title: Neuroanatomical correlates of cognitive functioning in prodromal Huntington disease.
abstract: BACKGROUND
  The brain mechanisms of cognitive impairment in prodromal Huntington disease (prHD) are not well understood. Although striatal atrophy correlates with some cognitive abilities, few studies of prHD have investigated whether cortical gray matter morphometry correlates in a regionally specific manner with functioning in different cognitive domains. This knowledge would inform the selection of cognitive measures for clinical trials that would be most sensitive to the target of a treatment intervention.
  
  
  METHODS
  In this study, random forest analysis was used to identify neuroanatomical correlates of functioning in five cognitive domains including attention and information processing speed, working memory, verbal learning and memory, negative emotion recognition, and temporal processing. Participants included 325 prHD individuals with varying levels of disease progression and 119 gene-negative controls with a family history of HD. In intermediate analyses, we identified brain regions that showed significant differences between the prHD and the control groups in cortical thickness and striatal volume. Brain morphometry in these regions was then correlated with cognitive functioning in each of the domains in the prHD group using random forest methods. We hypothesized that different regional patterns of brain morphometry would be associated with performances in distinct cognitive domains.
  
  
  RESULTS
  The results showed that performances in different cognitive domains that are vulnerable to decline in prHD were correlated with regionally specific patterns of cortical and striatal morphometry. Putamen and/or caudate volumes were top-ranked correlates of performance across all cognitive domains, as was cortical thickness in regions related to the processing demands of each domain.
  
  
  CONCLUSIONS
  The results underscore the importance of identifying structural magnetic resonance imaging (sMRI) markers of functioning in different cognitive domains, as their relative sensitivity depends on the extent to which processing is called upon by different brain networks. The findings have implications for identifying neuroimaging and cognitive outcome measures for use in clinical trials.
authors.affiliation: Department of Radiology, University of California San Diego, California ; Research Service, VA San Diego Healthcare System San Diego, California.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Harrington
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine Iowa City, Iowa.
authors.forename: Dawei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine Iowa City, Iowa.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Smith
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine Iowa City, Iowa.
authors.forename: James A
authors.initials: JA
authors.lastname: Mills
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine Iowa City, Iowa.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Long
authors.affiliation: Seattle Children's Research Institute Seattle, Washington.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Aylward
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine Iowa City, Iowa ; Department of Neurology, University of Iowa Carver College of Medicine Iowa City, Iowa.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000473:pathology* / Q000503:physiopathology; D062706:Prodromal Symptoms
keywords: Cognition; magnetic resonance imaging; prodromal Huntington disease