A new study has shed light on the perplexing question of what the optimal drug or drug combination is for Alzheimer’s Disease (AD).  AD affects 4.5 million people in the US and is characterized by cognitive decline, memory impairment, deterioration of activities of daily living, and the development psychiatric signs and symptoms.  Pharmacotherapy with cholinesterase inhibitors, such as donepezil, produces only modest benefits with early and continuous treatment that slow cognitive decline in AD, but does not reverse the disease.  Memantine, an NMDA-receptor antagonist, produces similar, modest efficacy in moderate to severe disease AD.
 
A new study enrolled 295 community-dwelling patients who had been receiving donepezil and had moderate or severe AD.  Patients were randomized to either: 1) continue donepezil, 2) discontinue donepezil, 3) discontinue donepezil and start memantine, or 4) continue donepezil and start memantine.  Patients received the study treatment for 52 weeks.  Results showed that in patients with moderate or severe AD, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months.  The benefits of starting memantine were less than the benefits of continuing donepezil, but they were significant.  There were no significant benefit of the combination of donepezil and memantine over donepezil alone.  This study suggests that it may be suitable to continue donepezil therapy in patients with moderate-to-severe AD if they have been on donepezil already and are tolerating it well.  The study also raises doubt whether the combination of donepezil and memantine confers any significant additional cognitive benefit over donepezil alone.
 

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