Geriatric medicine

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chapter 57 Geriatric medicine

INTRODUCTION AND OVERVIEW

The world’s population is ageing rapidly, particularly in developed countries, where life expectancy is over 80 years for women and just under 80 years for men in many countries. Rapid ageing is occurring in less developed countries too, with the number of people aged over 65 years increasing dramatically in many countries. Consequently, much of general practice now involves care of older people in a range of settings—community, residential and acute-care facilities. It is easy to form the impression that ageing normally involves disease, disability and dependency, but while these are more common with increasing age, they are far from inevitable. Most 90-year-olds are not demented, maintain excellent mobility, are independent in personal, domestic and most community activities of daily living and live in their own home.

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.

EVALUATION OF THE OLDER PERSON

Comprehensive geriatric evaluation requires a detailed assessment of both physical and cognitive status, but also involves assessment of function (basic and more complex tasks), social environment, psychological/psychiatric status, behavioural issues and support systems.

Particular attention needs to be paid to the features of geriatric medical syndromes, including dementia, impaired mobility and falls, incontinence and medication-related issues. There have been several checklists/proformas developed by GP divisions and individual practices to assist this assessment process. These are particularly useful when carrying out routine comprehensive assessments. A suggested checklist is shown in the appendix. Ideally, this information will then be transformed into a problem list with a management plan—an example is shown in Table 57.1. It will be seen that this is best developed as a dynamic process with additional management of the identified problems added as they occur—so a word processed document on computer would be more appropriate than a single hard copy.

TABLE 57.1 Example of a geriatric medical problem list and management plan

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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.

AETIOLOGY

A large part of the problem older people have with medication is that their bodies deal with drugs differently (altered pharmacokinetics) and may have a different response from younger people to the same drug concentration (altered pharmacodynamics). Absorption is relatively unaffected by age (much built-in reserve, to meet nutritional needs) but liver metabolism (so-called ‘first pass’ and oxidative cytochrome P-450 metabolism) is reduced, as is renal excretion. Drug distribution is also changed with age—relatively less body water and more body fat affects the peak level and elimination half-life of drugs, which tend to be either predominantly fat soluble (e.g. the benzodiazepines) or water soluble (e.g. digoxin). Protein binding is reduced in the unwell elderly person, leading to more free drug, but this free drug is consequently more available for metabolism and excretion.

Examples of altered pharmacodynamics include a less effective cardiovascular response to low blood pressure, increasing risk of postural hypotension and falls due to medications, and reduced beta-adrenergic receptors reducing the response to and efficacy of beta-blocking agents (older people are effectively already partly beta-blocked).

ASSESSMENT

Always ask older people about their medications and problems they may be experiencing with them. Older people do recognise minor adverse effects well (even though such effects can present atypically) but, surprisingly, have more difficulty recognising more serious adverse events. Sometimes more formal assessment of medication compliance and handling can be useful—pill counts, measuring blood levels of the drug and involving the pharmacist in this process. Poor disease control (e.g. ongoing fitting, depression or hypertension) may indicate poor compliance, and this should be excluded before increasing the medication dose or adding a new medication.

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.

BOX 57.1 De-prescribing principles1

1. Establish an accurate list of all current medications.
2. In partnership with the patient and carer, plan a de-prescribing regimen.
3. Cease all unnecessary medications and, if possible, those causing adverse effects.
4. Cease, if possible, medications with a high likelihood of causing adverse effects.
5. Review and support the patient (and carers) regularly.
6. Update medication list and consider repeating the cycle.

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.

IMPORTANT PITFALLS

It is all too easy to become complacent about the number and type of medications older people take, especially when many are commenced in hospital, by other doctors or earlier in life when the medication may well have been appropriate. Such complacency may not serve the patient well.

Also, when a medication is ceased the patient may reintroduce it if not supported and reviewed (e.g. temazepam—cessation in hospital is almost always followed by recommencement after discharge).

