Pharmacotherapy of Alzheimer's disease

Alzheimer's disease (AD) is a growing problem in an ageing population. Specific symptomatic treatments are now available for use in AD. The cholinesterase inhibitors (ChEIs) donepezil, galantamine and rivastigmine improve cholinergic function providing modest but clinically relevant improvements in cognition, activities of daily living, behaviour and consequently a reduction in caregiver burden. AD is a degenerative disorder and symptomatic treatments do not stop the underlying disease process. Nevertheless, despite an overall decline in cognitive scores over time, patients still maintain an advantage over untreated patients, demonstrated for donepezil in placebo-controlled studies of 1 year's duration. Continued treatment may help to delay the need for 24-hour care. The ChEIs have broadly similar efficacy despite some differences in modes of action and side-effects. Memantine is an NMDA receptor antagonists licensed for the treatment of moderate to severe AD, although, as with the ChEIs, there are studies demonstrating benefits in the whole spectrum of the disease. Memantine is well tolerated and although the original pivotal study in moderately severe AD showed benefits in terms of slowing of decline, improvements have been seen when used in conjunction with donepezil and in mild-to-moderate AD studies. The additional benefit demonstrated by addressing both the glutamatergic and cholinergic dysfunction may herald more combined approaches to treating this complex disease. Other avenues, such as antioxidants, oestrogens and anti-inflammatory drugs, have not shown any convincing benefits. The use of statins has shown some early positive results and a definitive trial is in progress.