easy to use, easily reproducible and suitable for both ambulatory patients and bedridden. The bioelectrical impedance measurement

**Table 3.** Measurements of muscle mass, strength and performance in research and clinical practice.

techniques have been studied for many years and the BIA results in standard conditions correlate with the predictions of the MRI [19].

Among measurements to assess muscle strength, it is necessary to emphasise the importance of handgrip test; even if lower limbs are more relevant than the upper limbs in physical function and walking, the evaluation of strength by isometric handgrip has been widely used. Measured under standard conditions, with a well‐studied model of dynamometer hand, it is closely correlated with lower limb muscles power and with the area of calf section.

The short physical performance battery (SPPB) is one of the most valid techniques to measure physical performance. It consists of a brief set of tests evaluating the functionality of the lower limbs. This battery is composed of three different sections. The first one is the assessment of balance in three tests: (a) maintenance of balance in stand position with feet together side‐by‐side for 10 seconds; (b) maintenance of balance in semi‐tandem position (heel of one foot against side of big toe of the other) for 10"; (c) maintenance of balance in tandem position (feet aligned heel to toe) for 10". The second section evaluates gait speed measuring the time required to walk 4 m linear at a normal pace. Finally, the third one measures the time required to perform five rises from a chair to an upright position as fast as possible without the use of the arms.

Other tests can be used in clinical practice, as they require a very simple execution setting. One of these is the sit to stand test, which evaluates the ability to move from sit to stand position without using arms. The timed up‐and‐go test (TUG), which evaluates the dynamic balance by measuring the time required to complete a series of tasks (getting up from a chair, walking a short distance, turning around an obstacle, walking back and sitting down again) [20, 21].

Specific mode and intensity of physical activity can act synergistically to maintain and even increase muscle mass, strength and power, both in healthy individual and in elderly patients with limited functionality. These interventions also have been found effective for all ages and there is evidence for similar responses in both female and male [22].

During aging, a sedentary lifestyle is associated with a decrease in lean body mass and with an increase in fat mass, which ultimately leads to an increase in mortality and functional limitations. This is demonstrated in studies showing the reduction of cardiovascular‐related risk and all causes of mortality in individuals highly physically active than those moderately active or worse sedentary.

Physical activity, in particular resistance exercises, is a powerful stimulus to promote muscle protein anabolism, resulting in specific metabolic and morphological adaptations of the skeletal muscle tissue. Resistance type exercise training can effectively increase muscle strength and muscle mass, thus improving physical performance and functional capacity. To stimulate muscle hypertrophy and to increase strength in elderly patients, it is known [23] that the traditional exercise of resistance at low speed (i.e. performing concentric and eccentric to each muscle in 2–3") is found to be a type of intervention that is safe, feasible and effective. The physiological response to resistance exercises may consist in an increase in protein synthesis, in an activation and proliferation of satellite cells, in a production of anabolic hormones and in a decreased activity of catabolic cytokines. Resistance exercises in elderly subjects appear to lead to an increased number of mitochondria and a reduction in oxidative stress. Recent scientific evidences suggest that muscle performance is a determining factor regarding the functional capabilities. A new and effective approach to increase power in elderly subjects is found to be the fast‐contraction‐velocity exercise. In addition, the aerobic exercise can generate benefits on elderly muscles through an increment in mitochondrial energy production, increased insulin sensitivity and/or reduction of the oxidative stress [24].

In elderly patients, the clinical relevance of a nutritional and rehabilitative intervention based on exercise, resides with the long‐term effects on not only strength and muscle mass but also on the implications concerning functional capacity and risk of developing chronic metabolic diseases. It is well known that the ability to respond to an anabolic stimulus, through the activation of muscle protein synthesis, is kept up even in elderly (though to a lesser extent) [24]. Definitely, it is possible to affirm that resistance‐type exercise interventions have been shown effective in increasing skeletal muscle mass, training muscle strength and/or improving functional capacity in elderly [24].

#### **3. Rehabilitation**

techniques have been studied for many years and the BIA results in standard conditions cor-

Among measurements to assess muscle strength, it is necessary to emphasise the importance of handgrip test; even if lower limbs are more relevant than the upper limbs in physical function and walking, the evaluation of strength by isometric handgrip has been widely used. Measured under standard conditions, with a well‐studied model of dynamometer hand, it is

The short physical performance battery (SPPB) is one of the most valid techniques to measure physical performance. It consists of a brief set of tests evaluating the functionality of the lower limbs. This battery is composed of three different sections. The first one is the assessment of balance in three tests: (a) maintenance of balance in stand position with feet together side‐by‐side for 10 seconds; (b) maintenance of balance in semi‐tandem position (heel of one foot against side of big toe of the other) for 10"; (c) maintenance of balance in tandem position (feet aligned heel to toe) for 10". The second section evaluates gait speed measuring the time required to walk 4 m linear at a normal pace. Finally, the third one measures the time required to perform five rises from a chair to an upright position as fast as possible without

Other tests can be used in clinical practice, as they require a very simple execution setting. One of these is the sit to stand test, which evaluates the ability to move from sit to stand position without using arms. The timed up‐and‐go test (TUG), which evaluates the dynamic balance by measuring the time required to complete a series of tasks (getting up from a chair, walking a short distance, turning around an obstacle, walking back and sitting down again)

Specific mode and intensity of physical activity can act synergistically to maintain and even increase muscle mass, strength and power, both in healthy individual and in elderly patients with limited functionality. These interventions also have been found effective for all ages and

there is evidence for similar responses in both female and male [22].

closely correlated with lower limb muscles power and with the area of calf section.

