Abstract
Our population is ageing. People are living for longer and with more complex medical problems, and this is placing increasing pressure on health services. It has never been more important for clinicians to understand what constitutes normal ageing. An understanding of normal ageing can help us to anticipate future healthcare needs, promote health and independence, and differentiate age-appropriate physiology from pathology. This article aims to highlight how ageing affects different body systems. Special consideration is then given to how such changes affect the use of medications and the interpretation of laboratory tests in older adults.
The GP curriculum and the normal changes of ageing
Know the epidemiology of older people’s problems presenting in primary care Understand the changes in the normal range of laboratory values that are found in older people Understand the special factors associated with drug treatment, e.g. the physiology of absorption, metabolism and excretion of drugs Understand the concept of health and be able to promote health on an individual basis as part of the consultation in the older patient Know the preventative strategies required in the care of older people Have appropriate communication skills for counselling, teaching and treating patients, their families and carers, recognising the difficulties of communicating with older patients
Introduction
Ageing affects every system within the human body. It produces changes in anatomy and physiology, and these changes have functional consequences. Figure 1 summarises the normal changes of ageing that this article will explore.
A summary of the normal changes of ageing.
Cardiovascular
Vascular changes
Age-related changes in the structure of blood vessels affect blood pressure. One of the main functions of large arteries is to smooth out surges in blood flow. Elastin in the arterial wall allows arteries to stretch during systole, and so cushion the surge in blood from the heart. Arteries then recoil during diastole. Over time, the elastin in blood vessels fragments, with the damaged elastin being replaced by collagen. With age, arteries thus become stiffer (a condition called arteriosclerosis) and this affects blood pressure.
Data from the Framingham Heart Study show that, even in healthy normotensive adults, there is a steady linear rise in both diastolic and systolic blood pressures from the age of 30 years. Between the ages of 50 and 60 years, diastolic blood pressure plateaus, and then may even slightly decline. Systolic blood pressure, however, continues to rise in a linear fashion until at least the age of 84 years. Adopting a healthy lifestyle, especially remaining active, may slow down arterial ageing, and therefore, reduce the risk of hypertension. Left untreated, hypertension accelerates arteriosclerosis, and so perpetuates a cycle of increasing blood pressure and arterial stiffness.
Not only does blood pressure increase with age, but blood pressure variability also increases. Blood pressure is controlled by the baroreflex. Fluctuations in blood pressure are sensed by baroreceptors and result in changes in heart rate, stroke volume and peripheral vascular resistance. Ageing is associated with impaired blood pressure homeostasis. Older adults are more likely to experience orthostatic and postprandial hypotension. They may also struggle to maintain their blood pressure during acute events, such as blood loss. Medications and co-morbidities are likely to be the main causes for this difficulty controlling blood pressure, but normal age-related changes in the cardiovascular system may also play a part. Reduced baroreflex responsiveness has been demonstrated in healthy older adults, and has been attributed to stiffer vessels being less able to constrict or sense blood pressure changes.
Cardiac changes
The two main structural changes that occur in the heart with age are enlargement of the atria and left ventricular hypertrophy. As blood pressure increases with age, the left ventricle hypertrophies to compensate.
Steenman and Lande (2017) describe a decline in left ventricular diastolic function as the ‘hallmark of cardiac ageing’. Ventricular filling can be divided into two phases: passive filling during early diastole, followed by active filling in late diastole caused by atrial contraction. Ventricular filling (and therefore cardiac output) becomes more reliant on atrial contraction as we age. As a result, the atria hypertrophy and dilate in older adults. Age-related atrial enlargement typically occurs after the age of 70 years. An alternative cause should be sought if atrial enlargement occurs before this age. The reason for the decline in passive ventricular filling with age is not clear, but reduced compliance and delayed relaxation of the myocardium are likely to contribute. The increased reliance on atrial contraction with age may explain why atrial fibrillation is often less well tolerated in older adults.
An equation to predict maximum heart rate.
Despite the decline that occurs in maximal heart rate with age, cardiac output at rest and during exercise is maintained in healthy older adults. With advancing age, the left ventricular wall hypertrophies and ventricular volumes increase. Increased ventricular stretch produced by a larger end diastolic volume results in a greater force of contraction (the Frank–Starling law). Thus, cardiac output is maintained with age by an increase in stroke volume.
Musculoskeletal
Bone
The human skeleton is constantly being remodelled. Under hormonal and physical influences, osteoclasts remove bone and osteoblasts form new bone matrix which is then mineralised. Remodelling allows fractures to be repaired. It allows bones to adapt to changing mechanical demands, and it is important in calcium homeostasis.
