Current Pharmaceutical Design - Volume 20, Issue 19, 2014

In this report we will provide additional insight on the individual features of age-related causes of mobility limitation, explaining why insulin resistance, related to lower muscle functioning, sub-inflammation and hormonal changes, may contribute to its onset and sustain it. According to the recent literature, the same factors playing a role in the onset and maintenance of insulin resistance are related to mobility limitation. Thus, the presence of insulin resistance can be considered a biomarker of susceptibility to mobility limitation among older persons. All described factors related to both conditions are strictly intertwined. Therefore, the identification and correction of a single factor is difficult to convert into clinical practice. Instead, insulin resistance may be considered not only an early biological marker, but also a predictive and modifiable marker of mobility limitation. Thus, interventions aimed at correcting insulin resistance may have a potential role in preventing or at least slowing down functional decline in the elderly population, promoting a better quality of life and potentially extending the “healthspan”.

The ability to remain mobile is an essential aspect of quality of life and is critical for the preservation of independence in old age. One of the cornerstones of comprehensive geriatric assessment is the evaluation of functional and mobility status, because it provides clinicians pivotal information on overall health status, quality of life, needs for formal and informal care, and short and long term prognosis. As a consequence, many assessment tools have been developed and proposed for clinical use, including simple self-report measures assessing basic abilities and more complex and challenging performance-based objective tools. Both self-report and objective measures might be used to investigate specific steps of the age-related disablement process. In general, self-report and performance based instruments should not be used interchangeably, since they provide different and complementary information. Selection of the more appropriate tool strongly depends on clinical setting, patient characteristics, and clinical or research objective.

The impact of depression on physical disability is undisputed. There is convincing evidence that depression increases the subsequent risk for physical disability and, in turn, physical disability results in increased depressive symptoms. Moreover, depression affects also the earlier stages of the disablement process (including functional limitation in mobility) and may accelerate the transitioning along the pathway to disability. Greater knowledge of the structure of this detrimental relationship and the underlying mechanisms should inform the clinical management of older persons at risk of physical decline and the development of effective interventions that break this downward spiral.

Mobility-disability is a common condition in older individuals. Many factors, including the age-related hormonal dysregulation, may concur to the development of disability in the elderly. In fact, during the aging process it is observed an imbalance between anabolic hormones that decrease (testosterone, dehydroepiandrosterone sulphate (DHEAS), estradiol, insulin like growth factor-1 (IGF-1) and Vitamin D) and catabolic hormones (cortisol, thyroid hormones) that increase. We start this review focusing on the mechanisms by which anabolic and catabolic hormones may affect physical performance and mobility. To address the role of the hormonal dysregulation to mobility-disability, we start to discuss the contribution of the single hormonal derangement. The studies used in this review were selected according to the period of time of publication, ranging from 2002 to 2013, and the age of the participants (≥65 years). We devoted particular attention to the effects of anabolic hormones (DHEAS, testosterone, estradiol, Vitamin D and IGF-1) on both skeletal muscle mass and strength, as well as other objective indicators of physical performance. We also analyzed the reasons beyond the inconclusive data coming from RCTs using sex hormones, thyroid hormones, and vitamin D (dosage, duration of treatment, baseline hormonal values and reached hormonal levels). We finally hypothesized that the parallel decline of anabolic hormones has a higher impact than a single hormonal derangement on adverse mobility outcomes in older population. Given the multifactorial origin of low mobility, we underlined the need of future synergistic optional treatments (micronutrients and exercise) to improve the effectiveness of hormonal treatment and to safely ameliorate the anabolic hormonal status and mobility in older individuals.

The rapidly increasing elderly population poses a major challenge for future health-care systems. Neurological diseases in older persons are particularly common and coexist with other clinical conditions. This is not surprising given that, for example, even patients with Alzheimer Disease (AD) could have relevant extrapyramidal signs at the moment of the diagnosis with motor signs having more negative prognostic value. Longitudinal studies conducted on Parkinson Disease (PD) showed that, after 20 years, dementia is not only present in almost all survivors but is also the main factor influencing nursing home admission. Recently, it has been reported the importance of Comprehensive Geriatric Assessment (CGA: comprehensive evaluation of cognition, depressive symptoms, mobility and functional assessment) as a tool reducing morbidity in frail older patients admitted to any acute hospital unit. The CGA should be considered as a technological device, for physicians who take care of older persons affected by overlapping neurological diseases. CGA is an extraordinary and cost effective instrument even in patients with advanced neurological diseases where allows to collect valuable information for an effective plan of management.

