The Biological Basis of Alcohol Induced Brain Damage

个人资料(申请人提供)：长期长期酗酒 与大脑结构变化和神经认知障碍有关。一些 研究表明，这些现象与它之间存在令人信服的相关性。 似乎不是结构改变的神经底物是基础 与酗酒和康复相关的认知变化。这个 这个项目的总体目标是检验轴突/树突状细胞的假设 和白质膜磷脂(可能还有灌流)的变化 这些可逆的结构和神经认知变化与 长期长期酗酒和康复。研究对象：50名少量饮酒者 (LD)和100名酗酒者。将在基线和9-12个月内对学习记忆进行研究 稍后，HD将在进入酒精滥用治疗时进行研究(以捕获 大量饮酒造成的全面脑损伤)，在2-4周 戒酒后9-12个月，在戒酒或 旧病复发。 测量：通过神经心理测试进行认知；通过 磁共振氢谱成像对轴突/树突状细胞和神经元活性的影响 (N-乙酰天冬氨酸，推测为神经元/轴突标记物)； 含胆碱化合物(CHO)和肌醇(Ml)及磷-31 MRS(通过膜磷脂及其分解产物和前体)； 将使用探索性自旋标记测量局部脑血流量 核磁共振灌注成像。这项研究的具体重点将是白质，但 皮质和皮质下灰质、小脑、海马体 颧骨、脑干、颅内体积及各脑区体积 原子核也将被评估。我们预计，最初较低的地区NAA和 磷脂指标和最初的高Cho和MI指标与 认知障碍的具体衡量标准以及这些结果衡量标准将 在戒酒期间康复，伴随着认知的改善；复发 会阻碍结构、新陈代谢和认知能力的改善。这个 这些结果的意义有几个方面：第一，这个项目将 开发非侵入性结果测量方法，提供客观的量化 酒精引起的脑损伤的测量。这在将来可能会有用。 使用药物或治疗方法减少饮酒的临床试验，或 监测旨在减少脑损伤的药物的效果，或促进 恢复。其次，这些结果还可能提供信息，这可能会导致 以开发特定的药物治疗，旨在预防脑部 神经元或细胞膜的损伤或促进恢复。

DESCRIPTION (Provided by applicant): Long-term chronic alcohol abuse is associated with structural brain changes and neuro-cognitive impairment. Few studies have shown a convincing correlation between these phenomena and it appears likely that neurosubstrates other than structural alterations underlie the cognitive changes associated with heavy drinking and recovery. The overall goal of this project is to test the hypothesis that axonal/dendritic and membrane phospholipid ( and possibly perfusion) changes in white matter underlie the reversible structural and neurocognitive changes associated with long-term chronic alcohol abuse and recovery. Subjects: 50 light drinkers (LD) and 100 heavy drinkers. LD will be studied at baseline and 9-12 months later, HD will be studied at entry into alcohol abuse treatment (to capture the full extent of brain damage due to heavy drinking), at 2-4 weeks of abstinence, and at 9-12 months after treatment entry during abstinence or relapse. Measurements: Cognition by neuropsychological testing; brain structures by MRI, axonal/dendritic and neuronal viability by 1H MR spectroscopic imaging (N-acetyl aspartate, a putative neuronal/axonal marker); lipids by choline-containing compounds (Cho) and myo-inositol (ml) and by phosphorus-31 MRS (via membrane phospholipids and their breakdown products and precursors); regional cerebral blood flow will be measured with exploratory spin-tagged perfusion MRI. The specific focus of the study will be on white matter, but cortical and subcortical gray matter, cerebellum, hippocampus, corpus callosum, and brain stem, intracranial volume and volumes of various brain nuclei will also be assessed. We expect that initially low regional NAA and phospholipid measures and initially high Cho and mI measures correlate with specific measures of cognitive impairment and that these outcome measures will recover during abstinence in association with cognitive improvements; relapse will arrest structural, metabolic, and cognitive improvements. The significance of these results is several fold: First, this project will develop non invasive outcome measures which provide objective quantitative measurements of alcohol-induced brain damage. This may be useful in future clinical trials in which drugs or treatments are used to reduce drinking, or to monitor effects of drugs aimed at reducing brain damage, or facilitating recovery. Second, these results may also provide information, which can lead to the development of specific drug treatments, aimed at preventing brain damage at the neuron or membrane or at facilitating recovery.