Progress in understanding variability in cognitive responses to cholinesterase inhibitor treatment.

Limitations on the duration of clinical trials, and the constraints of participant selection for such studies, have left many unanswered questions regarding the optimal duration of drug treatment for Alzheimer's disease patients, as well as the subgroups of patients that benefit most. Carefully designed observational studies in naturalistic settings can provide important supplementary information to aid clinical decision-making and patient counseling. A paper by Wattmo and colleagues published recently in Alzheimer's Research & Therapy has provided important new information on differential responses to cholinesterase inhibitor (ChEI) treatment in specific subgroups of patients over a 3-year follow-up period. All of the participants in their study were started on one of three ChEIs after their initial assessment, and periodic assessments of cognitive change and the dosage of ChEIs as well as concomitant medications were subsequently recorded. In addition to providing strong evidence of nondifferential effects on cognition of the three ChEIs as used in this practice, the study identified clinically significant differences in the responses of specific subgroups of patients to the initiation of ChEI treatment. Of particular interest to clinicians is the finding that older patients and those with worse cognitive functioning at baseline had a better treatment response. The notion that treatment may be futile in the oldest or the most impaired patients was thus not supported by Wattmo and colleagues' cohort. Additional well-designed naturalistic studies of this type are needed to advance our knowledge of the long-term outcomes obtained with different therapeutic agents, and of the covariates that significantly modify responses to Alzheimer's disease treatments.