Ageing and disease

Ageing and disease

M.D. Witham

Comprehensive geriatric assessment


Sweeping demographic change has meant that older people now represent the core practice of medicine in many countries. A good knowledge of the effects of ageing and the clinical problems associated with old age is thus essential in most medical specialties. The older population is extremely diverse; a substantial proportion of 90-year-olds enjoy an active healthy life, while some 70-year-olds are severely disabled by chronic disease. The terms ‘chronological’ and ‘biological’ ageing have been coined to describe this phenomenon. Biological rather than chronological age is taken into consideration when making clinical decisions about, for example, the extent of investigation and intervention that is appropriate.

Geriatric medicine is concerned particularly with frail older people, in whom physiological capacity is so reduced that they are incapacitated by even minor illness. They frequently have multiple comorbidities, and acute illness may present in non-specific ways, such as confusion, falls or loss of mobility and day-to-day functioning. These patients are prone to adverse drug reactions, partly because of polypharmacy and partly because of age-related changes in responses to drugs and their elimination (p. 36). Disability is common, but patients’ function can often be improved by the interventions of the multidisciplinary team (p. 167).

Older people have been neglected in research terms and, until recently, were rarely included in randomised controlled clinical trials. There is thus little evidence on which to base practice.


The demography of developed countries has changed rapidly in recent decades. In the UK, for example, the total population grew by 11% over the last 30 years, but the number of people aged over 65 years rose by 24%. The steepest rise occurred in those aged over 85 – from 600 000 in 1981 to 1.5 million in 2011 – and this number is projected to increase to 2.4 million by 2026, whilst the working-age population (20–64 years) is expected to grow by only 4% between 2011 and 2026. This will have a significant impact on the old-age dependency ratio, i.e. the number of people of working age for each person over retirement age. Young people support older members of the population directly (e.g. through living arrangements) and financially (e.g. through taxation and pension contributions), so the consequences of a reduced ratio are far-reaching. However, many older people support the younger population, through care of children and other older people.

Life expectancy in the developed world is now prolonged, even in old age (Box 7.1); women aged 80 years can expect to live for a further 10 years. However, rates of disability and chronic illness rise sharply with ageing and have a major impact on health and social services. In the UK, the reported prevalence of a chronic illness or disability sufficient to restrict daily activities is around 25% in those aged 50–64, but is 66% in men and 75% in women aged over 85.

Although the proportion of the population aged over 65 years is greater in developed countries, two-thirds of the world population of people aged over 65 live in developing countries at present, and this is projected to rise to 75% in 2025. The rate of population ageing is much faster in developing countries (Fig. 7.1) and so they have less time to adjust to its impact.

Functional anatomy and physiology

Biology of ageing

Ageing can be defined as a progressive accumulation through life of random molecular defects that build up within tissues and cells. Eventually, despite multiple repair and maintenance mechanisms, these result in age-related functional impairment of tissues and organs.

Many genes probably contribute to ageing, with those that determine durability and maintenance of somatic cell lines particularly important. However, genetic factors only account for around 25% of variance in human lifespan; nutritional and environmental factors determine the rest.

A major contribution to random molecular damage is made by reactive oxygen species produced during the metabolism of oxygen to produce cellular energy. These cause oxidative damage at a number of sites:

• Nuclear chromosomal DNA, causing mutations and deletions which ultimately lead to aberrant gene function and potential for malignancy.

• Telomeres, which are the protective end regions of chromosomes which shorten with each cell division because telomerase (which copies the end of the 3′ strand of linear DNA in germ cells) is absent in somatic cells. When telomeres are sufficiently eroded, cells stop dividing. It has been suggested that telomeres represent a ‘biological clock’ which prevents uncontrolled cell division and cancer. Telomeres are particularly shortened in patients with premature ageing due to Werner’s syndrome, in which DNA is damaged due to lack of a helicase.

• Mitochondrial DNA and lipid peroxidation, resulting in reduced cellular energy production and ultimately cell death.

• Proteins – e.g. those increasing formation of advanced glycosylation end-products from spontaneous reactions between proteins and sugars. These damage structure and function of the affected protein, which becomes resistant to breakdown.

The rate at which damage occurs is malleable and this is where the interplay with environment, particularly nutrition, takes place. There is evidence in some organisms that this interplay is mediated by insulin signalling pathways. Chronic inflammation also plays an important role, again in part by driving the production of reactive oxygen species.

Physiological changes of ageing

The physiological features of normal ageing have been identified by examining disease-free populations of older people, to separate the effects of pathology from those due to time alone. However, the fraction of older people who age without disease ultimately declines to very low levels, so that use of the term ‘normal’ becomes debatable. There is a marked increase in inter-individual variation in function with ageing; many physiological processes deteriorate substantially when measured across populations, but some individuals show little or no change. This heterogeneity is a hallmark of ageing, meaning that each person must be assessed individually and that one cannot unthinkingly apply the same management to all people of a certain age.

