Molecular Studies of Cognition in Chronic Alcoholism

慢性酒精中毒认知的分子研究

基本信息

批准号：
7661708
负责人：
JAY W PETTEGREW
金额：
$ 45.19万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7661708
关键词：
Acute Alcoholism Anterior Area Attention Basal Ganglia Biochemical Brain Brain region Chin Cholesterol Chronic Clinical Cognition Cognitive Control Groups Data Disease Ethanol Figs - dietary Future Gangliosides Glutamates Glutamine Gray unit of radiation dose Impaired cognition Impairment Individual Inferior Inositol Language Lead Left Lipids Lipoproteins Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measurement Measures Membrane Memory Metabolic Metabolism Molecular Morbidity - disease rate Motor N-acetylaspartate Neurons Neuropsychological Tests Parietal Phospholipids Phosphorylation Problem Solving Property Proteins Recording of previous events Reporting Sensory Severities Signal Transduction Signaling Protein Subgroup Testing Thalamic structure Therapeutic Time Tissues Transport Vesicles Wood material Writing abstracting addiction base cognitive change cognitive function cohort in vivo indexing inorganic phosphate insight macromolecule magnetic resonance spectroscopic imaging neuropsychological problem drinker receptor function sugar white matter

项目摘要

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.

描述（由申请人提供）：慢性酒精中毒通常被视为一种多样化和异质性疾病，可以将其二分为认知完整和认知受损的亚组。至少自1960年代以来，已知通过使用客观测试记录的慢性酒精中毒主体中神经心理缺陷的存在。 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.我们建议通过体内31p MRSI和短TE进行研究，脑膜磷脂中的MRS分子变化和高能磷酸代谢，突触/转运囊泡以及磷酸化的蛋白质和磷酸化蛋白质以及分子在N-乙酰基甲酸甲酯，粘膜甲状腺素和凝集膜中的分子变化（以及分子）的变化（与正常对照组（n = 40）相比，在慢性酒精中毒队列中的共鸣）（n = 80; 40个认知障碍，认知受损40）（n = 40）（n = 40）。认知状况将基于使用平均损伤等级的神经心理学测试确定，这是标准度量的全球认知功能指数。神经心理学测试用于评估抽象的推理和解决问题，记忆，注意力，语言，空间能力，感觉/感知和运动功能。成瘾的严重程度指数将用于评估成瘾的历史和严重程度，并与两个酒精中毒队列相匹配。鉴于与慢性酒精中毒受试者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见解可能会导致未来的治疗和预防措施。