It is exactly one hundred years since Dr Alois Alzheimer first described the disease that still bears his name, a condition involving placques and nerve tangles in the brain resulting in severe memory problems. There is no cure for the disease but in the last decade drug treatments have become available that can slow the progression of disease and preserve the ability to function normally for longer. The first of these, and the one most commonly prescribed worldwide, is the cholinesterase inhibitor Aricept (donepezil).
Some people suffering from Alzheimer’s Disease may be missing out on benefits from drug treatment, however, because their doctors erroneously decide therapy isn’t working and should be stopped or changed. A physician survey released at the International Conference on Alzheimer’s Disease and Related Disorders held in Madrid, July 2006, reveals many doctors who treat Alzheimer’s are uncertain about the criteria for stopping or continuing drug therapy. As a result 85 per cent say there is an urgent need for clear and consistent guidelines.
A recent study, AWARE, shows about a third of patients do not show a definite response to treatment with Aricept for over six months but that nine out of 10 will go on to derive benefit in cognitive functioning and other symptoms over a further 12 weeks if they continue on treatment (1).
The physician survey, however, shows three out of four of the 376 participating doctors said they would decide whether or not treatment is working within three months with only one in 12 waiting six months or longer. If patients are thought to be declining or to be stable but not improving, over a third of doctors would alter treatment – either stop drug therapy altogether, add a further drug or choose an alternative.
Bengt Winbllad, Professor of Geriatric Medicine at the Karolinska Institute, Stockholm, Sweden commented: ?Stabilisation of symptoms or a slowing of decline over time should be considered as treatment benefits when managing a progressive neurodegenerative disease such as Alzheimer’s. It is important that physicians take this into account when carrying out initial treatment evaluations.?
The survey findings echo sentiments expressed by authors of the AWARE study, where a randomised double-blind phase showed patients who derived uncertain clinical benefit from Aricept initially, improved if given a further three months treatment whilst patients given a placebo did not. The study authors claim a 3 to 6-month timeframe is insufficient to fully assess treatment benefits and add that assessment should consider cognitive, functional (daily living activity performance) and behavioural symptoms. They warn: ?Standard evaluations might miss the changes that are considered important and significant to patients and caregivers.? Clinicians in the study were very clearly biased towards cognitive scores on the standard mental functioning assessment tool, the Mini-Mental State Examination (MMSE) but patients and caregivers relied less on cognition and were more likely to recognise treatment benefits in all domains. The clinical reality in many countries is that treatment for Alzheimer’s is often discontinued if patients decline by a single point on the MMSE, claim the authors.
Professor Winblad remarked: ?The survey results, when analysed in light of the findings from AWARE, highlight the importance of continuous treatment and multi-domain assessment. Even in the absence of significant cognitive response to Alzheimer’s Disease treatment, benefits in behaviour and function may be seen in patients over the long term which could significantly improve their quality of life.? Clear and consistent guidelines for diagnosing and managing Alzheimer’s are necessary to standardise treatment and evaluation practices, he stressed.
Aricept is one of three cholinesterase inhibitors available for treatment of Alzheimer’s Disease; others include rivastigmine and galantamine. These drugs suppress activity of the enzyme acetylcholinesterase which breaks down acetylcholine, a chemical playing an important role in memory and mental functioning. In Alzheimer’s Disease certain neurons containing acetycholine degenerate so brain activity and memory are impaired. Increasing levels of acetychloline should enhance memory capacity.
Treatment with cholinesterase inhibitors such as Aricept has been shown to improve cognitive performance which includes memory, attention, reasoning, language, orientation and carrying out tasks when compared against placebo in double-blind, randomised, controlled trials. Treatment is well tolerated but some people experience side effects which are usually mild and diminish with time.
Guidelines for management and treatment of Alzheimer’s Disease exist but differ from country to country so there is currently no global standard for patient treatment.
By Olwen Glynn Owen
olwen@macline.co.uk