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Neuromolecular Alterations Associated with Cognitive Impairment

We conducted 31P-1H MRS studies of ten cognitively intact chronic alcoholism males (43.3 ± 7.9 years) and four cognitively impaired chronic alcoholism males (47.9 ± 3.0 years) who were matched on all other demographic variables (Cognitive Biomarker) (Goldstein, Pettegrew, Cornelius, 2005).  The striking findings were that although both groups of males had molecular evidence for damage to brain cell membranes, the males who were cognitively intact had findings consistent with membrane repair events taking place in their brains while in the cognitively impaired males, there was evidence for failed membrane repair attempts and loss of the critical nerve communication centers, i.e., the synapses.  The areas of brain involved in these processes were the areas of brain implicated in neuropsychological studies, and the molecular changes highly correlated with the neuropsychological deficits in these individuals.  In addition, these findings appear to be specific (Biomarker Specificity) for cognitive impairment in chronic alcoholism as they are not observed in cognitively impaired chronic schizophrenia subjects (Pettegrew et al., 2003) or in normal control subjects after nicotine patch exposure (McClure et al., 2004).  This is the first demonstration in living alcoholism subjects of brain membrane molecular alterations leading to cognitive deficits.