Alzheimer’s disease is a degenerative brain disorder characterised by progressive dementia that culminates in death. It affects 3% of those over the age of 65 and up to 50% over the age of 85, resulting in a cost of over $100 billion a year in the USA.1 Due to the ageing population, the societal burden of this disease is expected to increase over the next 40 years.2 The hallmark of Alzheimer’s disease is the insidious onset of memory loss, although one or more additional areas of cognitive impairment are usually evident on examination. Slow but relentless progression leads to worsening cognitive and behavioural problems, as the result of widespread areas of cortical dysfunction. Effective management consists of both pharmacological and non-pharmacological interventions to improve the quality of life of patients—and their carers.
PHARMACOLOGICAL TREATMENT
Current pharmacological treatments include both disease specific compounds as well as adjunctive therapies for the behavioural symptoms of Alzheimer’s disease.
Alzheimer’s disease specific therapiesAlthough there is no treatment that can either cure or permanently arrest the disease, there are presently available two types of Alzheimer specific therapies: symptomatic approaches based on enhancement of neurotransmitter systems, and neuroprotective strategies using antioxidants. The most successful strategy to date has comprised the class of compounds known as acetylcholinesterase inhibitors, which enhance the brain’s cholinergic system.
Acetylcholinesterase inhibitorsThe mechanism of action of acetylcholinesterase inhibitors is to reduce the metabolism of the neurotransmitter acetylcholine, which is deficient in the Alzheimer brain, thereby prolonging its action at cholinergic synapses. Three are currently marketed for the treatment of mild to moderate Alzheimer’s disease: donepezil, galantamine, and rivastigmine (table 1). As a class, these agents have measurable, albeit modest, effects on cognition, behaviour, activities of daily living, and global measures of functioning. Although cholinergic treatment probably does not alter the progression of neurodegeneration, possible long term benefits may include delayed institutionalisation, perhaps decreased mortality, and savings in the cost of patient care. The main adverse effects are gastrointestinal (nausea, vomiting, diarrhoea, anorexia, weight loss); not surprisingly, the drugs are better tolerated on a full stomach. Insomnia, vivid dreams, and leg cramps have also been reported.3 Although there are no large head-to-head comparisons of cholinesterase inhibitors in the literature, their main differences appear to be their adverse effect profile, titration schedule, and dosing regimen:
Donepezil is given once daily, either at bedtime or, alternatively, in the morning if insomnia or nightmares should occur. The initial dose is 5 mg once daily which should be increased to 10 mg once daily after six weeks if tolerated.
Rivastigmine requires twice daily dosing and should be slowly titrated from 1.5 mg twice daily taken with food. We recommend using four-week intervals to increase each dose by 1.5 mg; up to 6 mg twice daily if tolerated.
There is both an immediate release form of galantamine that, like rivastigmine, requires twice daily dosing, and an extended release form that, like donepezil, is given once daily. For the immediate release form, we start at 4 mg twice daily with food and at four-week intervals increase each dose by 4 mg; up to 12 mg twice daily if tolerated. The recommended starting dose of the extended release form is 8 mg once daily in the morning, preferably with food. After a minimum of four weeks, the dose should be increased to the initial maintenance dose of 16 mg per day; if tolerated, a further increase to 24 mg per day should be attempted after a minimum of four weeks.
Cochrane reviews of all three agents have reported cognitive, functional, and—except for rivastigmine—behavioural benefits in people with mild to moderate Alzheimer’s disease.4–6 However, a recent review of all the randomised trials of cholinesterase inhibitors questioned the scientific basis for recommending these compounds as preferred treatment.7 Citing minimal benefits on rating scales and poor methodological quality of the available trials, the authors concluded that the recommendations for the use of cholinesterase inhibitors are not evidence based.
