CENTRAL AND PERIPHERAL NERVOUS SYSTEM FUNCTION IN ABSTINENT ALCOHOLICS

酗酒者的行为缺陷被概念化为两种 神经病理学上不同的综合征：酒精性痴呆和Korsakoff‘s 精神病(酒精健忘症)。酒精性痴呆的特点是 主要由弥漫性皮质损伤引起的神经毒性 酒精；科萨科夫精神病与应激皮质下损害有关 营养(硫胺素)缺乏。严重的记忆障碍 相对较少的其他智力功能使科尔萨科夫 酒精性痴呆所致的精神病(临床上可能 与痴呆症最常见的原因阿尔茨海默氏症难以区分 疾病)。我们最近发现Korsakoff患者的睡眠是 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的REM潜伏期正常。此外，三角洲 阿尔茨海默病患者睡眠减少，但科尔萨科夫患者睡眠正常 病人。我们还证明了每天减少的主要排泄物 慢性阻塞性肺疾病患者尿褪黑素代谢产物--羟基黑素的研究 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。大多数酗酒者都有 认知障碍表现出两者的特征 综合症。神经递质系统的药物调节可能是 治疗皮质下综合征有效，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。该方案旨在利用临床、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。

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.