The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease

Background: Behavioral abnormalities are common in Alzheimer disease (AD); cholinergic treatment reduces the behavioral disturbances of some patients with AD. Characterizing the pretreatment profile of patients who are likely to respond to cholinergic therapy will aid the efficient use of clinical resources. Objective: To determine the baseline behavioral profile for 86 patients with AD treated with the cholinesterase inhibitor donepezil hydrochloride. Methods: Open-label retrospective study of treatment-related behavioral assessments. Based on previous double-blind placebo-controlled experience using the Neuropsychiatric Inventory (NPI), patients were divided into responder (greater than or equal to 4-point total NPI score decrease, indicating improvement), unchanged (+/-3-point total NPI score change),or nonresponder (greater than or equal to 4-point total NPI score increaser indicating worsening) groups. The Mini-Mental State Examination assessed cognitive response. Results: Behavioral improvement was seen in 35 patients (41%), worsening in 24 (28%), and no change in 27 (31%). Comparison of profiles in behavioral responders vs nonresponders revealed significantly worse delusions (P = .04), agitation (P = .04): depression (P = .006) anxiety (P = .02), apathy (P = .003); disinhibition (P = .02), and irritability (P < .001) at baseline in responders. Five behaviors changed significantly from baseline, improving for the responders and worsening for the nonresponders: delusions (P = .003 for nonresponders, P = .004 fbr responders), agitation (P = .01), anxiety (P = .006 for nonresponders, P = .004 for responders), disinhibition (P = .02 for nonresponders, P = .05 for responders), and irritability (P = .003 for nonresponders, P = .001 for responders). The behavioral changes were dose dependent. Cognition did not change significantly with donepezil treatment within any group. Conclusions: Donepezil has psychotropic properties, and pretreatment behaviors help predict patients' responses to treatment.