CENTRAL AND PERIPHERAL NERVOUS SYSTEM FUNCTION IN ABSTINENT ALCOHOLICS

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：酒精性痴呆和科尔萨科夫综合征 酒精性遗忘症（Alcohol Amnestic Disorder） 酒精性痴呆的特征是 弥漫性皮质损伤主要与神经毒性有关， 酒精; Korsakoff精神病与皮质下病变有关， 维生素B1缺乏症（B1） 严重的记忆障碍， 其他智力功能的相对节省使科萨科夫的 酒精性痴呆引起的精神病（临床上可能是 与最常见的痴呆症阿尔茨海默氏症没有区别 疾病）。 我们最近发现，科尔萨科夫患者的睡眠 其特征在于与正常志愿者相比REM潜伏期减少， 而阿尔茨海默病患者的REM潜伏期正常。 此外，Delta 老年痴呆症患者睡眠减少，但科萨科夫患者睡眠正常 患者 我们还证明了减少每日排泄的主要 褪黑激素的尿代谢产物--羟褪黑激素 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。 大多数酗酒者 认知障碍表现出两种特征， 综合征 神经递质系统的药理学调节可能是 有效治疗皮质下综合征，而酒精 痴呆症可能需要类似于阿尔茨海默氏症的治疗策略 疾病 本方案旨在利用临床、神经放射学、 生理学和神经药理学测试来区分这两种 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。

Behavioral deficits of 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 recently found that sleep in Korsakoff patients is characterized by a reduced REM latency compared to normal volunteers, whereas Alzheimer patients have normal REM latencies. Furthermore, delta sleep is reduced in Alzheimer's disease, but is normal in Korsakoff patients. We have also demonstrated reduced daily excretion of the major urinary metabolite of melatonin, hydroxymelatonin, in patients 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. The majority of alcoholics with cognitive impairment demonstrate features characteristic of both syndromes. Pharmacologic modulation of neurotransmitter systems may be efffective in treatment of the subcortical syndrome, whereas alcoholic dementia may require tratment strategies similar to those in Alzheimer's disease. This protocol is intended to utilize clinical, neuroradiological, physiological, and neuropharmacological tests to differentiate these two pathologic entities, to follow a longitudinal course, and to relate variables in treatment protocols to outcome.