The treatments options for dementia include both pharmacological and nonpharmacological therapeutic approaches. These can be further subdivided into therapies for cognitive impairments and neuropsychiatric disturbances (psychiatric symptoms and behavioural disturbances).

The American Academy of Neurology has produced an evidence-based review on the management of dementia [Doody, 2001] which contains information expected to help the clinician in the decision making for the clinical management of dementia. The results suggested that acetylcholinesterase inhibitors (AChEIs) benefit patients with AD, although the average benefit is small, and that vitamin E may delay deterioration in the disease, although the one randomized trial demonstrating benefit awaits replication. Selegiline, other antioxidants, anti-inflammatory agents and oestrogen were found to require further investigation.

For those patients who have dementia and are suffering from agitation or psychosis, antipsychotic drugs are effective after nonpharmacological interventions have failed, and antidepressants are as effective in patients suffering from depression with dementia as they are in those without dementia.

Nurses and home carers should be educated about AD to avoid the unnecessary use of psychotropic medication. For example, simple behaviour modification techniques are effective, and approaches like positive reinforcement, skills practice and graded assistance can aid functional independence.

The rationale for the treatment of cognitive deficits in AD focuses on cholinergic strategies in an attempt to potentiate deficient central cholinergic function. The treatment for this condition is based on knowledge of the pathophysiology of the condition and Figure 9 shows the synthesis and breakdown of acetylcholine (ACh) in the brain.

In the UK and the USA, three drugs - donepezil, rivastigmine and galantamine - are commonly used for the treatment of mild to moderate AD. Tacrine, the first licensed AChEI drug, is no longer used in the treatment of AD. Memantine is used for the treatment of moderately severe to severe AD (see Noncholinergic strategies).

The UK’s National Institute for Clinical Excellence (NICE) published guidance on the use of antidementia drugs in January 2001 [NICE, 2001]. The guidance summarized that donepezil, rivastigmine and galantamine should be made available on the UK National Health Service (NHS) as one component in the management of those people with mild and moderate AD, whose MMSE is above 12 points under the conditions listed in Table 17. Although the guidelines are conservative, they are generally consistent with the available data.

The drugs used to treat dementia are listed in Table 18.

AChEIs appear to be statistically and clinically superior to placebo in improving cognitive deficits global ratings of dementia and activities of daily living in AD. Cholinesterase inhibitors are considered the cornerstone of pharmacological treatment of the cognitive deficits associated with AD for the foreseeable future.

Apart from deficits in AChE, other neurotransmitter disturbances in AD include norepinephrine, 5-hydroxytryptamine (serotonin), gamma-amino butyric acid (GABA), somatostatin, vasopressin, corticotrophin releasing factor, substance P and neuropeptide Y. Therefore, drugs that act on these neurotransmitter systems may also have some effect on AD progression. Noncholinergic approaches have been tried in AD in a number of studies, and have involved neurotropic brain extracts, phosphatidyl serine, piracetam, hydergine, acetyl-l-carnitine, steroids, idebenone, selegilene and nimodipine. Despite all being used in one or two trials, there is no evidence of consistent benefit sufficient to recommend their use in practice.

AChE is not the only neurotransmitter abnormality found in patients with AD. Glutamate is a major excitatory neurotransmitter in the brain that activates a number of receptors, the best known being NMDA. Evidence suggests that glutamate may be involved in neurodegeneration: increased activity of the neurotransmitter is found in patients with AD (it is excitotoxic in high concentrations) and NMDA receptors activate beta-amyloid and also the production of tau protein (which when abnormally phosphorylated is associated with the development of neurofibrillary tangles). Memantine – an N-methyl-D-aspartate (NMDA) receptor antagonist – has been used with benefit in people with more severe dementia [Winblad, 1999; Reisberg, 2003]. Memantine is believed to replace the magnesium ion in a pathologically activated receptor and will maintain ion channel block at low concentrations of glutamate, thus protecting the neuronal system from pathological activation. However at higher concentrations of glutamate, the memantine block will be removed (just like the magnesium ion block in normal activation of the NMDA channel), thus preserving physiological activation.

In studies investigating AD and vascular dementia it was found that: 10 mg memantine a day, for 12 weeks, gave significant improvements in a global score as well as resulting in an improvement in the level of dependency as measured on a rating scale [Winblad, 1999]; 20 mg memantine a day, over 28 weeks, showed significant improvements in the Clinicians’ Interview-Based Impression of Change-Plus (CIBIC+ – a measure of activities of daily living) and in the Severe Impairment Battery (a measure of cognitive function in people with severe dementia) [Reisberg, 2000].

Memantine has been approved in the European Union and Australia for the treatment of moderately severe to severe AD.

Other noncholinergic therapies such as ginkgo biloba have shown efficacy in limited studies but the benefits were not of sufficient magnitude to recommend its routine use.

Despite the availability of these therapies there is no long-term clinical evidence to support the use of any of these, or any other agents, in the treatment of mixed dementia or vascular dementia, although trials of the AChE drugs are underway in patients with VaD. Research suggests that patients with VaD may benefit from treatment with cholinesterase inhibitors. A recent study [Black, 2003] demonstrated that donepezil is an effective and well-tolerated treatment for VaD and show that it may have an important place in the management of the condition. It is likely that, if a primary diagnosis of AD is made in the presence of vascular features, clinical improvements can be achieved in individual patients using treatment for AD.

A number of drug classes are being investigated as alternative treatments for dementia. Trials of beta and gamma-secretase inhibitors, statins, oestrogens, new and current cholinesterase inhibitors alone or in combination, and antihypertensives are being evaluated in addition to novel immunologically based therapies, anti-inflammatory agents, and vaccines [Wisniewski, 2002; Sano, 2002; Aisen, 2002]. Further enquiry into these drugs may bring about new treatment regimens for dementia, but it may be a number of years before these candidates are shown to be safe and efficacious.

A number of different drugs have been used in the treatment of neuropsychiatric features associated with dementia [Rosenquist, 2000, Burns, 1994]. There is increasing evidence that the cholinesterase inhibitors can also have a beneficial effect on the neuropsychiatric aspects of dementia, particularly in visual hallucinations and apathy.

Depressive symptoms are commonly seen in dementia and appear to be of two main types. There is no evidence that antidepressants are any less effective in treating depressive symptoms associated with AD, than in treating other late-onset depressions. Older antidepressants should be avoided because of their anticholinergic side effects, which potentially would cause additional memory impairment, but this is often not a problem in practice.

A list of antidepressants used for depression in dementia are listed in Table 10.

Agitation is probably the most common indication for the prescription of an antipsychotic drug and a number of different agents have been tried [Howard, 2001]. Antipsychotics are perhaps the mainstay of treatment and there is evidence to suggest they are of mild to moderate efficacy.

Older neuroleptics have more side effects than their newer counterparts and these are probably worse in people with dementia – sedation, postural hypotension, anticholinergic effects and extrapyramidal signs, especially tardive dyskinesia, are common. Agranulocytosis and liver and heart toxicity have also been seen. Neuroleptics have been shown to cause increased mortality in people with DLB [McKeith, 1992], leading to the UK Committee on Safety in Medicines ruling that particular caution needs to be exercised in patients with dementia who may have this diagnosis and who are prescribed the drugs [Committee on Safety of Medicines, 1994]. The new atypical antipsychotics are subject to rigorous clinical trials. Thioridazine has recently been withdrawn in the UK and Australia because of potential cardiotoxicity.

A host of other agents have been used to control agitation and Table 18 shows selected current pharmacological treatments for agitation in dementia.