title: Brain morphology links systemic inflammation to cognitive function in midlife adults.
abstract: BACKGROUND
  Inflammation is linked to cognitive decline in midlife, but the neural basis for this link is unclear. One possibility is that inflammation associates with adverse changes in brain morphology, which accelerates cognitive aging and later dementia risk. Clear evidence is lacking, however, regarding whether inflammation relates to cognition in midlife via changes in brain morphology. Accordingly, the current study examines whether associations of inflammation with cognitive function are mediated by variation in cortical gray matter volume among midlife adults.
  
  
  METHODS
  Plasma levels of interleukin (IL)-6 and C-reactive protein (CRP), relatively stable markers of peripheral systemic inflammation, were assessed in 408 community volunteers aged 30-54 years. All participants underwent structural neuroimaging to assess global and regional brain morphology and completed neuropsychological tests sensitive to early changes in cognitive function. Measurements of brain morphology (regional tissue volumes and cortical thickness and surface area) were derived using Freesurfer.
  
  
  RESULTS
  Higher peripheral inflammation was associated with poorer spatial reasoning, short term memory, verbal proficiency, learning and memory, and executive function, as well as lower cortical gray and white matter volumes, hippocampal volume and cortical surface area. Mediation models with age, sex and intracranial volume as covariates showed cortical gray matter volume to partially mediate the association of inflammation with cognitive performance. Exploratory analyses of body mass suggested that adiposity may be a source of the inflammation linking brain morphology to cognition.
  
  
  CONCLUSIONS
  Inflammation and adiposity might relate to cognitive decline via influences on brain morphology.
authors.affiliation: Department of Psychology, University of Pittsburgh, Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States. Electronic address: marsland@pitt.edu.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Marsland
authors.affiliation: Department of Psychology, University of Pittsburgh, Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gianaros
authors.affiliation: Department of Psychology, University of Pittsburgh, Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States.
authors.forename: Dora C-H
authors.initials: DC
authors.lastname: Kuan
authors.affiliation: Department of Psychology, University of Pittsburgh, Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States.
authors.forename: Lei K
authors.initials: LK
authors.lastname: Sheu
authors.affiliation: Department of Psychology, University of Pittsburgh, Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States.
authors.forename: Katarina
authors.initials: K
authors.lastname: Krajina
authors.affiliation: Department of Psychology, University of Pittsburgh, Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Manuck
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D056344:Executive Function; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology* / Q000523:psychology; D015850:Interleukin-6 / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D009929:Organ Size / Q000502:physiology
chemical_list: D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: Brain atrophy; C-reactive protein; Cognitive aging; Cognitive decline; Gray matter volume; Inflammation; Interleukin-6