Whether any modest improvements in cognitive status and daily functioning associated with cholinesterase inhibitors translate into economic benefits is unclear. Some cost effectiveness studies have suggested that the small savings are outweighed by the high cost of the drugs. The most notable of these is the AD2000 study of donepezil, which challenged claims that the drug has valuable effects on "real life" measures of disability.8 This publicly funded study was originally designed to enroll 3000 patients for a single phase of 60 weeks but was redesigned to follow all patients through a series of phases when only 566 subjects were enrolled. Underpowered to make conclusive assessments about its primary outcomes of institutionalisation and progression of disability, the study has been criticised for its biased subject selection and high patient attrition rates. Despite these shortcomings, the authors of the study and other specialists have suggested that the results deserve attention since they undermine the assumption that modest improvements in cognitive and functional test measures generalise to maintenance of function, delay in institutionalisation, or economic benefit. Partly on the basis of this study, the UK National Institute for Health and Clinical Excellence (NICE) remains uncertain as to whether these drugs are cost effective enough to be made available for the routine treatment of Alzheimer’s disease, an issue that is still being debated (see http://www.nice.org.uk/page.aspx?o=104058). The Cochrane reviews do not take sides, noting only that more data are needed on the cost effectiveness of these medications.
Whether any modest improvements in cognitive status and daily functioning associated with cholinesterase inhibitors translate into economic benefits is unclear
Although there is no question that better drugs are needed, as clinicians managing Alzheimer patients, we feel that a trial of a cholinesterase inhibitor is still warranted. In fact, it should be noted that even the AD2000 study confirmed a small but significant effect of donepezil on cognition and activities of daily living over two years—longer than any previous trial. Clinically, our experience has been consistent with these data. We see about a one to two year halt in deterioration with improvements in cognition and activities of daily living in some patients, followed by a decline that mirrors untreated patients. The vast majority of our patients tolerate the medications well, although some cannot abide the cholinergic gastrointestinal adverse effects of diarrhoea, nausea, and anorexia (often with significant weight loss), even when the medication is taken on a full stomach. If this occurs, switching to another agent is often helpful. If adverse effects occur even at low doses, waiting sometimes months before increasing to the next dose level can be helpful. Although patients may connect an increase in vivid dreams with their drugs, this does not typically cause them to abandon them.
We commonly find patients on a cholinesterase inhibitor are also on a centrally acting anticholinergic agent such as diphenhydramine for sleep, other antihistamines for allergy, meclizine for dizziness or vertigo, oxybutynin for bladder control, or a highly anticholinergic tricyclic (such as amitriptyline) for depression or chronic pain. Therefore, a careful review of all medications, including over-the-counter agents, is essential, whichever Alzheimer drug the patient is taking, or even if none is being prescribed. In addition to anticholinergics, the patients may also be taking medications frequently responsible for confusion in the elderly including benzodiazepines, sedative-hypnotics, xanthines, cardiovascular agents such as nifedipine, quinidine, disopyramide, amiodarone, and beta blockers, and both narcotic and non-narcotic analgesics. Optimal management of all medications and any comorbid medical illnesses, including depression, is crucial and may result in significant improvement in cognitive and functional status.
NMDA receptor antagonistsAlthough the neurobiological basis for its therapeutic activity is not fully understood, memantine is, among other things, a non-competitive (channel blocking) NMDA receptor antagonist that may protect against the excitotoxic destruction of certain neuronal populations.9 It is the only NMDA antagonist approved for use in Alzheimer’s disease.
Published data from two six month studies of patients with moderate to severe disease showed a small beneficial effect on cognition, activities of daily living, and behaviour, according to the Cochrane Review.10 In addition, a phase III trial of memantine treatment in patients with moderate to severe Alzheimer’s disease already receiving donepezil reported significantly better performance on cognitive, functional, behavioural, and global measures as compared to donepezil alone.11 In a single six month trial of patients with mild to moderate disease, memantine had a beneficial effect on certain aspects of cognition, behaviour, and clinical global impression of change, but no effect on activities of daily living. However, these benefits could be overturned by data from two unpublished studies that are known to show no significant effect.
