Geriatric medicine

Published on 17/03/2015 by admin

Filed under Basic Science

Last modified 17/03/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 967 times

chapter 57 Geriatric medicine

AGEING

Some changes with normal ageing are generally towards impaired function—for example, maximum heart rate and exercise capacity are reduced, glomerular filtration rate is lower, there is decline in some aspects of cognition and muscle mass is reduced. An emerging concept in geriatric medicine is that of ‘frailty’, which essentially is a condition in which these normal changes of ageing accumulate and lead to disease, predisposing the person to functional decline. Frailty is not, however, an inevitable part of ageing.

Essentially, most ageing is healthy and most of us age in a mostly healthy way. (Healthy ageing is covered in Ch 58.) However, with time the number of organ systems within an individual that begin to age in an unhealthy way increases, so that by age 90 years it is uncommon to exhibit only healthy ageing. Frailty can be seen as a transition stage between healthy and unhealthy ageing. Factors that increase the chance of healthy ageing include genes, physical activity, cognitive stimulation, social engagement, diet and aggressive detection and management of disease risk factors.

PHARMACOLOGICAL ISSUES, INCLUDING POLYPHARMACY

BACKGROUND AND PREVALENCE

Medication issues in older people include polypharmacy (taking a large number of medications), reduced compliance (‘concordance’), drug–drug interactions and adverse drug reactions. Older people consume a disproportionately large number of prescribed drugs, partly because they are more likely to be ill and partly because it can be more difficult to reach a precise diagnosis. On average, an older person in the community takes three prescribed drugs, and this rises to 7–10 in care settings. CAMs and other over-the-counter (OTC) medications are also used extensively by older people. Unfortunately, it is rare for a GP to have a completely accurate list of all the medications their patient consumes—this is partly because the patients themselves cannot always accurately recall them (and may not feel it necessary to mention OTC/CAM medications) and partly because of poor communication from acute-care facilities and specialists. The best way to obtain an accurate list is to visit the patient’s home and ask to see everything they use, or to ask them to put all the medications in a bag and bring them to your office.

Reduced compliance is common at all ages, but is particularly an issue in older people, who take more medications, may not hear or recall or be able to read instructions, may have difficulty opening packages and can be on complicated drug regimens. Fortunately, under-compliance may somewhat protect them from adverse drug reactions, but it does contribute to poorer disease control.

Drug–drug reactions and adverse drug reactions increase with age and with increasing numbers of medications used. Some 3% of all admissions to hospital are primarily due to adverse drug reactions and, if this is expanded to include poor disease control from suboptimal prescribing and compliance, the proportion of admissions rises to over 30%. Drug–drug interactions are almost unavoidable if a person is prescribed more than eight medications, and can cause adverse drug reactions and poor drug efficacy. The problem may be compounded by drug–nutrient or herb–drug interactions, particularly if the ingestion of herbs or nutrients is unknown to the doctor.

MANAGEMENT

Along with regular medication reviews, there should be a sustained intention to minimise the number of medications an older person takes, but also to ensure that all conditions are being treated effectively. ‘De-prescribing’ is both possible and beneficial, and the basic steps are shown in Box 57.1.1 Unnecessary medications may include analgesics and laxatives no longer needed, or an antipsychotic for behavioural symptoms that are no longer complicating dementia. Additionally, many prophylactic medications (e.g. statins, bisphosphonates) may no longer be necessary as death approaches (palliative care, end-stage dementia). High-risk medications include anticholinergics (benztropine and benzhexol) and long-acting benzodiazepines.

In residential and acute-care settings, medication audits are another approach to improving medication outcomes—for example, the appropriateness of benzodiazepine prescribing can be audited against an evidence-based algorithm and these results then fed back to the prescribing team. Pharmacist and GP can also work as a team to review an individual’s medication in residential and community settings—indeed, annual medication review is now required for those in residential care. Other approaches include academic detailing, and programs such as the National Prescribing Service GP education program in Australia.

CONFUSIONAL STATES: DELIRIUM AND DEMENTIA

DELIRIUM

Aetiology

Delirium always has a medical cause.2 The most common causes include infections, metabolic disturbances (e.g. electrolyte deficiencies, hyperglycaemia, hypercalcaemia) and drugs (adverse effects or drug withdrawal). Other causes include pain, intracerebral lesions, myocardial infarction, organ ischaemia, faecal impaction and epilepsy.

