We developed a structured search strategy with the assistance of an expert librarian at the University of Leeds, UK. We searched the Cochrane Library, CINAHL, Medline, Embase, PsycINFO, and PEDro; all searches were for 2000–12. We used the search terms “frailty”, “frail elderly”, or “sarcopenia” with the terms “aged” or “aged, 80 and over” or “ageing/genetics” or “longevity” or “centenarian” or “oldest old” or “very old” or “very elderly”. We did a further search in which the results were
SeminarFrailty in elderly people
Introduction
Population ageing is accelerating rapidly worldwide, from 461 million people older than 65 years in 2004 to an estimated 2 billion people by 2050,1, 2 which has profound implications for the planning and delivery of health and social care. The most problematic expression of population ageing is the clinical condition of frailty. Frailty develops as a consequence of age-related decline in many physiological systems, which collectively results in vulnerability to sudden health status changes triggered by minor stressor events. Between a quarter and half of people older than 85 years are estimated to be frail, and these people have a substantially increased risk of falls, disability, long-term care, and death.3, 4 However, up to three-quarters of people older than 85 years might not be frail, which raises questions about how frailty develops, how it might be prevented, and how it can be detected reliably.
Section snippets
Definition and presentations
Frailty is a state of increased vulnerability to poor resolution of homoeostasis after a stressor event, which increases the risk of adverse outcomes, including falls, delirium, and disability.3, 5, 6 Frailty is a long-established clinical expression that implies concern about an elderly person's vulnerability and outlook. Figure 1 shows this state of vulnerability diagrammatically; an apparently small insult (eg, a new drug, minor infection, or minor surgery) results in a striking and
Pathophysiology
Frailty is a disorder of several inter-related physiological systems (figure 2). A gradual decrease in physiological reserve occurs with ageing but, in frailty, this decrease is accelerated and homoeostatic mechanisms start to fail.8, 9 Therefore, an important perspective for frailty is to consider how the complex mechanisms of ageing promote cumulative decline in several physiological systems, the subsequent depletion of homoeostatic reserve, and vulnerability to disproportionate changes in
Pathway
Ageing is believed to result from the lifelong accumulation of molecular and cellular damage caused by many mechanisms that are regulated by a complex maintenance and repair network.10 The precise amount of cellular damage needed to cause impaired organ physiology is uncertain, but, importantly, many organ systems show notable redundancy, which provides the physiological reserve necessary to compensate for age-related and disease-related changes.13 For example, the brain and skeletal muscle
The frail brain
Ageing is associated with characteristic structural and physiological changes in the brain. The loss of individual neurons in most cortical regions is low,23 but neurons with high metabolic demands, such as the hippocampal pyramidal neurons, could be affected disproportionally by changes in synaptic function, protein transport, and mitochondrial function.23 The hippocampus has been identified as an important mediator in the pathophysiology of cognitive decline and Alzheimer's dementia24 and is
The frail endocrine system
The brain and endocrine system are linked intrinsically through the hypothalamo-pituitary axis, which controls metabolism and energy use through the signalling action of a series of homoeostatic hormones.23 During ageing, production of three major circulating hormones decreases. First, a lessening of growth hormone synthesis by the pituitary gland causes a reduction in production of insulin-like growth factor-1 (IGF-I) by the liver and other organs. IGFs are a family of small peptides that
The frail immune system
The ageing immune system is characterised by a reduction in stem cells, changes in T-lymphocyte production, blunting of the B-cell-controlled antibody response, and reduced phagocytic activity of neutrophils, macrophages, and natural killer cells.50, 51 This senescent immune system might function adequately in the quiescent state but fails to respond appropriately to the stress of acute inflammation.50 Evidence suggests that inflammation has a major role in the pathophysiology of frailty
Frail skeletal muscle (sarcopenia)
Sarcopenia has been defined as progressive loss of skeletal muscle mass, strength, and power, and is regarded as a key component of frailty.66, 67 Loss of muscle strength and power could be more important than changes in muscle mass.68 Under normal circumstances, muscle homoeostasis is maintained in a delicate balance between new muscle cell formation, hypertrophy, and protein loss. This balance is coordinated by the brain, endocrine system, and immune system, and is affected by nutritional
Frailty models
Reliable frailty models should be assessed by their success in predicting both natural history and response to therapeutic interventions and should be underpinned by biological principles of causality.70 The two main emerging models of frailty are the phenotype model3 and the cumulative deficit model, which forms the basis of the Canadian Study of Health and Aging (CSHA) frailty index.71
Epidemiology
Evidence for the importance of frailty as a leading cause of death in elderly people comes from a 10-year prospective cohort study of community-dwelling elderly people (n=754).88 Cause of death was based on clinical home-based assessments done at 18-month intervals and on death certificates. The most common disorder leading to death was frailty (27·9%); the others were organ failure (21·4%), cancer (19·3%), dementia (13·8%), and other causes (14·9%).
Prevalence
Investigators assessed the prevalence of frailty in a recent systematic review.89 21 community-based cohort studies of 61 500 elderly people were identified. The operational definitions for frailty and the inclusion or exclusion criteria varied between the studies, which largely explained the substantial variation in reported frailty prevalence rates of 4·0–59·1%. When the reported rates were restricted to the studies that used the phenotype model, the weighted average prevalence rate was 9·9%
Outcomes
The table shows the associations between frailty and adverse outcomes reported in four large prospective cohort studies,3, 92, 93, 94 with the worst outcomes in the most frail people. Frailty is a dynamic process95 but transition to a level of worse frailty is more common than is improvement in frailty, and the development of frailty often leads to a spiral of decline of increasing frailty and higher risk of worsening disability, falls, admission to hospital, and death.3 Risk of admission to
Instrumentation
The demonstration of large between-group differences for people who are frail compared with those who are not frail4 is important because it leads clinicians away from judgments based on chronological age towards the idea of frailty. Researchers and clinicians, therefore, need simple, valid, accurate, and reliable methods to detect frailty. Monitoring outcomes of interventions in frail people also needs methods that are sensitive to change.99
Interventions
Reduction of the prevalence or severity of frailty is likely to have large benefits for individuals, their families, and society. Several approaches have been investigated in clinical trials. Frail elderly people receiving inpatient comprehensive geriatric assessment on specialist elderly care wards are more likely to return home, are less likely to have cognitive or functional decline, and have lower in-hospital mortality rates than do those who are admitted to a general medical ward setting.
Conclusions
Modern health-care systems are mostly organised around single-system illnesses.139 However, many elderly people have multiorgan problems. Frailty is a practical, unifying notion in the care of elderly patients that directs attention away from organ-specific diagnoses towards a more holistic viewpoint of the patient and their predicament. It is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is strongly associated with adverse outcomes. Distinction of frail
Search strategy and selection criteria
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