Thus, we limit our use of memantine to at least moderately impaired individuals, starting at 5 mg bd and titrating to 10 mg bd over the course of a month. There is little interaction with other medications so memantine is often used in combination with acetylcholinesterase inhibitors and is generally well tolerated. Adverse effects are not common but include hallucinations, confusion, dizziness, and headache.9
AntioxidantsEvidence that free radicals may contribute to the pathological process in Alzheimer’s disease has led to interest in the use of antioxidants, such as vitamin E. One large trial compared the effects of 2000 IU and selegiline with placebo in 341 subjects with moderate Alzheimer’s disease.12 The primary outcome was survival to the first of four endpoints: death, institutionalisation, loss of two out of three basic activities of daily living, or severe dementia. There was perhaps some benefit from vitamin E with fewer patients reaching an endpoint, but more patients taking vitamin E suffered a fall. According to the Cochrane Review, it is not possible to interpret the results for the specific endpoints nor for the secondary outcomes of cognition, dependence, behavioural disturbance, and activities of daily living. Thus, there is insufficient evidence of efficacy of vitamin E in the treatment of people with Alzheimer’s disease.13
A careful review of all medications, including over-the-counter agents, is essential, whichever Alzheimer drug the patient is taking, or even if none is being prescribed
A recent meta-analysis of 19 randomised, controlled trials involving more than 135,000 participants reported that high dose vitamin E supplementation increased all-cause mortality. However, many question the conclusions on the basis of methodological flaws and the fact that most of the trials involved individuals with serious health conditions, including cardiovascular disease and cancer. Nevertheless, many practitioners do not prescribe vitamin E because of its perceived lack of efficacy and possible increased mortality. But, in the light of the Institute of Medicine’s view that vitamin E supplementation is safe for normal, healthy adults at up to 1000 mg (1600 IU) per day, we at least continue to recommend some vitamin E unless there is known cardiac disease or prominent vascular risk factors.
PreventionAlthough epidemiological and some small clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), oestrogens, and statins might reduce the risk of developing Alzheimer’s disease, there is no very good evidence to recommend either NSAIDs or statins. However, there is now substantial evidence that oestrogens do not benefit cognitive function after the onset of Alzheimer’s, or reduce the risk of its development. The Women’s Health Initiative Memory Study (WHIMS) monitored almost 3000 women aged 65 years or older for the development of dementia over approximately five years. Not only were oestrogens not protective, women assigned to the oestrogen arm had an even greater risk of cognitive decline and dementia from any cause.14
HERBAL REMEDIES
Ginkgo bilobaGinkgo biloba is the most well known herbal remedy for the treatment of cognitive disorders. Trial data are mixed, with some studies showing a small but significant advantage over placebo, but most did not include standard assessments of cognition and behaviour. One large multicentre, placebo controlled trial demonstrated modest benefits in patients treated with 120 mg/day Ginkgo biloba extract relative to placebo over one year.15 The Cochrane review concludes that although Ginkgo biloba appears to be safe, there is a need for a large trial using modern methodology.16 Since many patients seek out this herbal remedy without the advice of a physician, they should be warned about nausea, diarrhoea, and headache. Ginkgo biloba inhibits blood clotting, so concurrent use of warfarin or aspirin should be avoided.16,17
We limit our use of memantine to at least moderately impaired individuals, starting at 5 mg bd and titrating to 10 mg bd over the course of a month
Huperzine AHuperzine A is a natural cholinesterase inhibitor derived from the Chinese herb huperzia serrata. In addition, it has antioxidant and neuroprotective properties that suggest it may be useful as a disease modifying treatment for Alzheimer’s disease. Although several small studies have suggested short term benefit, there have been no controlled clinical trials outside China assessing its efficacy and tolerability. A large multicentre, placebo controlled phase II trial organised by the Alzheimer’s Disease Cooperative Group is currently underway to assess Huperzine A’s effect on cognitive function over six months.
ADJUNCTIVE THERAPIES FOR BEHAVIOURAL PROBLEMS
Alzheimer’s disease results in behavioural problems that can be especially challenging to the carers (table 2). The patients also suffer from the usual psychiatric disorders common in elderly populations, such as depression, which may compound their cognitive and behavioural difficulties. These problems can be effectively managed if properly identified, often in collaboration with a psychiatrist; indeed in many countries Alzheimer patients are looked after more often by psychiatrists than neurologists.
Agitation and psychosisAgitation and psychosis are common, especially in the later stages of the diease. As cognitive function becomes more and more impaired, small changes in a patient’s internal (for example, infection) or external (for example, change in environment) homeostasis produce agitation. Identification and treatment of any possible underlying cause of agitation is, therefore, important. Workup should be directed at common causes of delirium in the elderly: infections of the lungs or bladder, electrolyte disorders, medication changes or adverse effects, and pain. Sometimes a seemingly trivial environmental change can produce agitation in a cognitively impaired patient. If there is no inciting problem, agents that can be used to treat agitation include antipsychotics, mood stabilising anti-epileptic drugs, trazodone, and anxiolytics.
