Donepezil, rivastigmine, and vitamin E in Alzheimer disease: A combined P300 event-related potentials/neuropsychologic evaluation over 6 months

The latency of P300 "cognitive" event-related potentials changes if choline rgic activities of the central nervous system are pharmacologically manipul ated. We tested the hypothesis that the new cholinesterase inhibitors donep ezil (DPZ) and rivastigmine (Riv) may have an effect on the frequently abno rmal P300 component in patients with Alzheimer disease (AD), thereby allowi ng a significant evaluation of cholinesterase inhibitors. We evaluated 60 p atients with mild to moderately severe probable AD, ill comparison with 60 age-matched control subjects, with P300 recordings and neuropsychologic exa minations. Forty patients were randomly assigned in a double-blinded trial to 5-10 mg/d DPZ versus 2,000 IU/d vitamin E, and 20 patients were instead treated in an open trial with 1.5 to 12 mg/d Riv. In patients treated with vitamin E, we observed latency increments (7.4 +/- 3.5 msec) correlated wit h worsening neuropsychologic test scores. In patients treated with DPZ acid Riv, we found significant P300 latency reductions (15.3 +/- 3.2 msec and 2 2.0 +/- 3.3 msec). Shorter P300 latencies were associated with higher Wechs ler Adult Intelligence Scale scores and with lower AD Assessment Scale-cogn itive subscale (ADAS-cog) scores (R = 0.72). Correlations between ADAS-cog changes and P300 changes significantly separated patients treated with DPZ and Riv from those treated with vitamin E. Administration of DPZ and Riv re duced the latencies of P300 components proportionately to neuropsychologic test improvements. Combined P300 and neuropsychologic test evaluation signi ficantly separated DPZ-treated patients and Riv-treated patients from vitam in E-treated patients.