Management

The cause must be treated—for example, antibiotics for infection, correction of electrolyte disturbances, ceasing an offending medication or relief of faecal impaction. General management includes a safe environment with minimal disruptions and a minimal number of new care staff (not the norm in hospitals!). Hydration is essential, and glasses and hearing aids should be on and working. If agitation or physical aggression cannot be managed non-pharmacologically, haloperidol or newer antipsychotic agents such as olanzapine can be used, in low dose and for a short period only—e.g. 0.5 mg haloperidol once, or olanzapine wafer 2.5 mg once. Benzodiazepines may be more effective for delirium induced by drug or alcohol withdrawal.

Complementary therapies are not well researched for delirium but those that are effective for behavioural disturbance in dementia (e.g. lavender oil and other aromatherapy) may be tried in addition to the above approaches.

Prevention of delirium can be achieved—in a seminal study, Inouye and colleagues3 reduced the incidence by 40% through the multifactorial approach outlined in Box 57.2.

DEMENTIA

Dementia is a chronic, progressive impairment of cognition, including memory, which is usually irreversible and always causes some impairment of function. It affects 5% of those over age 60, but the incidence doubles every 5 years, with around 30% affected by age 80. The average GP is likely to have 5–10 patients with dementia, but this will vary depending on how many elderly patients he/she has.

Aetiology

It is not known why one individual develops dementia and another does not. There are genetic mutations that nearly always cause dementia, but this early-onset dementia (in the forties or fifties) is very rare. Risk factors for the much more common late-onset dementia include older age, family history of dementia, apolipoprotein E4 (a carrier of cholesterol), previous head injury, less formal education, lower socioeconomic status and cardiovascular risk factors (hypertension, diabetes, smoking, atrial fibrillation, past cardiac surgery). There are also protective factors, including active leisure activities, physical activity, social contact and marriage, moderate alcohol use, exposure to non-steroidal anti-inflammatory agents, omega-3 fatty acids and use of vitamins E and C. It is also becoming apparent that attentional training, such as mindfulness-based practices, is associated with cell maintenance and neurogenesis in the prefrontal cortex and hippocampus.4

The most common cause of dementia is Alzheimer’s disease (AD), usually mixed with cerebrovascular pathology. Pure vascular dementia (that is, with no AD pathology) is uncommon. The emerging concept of ‘cerebral reserve’ may explain this synergism and some protective factors—those with a lesser number of synapses (e.g. from less education or a past head injury) are more prone to the clinical syndrome of dementia once AD pathology develops, especially if they also have cerebrovascular damage (e.g. lacunar infarcts or extensive white matter changes).

Other relatively frequent causes of dementia include dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). In DLB there is a combination of cognitive impairment, fluctuations, parkinsonism, visual hallucinations and sleep disturbances—but not all features have to be present for the diagnosis to be made. The hallucinations are often of small animals or creatures just outside or coming into the room. Sleep disturbance affects the REM sleep component, with a failure to paralyse muscles during dreams, leading to violent movements. DLB is in the same spectrum as Parkinson’s disease with dementia (PDD)—the main difference is that in PDD the motor changes precede the cognitive changes.

Frontotemporal dementia usually begins with behavioural or language changes with relative preservation of memory initially. The behavioural changes reflect frontal lobe impairment and include disinhibition, apathy, lack of insight, and impaired judgment and reasoning. Language changes can occur with all forms of FTD but there are two language-specific forms, called semantic dementia (language is fluent but the meaning of words is lost) and primary progressive aphasia (language is simply lost, with mutism occurring early in the dementia).

There are over 200 other causes of dementia but these are uncommon. A few are occasionally at least partially reversible (e.g. hypothyroidism, vitamin B12 deficiency, syphilis) and explain why investigations for these are performed. Normal pressure hydrocephalus (characterised by dementia, urinary incontinence and gait disturbance) is also potentially reversible, although many neurosurgeons are reluctant to perform the required shunt, as results are often disappointing.

Pathology

Alzheimer’s disease is characterised by amyloid plaques and neurofibrillary tangles, which begin in the hippocampal/limbic region of the brain and progress throughout the cerebral cortex as the disease progresses. The plaques are composed of the amyloid beta (Ab) peptide, which is a fragment of the amyloid precursor protein (APP), a transmembrane protein whose function is not well understood. This fragment is cleaved off by two enzymes (beta and gamma secretase), and mutations in a component of the gamma secretase as well as mutations in APP cause most of the (rare) early-onset AD. The tangles are composed of hyperphosphorylated tau, a protein which normally stabilises the microtubules that neurons use to transport protein from their nucleus, down axons to the synapse. Which of these two main pathological processes is key to the development and severity of AD is hotly debated—probably both are.