Although many consider antipsychotics to be the mainstay in managing agitation, others reserve their use for psychosis, because these agents may produce serious adverse effects, including parkinsonism, tardive dyskinesia, confusion, and falls. Parkinsonism and tardive dyskinesia may persist for weeks to months after cessation of antipsychotics and, for some patients, may never remit. Extrapyramidal adverse effects are more common with typical than with atypical antipsychotics, which appear to be better tolerated than traditional agents. Atypical antipsychotics are, therefore, the treatment of choice for patients with psychotic symptoms; sedation is the most common adverse effect. The initial antipsychotic dose in Alzheimer patients should be low, about one quarter of that used in young adults, and the total daily dose should be gradually increased as needed, titrating against adverse effects such as cognitive deterioration, low blood pressure, and parkinsonism.18
The American Food and Drug Administration (FDA) recently issued a warning about higher mortality in association with the use of atypical antipsychotics in demented elderly. In the analysis of 17 placebo controlled trials of four drugs in this class, the death rate for elderly patients with dementia was about 1.6 to 1.7 times that of placebo. Thus, the need for these drugs for the treatment of behavioural disorders in patients with dementia should be continually reassessed.
There is some clinical evidence pointing to the utility of trazodone and divalproex (sodium valproate) in the management of agitation. Although these drugs have not been studied widely in elderly patients with dementia, we have found them to be effective alternatives to antipsychotics, especially when the response to an atypical antipsychotic is inadequate. The introduction of an acetyl anticholinesterase inhibitor can also sometimes reduce or obviate the need for antipsychotropic medications.
DepressionTreatment of depressive symptoms in Alzheimer’s disease commonly includes selective serotonin reuptake inhibitors (SSRIs) (table 4). Alternatively, tricyclic antidepressants with low anticholinergic adverse effects such as desipramine or nortriptyline, or the combined noradrenergic and serotonergic reuptake inhibitor venlafaxine can be tried.18 We make every attempt to avoid centrally acting cholinergic blockers such as paroxetine.
Anxiety and insomniaMost patients with anxiety do not require pharmacological treatment. For those that do, however, benzodiazepines should be avoided if at all possible, given their potential deleterious effects on cognition (table 5). Non-benzodiazepine anxiolytics such as buspirone are preferred. For insomnia, it is worth trying non-pharmacological sleep hygiene measures (described below) as an adjunct to pharmacological management. If medications are necessary, sedating antidepressants such as trazodone may be effective choices for promoting sleep, while anticholinergic hypnotics should be avoided.
Non-pharmacological managementIn addition to medical therapy, the physician should not overlook the non-pharmacological management interventions that can aid in the care of their patients with dementia.
CARING FOR THE CARER
Patients with more than mild dementia usually have at least one carer and it is important that the clinician recognises his or her vital role in management. Educating the carer about the disease, as well as his or her own emotional wellbeing is paramount, as is a close working relationship between the clinician and primary carer. We routinely emphasise to family and carers that allowing themselves to become physically or mentally exhausted will render them unable to care for their loved one. Family carers of relatives are at high risk of depressive symptoms, and indeed depression, far in excess of age matched comparison subjects.19 Long term social support through counselling and support group participation has been shown to have a significant and sustained effect on depression in carers.20 Therefore, the treating physician should routinely direct the carer to counselling, support groups, and medical care if necessary.
Studies have also shown that short term educational programmes for carers can have a positive effect by improving knowledge of the disease process and reducing perception of burden and level of depression. In one study, long term intensive education and support programmes for carers delayed time to nursing home placement by 12–24 months.21 A meta-analysis of 30 studies focusing on educational interventions for carers reported benefits in their knowledge, psychological morbidity, coping skills, and social support, in addition to less depression among the patients.22 Although such educational programmes are not always readily available, the Report of the Quality Standards Subcommittee of the American Academy of Neurology recommended directing carers to both short term and intensive long term education and support services.23 Several organisations offer these services (table 6). Additionally, several books are available for carers and family that focus on tips for caring for the demented patient during the various stages of the disease, finding available assistance, and addressing financial and legal issues (table 7).
