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: 3767563
• 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/3767563
• 关键词: Alzheimer's disease; REM sleep; Wernicke Korsakoff syndrome; alcoholic psychosis; alcoholism /alcohol abuse; alcoholism /alcohol abuse chemotherapy; dementia; drug withdrawal; human subject; interview; longitudinal human study; malnutrition; melatonin; memory disorders; neuropharmacology; neurotoxins; neurotransmitters; nutrition related tag; pineal body; thiamine deficiency; transaldolase /transketolase; urinalysis

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种 神经病理学上的不同症状：酒精性痴呆和 科尔萨科夫精神病(酒精健忘症)。酒精性痴呆症 以弥漫性皮质损害为特征，主要与 酒精的神经毒性；科萨科夫的精神病与 由于营养(硫胺素)缺乏造成的皮质下损害。严重者 记忆受损，其他智力功能相对较少 区分Korsakoff的精神病和酒精性痴呆(这可能是 在临床上与最常见的痴呆症原因无法区分， 阿尔茨海默病)。我们已经报道过Korsakoff患者的睡眠 特征是与正常志愿者相比，快速眼动潜伏期缩短， 而阿尔茨海默病患者有正常的潜伏期。此外，三角洲 阿尔茨海默病患者睡眠减少，但柯萨科夫病患者睡眠正常 精神错乱。大多数患者表现出每日排泄量减少 褪黑素的主要尿代谢物，羟褪黑素，与 科萨科夫的精神病。这一发现提示松果体受损。 功能。硫胺代谢的遗传差异可能是易感因素 患者会患上科萨科夫精神病。大多数柯萨科夫病患者 我们研究的精神病患者有一种转酮醇酶活性降低 对焦磷酸硫胺素的亲和力。修改激活和唤醒方式 神经递质系统的药物调节可能在 治疗柯萨科夫精神病，而酒精性痴呆可能需要 类似于阿尔茨海默病的治疗策略。这 该方案旨在利用临床、神经放射学、 生理学和神经药理学研究以区分这两者 病理实体，遵循一个纵向的过程，并联系 治疗方案中的变量对结果的影响。