In vascular dementia the pathology is brain tissue damage due to cerebral ischaemia and this can affect any region of the brain, although frontal lobe dysfunction is common, even if the damaged area is distant to the frontal region. There is a spectrum of pathology that can contribute to vascular dementia—a single large critical infarct, multiple large-vessel infarcts, multiple lacunar infarcts, extensive white matter lesions and multiple haemorrhages. Usually this vascular pathology coexists with AD pathology.

Dementia with Lewy bodies (DLB) is characterised by cortical Lewy bodies, which contain alpha-synuclein. Abnormal folding of this protein is thought to be a key precipitant of DLB.

Frontotemporal dementia has a range of pathology, including Pick bodies in one subtype. AD pathology is not found. Recently, a mutation of the progranulin gene has been found in a large proportion of FTD cases—progranulin appears to be a neuronal growth factor. This is associated with an abnormal form of the protein TDP 43 and this can be identified in (post mortem) diagnostic tests.

Diagnosis

Examination

Physical examination is necessary and should concentrate on neurological signs—such as parkinsonism in DLB and focal signs in some vascular dementias. The most important reason for performing the physical examination is to detect rarer, potentially reversible, causes of dementia (e.g. thyroid disorders) and comorbidities. Cognitive assessment is essential. The best known screening tool is the MMSE, a 30-item questionnaire that is useful in screening for AD but has less utility with the other dementias. The clock drawing test (CDT) is also useful—the patient is asked to draw a large circle (or the circle can be provided), place the numbers of a clock and then show a requested time with the hands (e.g. 11:10 or 1:50). Errors include incorrect number placement and inability to show the time. Combining the MMSE and the CDT achieves around 90% sensitivity for cognitive impairment—that is, an MMSE score below 26 and an abnormal CDT indicates a 90% chance that the person has significant cognitive impairment.

More-detailed assessment is required in order to characterise the dementia type. In FTD, questioning should concentrate on executive function (e.g. similarities, problem solving) and language (e.g. describe a complex task, name objects, read a paragraph). In DLB there are prominent visuo-spatial deficits, so assessment should include drawing a cube to supplement the CDT and the intersecting pentagons in the MMSE. For vascular dementia, assessment of frontal lobe function is useful but cognitive changes are influenced by the site and extent of the lesions—for instance, if they are in the dominant temporoparietal cortex there may be language changes.

More-detailed neuropsychological assessment usually requires referral to a specialist (geriatrician, psychogeriatrician or neurologist), who may use the expertise of a neuropsychologist.

Investigations

Routine blood tests and neuroimaging should be performed as shown in Box 57.3—mainly to rule out potentially reversible causes of dementia and comorbidities. Increasingly, specialists are ordering tests to ‘rule in’ a diagnosis of dementia and to characterise the type.

The MRI of the brain is moving towards this identification of dementia—for instance, hippocampal atrophy is seen in AD, and frontal atrophy in FTD. The PET scan is only available in a few centres but can be most useful. The FDG PET shows a characteristic pattern in AD (bilateral temporoparietal hypometabolism with sparing of occipital metabolism), whereas sparing of the posterior cingulate metabolism is very much against a diagnosis of AD. In DLB, occipital metabolism is reduced and in FTD frontal and temporal metabolism is down, with characteristic patterns in the language variants. Another PET technique available in even fewer centres is amyloid imaging using PIB or other agents. Absence of amyloid excludes AD, and its presence excludes FTD. Amyloid is frequently found in DLB and vascular dementia. Combining both PET techniques achieves very high diagnostic accuracy.

Management

Pharmacological

The great advance in dementia therapy has been the development of acetylcholinesterase inhibitors (AChEIs).5 In AD, and also in DLB and vascular dementia, there is a deficiency of acetylcholine (ACh). This is due to damage either to the central nucleus (nucleus basilis of Meynert) that produces the enzyme that makes ACh (in AD and DLB) or to the axons within which this enzyme is transported (vascular dementia). The AChEIs boost ACh levels by inhibiting another enzyme, at the synapse, which degrades ACh. These agents include donepezil (Aricept®), galantamine (Reminyl® or Razadyne®) and rivastigmine (Exelon®). They differ somewhat in action, with galantamine also stimulating nicotinic receptors and rivastigmine also inhibiting another enzyme that breaks down ACh (butyrylcholinesterase), but no study has convincingly demonstrated that one agent is superior to others. At this time, only rivastigmine is given more than once daily, but a once-daily patch preparation is marketed in many countries. These agents have predictable cholinergic side effects, including nausea, vomiting, abdominal pain, diarrhoea, anorexia and weight loss. Such symptoms can be significant in about 20% of patients but usually attenuate over 1–2 weeks. More serious and rarer adverse effects include bradycardia, peptic ulceration and precipitation of asthma, so they should not be used in patients with such conditions until the illness is well controlled (e.g. Helicobacter eradication or insertion of a pacemaker).