CARING FOR THE CARER
Patients with more than mild dementia usually have at least one carer and it is important that the clinician recognises his or her vital role in management. Educating the carer about the disease, as well as his or her own emotional wellbeing is paramount, as is a close working relationship between the clinician and primary carer. We routinely emphasise to family and carers that allowing themselves to become physically or mentally exhausted will render them unable to care for their loved one. Family carers of relatives are at high risk of depressive symptoms, and indeed depression, far in excess of age matched comparison subjects.19 Long term social support through counselling and support group participation has been shown to have a significant and sustained effect on depression in carers.20 Therefore, the treating physician should routinely direct the carer to counselling, support groups, and medical care if necessary.
Studies have also shown that short term educational programmes for carers can have a positive effect by improving knowledge of the disease process and reducing perception of burden and level of depression. In one study, long term intensive education and support programmes for carers delayed time to nursing home placement by 12–24 months.21 A meta-analysis of 30 studies focusing on educational interventions for carers reported benefits in their knowledge, psychological morbidity, coping skills, and social support, in addition to less depression among the patients.22 Although such educational programmes are not always readily available, the Report of the Quality Standards Subcommittee of the American Academy of Neurology recommended directing carers to both short term and intensive long term education and support services.23 Several organisations offer these services (table 6). Additionally, several books are available for carers and family that focus on tips for caring for the demented patient during the various stages of the disease, finding available assistance, and addressing financial and legal issues (table 7).
View this table:[in this window][in a new window]
TABLE 6 Support services for Alzheimer patients and their carers; the Alzheimer Europe website has links to all the European Alzheimer associations
View this table:[in this window][in a new window]
TABLE 7 Recommended books for carers and family The Internet has enhanced the educational and support needs of carers. The physician should direct carers to reputable websites, such as Alzheimer’s Caregiver Support Online (http://www.alzonline.net) which provides literature, tips on managing dementia patients at home, message boards, and even online classes for carers.24
Carers should be encouraged to seek out adult day care centres, as well as respite care and home health services, which are surprisingly underused by families caring for demented patients. Evidence suggests that adult day care reduces carer stress, improves the psychological wellbeing of carers, and provides a structured environment for patients that results in fewer behavioural problems.25,26 We find that adult day care also decreases carer isolation by allowing them to pursue their own interests while providing the patient with increased opportunities for social interaction.
CARING FOR THE PATIENT
The basis of non-pharmacological intervention for behavioural symptoms consists of modifying the patient’s environment and routine. Cummings et al27 propose the following recommendations for carers:
provide the patient with a predictable routine (exercise, meals, and bedtime should be at the same times every day and punctual)
allow patients to dress in their own clothing and to keep their possessions
before performing all procedures and activities, explain them to the patient in simple language
simplify all tasks, break complex tasks into steps, and provide instructions for each step
use distraction and redirection of activities to divert the patient from problematic situations
ensure that comorbid conditions are optimally treated
provide a safe environment (no sharp-edged furniture, no slippery floors or throw rugs, no electric cords)
equip doors and gates with safety locks
install grab bars by the toilet and in the shower
use calendars, clocks, labels, and newspapers for orientation to time
use colour coded or graphic labels (for example, on doors to closets, drawers) as cues for orientation in the home environment
use low level lighting to reduce confusion and restlessness at night
avoid glare from windows and mirrors, noise from television, and household clutter
reduce excess stimulation and outings to crowded places (overexposure to environmental stimulation can lead to agitation and disorientation)
consider using a day care programme
register the patient in the Alzheimer’s Association’s Safe Return Program, an identification programme for memory impaired adults.
Environmental modificationsWe recommend a home visit by a physio or occupational therapist to evaluate home safety and offer suggestions for home modifications. The home environment should remain familiar and uncluttered. Furniture should not be rearranged. Ample lighting in corridors and bathrooms should be provided to prevent falls and injuries during the night. In the kitchen, locks can be installed on cabinets, cupboards, and ovens. Knobs on the stove should be removed or childproofed.
