Pilot Study of
Molecular Studies of Cognition in Chronic Alcoholism
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 alcoholics documented through the
use of objective tests has been known since at least the 1960’s. No MRS
molecular studies to date have addressed the issue of cognitive
impairment in chronic alcoholism. The rationale for the present study
is to investigate possible molecular underpinnings for the cognitive
impairment observed in some chronic alcoholism subjects using 31P
and short echo time (TE) 1H magnetic
resonance spectroscopic imaging (31P-1H MRSI). We propose to study by
in vivo 31P- 1H MRSI 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 1H macromolecule resonances) in a chronic
alcoholism cohort (N=20; 10 cognitively unimpaired, 10 cognitively
impaired) compared to a normal control group of individuals (N=10)
matched for all relevant demographic variables. Cognitive status will
be determined on the basis of the Halstead-Reitan Neuropsychological
Test Battery (HRB) utilizing the Average Impairment Rating, a global
index of cognitive function, as the criterion measure. The HRB was
chosen as the core battery because of its extensive application in
alcoholism research and its capability of identifying the widely
accepted cognitive profile involving impaired spatial, conceptual and
psychomotor abilities with relatively well preserved language. The
Addiction Severity Index will be used to assess the history and severity
of the addiction and to match the two alcoholic cohorts. Given the
increased morbidity associated with cognitive impairment in chronic
alcoholic subjects, further insights into the molecular basis for the
cognitive changes could lead the way to future therapeutic and
preventative measures (Goldstein, Pettegrew, Cornelius, 2005).
Goldstein G,
Pettegrew JW, and Cornelius J. Molecular studies of cognition in
alcoholism. Santa Barbara, California. 28th
Annual Scientific Meeting of the Research Society on Alcoholism, 2005.