Gait is a complex motor task, initiated and governed by different areas of the brain. Studies have shown a clear association between gait and cognition. Impairments in both gait and cognition are prevalent in older adults. Older adults with gait impairment have an increased risk of developing cognitive impairments. Those with cognitive impairment often have gait impairments and more falls than cognitively healthy older adults. Recent studies have shown that quantitative gait analysis, particularly performed during dual task conditions, can detect gait deficits that cannot yet be seen by the naked eye, even to a trained specialist. Some studies have shown that such gait disturbances were measurable years before mild cognitive impairment or dementia or walking difficulties were clinically manifest. Quantitative gait analysis can provide early detection of gait and cognitive impairments as well as fall risk. Future quantitative gait studies may help distinguish dementia subtypes in early stages of the diseases. Early detection of gait and cognitive impairments would provide a better understanding of disease pathophysiology and progression. Early detection also allows the timely implementation of interventions with the ultimate goal of improving or maintaining mobility and functional independence for as long as possible. Quantitative gait analysis should be viewed as a clinical tool to aid diagnoses and treatment planning. This review examines the current literature on quantitatively measured gait impairment in older adults with mild cognitive impairment or a dementia subtype.

Movement disability has a high prevalence in elderly population, either healthy or with chronic disease. Impaired nutritional status is a very common condition in geriatric patients too, especially if we consider elderly subjects admitted to hospital. There are growing evidences that nutrition and disability are strictly interconnected. On the one side, nutritional status is one of the multiple elements that influence the onset and the course of a functional disability; on the other side, disability itself may contribute to malnutrition onset and worsening. Nutrition may not be the sole factor involved in movement impairment in the elderly, but consciousness of its importance in frail elderly population is growing among clinicians and scientific community. In this paper we review the existing knowledge of these complex relationships, discussing the main observational and interventional studies that explored the role of nutrition in movement disability onset and recovery. We also point out how specific kinds of diet, such as Mediterranean diet or high-protein diet, are involved in disability prevention. Finally, we take a look at the existing evidence of the role of single nutrient dietary intake, such as carotenoids, selenium or vitamin D, in mobility impairment in the elderly population.

Aging is associated with a progressive loss of bone-muscle mass and strength. When the decline in mass and strength reaches critical thresholds associated with adverse health outcomes, they are operationally considered geriatric conditions and named, respectively, osteoporosis and sarcopenia. Osteoporosis and sarcopenia share many of the same risk factors and both directly or indirectly cause higher risk of mobility limitations, falls, fractures and disability in activities of daily living. This is not surprising since bones adapt their morphology and strength to the long-term loads exerted by muscle during anti-gravitational and physical activities. Non-mechanical systemic and local factors also modulate the mechanostat effect of muscle on bone by affecting the bidirectional osteocyte-muscle crosstalk, but the specific pathways that regulate these homeostatic mechanisms are not fully understood. More research is required to reach a consensus on cut points in bone and muscle parameters that identify individuals at high risk for adverse health outcomes, including falls, fractures and disability. A better understanding of the muscle-bone physiological interaction may help to develop preventive strategies that reduce the burden of musculoskeletal diseases, the consequent disability in older persons and to limit the financial burden associated with such conditions. In this review, we summarize age-related bone-muscle changes focusing on the biomechanical and homeostatic mechanisms that explain bone-muscle interaction and we speculate about possible pathological events that occur when these mechanisms become impaired. We also report some recent definitions of osteoporosis and sarcopenia that have emerged in the literature and their implications in clinical practice. Finally, we outline the current evidence for the efficacy of available anti-osteoporotic and proposed antisarcopenic interventions in older persons.

The increase of life expectancy together with the decline of birth rates implies a global aging of populations living in industrialized countries. Since advanced age is associated with an exponential consumption of health care resources, this phenomenon is likely to pose a substantial threat to the stability of public health systems. Prevention of physical disability represents a major public health priority. Since disability is considered an irreversible condition, every effort should be made to prevent the onset of the disabling cascade and/or delay the physical function decline. The need for strategies against disability has led researchers to look for the most relevant risk factors potentially determining or accelerating the disabling cascade. In this context, cardiovascular and respiratory conditions have been indicated as playing prominent roles in the determination of frailty. Moreover, the high prevalence of these conditions among older persons makes them particularly amenable to targeting for preventive interventions. The aim of the present review is to show the impact of cardiovascular and respiratory conditions on physical function. Moreover, we will discuss the relationship of these conditions with the disabling process, and the importance of their assessment in the design of preventive interventions against disability in older persons.

