Thresholds for abnormality in the components of frailty
This phenotype model therefore does not include cognitive or psychosocial features that are also well known to be predictive of adverse health outcomes. Nevertheless, there is substantial evidence that this predominantly physical frailty phenotype has predictive power for adverse health outcomes in several cohorts of older people.
The deficit accumulation approach is quite different. It operationalises frailty as the sum total of factors that may be regarded as detrimental (“deficits”). These could be symptoms, sensory impairments, abnormal clinical findings or laboratory test results, diseases, disabilities or lack of social support. Generally each is regarded as present or absent and thus accorded a score of 0 or 1, although some domains lend themselves to be divided in three or occasionally more grades, so become fractions of one. The total score, termed the frailty index (FI), is calculated from the sum of all the deficit scores divided by the number of items included. The theoretical range of the FI is therefore between 0 (no deficits apparent, good health) to 1 (deficits in every item), but in practice a number of studies have now shown that survival is rare with scores above about 0.7. The deficit accumulation model is an approach rather than a fixed tool, and is therefore highly flexible. A FI can be constructed from any comprehensive dataset about an individual as long as it covers a broad range of these health related domains and includes upwards of 30 items.
Despite these approaches being quite distinct, they perform fairly similarly in identifying frailty when applied to a common dataset [5, 6].
4.1.2 Epidemiology of Frailty
Whatever approach is used to define frailty, it becomes more prevalent with increasing age, with estimates of 5–10 % in the 65+ population, rising to 20–50 % by age 85+ . Frailty is more common in women, but several studies suggest that women are more resilient to frailty than men. Geographical differences in frailty prevalence may be related to health inequalities, as rates are significantly associated with national economic indicators. Differences within countries may also be associated with socioeconomic factors including social deprivation .
4.1.3 Why and How Does Frailty Develop?
Frailty may be best understood from the standpoint of ageing and evolution. Ageing is the gradual and progressive process of acquiring deleterious changes to body structure and function, affecting all individuals to variable degrees and not associated with a specific external cause. Ageing is associated with an increased chance of certain “degenerative” diseases, but these are not universal. Disability results from the critical impairment of specific attributes, such as strength or balance, these impairments arising from ageing or disease or more usually both.
These ageing related impairments result from the lifelong accumulation of unrepaired molecular and cellular damage. This damage takes multiple forms, particularly important being random errors arising in DNA replication, protein translation and post-translational synthesis. Oxidative damage arising as an inevitable product of metabolic activity is an important mechanism. A number of detection and repair processes have evolved which limit the impact of these changes. The efficiency of these defences also reduces with ageing. The biological economy needed to optimise survival chances dictate that these processes are good enough to enable growth, development and reproduction, but do not need to be robust enough to provide centuries of protection. Thus the reserve capacity is limited, and when sufficient damage is done at cellular level, then the functioning of organs and systems will decline.
The pathophysiological pathway from these changes to clinically evident phenomena is not fully elucidated, but candidates include cytokines and other components of the inflammatory response . The vulnerability inherent in the notion of frailty comes from the loss of metabolic or physiological reserve to the point where additional stressors precipitate clinically significant loss of function. These age-related changes may affect organs differentially depending upon other individual factors such as particular exposures, different activity levels and chance as there are both independent and linked mechanisms operating across organ or physiological systems. The changes in the neuroendocrine and immune systems seem particularly important . The pro-inflammatory profile has prompted the idea of “inflammaging” producing a net catabolic profile associated with frailty.
At first glance, the phenotype model of identifying frailty more closely reflects this explanation than the deficit accumulation approach. Longitudinal study has suggested that in apparently healthy older people, the emergence of weakness, slower walking and reducing physical activity usually precede the other two dimensions of weight loss and exhaustion, the presence of which predicts earlier decline . The FI depends upon the number of deficits rather than which ones they are. The increased likelihood of disability or death with a higher FI is not necessarily driven by the specifc deficits detected, but as explained earlier, age related deficits do not arise in isolation from each other as there are common cellular and system level processes at work.
4.1.4 Frailty and Clinical Practice
If the key early pathophysiological changes could be identified, then it might become possible to intervene at a preclinical stage of frailty before operational phenotypic criteria develop. Even without this understanding, there is evidence that increasing physical activity levels, enhancing social participation, and optimising nutrition are associated with lower levels of age-related cellular damage suggesting that a public health approach is indicated.
