Kumari Veena, Aasen Ingrid, ffytche Dominic, Williams Steven C R, Sharma Tonmoy
Department of Psychology, Institute of Psychiatry, King's College London, London, UK.
Neuroimage. 2006 Jan 15;29(2):545-56. doi: 10.1016/j.neuroimage.2005.08.013. Epub 2005 Sep 21.
Facilitation of central cholinergic activity may form a potential treatment strategy for cognitive impairment in schizophrenia. In a randomized, placebo-controlled, double-blind, parallel-group design, we investigated the neural correlates of cognitive effects of rivastigmine, an acetylcholinesterase inhibitor, given as an add-on therapy to antipsychotic-treated schizophrenia patients. Thirty-six chronic schizophrenia patients with mild cognitive impairment took part. After 1 week on placebo (baseline), all patients entered a double-blind protocol; 18 were allocated to receive rivastigmine and 18 placebo for the next 12 weeks (final sample with usable imaging data: 11 patients on rivastigmine, 10 on placebo). All patients underwent functional magnetic resonance imaging during a parametric 'n-back' task, involving monitoring of dots in particular locations on a screen at a given delay from the original occurrence, twice: at baseline and 12 weeks post-rivastigmine/placebo treatment. Compared to placebo, rivastigmine produced only a small and non-significant improvement in task accuracy across all conditions with no change in response latency, and increased activity in the extrastriate visual cortex in areas associated with visual and spatial attention but not in any region within the working memory network. Our observations suggest that cholinergic enhancement with rivastigmine at doses known to be effective in Alzheimer's disease does not produce strong and clinically meaningful cognitive and neural changes in schizophrenia patients treated with atypical antipsychotics although the neural effects in terms of enhanced neuronal activity in regions associated with visual and spatial attention are consistent with those reported previously with cholinergic enhancement in healthy subjects.
增强中枢胆碱能活性可能构成治疗精神分裂症认知障碍的一种潜在策略。在一项随机、安慰剂对照、双盲、平行组设计中，我们研究了卡巴拉汀（一种乙酰胆碱酯酶抑制剂）作为抗精神病药物治疗的精神分裂症患者的附加疗法时，其认知效应的神经相关性。36名患有轻度认知障碍的慢性精神分裂症患者参与了研究。在服用安慰剂1周（基线期）后，所有患者进入双盲方案；接下来的12周内，18名患者被分配接受卡巴拉汀治疗，18名患者接受安慰剂治疗（最终有可用成像数据的样本：11名接受卡巴拉汀治疗的患者，10名接受安慰剂治疗的患者）。所有患者在参数化“n-back”任务期间接受功能磁共振成像检查，该任务涉及在给定延迟时间后监测屏幕上特定位置的点，共进行两次：基线期和卡巴拉汀/安慰剂治疗后12周。与安慰剂相比，卡巴拉汀在所有条件下仅使任务准确性有小幅且无统计学意义的改善，反应潜伏期无变化，并且在与视觉和空间注意力相关的纹外视觉皮层区域活动增加，但工作记忆网络内的任何区域均未出现这种情况。我们的观察结果表明，对于接受非典型抗精神病药物治疗的精神分裂症患者，使用已知对阿尔茨海默病有效的剂量的卡巴拉汀增强胆碱能作用，并不会产生强烈且具有临床意义的认知和神经变化，尽管在与视觉和空间注意力相关区域增强神经元活动方面的神经效应与先前在健康受试者中报道的胆碱能增强效应一致。
