Biomarker of Cognitive Impairment in Chronic Alcoholism

慢性酒精中毒认知障碍的生物标志物

• 批准号: 7102960
• 负责人: Samuel Gershon
• 金额: $ 10.04万
• 依托单位: PHFR, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102960
• 关键词: alcoholism /alcohol abuse; basal ganglia; behavioral /social science research tag; biomarker; biomaterial development /preparation; brain imaging /visualization /scanning; clinical research; cognition disorders; drug addiction; human data; lipid metabolism; metabolomics; nicotine; parietal lobe /cortex; phospholipids; psychopharmacology; schizophrenia; smoking; statistics /biometry; substance abuse related behavior; temporal lobe /cortex

DESCRIPTION (provided by applicant): This Phase I, STTR application focuses on developing a novel brain molecular metabolomic biomarker for cognitive impairment in chronic alcoholism. Approximately 1 1/2 to 2/3rds of recently detoxified chronic alcoholics have cognitive impairment. The molecular underpinnings for the cognitive impairment and why some chronic alcoholics became cognitively impaired and not others is unknown. At a molecular level, ethanol has been shown to have both acute and chronic effects on membrane associated function and properties. The purpose of the present application is to analyze existing NIHfunded multi-voxel 31P and 1H magnetic resonance spectroscopic imaging (31P-1H MRSI) data sets to develop a brain molecular biomarker for the Cognitive impairment observed in some chronic alcoholism subjects. Since cognitive deficits are present in other neuropsychiatric disorders, for example chronic schizophrenia, a comparison of molecular measures associated with cognitive impairment in chronic schizophrenia with those of chronic alcoholism will help to establish a biomarker specific for cognitive impairment in alcoholism. Since the majority of alcoholics smoke, the effect of nicotine on the MRSI measures will be provided by a (NIH-funded) nicotine challenge to middle age smokers which will be included in the analysis. Funds are requested for Phfr, Inc., a small business focused on the development and commercialization of novel, non-invasive brain imaging biomarkers for neuropsychiatric disorders such as chronic alcoholism, Alzheimer's disease, major-depressive disease, and schizophrenia with the University of Pittsburgh as the nonprofit partner. In Phase I, we propose to analyze 31P-1H data from: a pilot study of cognition in chronic alcoholism (males, cognitively impaired N=4; cognitively unimpaired N=5; control subjects N=16); an NIH funded study (MH058308) of cognition in chronic schizophrenia (males, cognitively impaired N=19; cognitively unimpaired N=16; control subjects N=10); and an NIH funded study (DA11735) of the effect of nicotine (smokers, males N=4, females N=4). The data from these in vivo multi-voxel 31P-1H MRSI studies provide measures of molecular alterations in brain membrane phospholipid and high-energy phosphate metabolism, synaptic/transport vesicles and phosphorylated proteins and metabolites with N-acetyl moieties from right and left prefrontal, superior temporal, inferior parietal, occipital, basal ganglia, and centrum semiovale brain regions. The brain molecular biomarker will provide insights into the molecular basis for cognitive impairment in chronic alcoholism which could lead to future therapeutic and preventative measures.

描述（由申请人提供）：本I期，STTR应用的重点是开发一种新型的脑分子代谢组生物标志物，以用于慢性酒精中毒的认知障碍。最近排毒的慢性酗酒者约有1 1/2至2/3摄氏度具有认知障碍。认知障碍的分子基础，以及某些慢性酗酒者的认知受损而不是其他人未知的原因。在分子水平上，乙醇已被证明对膜相关功能和特性具有急性和慢性作用。本应用的目的是分析现有的NIHUND的多素31p和1H磁共振光谱成像（31p-1h MRSI）数据集，以开发出在某些慢性酒精中毒受试者中观察到的认知障碍的脑分子生物标志物。由于认知缺陷存在于其他神经精神疾病中，例如慢性精神分裂症，因此比较了与慢性精神分裂症认知障碍与慢性酒精中毒相关的分子测量的比较，将有助于确定对酒精中毒中认知障碍的生物标志物。由于大多数酗酒者烟雾，尼古丁对MRSI措施的影响将由（NIH资助的）尼古丁对中年吸烟者的挑战提供，这将包括在分析中。要求为PHFR，Inc。提供资金，这是一家小型企业，该企业旨在开发和商业化，用于神经精神疾病的新型，非侵入性的脑成像生物标志物，例如长期酒精中毒，阿尔茨海默氏病，阿尔茨海默氏病，重大抑制疾病，以及匹兹堡大学（匹兹堡大学）作为非专业伙伴。在第一阶段，我们建议分析31p-1h的数据：慢性酒精中毒的认知试点研究（男性，认知受损的n = 4;认知障碍n = 5;对照对象n = 16）; NIH资助的慢性精神分裂症认知认知的研究（MH058308）（男性，认知受损的n = 19;认知无影响的n = 16;对照对象n = 10）;以及NIH资助的研究（DA11735）（吸烟者，男性n = 4，雌性n = 4）的作用。这些体内多素31p-1h MRSI研究的数据提供了脑膜膜磷脂和高能量磷酸代谢，突触/转运囊泡的分子变化的措施，以及磷酸化的蛋白质，磷酸化的蛋白质，并用左右的N-乙酰基，左右的底部和底层底层，底部和底层底层，底部和底部层次，底层层次，底部和底层层次，层次层次，底层和代谢。半决赛大脑区域。脑分子生物标志物将为慢性酒精中毒的认知障碍提供见解，这可能导致未来的治疗和预防措施。