Finally, the original condition may re-emerge once a medication is ceased—for example, hypertension may recur if a calcium channel blocker causing swollen legs is ceased. The patient should therefore be monitored, often for up to a year, for this.

PATIENT EDUCATION

The GP may want to have available notices and pamphlets on the importance of correct use of medication and the hazards of unnecessary medications. More detailed brochures can alert patients that any new symptoms may be due to their medications, and to always discuss their medication with their doctor.

CONFUSIONAL STATES: DELIRIUM AND DEMENTIA

DELIRIUM

Background and prevalence

Delirium is an acute-onset confusional state characterised by impairment of cognition—especially attention—with marked fluctuations. There is a hypoactive form, more prevalent in older people, and a hyperactive form, where a person may have difficulty sleeping and may be physically active or even aggressive. Hallucinations (usually visual) and paranoia are common. Delirium affects about 30% of hospitalised elderly people at any one time, with 20% having delirium on admission and up to another 20% developing delirium during their hospitalisation. Prevalence in the community is less, but it must always be considered when there is a sudden change in cognitive status.

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.

Diagnosis

The diagnosis of the clinical syndrome of delirium is frequently missed, especially as lucid periods tend to coincide with morning contact with the doctor. Screening in hospital is worthwhile—the Confusion Assessment Method is more accurate than the Mini-Mental State Examination (MMSE). Once the syndrome is suspected, it must be differentiated from dementia, although they can coexist. The differential characteristic of delirium is its acute onset, although dementia may begin acutely (e.g. often after a stroke). A collaborative (informant) history is essential here. The other major differential is depression, and again they may coexist. Depression usually lacks the fluctuations.

Once the clinical syndrome is diagnosed, a cause must be sought. After physical examination, investigations are usually required and include urea and electrolytes, full blood count, random blood glucose, oxygen saturation, calcium/phosphorus, liver function tests and mid-stream urine (or dipstick). Other investigations that may be indicated, or can be used if no cause is yet apparent, include EEG, chest X-ray, CT brain, drug levels, ECG and cardiac enzymes, lumbar puncture, X-ray of painful areas, joint aspiration and so on. It is usually necessary to hospitalise a delirious person as the syndrome indicates significant underlying illness.

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.

BOX 57.2 Prevention of delirium

1. Maintain hydration.
2. Reduce noise and other disturbances.
3. Avoid hypno-sedatives—encourage sleep with a back rub and relaxing music. Check other medications for delirium as a side effect before prescribing for the elderly, and seek alternative treatments.
4. Ensure glasses and hearing aids are working/clean and used.
5. Orientation to time and place with an orientation board in the room.
6. Aggressively manage pain.
7. Treat/prevent dehydration.
8. Encourage mobility.

Pitfalls

Although delirium affects cognition, it is not usually primarily due to brain disease. Routine CT of the brain is therefore an inappropriate investigation.

Not listening to nursing staff/family’s description of the person being confused when you are not there can lead to delays in the diagnosis.

Using chemical restraint (antipsychotics) too early and in too high a dose can lead to unnecessary complications, such as falls and fractures. Similarly, physical restraint has almost no place in delirium management, and can lead to patient injury and even death.

Under-investigating delirium can worsen the outcome—delirium is a sign that something serious is underlying.

Prognosis

Most recover at least partially from delirium, within 1–4 weeks. Unfortunately, at least 50% can be shown to have cognitive deficits up to 6 months after the onset, suggesting that delirium itself may damage brain function. Some of these cases are due to pre-existing cognitive impairment not diagnosed before the episode of delirium.

Patient education

Most people retain some memory of the episode of delirium—and these may be very frightening memories. The person should be reassured that they are not ‘mad’ but have simply suffered from an illness that also affected their brain function.

During the episode, family members require similar reassurance that the person is not going ‘mad’, and also should be taught ways in which they can assist (e.g. bring in relaxing music, offer drinks, fix hearing aids). They should also be told that too many visitors—even close family—can be detrimental.

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.