Although some genetic influences contribute to heterogeneity, environmental factors, such as poverty, nutrition, exercise, cigarette smoking and alcohol misuse, play a large part, and a healthy lifestyle should be encouraged even when old age has been reached.

The effects of ageing are usually not enough to interfere with organ function under normal conditions, but reserve capacity is significantly reduced. Some changes of ageing, such as depigmentation of the hair, are of no clinical significance. Figure 7.2 shows many factors that are clinically important.


Frailty is defined as the loss of an individual’s ability to withstand minor stresses because the reserves in function of several organ systems are so severely reduced that even a trivial illness or adverse drug reaction may result in organ failure and death. The same stresses would cause little upset in a fit person of the same age.

It is important to understand the difference between ‘disability’, ‘comorbidity’ and ‘frailty’. Disability indicates established loss of function (e.g. mobility; see Box 7.13, p. 176), while frailty indicates increased vulnerability to loss of function. Disability may arise from a single pathological event (such as a stroke) in an otherwise healthy individual. After recovery, function is largely stable and the patient may otherwise be in good health. When frailty and disability coexist, function deteriorates markedly even with minor illness, to the extent that the patient can no longer manage independently. Similarly, comorbidity (the number of diagnoses present) is not equivalent to frailty; it is quite possible to have several diagnoses without major impact on homeostatic reserve.

Unfortunately, the term ‘frail’ is often used rather vaguely, sometimes to justify a lack of adequate investigation and intervention in older people. However, it can be specifically identified by assessing function in a number of domains. Two main approaches to evaluating frailty exist: measurement of physiological function across a number of domains (e.g. the Fried Frailty score, Box 7.2), or a score based on the number of deficits or problems – for example, the Rockwood score.

Frail older people particularly benefit from a clinical approach that addresses both the precipitating acute illness and their underlying loss of reserves. It may be possible to prevent further loss of function through early intervention; for example, a frail woman with myocardial infarction will benefit from specific cardiac investigation and drug treatment, but may benefit even further from an exercise programme to improve musculoskeletal function, balance and aerobic capacity, with nutritional support to restore lost weight. Establishing a patient’s level of frailty also helps inform decisions regarding further investigation and management, and the need for rehabilitation.


Comprehensive geriatric assessment

Although not strictly an investigation, one of the most powerful tools in the management of older people is the Comprehensive Geriatric Assessment, which identifies all the relevant factors contributing to their presentation (p. 166). In frail patients with multiple pathology, it may be necessary to perform the assessment in stages to allow for their reduced stamina. The outcome should be a management plan that not only addresses the acute presenting problems, but also improves the patient’s overall health and function (Box 7.3).

Comprehensive Geriatric Assessment is performed by a multidisciplinary team (p. 167). Such an approach was pioneered by Dr Marjory Warren at the West Middlesex Hospital in London in the 1930s; her comprehensive assessment and rehabilitation of supposedly incurable, long-term bedridden older people revolutionised the approach of the medical profession to older, frail people and laid the foundations for the modern specialty of geriatric medicine.

Decisions about investigation

Accurate diagnosis is important at all ages but frail older people may not be able to tolerate lengthy or invasive procedures, and diagnoses may be revealed for which patients could not withstand intensive or aggressive treatment. On the other hand, disability should never be dismissed as due to age alone. For example, it would be a mistake to supply a patient no longer able to climb stairs with a stair lift, when simple tests would have revealed osteoarthritis of a hip and vitamin D deficiency, for which appropriate treatment would have restored his or her strength. So how do doctors decide when and how far to investigate?

Advance directives

Advance directives or ‘living wills’ are statements made by adults at a time when they have the capacity to decide about the interventions they would refuse or accept in the future, should they no longer be able to make decisions or communicate them. An advance directive cannot authorise a doctor to do anything that is illegal and doctors are not bound to provide a specific treatment requested if, in their professional opinion, it is not clinically appropriate. However, any advance refusal of treatment, made when the patient was able to make decisions based on adequate information about their implications, is legally binding in the UK. It must be respected when it clearly applies to the patient’s present circumstances and when there is no reason to believe that the patient has changed his or her mind.

Presenting problems in geriatric medicine

Characteristics of presenting problems in old age

Problem-based practice is central to geriatric medicine. Most problems are multifactorial and there is rarely a single unifying diagnosis. All contributing factors have to be taken into account and attention to detail is paramount. Two patients who share the same presenting problem may have completely disparate diagnoses. A wide knowledge of adult medicine is required, as disease in any, and often many, of the organ systems has to be managed at the same time. There are a number of features that are particular to older patients.

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Apr 9, 2017 | Posted by in GENERAL SURGERY | Comments Off on Ageing and disease

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