**Variable Exams Clinical practice**

Total or partial body potassium per fat‐free tissue

BIA DXA

SPP

Anthropometry

Handgrip strength

Usual gait speed Timed up and go test

Magnetic resonance imaging (MRI) Dual energy X‐ray absorptiometry (DXA)

**Table 3.** Measurements of muscle mass, strength and performance in research and clinical practice.

Bioimpedance analysis (BIA)

Knee flexion/extension Peak expiratory flow

Physical performance Short Physical Performance Battery (SPPB) Usual gait speed Timed up and go test Stair climb power test

relate with the predictions of the MRI [19].

Muscle mass Computed tomography (CT)

108 Frailty and Sarcopenia - Onset, Development and Clinical Challenges

Muscle strength Handgrip strength

the use of the arms.

[20, 21].

#### **3.1. Scientific researches**

Over the years, we have therefore investigated the effects of exercise and mechanical stimulation in primary prevention and treatment of sarcopenia.

In 2006, the first study [25] evaluated the selective development of muscle strength in 20 female subjects with severe atrophy of the femoral quadriceps muscle, with a mean age of 31 years. Subjects were randomly divided in two groups, named A and B. Group A performed 10 rehabilitation sessions, 5 times per week, lasting 10 minutes each, with mechano‐sound vibration (without performing voluntary contraction) with a defined frequency of 300 Hz. Group B performed 10 sessions of strengthening every other day through isokinetic Cybex equipment at 90°/second in concentric‐eccentric mode. The evaluation was performed at first visit (T0), after the treatment period (T1) and at a 6 months follow‐up (T2) by isokinetic testing (Cybex) with flexion‐extension movement of right and left knee at 180 and 60°/second, in both study groups. At T1 evaluation, it was found in both groups a significant increase in muscle strength and working ability as well as an improvement in muscular coordination. The increase in contractile strength in group A was comparable to that obtained with a conventional rehabilitation protocol (group B). Differences between the two groups were the longest duration of treatment effectiveness (about 6 months) and the faster achievement of these results, already during the protocol, in Group A. High speed contractile improvements induced by the local vibrational method appeared more effective; in fact, in group A, contralateral muscle strength improved too, unlike the group B.

In a 2008 study, we compared the efficacy of three methods of training in elderly subjects with postural instability and sarcopenia [26]. Nineteen subjects (11F and 8M, aged between 64 and 80 years) took part in the study. Evaluations at T0 and T1 have been carried out through clinical examination, needle biopsy of the vastus lateralis muscle (measuring specific development of the individual fibres), expression of myosin heavy chains, transcriptional and regenerative capacity profile of satellite cells. Subjects were divided randomly into three groups of six subjects each; group A performed aerobic training (endurance), group B anaerobic training (power), group C mechano‐sound vibration at a frequency of 300 Hz. The protocol frequency was three sessions per week for all study groups. The results obtained showed that the development of single fibre strength did not change in any of the training protocols; gene expression profiles showed, for each type of intervention, the stimulation of a specific metabolic pathway, as both resistance and vibration training increased aerobic metabolism, while resistance training stimulated creatine metabolism. All trainings protocols stimulated in a different way the expression of sarcomeric and cytoskeletal proteins; in particular, mechano‐sound vibration training has stimulated proteins associated with the Z‐line. It was also found that satellite cells contribute to regeneration and trophism of muscle fibre. The results therefore suggested that all training protocols are effective in contrasting the progression of sarcopenia and each one is able to stimulate specific molecular signals. The effects are specific because there is a relationship between the type of exercise and the metabolism stimulated.

