Brain cholinergic system and Delirium in the aged

1)临床研究我们研究了一家老年综合医院连续120例出现谵妄的老年患者（年龄范围60-93岁）。临床调查显示，120例患者中有20例诊断为药物中毒谵妄。服用抗胆碱能药物如抗帕金森药或抗抑郁药是引起药物中毒谵妄的主要原因（18/20）。这些结果表明，抗胆碱能药物可在老年人中引起谵妄。这项研究发表在华盛顿召开的第19届CINP大会上。本研究的部分内容也发表在《神经病学》杂志上。2)谵妄新药治疗的发展我们进行了一项公开试验研究，以验证四环抗抑郁药米安色林对老年人谵妄症状的疗效。研究对象为62例老年谵妄患者。我们发现米安色林对谵妄有良好的治疗作用，这种作用可能与米安色林抗胆碱能作用较小有关。这项研究已提交并接受发表在《神经精神药理学和生物精神病学进展》（1996年出版）上。3)提出可能的谵妄新疗法我们的目标是激活人类大脑中的胆碱能系统。我们发现维生素B12是日本可用的中枢胆碱能药物中最安全的药物。我们给健康的正常志愿者服用维生素B12，并评估其对昼夜节律的影响。我们发现维生素B12增强了昼夜节律的幅度，提高了白天的警惕性。维生素B12的这一特性可能适用于谵妄的治疗，因为大多数谵妄患者表现出昼夜节律紊乱。雌激素作为中枢胆碱能增强剂谵妄是老年痴呆最常见的症状之一。我们给痴呆女性患者注射雌激素。我们发现这种激素具有改善痴呆症状的特性，包括谵妄。我们推测这种特性可能与雌激素对脑内胆碱乙酰转移酶的激活作用有关。少

1) Clinical studyWe studied consecutive 120 elderly patients (range of age, 60-93y) who developed delirium in a geriatric general hospital. Clinical investigation revealed that 20 cases out of 120 were diagnosed as drug intoxication delirium. Administration of anti-cholinergic agents such as anti-parkinsonian drug, or anti-depressants, were the main cause of drug intoxication delirium (18/20). These results indicate that anti-cholinergic agents may frequently develop delirium in the aged. This study was presented in 19th CINP Congress held in Washington. A part of this study was also published in Neurology.2) Development of new drug treatment for deliriumWe conducted an open trial study to validate an efficacy of tetra-cyclic antidepressant mianserin on symptoms of delirium in the aged. Subjects were 62 elderly patients with delirium. We found that mianserin had favorable effect on delirium and that this efficacy may be related to the drug's less anti-cholonergic property. This study w … More as submitted and accepted for publication in Progress in Neuro-Psychopharmacology and Biological Psychiatry (in press 1996).3) Proposal of possible newer treatment for deliriumWe aimed to activate human cholinergic system in the brain. We found that vitamin B12 was the safest drug among central cholinergic agents available in Japan. We administered vitamin B12 on healthy normal volunteers and assessed its effect on the circadian rhythm. We found that vitamin B12 enhanced the amplitude of circadian rhythm and increased the vigilance of the daytime. This property of vitamin B12 may be applicable to treatment of delirium because most patients with delirium displayd disturbances of the circadian rhythm.4) Estrogen as a central cholinergic enhancerDelirium is one of the most frequent symptoms in demented elderly. We administered estrogen on demented female patients. We found that this hormone had a property to ameliorate the symptoms of dementia including delirium. We postulated that this property may be related to estrogen's activating effect on cholin acetyl transferase in the brain. Less