The treating physician should ask about access to firearms in the home and suggest their safe storage or removal. Families and carers should be instructed to keep poisonous or harmful substances and sharp objects out of reach. Dangerous appliances and tools should be kept unplugged or out of sight.
Behavioural modificationsCarers should be urged to use strategies that will reduce troublesome behaviours in the demented patient. One such approach, "The 3Rs" (Repeat, Reassure, and Redirect) (table 8), encourages the carer to transform a problematic situation into a useful activity.28 An instruction or answer to a question is repeated as needed and the patient is redirected to a different activity to divert attention from the problematic situation. Behavioural approaches for some specific situations are outlined below and in tables 9 and 10.
View this table:[in this window][in a new window]
TABLE 8 The Three Rs approach of behavioural modification28
View this table:[in this window][in a new window]
TABLE 9 Behavioural approaches for various situations in Alzheimer’s disease (California Workgroup on Guidelines for Alzheimer’s Disease Management 1999)35
View this table:[in this window][in a new window]
TABLE 10 Bathing tips for the carer (modified from Young 2001)36 Sleep disturbanceSleep disturbances are common. Non-pharmacological interventions should always be tried before pharmacological ones to avoid problematic adverse effects (table 9). These include sleep hygiene (regular sleep and waking times, limitation of daytime sleeping, avoidance of caffeine and evening fluid intake, and using a bed for sleep only), calming bedtime rituals (such as reducing noise and light after a bath and warm milk with soothing music), and daytime physical and mental activity.29 There is some support for bright light therapy, but this is not widely recommended at this time.30 The burden of caring for the dementia patient during the night can hasten and precipitate institutionalisation; thus, the use of overnight respite care has been recommended as an option in certain situations.
WanderingOne potentially dangerous behaviour that the physician must advise the carer about is wandering. This hazard can be diminished with simple measures such as installing complex door locks, in-house alarms or bells, and safety gates, and the consequences minimised by having the patient wear an identification bracelet at all times. Activities that reduce wandering, such as music or television, should be identified. The Alzheimer’s Association Safe Return Program (http://www.alz.org/Services/SafeReturn.asp) is an identification, support, and enrollment service that provides assistance when a person with dementia becomes lost. Help is available 24 hours a day, seven days a week.
DrivingDecisions about driving for dementia patients generally rest on the judgment of family members whose opinion is often at odds with the patient’s perception of his or her own driving skill.31 Physicians are encouraged to report patients who have conditions that may impair driving ability according to local laws. Patients with moderate and severe dementia should not drive.32
OTHER ISSUES IN ALZHEIMER’S DISEASE MANAGEMENT
Genetic counsellingAn individual’s apolipoprotein E (ApoE) gene status has received significant attention as an important genetic susceptibility risk factor for the development of Alzheimer’s disease. ApoE is a protein involved in cholesterol transport with three possible alleles: 2 (rare), 3 (most frequent), and 4. Individuals who are homozygous and carry two ApoE 4 alleles have an increased probability ( 90%) of developing Alzheimer’s disease by age 85 and do so about 10 years earlier than individuals carrying the 2 or 3 allelic variants. However, the exact mechanism by which this occurs and the utility of ApoE genotyping for diagnostic purposes remain unsettled. As up to 50% of late onset Alzheimer patients do not possess an 4 allele, genotyping is currently not recommended for predictive risk assessment except within specific research environments.33
Advance directivesAdvance directives and healthcare surrogates should be discussed soon after the diagnosis so as to include the patient to the greatest possible extent in likely future decisions. The patient and family should be instructed to begin advance planning for durable power of attorney, estate management, advance directives, as well as for surrogates for medical, financial, and legal decisions. Topics such as "do not resuscitate" orders, initiation of tube feeding, and the use of antibiotics for infections will help foster physician understanding of the family’s wishes as well as prepare the family for difficult decisions.27 In the late stages of the disease, hospices are recommended given their expertise and resources necessary to help with palliative care.
