Cognitive predictors of donepezil therapy response in Alzheimer disease

To examine whether the presence of domain-specific cognitive impairments would predict a response to donepezil medication in patients with mild-to-moderate Alzheimer disease (AD).

The protocol was an open-label study of 30 AD subjects (mean age 74 years; education 11 years; Mini-Mental State Exam (MMSE) 23 of 30) beginning a 6-month course of treatment with donepezil. Global response to treatment was determined using a combination algorithm based on changes over 6 months in the ADAS-cog, MMSE and CIBIC. In addition, a set of neuropsychological and experimental cognitive tests designed to test five domains of cognition were administered before beginning therapy in order to determine which domain of testing would be predictive to response to treatment. The tests examined attention, short-term and working memory, learning and memory, visuo-spatial motor skills, and lexical-semantic knowledge.

Eighteen of the thirty subjects were rated as having responded (stable or improved scores on the combination algorithm) to the therapy. Responders were significantly less impaired prior to treatment on the following tests: the Clock Drawing Test, a Visual-Spatial Motor Tracking Test, and the Boston Picture Naming Test. No significant initial group differences were noted on the other neuropsychological or experimental cognitive measures.

The tests that most reliably predicted response to donepezil in AD subjects were in the domains of visual-spatial motor abilities and lexical-semantic functioning.