Treatment Response in Alzheimer's Disease
Ever since the licensing of cholinesterase inhibitors (ChEIs) and memantine for the treatment of AD, there has been considerable debate about their clinical relevance, despite the statistically significant clinical effectiveness benefits demonstrated in the pivotal licensing trials.^3–5

Cognitive impairment is a key feature of AD and this is thought to be related to brain pathology. Improvement on a cognitive scale has become a frequently accepted tool for deciding clinically relevant treatment benefits. This narrow view of treatment response as improvement may have been chosen more for its sensitivity for detecting treatment effects than for its clinical relevance. Bullock suggested that even labeling acetylcholinesterase inhibitors as cognitive enhancers at all was overly simplistic.⁶ It could be argued that by focusing purely on improvement, this narrow view does not capture the totality of this rapidly and predictably deteriorating condition. The nature of the disease or syndrome of AD makes it seem unlikely that one specific treatment will provide a cure for a condition that is more akin to a metabolic syndrome if one considers the risk factors that predict its development. While age is the predominant risk factor, others include hypertension, raised cholesterol, diabetes, obesity, and cerebrovascular disease, and allied to this there is at least one common susceptibility gene. This suggests that a complex treatment will be necessary. Although our traditional goals in medicine are preventing the onset of, or curing, a disease, preventing worsening of the clinical condition is a clinically relevant, realistic treatment option and a very desirable outcome.⁷ When treatment options are discussed with patients and carers, prevention of worsening is often what they expect from treatment, reporting that they would be content to manage if things got no worse. Stabilization is of the greatest importance in the moderate to severe stages of the disease, where the rate of deterioration is highest. It is the increase in patient dependency in these stages of AD that causes the largest burden to families and society.

Improvement or Stabilization?
The clinical relevance of deterioration in function and behavior is clear. The fact that all the current therapies are assessed on their ability to improve, rather than stabilize, what is loosely termed ‘cognition’ is an erroneous and unhelpful paradigm. What the pivotal benefit of treatment should be has to be reconsidered in the light of what we now know from our experience in the last 10 years with the ChEIs and, more recently, with memantine.

Assessment Tools
The Alzheimer’s Disease Assessment Scale—cognitive subscale (ADAS-cog) is the tool that was used in the first successful license application for a ChEI and has consequently been used in all pivotal trials since.^9–11 The ADAS-cog assesses disparate functions of the brain (memory, language, praxis, and orientation), which are coalesced into a composite score. The score is weighted by memory impairment, but has validity as a measure of change.