Hospitalisation for patients with Alzheimer’s can be hazardous
NutritionMaintaining good nutrition can be difficult in all stages of Alzheimer’s disease. Nutritional supplementation is widely available and is recommended. Initially, supplementation can be used between meals but, as the disease progresses, can replace traditional meals. Meals On Wheels, senior citizen programmes, and other social services can help make meals available to patients when they are no longer able to shop and prepare meals on their own. In late dementia, patients will no longer be able to feed themselves. Spoonfeeding by carers and consultation with a dietitian and speech therapist may postpone the issue of feeding tube placement. Percutaneous endoscopic gastrostomy (PEG) tubes are a comfortable measure for nutrition maintenance once the patient is unable to eat normally; however, the ethical issues involved should be discussed with the family early in the course of the disease. We do not routinely recommend feeding tube placement for end-stage patients.
HospitalisationHospitalisation for Alzheimer patients can be hazardous. An unfamiliar environment in addition to the added stress of an illness and/or pain often makes the patient more confused and disoriented than ever. Physicians should encourage family members to accompany the patient to reduce anxiety and disorientation and to help maintain mobility skills. The patients can decondition quickly and lose skills of daily living if they do not perform a given function for several days. Medications are commonly changed during hospitalisations, and the carer should understand the indication for a new medication, in addition to its dosing and potential adverse effects.
PRACTICE POINTS
Although there is no treatment that either cures or permanently arrests the disease, there are presently available two types of Alzheimer specific therapies: symptomatic approaches to improve memory based on enhancement of neurotransmitter systems, and neuroprotective strategies using antioxidants.
Acetylcholinesterase inhibitors reduce the metabolism of the neurotransmitter acetylcholine, and although they probably do not alter the progression of neurodegeneration, possible long term benefits may include delayed institutionalisation, perhaps decreased mortality, and savings in the cost of patient care.
Optimal management of all medications and any comorbid medical illnesses, including depression, is crucial and may result in significant improvement in cognitive and functional status.
There is insufficient evidence of efficacy of vitamin E in the treatment of people with Alzheimer’s disease.
Oestrogens do not benefit cognitive function after the onset of Alzheimer’s, or reduce the risk of its development.
Alzheimer’s disease results in behavioural problems that can be especially challenging to carers but effectively managed if properly identified.
In addition to medical therapy, the physician should not overlook the non-pharmacological management interventions that can aid in the care of patients with dementia.
Patients with more than mild dementia usually have at least one carer and it is important that the clinician recognises his or her vital role in management.
Nursing home placementFor many carers, there comes a time when they can no longer adequately manage the patient’s medical needs and personal care in the home setting. Advance planning with regard to a long term care facility will help prevent hasty decisions in pressure situations. Important considerations in choosing a nursing home include geographic location, performance record, attentiveness of nursing staff, cleanliness, and cost. Specialised training of nursing home staff may significantly reduce the use of antipsychotic medications, and carers should be advised to seek out nursing homes with staff that have received dementia education.
Elder abuse and neglectMalnutrition, non-compliance with medications, bruises, decubitus ulcers, poor hygiene, and other signs of trauma are indicators of possible abuse or neglect, a significant problem in dementia patients.34 Physicians should be aware of local laws for reporting, as they vary. Interventions through counselling, family psychotherapy, respite care, and alternative living situations many be beneficial.29
ACKNOWLEDGEMENTS
This article was reviewed by Professor Gunhild Waldemar, Copenhagen Denmark
REFERENCES
Jorm AF. Cross-national comparisons of the occurrence of Alzheimer’s and vascular dementias. Eur Arch Psychiatry Clin Neurosci 1991;240:218–22.[Medline]
Hebert LE, Scherr PA, Bienias JL, et al. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 2003;60:1119–22.[Abstract/Free Full Text]
Lleo A, Greenberg SM, Growdon JH. Current pharmacotherapy for Alzheimer’s disease. Annu Rev Med (in press).
Birks J, Grimley Evans J, Iakovidou V, et al. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev 2000;4:CD001191.
Birks JS, Melzer D, Beppu H. Donepezil for mild and moderate Alzheimer’s disease. Cochrane Database Syst Rev 2000;4:CD001190.
Loy C, Schneider L. Galantamine for Alzheimer’s disease. Cochrane Database Syst Rev 2004;4: CD001747.
Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP, et al. Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomised clinical trials. BMJ 2005;331:321–7.[Abstract/Free Full Text]
Courtney C, Farrell D, Gray R, et al. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet 2004;363:2105–15.[Medline]
Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer’s disease. CNS Drug Review 2003;9:275–308.
