@ARTICLE\{IMM2007-05287,
    author       = "P. Yeh and S. Gazdzinski and T. C. Durazzo and K. Sj{\"{o}}strand and D. J. Meyerhoff",
    title        = "Hierarchical Linear Modeling of Longitudinal Brain Structural and Cognitive Changes in Alcohol-dependent Individuals during Sobriety",
    year         = "2007",
    month        = "may",
    keywords     = "hierarchical linear models, boundary shift integral, brain {MRI,} alcoholism, smoking, cognition",
    journal      = "Drug and Alcohol Dependence (accepted)",
    volume       = "",
    editor       = "",
    number       = "",
    publisher    = "",
    url          = "http://www2.compute.dtu.dk/pubdb/pubs/5287-full.html",
    abstract     = "Background:  Hierarchical linear modeling (HLM) can reveal complex relationships between longitudinal outcome measures and their covariates under proper consideration of potentially unequal error variances.  We demonstrate the application of {HLM} to the study of magnetic resonance imaging (MRI)-derived brain volume changes and cognitive changes in abstinent alcohol dependent individuals as a function of smoking status, smoking severity, and drinking quantities. 
Methods: Twenty non-smoking recovering alcoholics (nsALC) and 30 age-matched smoking recovering alcoholics (sALC) underwent quantitative {MRI} and cognitive assessments at one week, one month, and seven months of sobriety. Eight non-smoking light drinking controls were studied at baseline and seven months later. Brain and ventricle volumes at each time point were quantified using {MRI} masks, while the boundary shift integral method measured volume changes between time points. Using {HLM,} we modeled volumetric and cognitive outcome measures as a function of cigarette and alcohol use variables. 
Results: Different hierarchical linear models with unique model structures are presented and discussed. The results show that smaller brain volumes at baseline predict faster brain volume gains, which were also related to greater smoking and drinking severities. Over 7 months of abstinence from alcohol, sALC compared to nsALC showed less improvements in visuospatial learning and memory despite larger brain volume gains and ventricular shrinkage . 
Conclusions: Different and unique hierarchical linear models allow assessments of the complex relationships among outcome measures of longitudinal data sets. These {HLM} applications suggest that chronic cigarette smoking modulates the temporal dynamics of brain structural and cognitive changes in alcoholics during prolonged sobriety."
}