Molecular Studies of Cognition in Chronic Alcoholism

描述(申请人提供)：慢性酒精中毒通常被认为是一种多样化和异质性的障碍，可以分为认知正常和认知受损两个亚组。通过客观测试证实慢性酒精中毒受试者存在神经心理缺陷早在20世纪60年代的S就已为人所知。本研究的基本原理是利用31P磁共振波谱成像(31P MRSI)和短回声时间(TE)H MRSI研究一些慢性酒精中毒受试者认知障碍的可能分子基础，并将局部分子结果与神经心理测试分数和体素分子水平与体素组织成分相关联。我们建议通过活体31P MRSI和短TE‘H MRS研究慢性酒精中毒队列(N=80；认知未受损，40例认知受损)与正常对照组(N=40)相比，脑膜磷脂和高能磷酸盐代谢、突触/运输小泡和磷酸化蛋白的分子变化，以及N-乙酰基、谷氨酸-谷氨酰胺和神经节苷脂代谢物的分子变化(通过测量’H大分子共振)。认知状态将在神经心理测试的基础上确定，使用平均损伤等级作为标准衡量标准，平均损伤等级是认知功能的全球指数。神经心理学测试用于评估抽象推理和解决问题、记忆力、注意力、语言、空间能力、感觉/知觉和运动功能。上瘾严重程度指数将被用来评估上瘾的历史和严重程度，并将两个酒精中毒队列进行匹配。鉴于慢性酒精中毒患者中与认知障碍相关的发病率增加，对认知变化的分子基础的进一步了解可能会为未来的治疗和预防措施指明方向。

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.