Drugs in Alzheimer's disease Dementia: An overview of current pharmacological management and future directions.
BACKGROUND
Alzheimer's dementia is one of the most significant health burdens of the modern age in both industrialised and non-industrialised nations as it is a major cause of morbidity and functional impairment in the elderly. Currently there are no cures for progressive dementias, including Alzheimer's disease, and no treatments that would modify their progress. Intervention involves pharmacological treatment to temporarily relieve the symptoms, including three cholinesterase inhibitors and a noncompetitive NMDA antagonist, and the efficacy of these is widely debated. While our understanding of the underlying pathology of Alzheimer's continues to grow, we have yet to fully elucidate the mechanisms that drive neuronal loss in this condition. Any truly disease-modifying treatment must be developed to target these pathological pathways.


METHODS
An extensive analysis of the available literature is presented here, including a number of trials, meta-analyses and reviews, with the aim of assessing current management, establishing best practice and summarising the future of dementia care.


RESULTS
The efficacy of acetylcholinesterase inhibitors remains controversial due to uncertainty over what change is considered clinically significant. Any derived benefit seems to be independent of dementia severity and donepezil is the most cost-effective for Alzheimer's dementia. Memantine potentially influences the underlying pathological processes in Alzheimer's disease and may be more effective in moderate to severe Alzheimer's dementia. The role of combination therapy remains uncertain. Future therapies are aimed at modulating the disease process by using chemical agents to inhibit amyloid and tau deposition. None have been approved clinically.


CONCLUSIONS
Current pharmacological therapy for Alzheimer's dementia is very limited and primarily aims at achieving symptom control. A major limitation is our lack of knowledge of the underlying pathology and it is only by better understanding the disease process that we can optimize therapeutic agents that modify disease progression.
Emmanuel College, University of Cambridge, Cambridge, CB2 3AP, UK, se317@cam.ac.uk.
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