Longitudinal Brain Metabolic Characterization of Chronic Alcoholics With Proton Magnetic Resonance Spectroscopy

Abstract

Background Proton magnetic resonance spectroscopy may elucidate the molecular underpinnings of alcoholism-associated brain shrinkage and the progression of alcohol dependence. Methods Using proton magnetic resonance spectroscopy, we determined absolute concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline (Cho)-containing compounds and myo-inositol (mI) in the anterior superior cerebellar vermis and frontal lobe white matter in 31 alcoholics and 12 normal controls. All patients were examined within 3 to 5 days of their last drink. Patients who did not relapse were again studied after 3 weeks and 3 months of abstinence by using an on-line repositioning technique that allows reliable localization of volumes of interest (VOIs). Results At 3 to 5 days after the last drink, frontal white matter metabolite concentrations were not significantly different from those of normal controls, whereas brain tissue in the VOI was reduced. Cerebellar [NAA] and [Cho] and brain and cerebellar volumes were decreased, but [Cr], [mI], and VOI brain tissue volume were not significantly different. Eight patients relapsed before 3 weeks (ER), 12 relapsed between 3 weeks and 3 months (LR), and 11 did not relapse (NR) during 3 months. Cerebellar [NAA] was reduced only in ER patients, despite the fact that ER patients drank for significantly fewer years and earlier in life than LR or NR patients. After 3 months, in the 11 continuously abstinent patients, cerebellar [NAA] and brain and cerebellar volumes increased; cerebellar [Cho], [Cr], and [mI] and VOI brain tissue did not change significantly. Conclusions Decreased [NAA] and [Cho] in cerebellar vermis indicate a unique sensitivity to alcohol-induced brain injury. Cerebellar [NAA] increased with abstinence, but reduced [Cho] persisted beyond 3 months. Further studies are needed to determine whether low cerebellar [NAA] is a risk factor for, or consequence of, malignant, early-onset alcoholism.