P2‐305: Donepezil for memory decline in mild cognitive impairment: Efficacy and limitations in a seven‐year follow‐up study

Abstract

Background: Donepezil hydrochloride (Aricept) is a selective acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease (AD). However, the memory domains for which the agent is effective, especially in very early phase of the disease, have not been clarified.We observed patients with amnestic mild cognitive impairment (aMCI) for seven years to determine the efficacy and limitations of donepezil. Methods: Ten patients with aMCI were diagnosed on the basis of intact daily activity, normal Mini-Mental State Examination (MMSE) score, and deviated memory reduction (less than 85) on at least one index of the Wechsler Memory Scale Revised (WMS-R). Single photon emission tomography (SPECT) showed AD patterns in the Three-Dimensional Stereotactic Surface Projection (3DSSP) analysis. All patients received Aricept, 5 mg/day, with informed consent. The WMS-R and a set of spatial memory tests (SMT) we devised were administered at baseline and at months 6, 12, 36, 60, and 84. The SMT comprised two subtests: (a) a spatial source memory test, assessing the memory of the agent of an action (who acted) and the reality of an action (acted or imagined) using line drawings of furniture on small pieces of paper and a virtual room and (b) a line drawing furniture completion test, assessing the ability to organize spatial representations, in which patients were requested to insert an important part of a piece of furniture in the appropriate position. Both subtests assess cognitive ability to manipulate three-dimensional ideations underlying memory of a space. Results: At baseline, all patients showed one or moreWMS-R index scores below 85 along with errors on SMT. At month 6, all patients scored WMS-R index scores higher than 85, and this improvement was preserved till month 84. However, the error on SMT remained in all patients throughout the study.Conclusions:Donepezil hydrochloride, prescribed early in the course of AD, improves general (verbal and visual) memory function, as assessed by a standardized memory test, and preserves it for a considerable period of time; however, it does not affect spatial memory function, which requires three-dimensional ideation. The memory impairment related to manipulation of spatial representations might be germane to AD.