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FIGURE 57.1 Differential diagnosis of dementia and Alzheimer’s disease

Diagnosis

History

The key to diagnosing the dementias is the clinical history, combined with judicious use of specific investigations. AD is characterised by an insidious onset of memory loss—usually at least 1–2 years before presentation—and progressive decline. (Ask: ‘Has there been definite decline in the past 6 months?’) Specific questions may include:

• Does he/she repeat information or questions?
• Does he/she frequently misplace objects or put items away in unusual places?
• Doe he/she forget to turn things off/close things?
• Does he/she forget appointments/arrangements?
• Does he/she forget names of family members?

It is also important to establish whether the cognitive changes are affecting function (e.g. unable to manage finances, unable to operate appliances previously used independently, unable to fix broken items around the house). Cognitive impairment with no effect on function suggests mild cognitive impairment (MCI), which is not dementia, although it is increasingly recognised as a prodromal state.

In vascular dementia there will usually be a history of more sudden episodes of decline associated with other features of cerebral ischaemia events—but not always (e.g. in progressive white matter damage). The history of DLB, FTD and the rarer dementias is driven by enquiring about the specific features described above.

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FIGURE 57.2 Brain scan showing Alzheimer’s disease

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.

BOX 57.3 Investigations for dementia

Routine

• blood tests:

• U&E
• Ca/P
• RBG (or FBG)
• LFT
• B12 & folate
• TFTs
• syphilis serology

• neuroimaging:

• CT brain (non-contrast acceptable)

Additional, as indicated

• EEG
• LP
• MRI brain scan
• ‘Rule in’ investigations
• PET scan

• with the radiotracer fluorodeoxyglucose (FDG)
• with the 11C-labelled Pittsburgh Compound-B (11C-PIB)

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

Prevention

To what extent dementia can be prevented is not fully known, but individual risk reduction is achievable through attention to risk and protective factors. Alzheimer’s Australia has an excellent program that outlines this (‘Mind Your Mind’) and it can obtained from their website or by contacting them directly. Much of the focus is on diet, lifestyle and cardiovascular risk factors—‘what is good for your heart is also good for your mind’. All newly diagnosed people should be advised to follow the recommendations of the program, as should family members. Those with MCI should be particularly encouraged to pursue these practices, although they have not been proved to prevent progression to dementia. At this time, no medication is recommended as a preventative strategy, although two large trials, of Ginkgo biloba (United States and Europe—‘GEM’ and ‘GUIDANCE’) examined this.

General supportive measures

It is important to diagnose the presence and type of dementia in the early stages—this can allow planning for the course of the disease and assists the family/caregivers in understanding symptoms. For instance, the sexually explicit repetitive joking of a person with FTD, while not pleasant, can be understood and arrangements made to avoid contact with younger relatives and friends. In later stages, dementia type is less relevant—the very dependent high-level care resident with severe AD has similar symptoms and care needs to the person with severe DLB or FTD.

Not initiating treatment with medication is also a valid option, as current therapies (see below) are only modestly effective. However, pharmacological therapy is becoming a standard of practice (for those dementias responsive to it), with over 50% of people diagnosed with AD receiving such therapy.

For FTD and most of the rarer dementias there is no specific drug therapy, and ‘general supportive measures’ in that therapeutic domain are valid. As described above, for normal pressure hydrocephalus it is not uncommon for the specialist team to elect to not shunt.

Self-help and lifestyle

The preventative strategies described in ‘Mind Your Mind’ are still appropriate in early dementia and should be encouraged. These include physical exercise, engaging in social and leisure activities, a well-balanced diet (rich in omega-3 fatty acids and vitamins C and E, with only modest amounts of saturated fat) and avoiding cardiovascular risk factors (e.g. cease smoking and control diabetes well).

General practitioners can be a powerful motivating force in encouraging individuals to pursue these sage approaches. An individual program can be constructed. This could include:

• walking for 40 minutes
• dining with others at least five times a week
• attending the elderly citizens’ club (or similar) twice a week
• recommencing knitting as a leisure activity
• doing three sudokus a week
• eating a freshly prepared salad five times a week
• moderate use of alcohol—3–5 drinks a week
• taking a daily multivitamin/mineral and omega-3 supplement
• going on an (accompanied) country trip, for a week, within the next year.

