CENTRAL AND PERIPHERAL NERVOUS SYSTEM FUNCTION IN ABSTINENT ALCOHOLICS

戒酒者的中枢和周围神经系统功能

• 批准号: 3745227
• 负责人: M ECKARDT
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3745227
• 关键词: Alzheimer's disease; REM sleep; Wernicke Korsakoff syndrome; alcoholic psychosis; alcoholism /alcohol abuse; dementia; drug withdrawal; histopathology; human subject; longitudinal human study; melatonin; memory disorders; neuropharmacology; neurotoxins; nutrition related tag; thiamine deficiency

Behavioral deficits in alcoholics have been conceptualized in terms of two neuropathologically distinct syndromes: alcoholic dementia and Korsakoff's psychosis (alcohol amnestic disorder). Alcoholic dementia is characterized by diffuse cortical damage primarily related to the neurotoxicity of alcohol; Korsakoff's psychosis is associated with subcortical lesions due to nutritional (thiamine) deficiency. Severe memory impairment with relative sparing of other intellectual functions distinguishes Korsakoff's psychosis from alcoholic dementia (which may be clinically indistinguishable from the most common cause of dementia, Alzheimer's disease). We have reported that sleep in Korsakoff patients is characterized by a reduced REM latency compared to normal volunteers, whereas Alzheimer patients have normal latencies. Furthermore, delta sleep is reduced in Alzheimer's disease, but is normal in Korsakoff's psychosis. Most patients with demonstrated reduced daily excretion of the major urinary metabolite of melatonin, hydroxmelatonin, present with Korsakoff's psychosis. This finding is suggestive of impaired pineal function. Genetic differences in thiamine metabolism may predispose patients to develop Korsakoff's psychosis. Most patients with Korsakoff's psychosis whom we have studied have had a transketolase with reduced affinity for thiamine pyrophosphate. Modifying activation and arousal by pharmacologic modulation of neurotransmitter systems may be effective in treatment of Korsakoff's psychosis, whereas alcoholic dementia may require treatment strategies similar to those in Alzheimer's disease. This protocol is intended to utilize clinical, neuroradiological, physiological, and neuropharmacological studies to differentiate these two pathologic entities, to follow a longitudinal course, and to relate variables in treatment protocols to outcome.

酗酒者的行为缺陷被概念化为两个方面 神经病理学上不同的综合征：酒精性痴呆和 Korsakoff精神病（酒精遗忘症）。 酒精性痴呆是 以弥漫性皮质损伤为特征，主要与 酒精的神经毒性; Korsakoff精神病与 由于营养（硫胺素）缺乏引起的皮质下病变。 严重 记忆障碍伴其他智力功能相对保留 将Korsakoff精神病与酒精性痴呆区分开来（酒精性痴呆可能是 在临床上与痴呆症的最常见原因无法区分， 阿尔茨海默病）。 我们已经报道了科尔萨科夫患者的睡眠 其特征在于与正常志愿者相比REM潜伏期缩短， 而阿尔茨海默病患者的乳酸水平正常。 此外，Delta 老年痴呆症患者睡眠减少，而科萨科夫病患者睡眠正常 精神病 大多数患者表现出减少每日排泄的 褪黑激素的主要尿代谢物，羟褪黑激素，存在于 科萨科夫精神病 这一发现提示松果体受损 功能 硫胺素代谢的遗传差异可能导致 发展为科萨科夫精神病 大多数科萨科夫病患者 我们研究过的精神病患者的转酮醇酶减少， 对焦磷酸硫胺素的亲和力。 通过以下方式改变激活和唤醒 神经递质系统的药理学调节可有效地 治疗科尔萨科夫精神病，而酒精性痴呆可能需要 治疗策略类似于阿尔茨海默病。 这 方案旨在利用临床，神经放射学， 生理学和神经药理学研究来区分这两种 病理实体，遵循纵向过程，并与 治疗方案中的变量对结果的影响。