A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD

To the Editor: In their recently published, 1-year prospective, double blind, placebo-controlled study, Winblad et al.1 examined the long-term clinical efficacy and safety of donepezil in mild to moderate AD. I congratulate the investigators for their effort. Unfortunately, it remains puzzling to me why the investigators restricted the entry criteria and consequently selected a population that was not representative of general clinical practice. By excluding patients with frequently coexisting medical conditions such as diabetes, chronic obstructive pulmonary disease, and endocrine diseases, the demonstrable effect of the treatment is not obscured by comorbid conditions and is therefore probably the greatest possible effect that can be observed. One clinical trial revealed that including patients with significant comorbidity reduced the beneficial effect of donepezil by almost 50% of that observed in trials with more rigorous entry criteria.2 In addition, the strict lack of any significant effect at the end point (last observation carried forward; LOCF) on the primary efficacy parameter raises questions. Furthermore, it is questionable whether the magnitude of change taken at its highest value (week 52 [6.2 units or 9.6%]) is detectable by the physician and caregivers. …