Addressing frailty with a generic approach may also provide additional clinical benefit along with the condition-specific management of patients with chronic diseases. Disease-specific factors do not fully explain well-being and quality of life and frailty may contribute independently of disease. Comprehensive geriatric assessment encompasses an approach that combines disease-specific and non-specific aspects to the assessment and treatment of older people. Frailty recognition would enable targeting of this approach.
Recognition of frailty through better definition may also improve clinical decision making by informing the prediction of benefit or the risk of the adverse effects of clinical interventions including medications, surgical interventions, physical displacement and so on. For example, the ability to improve prediction of post-operative functional recovery would be invaluable, as disease-based predictive models are far from perfect. The NICE guidance on management of multimorbidity emphasises the need for individual patient judgements about treatments incorporating a measure of their frailty (due for publication in September 2016).
184.108.40.206 Assessment of Frailty in Clinical Practice
Neither the phenotype model nor the FI are particularly feasible however in routine clinical practice, so simpler tools are more commonly used such as the Clinical Frailty Scale  or the Edmonton Frail Scale . The Clinical Frailty Scale uses descriptors covering the domains of mobility, energy, physical activity, and function to enable a standard clinical assessment to characterise seven levels from very fit, healthy to very severely frail (Fig. 4.2). This provides a feasible description based on routine clinical assessment but does not conceptually distinguish frailty from multimorbidity or disability. Its mortality prediction is comparable to that of the more detailed FI.
The Clinical Frailty Scale
The Edmonton scale requires a number of specific but fairly simple clinical measures to be performed which would be additional to routine clinical practice. The domains included are cognition (the clock drawing test), general health status, functional ability, social support, medication use, nutrition, mood, continence and a mobility function test – the Timed Up and Go. Scores range from zero to 17, scores of 8 or above usually being considered to be frail, but relevant cut offs can be established empirically depending upon the purpose. For example, prediction of likely higher rate of postoperative complications may be associated with lower scores. In contrast to the phenotype approach, the Edmonton scale identifies potential targets for intervention across a number of clinically important domains.
In community or primary care settings, the issue may be to identify a target group for health-promoting interventions such as optimising nutrition and increasing physical activity levels. Here a more simple screening approach may be needed. A recent systematic review assessing available tools suggested that PRISMA-7 may be the most accurate , a score of 3 or more suggesting increased likelihood of incident disability  (Fig. 4.3).
4.2 Frailty and Sarcopenia
Sarcopenia was the term suggested by Rosenberg for the well-recognised loss of muscle with ageing . It is a major component of frailty. Skeletal muscle accounts for a third or more of total body mass. As well as movement, muscle plays a key role in temperature regulation and metabolism. Low muscle mass is associated with poor outcomes from acute illness, probably because of reduced metabolic reserve, as muscle is a reservoir for proteins and energy that can used for synthesis of antibodies and for gluconeogenesis. Muscle mass and strength are of course related but not linearly . Function is more important than mass for physical performance and disability .
4.2.1 Key Features of Sarcopenia
Sarcopenia is characterised by motor neurone loss, reduced muscle mass per motor unit, relatively more loss of fast twitch fibres and reduced strength per unit of cross sectional area.
Muscle fibres are lost by drop-out of motor neurones. Reinnervation of fibres by sprouting from surviving neurones cause a less even distribution of fibre types cross-sectionally and a relatively greater loss of type II fibres which are associated with generation of power (the product of force generation and speed of muscle contraction) . Loss of efficiency also results from an accumulation of fat within and between fibres and an increase in non-contractile connective tissue material. Leg power accounts for 40 % of the decline in functional status with ageing . Men who maintain physical activity into their 80s show compensatory hypertrophy of muscle fibres to compensate for the decrease in fibre number.
4.2.2 How and Why Does Sarcopenia Develop?
Muscle fibre development occurs before birth but fibres enlarge during childhood reaching a peak in early adulthood. Mass and function then gradually decline into older age . Peak mass is affected by maternal, genetic and early life influences. Decline is affected by physical activity, nutrition and sex. Decline is more pronounced in women from menopause onwards. Adding to the inevitable moderate decline of some 15–25 % by old age is the impact of acute illness or chronic conditions, which have generally negative effects through the mechanisms of catabolic stress, reduced food intake and physical activity.
The loss of muscle mass is thought to be multifactorial with potential factors illustrated in Fig. 4.4.
