Donepezil (Aricept), widely used to treat mild to moderate Alzheimer disease (AD), has demonstrated benefit when patients continued to take the drug as their condition progressed.

The study yielding this finding involved 295 community-dwelling patients in the United Kingdom who had been treated with donepezil for at least three months and who had moderate or severe AD. Donepezil, a cholinesterase inhibitor and the most commonly prescribed of the dementia drugs, is recommended for persons in the earliest stages of AD. Clinicians are advised to stop prescribing the drug once the patient has advanced to moderate to severe Alzheimer status; there had been no clear evidence that continuing treatment was of benefit to patients.

In this study, however, patients assigned to continue receiving donepezil scored an average of 1.9 points higher on the Standardized Mini-Mental State Examination (SMMSE) than did patients assigned to discontinue the drug, with the higher scores indicating better cognitive function. The donepezil group also scored 3.0 points lower on the Bristol Activities of Daily Living Scale (BADLS) than did the patients no longer taking the drug, which indicated less impairment.

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Investigators also assigned some patients to receive memantine (Namenda) either while taking donepezil or upon discontinuing donepezil. Memantine is an N-methyl-D-aspartate (NMDA)-receptor antagonist prescribed to control AD. Compared with those assigned to receive a memantine placebo, memantine users scored an average of 1.2 points higher on the SMMSE, and 1.5 points lower on the BADLS. 

The efficacy of each agent did not differ significantly in the presence or absence of the other, and combining donepezil and memantine use did not offer significant benefits over the use of donepezil alone (N Engl J Med. 2012;366:893-903).

A separate study published in BMC Geriatrics (2012;12:3; available at, accessed March 15, 2012) described a 21-item questionnaire that can be used not only to help primary-care providers diagnose AD, but also to help them distinguish between normal memory loss and amnestic mild cognitive impairment (aMCI). The items are divided into five domains including memory, orientation, functional ability, visuospatial ability, and language. Six of the items are predictive of clinical AD, and four items—all memory-related—were found to be predictive of aMCI.