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:

• Ginkgo biloba—this herbal preparation from the bark of a tree does have some trial evidence of efficacy in dementia. The preparation used in one trial was Egb 761, at doses of 120–240 mg/day. The product is marketed as Tebonin® and efficacy was about half that of the cholinesterase inhibitors. There was no significant toxicity. Other ginkgo preparations vary in content and efficacy has been inadequately trialled.
• brahmi—this preparation has no positive published trial evidence but is often used. It is derived from an Indian plant and recommended dosing is 400 mg daily. Adverse effects include nausea, fatigue and urinary frequency but are insignificantly more frequent than with placebo.
• Curcumin—this component of turmeric, an Indian spice, may be beneficial—consumption was found to be associated with a lower risk of having AD, and in vitro studies support efficacy. There is no significant toxicity but there is no recommended dose.
• polyphenols—these antioxidants are found in a wide range of plant products including berries, tea and also wine. Highest concentrations are in thin-skinned berries (they have a ‘sunscreen’ effect) such as blueberries and pinot noir grapes. Epidemiological studies have associated higher consumption with reduced risk of developing dementia but no prospective study has established therapeutic benefit. A number of commercial preparations include polyphenols.
• 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.

• aromatherapy—there is some support in the literature for this for behavioural problems, especially lavender oil. This can be rubbed on or administered as a vapour but be sure that it cannot be inadvertently consumed.
• other environmental therapies—bright light, music, pets and other approaches have been successfully used to modify agitation and aggression, and improve sleep in those with dementia. Music is more effective if items that the person has liked are used (i.e. individualised), and light seems more effective in the morning, or all day, than in the afternoon. One recent study in a residential care facility6 demonstrated that bright light in common areas improved sleep more in those with more severe dementia, adding 16 minutes of sleep each night, on average. This compared very favourably with 4.5 minutes of sleep added by the use of temazepam in one study of older people.

Ongoing review/monitoring

Ongoing review/monitoring is important for all those with dementia. The disease inevitably progresses and both carers and the patient face new challenges as this occurs. Progress can be quantified with the MMSE repeated 3–6 monthly but other issues should also be enquired about—behaviour, function, comorbidity, medications, caregiver stress, support services. It is helpful to interview the caregiver and the person with dementia separately. Eventually, most people with dementia require residential care, and an aged care assessment team (ACAT) referral is needed to allow this. The ACAT should also be involved earlier to facilitate extra home supports such as through community aged care packages and extended aged care at home (dementia).

Important pitfalls

• In diagnosis, it is easy to incorrectly diagnose vascular dementia because an infarct/lacune is seen on neuroimaging. The history is vital—if it suggests AD, the ischaemic lesion is probably incidental.
• A low MMSE does not diagnose dementia—other causes include poor education, very old age (a normal MMSE at 90 can be 20 or 21) and coming from a culturally and linguistically diverse background. When in doubt, seek a specialist opinion.
• AChEIs should only be used when dementia is diagnosed—not for other cognitive disorders.
• Memantine may not be offered because the doctor feels the family and/or patient cannot afford it.
• Antipsychotic agents are often used too early, without a trial of non-pharmacological management, or for too long (sometimes years). Behavioural disturbances do not usually persist in those with dementia and attempts to cease the agent need to be frequent.
• Caregiver stress is not always adequately recognised or addressed. A well supported caregiver can delay institutionalisation of the person with dementia, improving their quality of life. National Alzheimer’s disease associations are a valuable source of information to assist caregivers, and all caregivers should be aware of them.

Prognosis

The average time course of dementia, from first symptoms to death, is less than 10 years (around 7–8 years for AD, more variable for vascular dementia and shorter for DLB and FTD) but there is much variability. If the diagnosis is correct, sustained improvement is extremely rare—it is only transient when there is a response to an AChEI.

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