The efficacy of the AChEIs is significant but modest. On average, there is a stabilisation of cognition for 6–12 months, then a continued decline that would be worse if the agent was ceased. Some do show a clinically apparent improvement and, indeed, the Australian Pharmaceutical Benefits Schedule (PBS) requires that this be demonstrated for subsidised supply to be continued beyond the first 6 months. The scheme requires that these agents only be used in those with mild to moderate AD and that the initial MMSE be above 9 (but lower MMSE is acceptable if due to a non-cognitive cause such as aphasia). The MMSE must improve by two points or more within the first 6 months for subsidised supply to continue. For those with an initial MMSE score above 24, it is harder to show a two-point improvement (ceiling effect), so a baseline ADAS-Cog (another cognitive scale with scores ranging from 0 to 70 and used mainly in research settings) is recommended, with a four-point improvement required. The ADAS-Cog can be performed by some medical specialists and memory clinics, or by some psychologists. Once sufficient initial improvement on one of these scales has been demonstrated, no further scores are required by the PBS (or the DVA equivalent, the RSPB) but the prescriber must confirm, each time a new script is authorised, that the patient still has mild to moderate AD. It is not inappropriate to continue these agents until the end stages of dementia, especially as trials have suggested that they may also have beneficial effects on behaviour and function. Recently, donepezil has gained marketing approval for severe AD, based on recently published trials where it was initiated in those with severe AD.

The other drug with marketing approval for AD is memantine (Ebixa®). It only has marketing approval for moderately severe AD, based on trials where it was used as monotherapy rather than as add-on therapy (to an AChEI). There is trial data, however, to support its use in milder AD and as add-on therapy and, indeed, it is increasingly being used this way. The agent works on a different neurotransmitter system (the glutamatergic system), which is also affected by AD. It has remarkably few side effects. Efficacy has been demonstrated on cognition and behaviour.

None of these agents (AChEIs or memantine) has approval in Australia for other dementias, but in some countries memantine has approval for vascular dementia. There are trial data to support AChEI use in DLB (and in PDD), where there is a cholinergic deficit and where AD pathology is usually also present. No agent has yet proved beneficial in preventing progression from MCI to dementia.

The other pharmacological area of management is the use of atypical antipsychotic agents for the behavioural disturbances (‘challenging neuropsychiatric symptoms’) that can complicate dementia.6 Several trials have demonstrated modest efficacy of low doses of risperidone for agitation, aggressive and psychosis complicating more severe dementia, and there is also some (but less) data to support olanzapine and haloperidol. As these agents are usually used for weeks and months rather than days, side-effect profiles must be considered, and the extrapyramidal effects of haloperidol make it usually an inappropriate choice. While quetiapine has some support due to it almost completely lacking extrapyramidal adverse effects, there are almost no data to support its efficacy for this syndrome.

The antipsychotic agents should only be used when non-pharmacological approaches have failed. Adverse effects include an increased risk of cerebrovascular events and death, which affects all agents recommended for these symptoms (all antipsychotics including older agents, and the benzodiazepines). The agents should therefore be used in low doses (risperidone 0.25 mg b.i.d. up to 1 mg b.i.d., olanzapine 2.5 mg daily up to 10 mg daily) and they should be back-titrated and ceased as soon as possible (e.g. target symptom controlled for 1–2 months). Because of their risks, consent for their use should be sought from family and, if feasible, the patient.

Other agents for behavioural disturbance have much less supportive efficacy data and include benzodiazepines (some role for anxiety), antidepressants (appropriate for depression, which not infrequently complicates dementia) and mood stabilisers (e.g. valproate). A psychogeriatrician or geriatrician can be a useful resource if behavioural disturbances are proving difficult to manage.

Complementary therapies

A number of products are purported to have efficacy in those with dementia (usually the dementia type is not specified, or merely for ‘memory problems’). These include:

vitamins—consumption of vitamins E and C, as food or tablets, has been associated with a lower risk of developing dementia. There is less, but some, evidence for consumption of B-group vitamins including B6 and folate. One study in severe dementia7 showed that high doses of vitamin E (2000 IU/day) reduced risk of progression to greater dependency or nursing home care, but this has not been replicated. Vitamin E was not effective, in another trial,8 in preventing conversion of MCI to dementia, and in the Heart Protection Study9 multivitamin supplements did not prevent cognitive decline.

High doses (above 400 IU/day) of vitamin E have been shown in a meta-analysis10 to be associated with increased mortality and other adverse events, so daily doses should not exceed this.