The balance between bone resorption and bone formation shifts with age. From birth until early adulthood, bone formation exceeds bone resorption, and there is a gradual increase in bone strength and mass. Peak bone mass is typically reached around the age of 30 years. After this age, bone strength and mass gradually decline.
Despite bone deteriorating with age, age is not a guarantee of osteoporosis. Many factors, such as exercise and calcium intake, affect how high an individual’s bone mass peaks and how slowly it declines thereafter. Without a clear understanding of why bone strength declines with age, osteoporosis management currently focuses on preventative measures and medications that largely act by impairing bone resorption such as bisphosphonates.
Muscle
Senile sarcopenia is the loss of skeletal muscle mass, strength and speed that occurs with age. It is largely the result of a decline in the number of muscle fibres. Muscle atrophy also contributes. As ageing affects fast-twitch muscle fibres to a greater extent than slow-twitch fibres, reaction times slow with age. Older adults may find it harder to catch an object before it falls. They may also find it more difficult to quickly adjust their posture to prevent themselves from falling.
Maximum muscle mass and strength is typically achieved by the age of 40 years. A gradual reduction in muscle function occurs thereafter, which becomes accelerated after the age of 70 years. A negative cycle may be established, where declining muscular function makes physical exertion more difficult and thus creates a barrier to activity.
Sarcopenia has both functional and metabolic consequences. As muscles weaken and tire quicker, older adults are more likely to experience problems with mobility and balance. Gait speed slows with age, and the risk of falling increases. As a result, sarcopenia has been associated with a loss of independence in the elderly.
The Cockroft–Gault formula for estimating creatinine clearance.
Regular physical activity can slow and delay senile sarcopenia, as well as limit its functional impact. Indeed, prescribing exercise may be one of the best ways to encourage independence and health in the elderly. The type of activity that has the biggest impact on sarcopenia is resistance training. Progressive resistance training has been shown to improve gait speed, muscle strength and the time to climb stairs (Liu and Lantham, 2009). Although most studies have assessed resistance training using machines in a gymnasium, benefits have been shown with entirely home-based programmes. Indeed, one study showed improvements in pain, physical function and quality of life in patients with knee osteoarthritis who performed home exercises (Baker et al., 2001). Patients in the study’s training arm were asked to perform squats and step-ups (thus utilising their own body weight for resistance), as well as isotonic exercises using ankle weights for resistance.
Body composition
Age is associated with not only a decline in muscle mass, but also an increase in body fat and a decline in total body water. As muscle mass declines and body fat increases, body weight may not significantly alter. The age-associated decline in muscle mass and increase in body fat is seen in all individuals irrespective of physical activity levels, but both changes are exacerbated by inactivity.
Kidneys
Even in the absence of co-morbidity, ageing is associated with increased glomerulosclerosis, arteriosclerosis of renal arteries and progressive nephron loss. These changes are thought to be at least partly responsible for the gradual decline in renal function that occurs with age. Longitudinal studies of healthy adults have shown that, from the age of 30 years, there is a decline in estimated glomerular filtration rate (eGFR) by 6–8 ml/min per decade.
As functional kidney reserve declines, older adults are at greater risk of developing chronic kidney disease (CKD) and acute kidney injury. When to diagnose CKD in older adults is disputed. The National Institute for Heath and Care Excellence (NICE) makes no reference to age in its CKD guidelines (NICE, 2014), but relying on fixed eGFR thresholds to diagnose CKD is likely to lead to over-diagnosis, especially in older adults. Glassock et al. (2015) argue that, in the absence of proteinuria or structural kidney disease, CKD should not be diagnosed in those over the age of 65 years unless the eGFR is less than 45 ml/min. Their recommendation is based on the statistic that less than 0.1% of adults aged over 65 years, with no proteinuria and an eGFR of 45–59 ml/min, develop end-stage kidney disease. Patients with a progressively declining eGFR, an eGFR less than 45 ml/min, structural kidney disease or other signs of kidney impairment (such as proteinuria) are much more likely to develop end-stage renal failure.
Gastrointestinal tract
The stomach
With advancing age, the stomach loses capacity and empties more slowly. Delayed gastric emptying, as well as a decline in the tension in the lower oesophageal sphincter, makes gastric reflux more common in older adults.
With age, the gastric mucosa becomes more vulnerable to injury. Advancing age is associated with declines in mucus and bicarbonate secretion, prostaglandin production and mucosal blood flow.
Liver
Age is associated with a progressive decline in liver volume and blood flow, which affects the liver’s functional capacity. As the liver takes longer to metabolise drugs, drug doses may need to be adjusted for age. The production and flow of bile also becomes slower with age, and so older adults are more likely to form gallstones.
