Onofrj Marco, Thomas Astrid, Luciano Anna Lisa, Iacono Diego, Di Rollo Andrea, D'Andreamatteo Giordano, Di Iorio Angelo
Department of Oncology and Neuroscience, Institute of Neurophysiopathology, University G.D'Annunzio, Italy.
Clin Neuropharmacol. 2002 Jul-Aug;25(4):207-15. doi: 10.1097/00002826-200207000-00004.
Early studies showed that the latency of P300 (P3) event related potential increases or diminishes when anticholinergic or cholinergic drugs are administered. We tested the hypothesis that new cholinesterase inhibitors like Donepezil (DPZ) may have an effect on the often abnormal P300 of patients with Alzheimer's Disease (AD), and therefore, that P300 recordings might simplify the evaluation of responses to cholinesterase inhibitor in patients with mild and moderate-severe AD. We evaluated 60 patients with AD: 30 patients with "mild" (Mini Mental State Examination 26-19) and 30 patients with "moderate-severe" (Mini Mental State Examination 18-10), according to the National Institute of Neurological and Communicative Disorders and Alzheimer's Disease and Related Disorders Association criteria in comparison with 40 age-matched controls. All subjects underwent P300 recordings and neuropsychologic examinations (Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale) during the 6-month follow-up. Patients were divided into four groups of 15 patients each: Group I DPZ (10 mg/day) and Group I Vitamin E (2000 IU/day) with "mild" AD; Group II DPZ and Group II Vitamin E with "moderate-severe" AD and same drug dosages. In patients treated with Vitamin E, we observed P3 latency increments (delta) by 11.8 +/- 1.8 ms in Group I and by 12.8 +/- 2.8 ms in Group II at 6 months; neuropsychologic test scores significantly worsened at 6 months (p < 0.001) in Group II patients. Donepezil induced significant P3 latency reductions (11.2 +/- 2.4 ms) in nine patients of Group I and all patients of Group II (16.1 +/- 4.0 ms), reaching a maximum at 3 months (23.2 +/- 2.7 ms). Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale scores improved during the same period, and the difference between Vitamin E and DPZ treated patients was highly significant for P3 (analysis of variance) and for P3-Alzheimer's Diseases Assessment Scale-Cognition (analysis of covariance) with p < 0.001 for pooled groups of patients with AD and Group II (DPZ) versus Group II (Vitamin E). Combined P3 event related potentials measurements, neuropsychologic test comparison evidences significant effects of DPZ in mild and in moderate-severe AD.
早期研究表明，给予抗胆碱能或胆碱能药物时，P300（P3）事件相关电位的潜伏期会增加或减少。我们检验了这样一个假设，即像多奈哌齐（DPZ）这样的新型胆碱酯酶抑制剂可能会对阿尔茨海默病（AD）患者常常异常的P300产生影响，因此，P300记录可能会简化对轻度和中度 - 重度AD患者胆碱酯酶抑制剂反应的评估。我们根据美国国立神经病学、语言障碍和卒中研究所及阿尔茨海默病及相关疾病协会的标准，评估了60例AD患者：30例“轻度”（简易精神状态检查表评分26 - 19）患者和30例“中度 - 重度”（简易精神状态检查表评分18 - 10）患者，并与40名年龄匹配的对照者进行比较。所有受试者在6个月的随访期间接受了P300记录和神经心理学检查（阿尔茨海默病评估量表 - 认知部分和韦氏成人智力量表）。患者被分为四组，每组15例：第一组为服用DPZ（10毫克/天）的“轻度”AD患者和服用维生素E（2000国际单位/天）的“轻度”AD患者；第二组为服用DPZ的“中度 - 重度”AD患者和服用维生素E的“中度 - 重度”AD患者，药物剂量相同。在服用维生素E治疗的患者中，我们观察到第一组在6个月时P3潜伏期增加（δ）了11.8±1.8毫秒，第二组增加了12.8±2.8毫秒；第二组患者在6个月时神经心理学测试分数显著恶化（p < 0.001）。多奈哌齐使第一组的9例患者和第二组的所有患者（16.1±4.0毫秒）的P3潜伏期显著缩短（11.2±2.4毫秒），在3个月时达到最大缩短值（23.2±2.7毫秒）。在此期间，阿尔茨海默病评估量表 - 认知部分和韦氏成人智力量表评分有所改善，对于P3（方差分析）以及P3 - 阿尔茨海默病评估量表 - 认知部分（协方差分析），维生素E治疗组和DPZ治疗组患者之间的差异非常显著，AD患者合并组以及第二组（DPZ）与第二组（维生素E）相比，p < 0.001。联合P3事件相关电位测量、神经心理学测试比较证明了DPZ对轻度和中度 - 重度AD有显著影响。
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