Assessing individual patients for cognitive benefits from acetylcholinesterase inhibitors

To evaluate an objective method for individually assessing Alzheimer patients for cognitive benefits from acetylcholinesterase inhibitors, we conducted a secondary analysis of data from 234 subjects enrolled in a 30-week efficacy trial of tacrine hydrochloride. We determined which patients showed treatment-related improvement on the Alzheimer Disease Assessment Scale--Cognitive subscale (ADAS-Cog) and the MiniMental State Examination (MMSE). Four weeks after administration of the maximum dose, 14% showed significant improvement from baseline in their ADAS-Cog scores, and 30.6% showed significant improvement in their MMSE scores. Examination of response patterns over time revealed that 65% of patients showed no improvement in MMSE scores during the 120-160-mg phases of the trial, whereas 18% showed consistent improvement in MMSE scores during that time. Three percent of patients showed improvement in their MMSE scores only for the 160-mg assessment. How the methodology from this study can be generalized to other Alzheimer patients is discussed. We calculated prediction intervals to document the magnitude of fluctuation in performance that is normal for Alzheimer patients similar to those in this study. Patients who change more than the limit specified by the prediction interval have statistically significantly improved performance. We determined that an improvement on the MMSE of three or more points across a time period of 6 weeks marks statistically significant change for an individual. For intervals between 6 and 16 weeks, improvement of four or more points on the MMSE is statistically significant. The results indicate that monitoring individual patients for statistically significant improvements in cognitive functioning is feasible, sensitive to drug-related changes in performance, and could facilitate drug monitoring in patients.