The effect of tacrine and lecithin in Alzheimer's disease

✍ Scribed by K. Peace; N. H. G. Holford

• Publisher: Springer
• Year: 1994
• Tongue: English
• Weight: 602 KB
• Volume: 47
• Category: Article
• ISSN: 0031-6970
• DOI: 10.1007/bf00193473

✦ Synopsis

Tacrine, a cholinesterase inhibitor, has beneficial effects on cognition and global status in patients with Alzheimer's disease. These effects have been demonstrated in clinical trials by double-blind comparisons with placebo. Tacrine dosages have been studied in 5 protocols that used either enrichment or parallel designs.

We have used a population pharmacodynamic model to describe the response to tacrine and placebo in the 3 trials that used the enrichment design. The time-course of the response and its relation to tacrine dosage obtained from the enrichment design analysis were used to define the parallel design.

The effects of tacrine on cognition and global status was estimated separately from each trial. Analysis of the 2 trials using the parallel design confirmed the predictions from the enrichment design. By combining the data from all 5 trials it was possible to show that tacrine potency was similar in all studies, but that the placebo response was different in some. The effect of tacrine was linearly proportional to dosage from 40 to 160 mg per day.

One of the enrichment design trials included a subgroup treated with lecithin, a choline precursor. The potency of lecithin was equivalent to about 40 mg per day of tacrine. Using the combined data from all 5 trials it was possible to distinguish a responder population, approximately one-third of all patients, with a 4-fold greater effect compared with poor responders.

Tacrine has beneficial effects on cognitive status in patients with Alzheimer's disease. Lecithin has a small additional benefit independent of tacrine. The pharmacodynamic model predicts a 1.94 year delay in disease