Herrmann Nathan, Rothenburg Lana S, Black Sandra E, Ryan Michelle, Liu Barbara A, Busto Usoa E, Lanctôt Krista L
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
J Clin Psychopharmacol. 2008 Jun;28(3):296-301. doi: 10.1097/JCP.0b013e318172b479.
Apathy is a common behavioral symptom of Alzheimer's disease (AD), being present in up to 70% of patients. Apathy in AD and non-AD populations has been associated with dysfunction in the dopaminergic brain reward system, suggesting that pharmacotherapeutic targeting of this system may be an effective treatment for apathy in AD. We therefore performed a randomized, double-blind, placebo-controlled crossover trial of methylphenidate in a sample of 13 apathetic AD patients (6 men, 7 women; age mean 77.9 years [SD, 7.8 years]; Mini Mental Status Examination score, 19.9 [SD, 4.7]). Patients were treated with methylphenidate (10 mg PO twice a day) or an identical placebo in two 2-week phases separated by a 1-week placebo washout. All patients participated in a dextroamphetamine challenge test (one 10-mg oral dose) before treatment with methylphenidate to gauge the functional integrity of the dopamine brain reward system. Overall, patients demonstrated greater improvement with methylphenidate compared with placebo according to Apathy Evaluation Scale total change scores (end of treatment - baseline: Wilcoxon Z = -2.00; P = 0.047). However, a significantly greater proportion of patients experienced at least 1 adverse event with methylphenidate compared with placebo (3 vs 1; chi = 4.33, P = 0.038). Two patients experienced serious adverse events with methylphenidate, consisting of delusions, agitation, anger, irritability, and insomnia, which resolved upon discontinuation of the medication. Response to methylphenidate was associated with increases in inattention on a continuous performance task after dextroamphetamine challenge. Psychostimulants may be effective in treating features of apathy in AD, and dopaminergic changes may predict response.
冷漠是阿尔茨海默病（AD）常见的行为症状，高达70%的患者存在该症状。AD患者及非AD人群中的冷漠与多巴胺能脑奖赏系统功能障碍有关，这表明针对该系统进行药物治疗可能是治疗AD患者冷漠症状的有效方法。因此，我们对13例冷漠型AD患者（6例男性，7例女性；平均年龄77.9岁[标准差7.8岁]；简易精神状态检查表评分19.9[标准差4.7]）进行了一项关于哌醋甲酯的随机、双盲、安慰剂对照交叉试验。患者在两个为期2周的阶段中分别接受哌醋甲酯（口服10 mg，每日两次）或相同的安慰剂治疗，两个阶段之间有1周的安慰剂洗脱期。所有患者在接受哌醋甲酯治疗前均参加了右旋苯丙胺激发试验（口服10 mg单剂量），以评估多巴胺脑奖赏系统的功能完整性。总体而言，根据冷漠评估量表的总变化评分，与安慰剂相比，患者使用哌醋甲酯后有更大改善（治疗结束 - 基线：Wilcoxon Z = -2.00；P = 0.047）。然而，与安慰剂相比，使用哌醋甲酯的患者发生至少1次不良事件的比例显著更高（3例 vs 1例；卡方 = 4.33，P = 0.038）。两名患者使用哌醋甲酯后出现严重不良事件，包括妄想、激动、愤怒、易怒和失眠，停药后症状缓解。对哌醋甲酯的反应与右旋苯丙胺激发试验后持续性操作任务中注意力不集中的增加有关。精神兴奋剂可能对治疗AD患者的冷漠症状有效，多巴胺能变化可能预测反应。
