Alzheimer’s Disease Therapy: Relating Clinical Information to Patients and Caregivers
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Introduction
Consider this common scenario, no doubt very familiar: A patient with moderate Alzheimer’s disease (AD) arrives at the office with his daughter. The daughter has seen advertisements in magazines and asks for medication for her parent. This not only provides an opening for discussions on treatment and expectations of therapy, but also challenges the clinician to translate the clinical trial data and published treatment guidelines into meaningful information for the patient and his relative. Of course, the type of therapy offered will depend on the symptoms displayed by the patient and the stage of his illness, but the question for the clinician always is: What will be the value of intervention to the patient and his caregiver?
Guidelines for Treating Alzheimer’s Disease
Guidelines exist that assess published and unpublished data, taking into account the opinions of clinicians, caregivers, and patients to provide evidence-based guidance on the best course of action for patients. Well-known guidelines are those from the American Academy of Neurology,1 which state that the cognitive symptoms of AD should be treated with the cholinesterase inhibitors (ChEIs)donepezil, rivastigmine, and galantamineand vitamin E (although this has fallen into disfavor at the time of writing), particularly in those patients with mild-to-moderate AD. Agitation, psychosis, and depression in patients should also be addressed.
The United Kingdom National Institute for Clinical Excellence (NICE) initially published similar advice in January 2001,2 recommending that donepezil, rivastigmine, or galantamine should be prescribed for people with mild-to-moderate AD (Mini-Mental State Examination [MMSE] score ≥ 12) once diagnosis (including tests of cognition, global and behavioral function, and activities of daily living [ADLs]) has been made by a specialist. However, updated guidance from NICE released in November 2006 stated that ChEIs are now only recommended for patients with AD of moderate severity (MMSE, 10-20).3
Clinical guidelines are useful in fueling discussions with patients and their caregivers, as they are based on expert appraisal of available information. They also take into consideration significant differences in healthcare systems, but generally have their own unique set of biases and have to consider patients with AD in entirety rather than on a patient-by-patient basis. As a clinician, one is pleased that the family wants help for the patient, but considering these guidelines, where do you start and with what therapy?
Clinical Trial Data
In addition to the guidelines, there are published clinical trials. In these trials, treatment success is formally judged on cognition, function, and behavior, with additional tests included sometimes for ADLs, quality of life (QoL), financial costs, and caregiver impact. A personal appraisal of these data can be of help for decisions that must be made in the office.
Cognition
There is good evidence from randomized, placebo-controlled clinical trials (lasting 3-12 months) that ChEIs benefit cognition in patients with mild-to-moderate AD and that donepezil has a positive impact on cognition in patients with severe AD. All three drugs (donepezil, rivastigmine, and galantamine) have published studies utilizing either the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), the MMSE, or both in patients with mild-to-moderate AD, and donepezil has published efficacy data in severe patients using the Severe Impairment Battery (SIB).
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