Brain cholinergic system and Delirium in the aged

脑胆碱能系统与老年人谵妄

• 批准号: 06670990
• 负责人: UCHIYAMA Makoto
• 金额: $ 0.83万
• 依托单位: National Institute of Mental Health, National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670990/
• 关键词: Delirium; Central cholinergic agent; Drag intoxication; Circadian rhythm; Melatonin rhythm; 概ロリズム; メラトニン; コルチゾール

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

1)临床研究我们连续研究了120例在老年综合医院发生谵妄的老年患者（年龄范围，60- 93岁）。120例中20例诊断为药物中毒性谵妄。使用抗胆碱能药物如抗帕金森病药物或抗抑郁药是药物中毒性谵妄的主要原因（18/20）。这些结果表明，抗胆碱能药物可能经常发展谵妄的老年人。本研究在华盛顿举行的第19届CINP大会上发表。这项研究的一部分也发表在《神经病学》上。2）治疗谵妄的新药开发我们进行了一项开放性试验研究，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效果，这种疗效可能与药物的抗胆碱能性质有关。这项研究W ...更多信息 如提交并接受出版的Progress in Neuro-Psychopharmacology and Biological Psychiatry（in press 1996）。3）可能的更新的谵妄治疗的建议我们旨在激活人类大脑中的胆碱能系统。我们发现，维生素B12是最安全的药物中枢胆碱能药物在日本。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并提高了白天的警惕性。维生素B12的这一特性可能适用于治疗谵妄，因为大多数谵妄患者表现出昼夜节律紊乱。4）雌激素作为中枢胆碱能增强剂谵妄是老年痴呆症最常见的症状之一。我们给女性痴呆患者服用雌激素。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，这种性质可能与雌激素对脑中胆碱乙酰转移酶的激活作用有关。少

项目成果

T Ohkura, K Isse, K Akazawa, M Hamamoto, Y Yaoi, N Hagino: "Long-term estrogen replacement therapy in female patients with dementia of the Alzheimer type : 7 case reports." Dementia. 6. 99-107 (1995)

T Ohkura、K Isse、K Akazawa、M Hamamoto、Y Yaoi、N Hagino：“阿尔茨海默型痴呆女性患者的长期雌激素替代疗法：7 个病例报告。”

M Uchiyama, K, Tanaka.: "Circadian rhythm and Demendia." Clinics and drug hterapy. 14. 1135-1138 (1995)

M Uchiyama, K, Tanaka.：“昼夜节律和痴呆症。”

内山真: "現代のエスプリ 332号(勤労者の睡眠障害と生体リズム障害)" 至文堂, 11 (1995)

内山诚：“Gendai no Esprit No. 332（工人的睡眠障碍和生物节律障碍）”Shibundo，11（1995）

M. Uchiyama, G. Mayer, et al.: "Effects of vitamin B12 on human circadian body temperature rhythm." Neuroscience Letters. 192. 1-4 (1995)

M. Uchiyama、G. Mayer 等人：“维生素 B12 对人体昼夜节律的影响。”

M.Uchiyama,G.Mayer,K Meier-Ewert:"Effects of vitamin B12 on circadian body temperature rhythm," Japanese Journal of Psychiatry and Neurology,. 48. 504-505 (1994)

M.Uchiyama、G.Mayer、K Meier-Ewert：“维生素 B12 对昼夜体温节律的影响”，日本精神病学和神经病学杂志，。