Cognition
Age-related changes in cognition
Cognition is ‘the mental action or process of acquiring knowledge through thought, experience and the senses’ (Concise Oxford English Dictionary, 2008). Normal ageing encompasses a wide range of cognitive changes, which affect different people to different degrees and at different rates. The challenge is determining what lies within the spectrum of ‘age-appropriate cognition’ and what does not.
When considering normal cognitive ageing, an awareness of Raymond Cattell’s work from the 1940s is useful. Dr Cattell proposed that human cognitive ability can be broadly divided into two components: fluid intelligence and crystallised intelligence. These two components are affected differently by age. Fluid intelligence is an innate ability to think abstractly, use logic and problem-solve in situations not seen before. Most fluid cognitive abilities peak in the third decade of life and then slowly decline thereafter.
Crystallised intelligence is the ability to use knowledge and skills that have arisen from previous learning and experience. Vocabulary, numeracy skills and general knowledge are examples of crystallised knowledge. With repeated use, crystallised intelligence increases and strengthens with age. This improvement continues until at least the fifth decade of life. Vocabulary skills may not peak until the seventh decade in some people (Hartshorne and Germine, 2015). Older adults tend to perform better than younger adults at tasks that require crystallised intelligence. Consider how you would fare at completing a crossword if you were competing against your younger self.
However, pathology should not be assumed if an older adult struggles when their crystallised knowledge is tested. Performance in cognitive tests is often influenced by age-related declines in recall, attention and cognitive processing speed. An example of this is that older adults are more likely to experience temporary blocks in knowledge recall. The piece of information that is on the ‘tip of their tongue’ is often retrieved later, or can be easily recognised if offered, highlighting that the underlying knowledge store remains intact. Asking questions that require a ‘yes’ or ‘no’ answer may help to test information not immediately recalled.
Cognitive ageing in clinical practice
As a rule, normal cognitive ageing does not cause functional impairment. Causes other than ageing should be considered in anyone presenting with a cognitive impairment that affects day-to-day activities. The exception to this rule is that competence in complex tasks, such as driving and financial management, may decline with age to a level that eventually causes impairment. Declines in cognition, especially reduced cognitive speed and attention, have been attributed to an increased risk of errors and accidents in older, but otherwise healthy, drivers (Wood, 2011).
Finally, there is the hope that if we understand normal cognitive ageing, we may be able to influence it. Observational studies show that older adults with higher cognitive function are more likely to engage in physical exercise, mentally challenging activities and social interaction. However, whether cognitive ability is the cause or product of these activities is not known; observational studies cannot establish cause-and-effect relationships. Nevertheless, there is some evidence that cognitive training can improve the score that older adults attain on cognitive tests, and this improvement can last for up to 6 months after training. Whether this translates into everyday functional improvement, however, has not been determined (Kelly et al., 2014).
Sensory changes
Vision
The best understood signs of eye ageing are associated with changes in the lens. As the lens ages, its elasticity reduces and long-sightedness increases. The long-sightedness associated with age (presbyopia) commonly develops after the fourth decade. However, worsening near vision is not a guarantee of old age. As the lens ages it also hardens and becomes more dense (nuclear sclerosis), and this can increase its refractive power. Nuclear sclerosis may progress to cataract formation, but in its early stages it can improve near vision, a phenomenon termed ‘second sight’.
Almost every measure of visual function deteriorates with age. Visual acuity, colour discrimination and scoptic vision (the ability to see in poorly lit conditions) all deteriorate with age. Increased light scatter in the optic media increases susceptibility to glare, which often presents with older adults experiencing difficulty during night-time driving.
Vision in older people can be aided by good lighting and using contrasting colours. Glare can be reduced by using matte surfaces and by providing low-intensity diffuse lighting. Important notices or objects may be seen more easily if they are brightly coloured.
Hearing
As with vision, both cognitive and sensory changes affect hearing as we age. The sensorineural hearing impairment associated with age is called presbycusis. It is symmetrical, progressive and results from the accumulation of multiple acquired deficiencies. With age we become less able to hear all sounds. Perception of low-intensity sounds and high-pitched notes is most affected by age. Differentiating between noises that occur close together also becomes more difficult. As a result, older people often have difficulty hearing conversational speech and discerning it from background noise. To compensate, they may rely more on non-verbal cues, lip reading and expected linguistic patterns to understand speech.
Adjusting how we communicate to accommodate for hearing impairment is important. In Europe, hearing impairment affects roughly 20% of women and 30% of men by the age of 70 years, yet few of these people seek help (Roth et al., 2011). Using other sensory stimuli to reinforce sound can help those with poor hearing, such as using a telephone that vibrates as it rings or using gestures to support spoken word. When speaking, background noise should be minimised and the speaker should be mindful of the tone and pace of their voice.
