To evaluate an objective method for individually assessing Alzheimer patien
ts for cognitive benefits from acetylcholinesterase inhibitors, we conducte
d a secondary analysis of data from 234 subjects enrolled in a 30-week effi
cacy trial of tacrine hydrochloride. We determined which patients showed tr
eatment-related improvement on the Alzheimer Disease Assessment: Scale-Cogn
itive subscale (ADAS-Cog) and the Mini-Mental State Examination (MMSE). Fou
r weeks after administration of the maximum dose, 14% showed significant im
provement from baseline in their ADAS-Cog scores, and 30.6% showed signific
ant improvement in their MMSE scores. Examination of response patterns over
time revealed that 65% of patients showed no improvement in MMSE scores du
ring the 120-160-mg phases of the trial, whereas 18% showed consistent impr
ovement in MMSE scores during that time. Three percent of patients showed i
mprovement in their MMSE scores only for the 160-mg assessment. How the met
hodology 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 performan
ce. We determined that an improvement on the MMSE of three or more points a
cross a time period of 6 weeks marks statistically significant change for a
n 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 improveme
nts in cognitive functioning is feasible, sensitive to drug-related changes
in performance, and could facilitate drug monitoring in patients.