The factors implicated in sarcopenia overlap with those for frailty. A central feature of sarcopenia is a decrease in the rate of muscle protein synthesis. This leads to reduced protein levels including mitochondrial oxidative enzymes responsible for enabling work intensity. The age-related shift of the hormonal balance towards low testosterone, growth hormone and IGF-I contributes to the lower muscle protein synthesis rates, which also limits the structural recovery from muscle damage or apoptosis and possibly reduces the synthetic stimulus of exercise .
The role of cytokines such as interleukins IL-1β and IL-6, and TNF-α is less certain. They play a role in the catabolic processes of acute illness and chronic inflammatory conditions, but whether the small differences in circulating levels associated with frailty reported from some population studies is relevant to the age related sarcopenia is not established.
4.2.3 Identifying Sarcopenia
There are several different diagnostic definitions resulting in variable prevalence rates being reported in community dwelling populations of older people. A consensus definition and approach to screening and classification has been proposed by the European Union Geriatric Medicine Society . This is shown in Fig. 4.5.
Measuring gait speed is feasible in almost any setting and is a useful global indicator of health, slower gait being associated with greater likelihood of incident disability, falls, institutionalisation and death . Grip strength was chosen as it is a portable, simple, reliable and valid proxy measure of body strength, and has good correlation with lower limb physical performance. Low grip strength of community dwelling older people is associated with falls, increased incident disability and earlier mortality. It also predicts slower and less complete functional recovery from illness in men . Measurement of muscle mass can be done with CT scan or, less accurately, with impedance techniques.
4.3 Frailty, Sarcopenia and Falls
Falls are one of the “geriatric giants”, syndromes that are more prevalent with increasing age, have multifactorial causes and are associated with worse health outcomes including disability, institutionalisation and death. A fall can be defined as “an event whereby an individual comes to rest on the ground or another lower level with or without a loss of consciousness.” This definition was adopted for the guidelines issued from the American and British Geriatrics Societies and the National Institute for Health and Care Excellence (NICE) [26, 27]. The definition does not attempt to exclude syncope for the good reason that an overlap exists in the phenomenology, experience, and pathophysiology of these events.
In a clinical context with an individual patient, assessment involves an attempt to place the event in the spectrum with syncope at one end and loss of balance due to postural instability at the other. Sometimes this is clear-cut, sometimes not. Falls may occur in individuals with a specific condition leading to an obvious balance disturbance such as a stroke causing hemiparesis. The majority of falls in older people however are associated with multicomponent impairments, particularly of muscle function, balance and cognition, so are best understood as resulting from complex systems failure as part of the frailty syndrome.
4.3.1 Epidemiology of Falls
Falls rates vary internationally but in most populations studied they occur in about one third of community dwelling individuals aged over 65 each year, about half of these being multiple falls, and rates then increase with age to over 50 % of those 80 plus [27, 28]. Falls rates seem higher among Caucasian populations compared with the Chinese. Rates are particularly high in older people with dementia unless mobility is lost [27, 29]. Living in long-term care facilities is also associated with higher falls rates. This relates both to the clinical characteristics of the residents and the complexity of the environment. WHO reported in 2007 from international data that falls result in 5.5–8.9 Emergency Department attendance visits per 10,000 people aged 60 plus, with about a third being admitted . Falls account for over half of all injury-related hospital admissions for older people aged 65 plus, head injuries and fractures being the most common and serious. Older women fall relatively more than men but sustain relatively fewer injuries. People with lower socioeconomic status and those living alone have more falls.
4.3.2 Risk Factors and Assessment
Prospective observational studies have produced a long list of risk factors that may help identification of higher risk groups . Falls happen to individuals with intrinsic impairments, performing specific activities in specific environments. It is the combination that matters. Most falls are associated with impairments of mobility function and/or cognitive decline, particularly of higher-order functions that affect gait pattern, balance, and executive function. Low muscle strength itself has been reported to increase risk but it is functional mobility that seems more important. Environmental hazards alone are seldom responsible. Likewise, most fallers were doing something fairly routine, even mundane. For an individual with dynamic balance that is only just sufficient for their usual activities, the fall may occur from chance variation in performance, or may have been compromised by cognitive distraction, pain or anxiety. For someone with limited functional mobility reserve, intercurrent illness will often determine the exact time and place of the fall. For example, a urinary tract infection may require more frequent visits to the toilet, perhaps at night in the dark and may prompt the individual to move faster than usual.