Cerebral white matter recovery in abstinent alcoholics--a multimodality magnetic resonance study

Abstract

Most previous neuroimaging studies of alcohol-induced brain injury and recovery thereof during abstinence from alcohol used a single imaging modality. They have demonstrated widespread microstructural, macrostructural or metabolite abnormalities that were partially reversible with abstinence, with the cigarette smoking potentially modulating these processes. The goals of this study were to evaluate white matter injury and recovery thereof, simultaneously with diffusion tensor imaging, magnetic resonance imaging and spectroscopy in the same cohort; and to evaluate the relationships between outcome measures of similar regions. We scanned 16 non-smoking and 20 smoking alcohol-dependent individuals at 1 week of abstinence from alcohol and 22 non-smoking light drinkers using a 1.5 T magnetic resonance scanner. Ten non-smoking alcohol-dependent individuals and 11 smoking alcohol-dependent individuals were re-scanned at 1 month of abstinence. All regional diffusion tensor imaging, magnetic resonance imaging and spectroscopic outcome measures were calculated over comparable volumes of frontal, temporal, parietal and occipital white matter. At 1 week of abstinence and relative to non-smoking light drinkers, non-smoking alcohol-dependent individuals had higher mean diffusivity in frontal, temporal and parietal white matter (all P<0.008), whereas smoking alcohol-dependent individuals had elevated mean diffusivity only in frontal white matter (P=0.03). Smoking alcohol-dependent individuals demonstrated lower concentrations of N-acetyl-aspartate (a marker of neuronal viability) in frontal white matter (P=0.03), whereas non-smoking alcohol-dependent individuals had lower N-acetyl-aspartate in parietal white matter (P=0.05). These abnormalities were not accompanied by detectable white matter atrophy. However, the patterns of white matter recovery were different between non-smoking alcohol-dependent individuals and smoking alcohol-dependent individuals. In non-smoking alcohol-dependent individuals, the increase in fractional anisotropy of temporal white matter (P=0.003) was accompanied by a pattern of decreases mean diffusivity in all regions over 1 month of abstinence; no corresponding changes were observed in smoking alcohol-dependent individuals. In contrast, a pattern of white matter volume increase in frontal and temporal lobes was apparent in smoking alcohol-dependent individuals but not in non-smoking alcohol-dependent individuals. These results were not accompanied by significant changes in metabolite concentrations. Finally, there were no consistent patterns of association between measures obtained with different imaging modalities, either cross-sectionally or longitudinally. These data demonstrate significant white matter improvements with abstinence from alcohol, reflected either as microstructural recovery or volumetric increases that depend on the smoking status of the participants. We believe our results to be important, as they demonstrate that use of a single imaging modality provides an incomplete picture of neurobiological processes associated with alcohol-induced brain injury and recovery thereof that may even lead to improper interpretation of results.

Figure 1

Brain regions scanned with our magnetic resonance spectroscopic sequence. Mean absolute atrophy-corrected metabolite concentrations were calculated over anatomically defined white matter lobar regions. The DTI and MRI sequences covered basically all lobar white matter.

Figure 2

MD (A) and FA (B) in frontal white matter of nsLDs, nsADIs and sADIs. The statistical significance of MD was not driven by the two nsADIs with highest MD values. Same baseline patterns were observed among participants who were rescanned at follow-up.

Figure 3

Patterns of longitudinal frontal white matter changes in (A) MD, (B) FA, (C) volume and (D) NAA concentration observed in participants who were scanned at baseline and follow-up: the P-values pertain to longitudinal changes. Please, note the significant decrease in MD of nsADIs (A) is not accompanied by any volume change (C), whereas the volume increase in sADIs (C) is not accompanied by a MD change (A). The range of corresponding measures in 22 nsLDs is depicted in grey (mean ± standard error). NAA concentrations reported after correction for age and BMI.