Altering the delivery of speech may also help those who are hearing impaired. Examples include explicitly introducing new topics of conversation or pausing to allow time for comprehension to be checked. As those who have a hearing impairment rely more on expected linguistic patterns to understand speech, non-native speakers may be better understood if they respectfully mimic the speech patterns of native speakers.
The challenges of communicating with a patient who is hearing impaired increases when the patient is also sight impaired. Twenty-one percent of people over the age of 74 years report some degree of both sight and hearing impairment (Brennan et al., 2005). Telephone contact limits what adaptations can be made to facilitate hearing; surgeries that offer telephone appointments or triage services should be mindful of this point.
Prescribing for older patients
Prescribing for older adults presents significant challenges. Multimorbidity and polypharmacy are more common in older adults and increase the risk of adverse drug events. In the UK, 45% of prescriptions are dispensed to patients over the age of 65 years (Wynne and Blagburn, 2010).
The guidelines for many chronic diseases focus on achieving treatment targets and recommend the addition of new medicines if targets are not met. However, careful consideration should be taken before medicines are prescribed, especially in the elderly. As most subjects in clinical trials are below the age of 65 years, it may be difficult to relate older patients to the research base upon which many clinical guidelines are formed. It should not be assumed that a medication known to benefit younger adults will be as useful or as safe in older adults. Although pharmacological treatments should not be withheld when appropriate, the same treatment outcome may be achievable without the use of medications, thus avoiding the risk of adverse drug events.
Medicines that should be used cautiously in older adults.
Good medicines use requires an awareness of age-related changes in pharmacokinetics. Pharmacokinetics is the study of drug absorption, distribution, metabolism and excretion. Age-related changes in the different systems of the body affect the pharmacokinetics of many drugs.
Ageing and drug absorption
The total absorption of most drugs is not significantly affected by age. However, age-related changes in the gastrointestinal tract can alter absorption rate, and so pharmacological responses may be less predictable in older patients. Moreover, the delay in gastric emptying associated with age increases the risk of drug-induced gastric ulceration, as medications have more contact time with the gastric mucosa.
Ageing and drug distribution
Ageing is associated with an increase in body fat and a decrease in total body water. With increasing age, water-soluble drugs tend to have smaller volumes of distribution, and so achieve higher serum levels and have shorter half-lives. Gentamicin and digoxin are examples of water-soluble drugs. Their loading doses should be reduced for older adults.
Conversely, lipid-soluble medications tend to acquire a larger volume of distribution with age, which may result in drug accumulation. Many analgesics, anti-epileptics and sedative medications should be prescribed more cautiously in older adults, as their risk of toxicity increases with age.
Ageing and drug metabolism
Medicines whose bioavailability may increase with age.
Ageing and drug excretion
Many drugs are renally excreted and may accumulate in the body as renal function declines. The significance of this accumulation depends on how narrow the therapeutic index of the drug is, and the level of toxicity of the drug. Aminoglicoside antibiotics, digoxin and lithium are all renally excreted. Each of these medicines has a narrow therapeutic index and they can all cause serious adverse effects when they accumulate only slightly above therapeutic levels. Their doses should be adjusted according to renal function.
Laboratory tests in older adults
When interpreting laboratory tests, it is important to be mindful of how laboratory reference ranges are produced. A normal or acceptable result for an individual may fall outside the reference range. Adult reference ranges are usually derived from the results of healthy, often young, individuals. A reference range purely describes where 95% of test results fall in a healthy population.
Community studies have shown that a majority of older adults have haematological and biochemistry results that lie outside the reference range. Test results in older adults show a greater variability than results in younger adults. Defining a ‘normal range’ for laboratory tests in older adults is difficult, as co-morbidities, the normal changes of ageing and the use of medications are all likely to affect results. The significance of a result may be made clearer by considering the individual’s health and their previous results.
KEY POINTS
Ageing is associated with a progressive loss of bone and muscle, but the rate of this loss can be slowed by regular physical activity Arteries become stiffer with age (a process called arteriosclerosis) and this causes a rise in blood pressure and may impair blood pressure homeostasis Most cognitive abilities decline after the third decade of life, but crystallised abilities (such as general knowledge and vocabulary skills) continue to improve until at least the fifth decade Consideration of the tone and pace of speech, as well as using expected linguistic patterns, can facilitate communication with those who are hearing impaired Renal function declines by 6–8 ml/min per decade in healthy adults after the age of 30 years Safe prescribing for older adults requires an awareness of the normal changes of ageing and how pharmacokinetics change with age