The article by Winblad et al. in the July 2001 issue of the International Journal of Geriatric Psychiatry reported the results of a roundtable discussion held at the World Alzheimer Congress in Washington DC, USA in July 2000. Ten academic leaders met to reassess the definition of treatment success using cholinesterase inhibitors for patients with Alzheimer's disease (AD).
The issue at hand emanates from the successful development of cholinesterase inhibitors to treat cognitive dysfunction. Historically, this class of agents was developed to produce cognitive improvement based on observations made in the 1970s that loss of acetylcholine-containing cells occurred in AD and that the loss of cholinergic activity correlated with the degree of cognitive decline. Thus, the development of cholinesterase inhibitors represented a rational approach to the treatment of patients with AD. Following the initial report of a remarkable improvement in 17 patients treated with tacrine (Summers et al., 1986), a large multicentre clinical trial was conducted to test the efficacy of tacrine in AD. The conduct of this trial paved the way for the US Food and Drug Administration (FDA) to consider the regulatory pathway by which drugs with an antidementia claim could seek approval. The results of these discussions appeared in draft guidelines (Leber, 1990), which required a treatment-placebo difference on a suitable performance-based cognitive instrument which was representative of the core features of the disease. In addition, to make certain that the effect size was not trivial, a treatment-placebo difference on a clinician's global evaluation was also required.