title: Hierarchical linear modeling (HLM) of longitudinal brain structural and cognitive changes in alcohol-dependent individuals during sobriety.
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 1 week, 1 month, and 7 months of sobriety. Eight non-smoking light drinking controls were studied at baseline and 7 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.
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Administration Medical Center, United States; Northern California Institute for Research and Education, USA. ping-hong.yeh@ucsf.edu
authors.forename: Ping-Hong
authors.initials: PH
authors.lastname: Yeh
authors.forename: Stefan
authors.initials: S
authors.lastname: Gazdzinski
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Durazzo
authors.forename: Karl
authors.initials: K
authors.lastname: Sjöstrand
authors.forename: Dieter J
authors.initials: DJ
authors.lastname: Meyerhoff
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000473:pathology* / Q000534:rehabilitation*; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D012907:Smoking / Q000473:pathology; D013695:Temperance / Q000706:statistics & numerical data*