Areosa SA, Sherriff F, McShane R. Memantine for dementia. Cochrane Database Syst Rev 2005;CD003154.
Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil. A randomized controlled trial. JAMA 2004;291:317–24.[Abstract/Free Full Text]
Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997;336:1216–22.[Abstract/Free Full Text]
Tabet N, Birks J, Grimley Evans J. Vitamin E for Alzheimer’s disease. Cochrane Database Syst Rev 2000;4:CD002854.
Espeland M, Rapp S, Shumaker S, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 2004;291:2959–68.[Abstract/Free Full Text]
Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of ginkgo biloba for dementia. North American EGb Study Group. JAMA 1997;278:1327–32.[Abstract]
Birks J, Grimley EV, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2002;4:CD003120.
Ott BR, Owens NJ. Complementary and alternative medicines for Alzheimer’s disease. J Geriatr Psychiatry Neurol 1998;11:163–73.[Medline]
Smith A. Behavioral problems in dementia. Strategies for pharmacologic and nonpharmacologic management. Postgrad Med 2004;115:47–52, 55–6.
Schultz R, O’Brien AT, Bookwala J, et al. Psychiatric and physical morbidity effects of dementia caregiving: prevalence, correlates, and causes. Gerontologist 1995;35:771–91.[Abstract]
Mittelman MS, Roth DL, Coon DW, et al. Sustained benefit of supportive intervention for depressive symptoms in caregivers of patients with Alzheimer’s disease. Am J Psychiatry 2004;161:850–6.[Abstract/Free Full Text]
Brodaty H, Gresham M. Effect of a training programme to reduce stress in carers of patients with dementia. BMJ 1989;299:1375–9.[Medline]
Brodaty H, Green A, Koschera A. Meta-analysis of psychosocial interventions for caregivers of people with dementia. J Am Geriatr Soc 2003;51:657–64.[Medline]
Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1154–66.[Abstract/Free Full Text]
Glueckauf RL, Ketterson TU, Loomis JS, et al. Online support and education for dementia caregivers: overview, utilization, and initial program evaluation. Telemed J E Health, 2004;10:223–32.[Medline]
Small GW, Rabins PV, Barry PP, et al. Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. JAMA 1997;278:1363–71.[Abstract]
Zarit SH, Stephens MA, Townsend A, et al. Stress reduction for family caregivers: effects of adult day care use. J Gerontol B Biol Sci Med Sci 1998;53: S267–77.
Cummings JL, Frank JC, Cherry D, et al. Guidelines for managing Alzheimer’s disease: Part II. Treatment. Am Fam Physician 2002;65:2525–34.[Medline]
Sultzer D, Cummings JL. Alzheimer’s disease. In: Rakel RE, Conn HF (eds). Current therapy: latest approved methods of treatment for the practicing physician Philadelphia: WB Saunders, 1993:838–40.
Grossberg GT, Desai AK. Management of Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 2003;58:331–53.
Ancoli-Israel S, Martin JL, Kripke DF, et al. Effect of light treatment on sleep and circadian rhythms in demented nursing home patients. J Am Geriatr Soc 2002;50:282–9.[Medline]
Wild K, Cotrell V. Identifying driving impairment in Alzheimer disease: a comparison of self and observer reports versus driving evaluation. Alzheimer Dis Assoc Disord 2003;17:27–34.[Medline]
Dubinsky RM, Stein AC, Lyons K. Practice parameter: risk of driving and Alzheimer’s disease (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2000;54:2205–11.[Abstract/Free Full Text]
American College of Medical Genetics/American Society of Human Genetics Working Group on ApoE and Alzheimer disease. Statement on use of apolipoprotein E testing for Alzheimer disease. JAMA 1995;274:1627–9.[Abstract]
Coyne AC, Reichman WE, Berbig LJ. The relationship between dementia and elder abuse. Am J Psychiatry 1993;150:643–6.[Abstract/Free Full Text]
California Workgroup on Guidelines for Alzheimer’s Disease Management. Guidelines for Alzheimer’s disease management: final report. Department of Health Services, 1999.
Young MG. Providing care for the caregiver. Patient Care 2001;35:68.