The clinical use of P300 event related potentials for the evaluation of cholinesterase inhibitors treatment in demented patients.
Centrally acting cholinesterase inhibitors (ChEIs) improve cognitive functions in Alzheimer's disease (AD) and other forms of dementia. Evaluation of treatment efficacy is based mainly on subjective assessment methods such as standardized neuropsychological tests. Therefore, an additional objective tool for the evaluation of drug response would be most helpful.Thirty-two patients suffering from dementia of several etiologies were treated with ChEIs (tacrine 19, donepezil 5, rivastigmine 8). Cognitive response was assessed pre ChEIs initiation (baseline) and after 26 weeks, as optimal tolerated doses were achieved and maintained (endpoint). Evaluation included repeated measurements of Mini Mental State Examination (MMSE), Alzheimer's disease assessment scale cognitive part (ADAS-cog) and P300. For statistical analysis we used ANOVA with repeated measures and Pearson correlation coefficient. Results demonstrated improvement of mean ADAS-cog by 2.0 points (from 29.4, n = 31 to 27.4, n = 29; p = 0.08) while MMSE remained almost unchanged (20.1, n = 29 to 19.8, n = 28). Mean P300 latency reduced significantly by 24 ms (from 383 +/- 7.9 msec, n = 32 to 359 +/- 7 msec, n = 32; p = 0.0001). However mean amplitudes did not change significantly from baseline to endpoint (13.5 +/- 6.2, n = 31 to 12.8 +/- 6.1, n = 31). Significant correlations were found between mean ADAS-cog and mean P300 latency at baseline and end-point (R = 0.485 p = 0.019, R = 0.626 p = 0.001 respectively, n = 23) and between mean MMSE and P300 latency at baseline and endpoint (R = -0.420 p = 0.046, R = -0.703 p < 0.001 respectively, n = 23). Our data suggests that P300 is a reliable instrument for assessment of cognitive response to ChEIs in demented patients.
Werber
E A
EA
Department of Neurology, Assaf Harofe Medical Center, Zerifin, and Sackler School of Medicine, Tel-Aviv University, Israel. werbered@bezeqint.net
Gandelman-Marton
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R
Klein
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C
Rabey
J M
JM
D000109:Acetylcholine / Q000172:deficiency*; D000368:Aged; D002219:Carbamates / Q000009:adverse effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D003704:Dementia / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D000077265:Donepezil; D004569:Electroencephalography / Q000187:drug effects*; D018913:Event-Related Potentials, P300 / Q000502:physiology*; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates; D010880:Piperidines / Q000009:adverse effects; D011446:Prospective Studies; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D000068836:Rivastigmine; D013619:Tacrine / Q000009:adverse effects; D016896:Treatment Outcome
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D013619:Tacrine; D000077265:Donepezil; D000109:Acetylcholine; D000068836:Rivastigmine