Introduction: Inflammation is related to muscle wasting in elderly persons. Since surgery is accompanied by an important inflammatory response, the degree of muscle wasting and related symptoms such as weakness and tiredness might exacerbate very rapidly in elderly surgery patients. Methods: PubMed and Web of Science were systematically screened for articles reporting the influence of surgery-induced inflammation on muscle performance and/or fatigue in elderly patients. Studies reporting surgery-induced inflammation and changes in muscle performance and/or fatigue, but without analyzing their association were excluded. Although 5 relevant articles were identified including older patients (highest ages reported were 71-92 years), none focused exclusively on elderly patients. Only 2 studies assessed muscle performance, and in none muscle mass was evaluated. Overall, we found evidence that in elderly patients higher surgery-induced inflammation was significantly related to worse muscle performance and fatigue in the first postoperative days as well as after more than one month (especially for fatigue) following the intervention. Pre-operative anti-inflammatory treatment using steroids or glucocorticoids can reduce the surgery-induced inflammatory response and improve the recovery of muscle performance and postoperative fatigue in elderly elective abdominal surgery or arthroplasty patients. Conclusion: We can conclude that to date, only few studies have investigated the association between surgery-induced inflammation and changes in postoperative muscle performance and fatigue in elderly patients. More research is warranted focusing on both the short -and long-term effects of surgical stress on muscle performance in elderly patients as well as the on risks and benefits of peri-operative anti-inflammatory treatment.

Due to the progressive ageing of the worldwide population, prevention and treatment of late-life dysfunctions, including functional decline and mobility limitations, represent leading targets of scientists and clinicians, but are also receiving growing attention from governments and healthcare systems. The early identification of elderly patients more prone to physical decline represents a crucial step for establishing preventive measures. Although functional capacity can easily be assessed, the use of additional criteria that anticipate the onset of mobility limitations seems much more advantageous. The most challenging issues in the identification of biological markers for assessing the risk of functional decline in the elderly originates from the complex and multifaceted pathogenesis of sarcopenia and the resulting physiological decrement, so that bridging the gap between basic research and clinical practice may appear intricate. Nevertheless, several lines of evidence now confirm the existence of negative associations between functional mobility and values of hemoglobin, total and HDL-cholesterol, vitamin D, testosterone, adiponectin and antioxidants such carotenoids, vitamin C and E, selenium and magnesium, whereas positive associations have been reported with the values of uric acid, white blood cells, plasma and blood viscosity, erythrocyte sedimentation rate (ESR), triglycerides, homocysteine, plasma glucose, glycated hemoglobin (HbA1c), markers of renal functions (i.e., creatine and cystatin C), insulin-like growth factor-1 (IGF-1), as well as several inflammatory (e.g., C reactive protein, Intereleukin-6, Interleukin- 1 receptor antagonist), hemostatic (e.g., fibrinogen, Von Willebrand Factor, factors VIII and IX) and oxidative (oxidized lipoproteins, 8-oxo-7,8-2’-deoxyguanosine, protein carbonylation) biomarkers. In the foreseeable future, proteomic studies might predictably help identify novel associations between putative biomarkers and functional decline.

With body composition it is possible to divide human body in compartments on the basis of different physical properties. The two level body composition model subdividing the whole body in fat mass and fat free mass is the most used in epidemiological and clinical studies in the elderly. Body composition techniques may be used to study ageing process. Changes in body composition occur as part of the normal ageing process and are associated with important effects on health and function. It has been shown that body composition changes with aging, with an increase in fat mass and a decrease in muscle mass, have important consequences on health and physical disability. Moreover body fat distribution changes with adverse metabolic profiles and increased cardiovascular risk. The purpose of this review is to describe the basic principles and techniques for fat free mass and fat mass evaluation, highlighting the advantages and limitations of different available body composition methods.

Current evidence suggests that functional status is an important outcome of pharmacologic treatments in older people. At the moment, studies have shown diverse effects of medications on functional status. For example, some have shown potentially detrimental effects, while others have found improvements on physical function in elders. Overall, suboptimal prescribing and the occurrence of adverse drug reactions (ADRs) may negatively affect functional status. The use of selected drugs acting on central nervous system (CNS), e.g. benzodiazepines and antipsychotics, is generally associated with an increased risk of functional decline. The greater sensitivity of older people to these drugs, together with age-related changes in pharmacokinetics and pharmacodynamics, account for the observed detrimental effect and suggests a cautious approach to older and frail patients when prescribing CNS agents. On the other hand, selected drugs may slow or delay functional decline in older people. In particular, drugs aimed at targeting sarcopenia (loss in muscle mass and strength), such as testosterone in androgen deficiency, ACE-inhibitors, vitamin D and β-hydroxy β-methyl butyrate (HMB), as well as the recently developed selective androgen receptor modulators (SARMs) may hold extreme importance. This review will provide available evidence of the diverse impacts of drug medications on functional status in older persons.