Molecular Studies of Cognition in Chronic Alcoholism

描述（由申请人提供）：慢性酒精中毒通常被认为是一种多种多样的异质性疾病，可分为认知完好亚组和认知受损亚组。至少从20世纪60年代起，通过客观测试证明慢性酒精中毒受试者存在神经心理缺陷。本研究的基本原理是利用31P磁共振波谱成像（31P MRSI）和短回波时间（TE） H磁共振成像（TE）研究在一些慢性酒精中毒受试者中观察到的认知障碍的可能分子基础，并将区域分子发现与神经心理学测试分数和体素分子水平与体素组织组成联系起来。我们建议通过体内31P磁共振成像和短TE ‘H MRS研究慢性酒精中毒队列中脑膜磷脂和高能磷酸盐代谢、突触/运输囊泡和磷酸化蛋白的分子改变以及N-乙酰基部分、谷氨酸-谷氨酰胺和神经节苷类代谢物的分子改变（通过测量’H大分子共振）(N=80；与所有相关人口变量匹配的正常对照组（N=40）相比，40名认知未受损，40名认知受损)。认知状态将在神经心理学测试的基础上确定，使用平均损伤评级，一种认知功能的全球指数，作为标准测量。神经心理学测试用于评估抽象推理和解决问题、记忆、注意力、语言、空间能力、感觉/知觉和运动功能。成瘾严重程度指数将用于评估成瘾的历史和严重程度，并匹配两个酗酒队列。鉴于慢性酒精中毒患者认知功能障碍的发病率增加，进一步了解认知功能改变的分子基础可能会为未来的治疗和预防措施提供途径。

DESCRIPTION (provided by applicant): Chronic alcoholism is generally regarded as a diverse and heterogeneous disorder that can be dichotomized into cognitively intact and cognitively impaired subgroups. The existence of neuropsychological deficits in chronic alcoholism subjects documented through the use of objective tests has been known since at least the 1960's. The rationale for the present study is to investigate possible molecular underpinnings for the cognitive impairment observed in some chronic alcoholism subjects using 31P magnetic resonance spectroscopic imaging (31P MRSI) and short echo time (TE) 'H MRSI and to correlate regional molecular findings with neuropsychological test scores and voxel molecular levels with voxel tissue composition. We propose to study by in vivo 31P MRSI and short TE 'H MRS molecular alterations in brain membrane phospholipid and high-energy phosphate metabolism, synaptic/transport vesicles and phosphorylated proteins as well as molecular alterations in metabolites with N-acetyl moieties, glutamate-glutamine, and gangliosides (by measuring 'H macromolecule resonances) in a chronic alcoholism cohort (N=80; 40 cognitively unimpaired, 40 cognitively impaired) compared to a normal control group of individuals (N=40) matched for all relevant demographic variables. Cognitive status will be determined on the basis of neuropsychological testing utilizing an Average Impairment Rating, a global index of cognitive function, as the criterion measure. Neuropsychological tests are used to assess abstract reasoning and problem solving, memory, attention, language, spatial abilities, sensory/perceptual, and motor function. The Addiction Severity Index will be used to assess the history and severity of the addiction and to match the two alcoholism cohorts. Given the increased morbidity associated with cognitive impairment in chronic alcoholism subjects, further insights into the molecular basis for the cognitive changes could lead the way to future therapeutic and preventative measures.