Molecular Studies of Cognition in Chronic Alcoholism

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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.