In another study, we further evaluated the effect of focused vibration on elderly skeletal muscle [27]. Eleven subjects (5F and 4M, aged between 65 and 82 years), diagnosed with sarcopenia in accordance with the guidelines of the Centers for Disease Control and Prevention (CDC) were evaluated and treated. Inclusion criteria for the study were patients older than 18 years, diagnosis of sarcopenia in absence of joint pathology. Exclusion criteria were cardiovascular and/or metabolic diseases, hereditary or acquired muscular disorders, respiratory and psychiatric disorders, treatment with testosterone or other drugs affecting muscle mass. Mechanical vibrations were applied at local level at a frequency of 300 Hz on thigh muscles for a period of 12 weeks, starting from a 15‐minute per session once a week to progressively reach 3 sessions per week. The evaluation consisted of clinical examination, resting ECG and isometric tests. These were carried out the week before the beginning of the study (T0, pre‐session), at the end of the therapeutic protocol (T1, post‐session) and 16 weeks after the end of treatment (T2, follow‐up). Moreover, it was evaluated the body mass index (BMI), the measurement of the circumference of proximal and distal thigh and it was performed the vastus lateralis muscle biopsy. Maximal isometric strength evaluation of lower limb extensor muscles showed an increase in strength since 4 weeks of treatment in women and after 8 weeks in men; increasing strength reached a plateau phase at week 12. As it regards the circumferences, it was found a significant increase of the distal circumference of 0.5–3 cm and a non‐significant increase of the thigh circumference at the proximal zone. Vastus lateralis biopsy results showed the increase of muscle fibre section width (T0: 3667 ± 310.7, T1: 4238 ± 357.4 μm2 ); changing in myosin chains, which switched from the isoform slow (MyHC‐1) to the isoform fast (MyHC‐2X). Other interesting observations were the stimulation of genes involved in energetic metabolism (PIK3R3; GSK‐3), in protein synthesis and degradation, in calcium homeostasis (ACTA2; MLCB; ARL5A; LCCP; TTID; POP3; RyR3; CHERP) and in oxidative stress processes (P12; PRDX3; MSRA). It was also found a down‐regulation of the gene coding for nitric oxide synthase (NOS‐1). The results showed that sarcopenic skeletal muscle reduced metabolic power because of several factors, such as a reduction in blood supply, fibrosis processes and atrophy development. Muscle tissue undergoes continuous oxidative phenomena; this leads to imbalance between oxidant and antioxidant capacity; in fact, in elderly, several genes coding for antioxidant factors are down‐regulated. The reduced expression of NOS leads to a reduction of the amount of nitric oxide circulating, compromising vasodilatation. Therefore, focused mechano‐sound vibration, increasing the expression of genes coding for antioxidant factors, while enhancing the maximal isometric force, can be considered effective in combating sarcopenia.

performed 10 sessions of strengthening every other day through isokinetic Cybex equipment at 90°/second in concentric‐eccentric mode. The evaluation was performed at first visit (T0), after the treatment period (T1) and at a 6 months follow‐up (T2) by isokinetic testing (Cybex) with flexion‐extension movement of right and left knee at 180 and 60°/second, in both study groups. At T1 evaluation, it was found in both groups a significant increase in muscle strength and working ability as well as an improvement in muscular coordination. The increase in contractile strength in group A was comparable to that obtained with a conventional rehabilitation protocol (group B). Differences between the two groups were the longest duration of treatment effectiveness (about 6 months) and the faster achievement of these results, already during the protocol, in Group A. High speed contractile improvements induced by the local vibrational method appeared more effective; in fact, in group A, contralateral muscle strength

In a 2008 study, we compared the efficacy of three methods of training in elderly subjects with postural instability and sarcopenia [26]. Nineteen subjects (11F and 8M, aged between 64 and 80 years) took part in the study. Evaluations at T0 and T1 have been carried out through clinical examination, needle biopsy of the vastus lateralis muscle (measuring specific development of the individual fibres), expression of myosin heavy chains, transcriptional and regenerative capacity profile of satellite cells. Subjects were divided randomly into three groups of six subjects each; group A performed aerobic training (endurance), group B anaerobic training (power), group C mechano‐sound vibration at a frequency of 300 Hz. The protocol frequency was three sessions per week for all study groups. The results obtained showed that the development of single fibre strength did not change in any of the training protocols; gene expression profiles showed, for each type of intervention, the stimulation of a specific metabolic pathway, as both resistance and vibration training increased aerobic metabolism, while resistance training stimulated creatine metabolism. All trainings protocols stimulated in a different way the expression of sarcomeric and cytoskeletal proteins; in particular, mechano‐sound vibration training has stimulated proteins associated with the Z‐line. It was also found that satellite cells contribute to regeneration and trophism of muscle fibre. The results therefore suggested that all training protocols are effective in contrasting the progression of sarcopenia and each one is able to stimulate specific molecular signals. The effects are specific because

there is a relationship between the type of exercise and the metabolism stimulated.

In another study, we further evaluated the effect of focused vibration on elderly skeletal muscle [27]. Eleven subjects (5F and 4M, aged between 65 and 82 years), diagnosed with sarcopenia in accordance with the guidelines of the Centers for Disease Control and Prevention (CDC) were evaluated and treated. Inclusion criteria for the study were patients older than 18 years, diagnosis of sarcopenia in absence of joint pathology. Exclusion criteria were cardiovascular and/or metabolic diseases, hereditary or acquired muscular disorders, respiratory and psychiatric disorders, treatment with testosterone or other drugs affecting muscle mass. Mechanical vibrations were applied at local level at a frequency of 300 Hz on thigh muscles for a period of 12 weeks, starting from a 15‐minute per session once a week to progressively reach 3 sessions per week. The evaluation consisted of clinical examination, resting ECG and isometric tests. These were carried out the week before the beginning of the study (T0, pre‐session), at the end of the therapeutic protocol (T1, post‐session) and

improved too, unlike the group B.

110 Frailty and Sarcopenia - Onset, Development and Clinical Challenges