title: Brain hyperintensity location determines outcome in the triad of impaired cognition, physical health and depressive symptoms: A cohort study in late life.
abstract: OBJECTIVE
  Brain hyperintensities, detectable with MRI, increase with age. They are associated with a triad of impairment in cognitive ability, depression and physical health. Here we test the hypothesis that the association between hyperintensities and cognitive ability, physical health and depressive symptoms depends on lesion location.
  
  
  METHODS
  244 members of the Aberdeen 1936 Birth Cohort were recruited to this study. 227 participants completed brain MRI and their hyperintensities were scored using Scheltens's scale. 205 had complete imaging, cognitive, physical health and depressive symptom score data. The relationships between hyperintensity location and depressive symptoms, cognitive ability and physical health were examined by correlation and structural equation analysis.
  
  
  RESULTS
  We found that depressive symptoms correlated with hyperintensity burden in the grey matter (r=0.14, p=0.04) and infratentorial regions (r=0.17, p=0.01). Infratentorial hyperintensities correlated with reduced peak expiratory flow rate (r=-0.26, p<0.001) and impaired gait (r=0.13, p=0.05). No relationship was found between white matter and periventricular (supratentoral) hyperintensities and depressive symptoms. Hyperintensities in the supratentorial and infratentorial regions were associated with reduced cognitive performance. Using structural equation modelling we found that the association between hyperintensities and depressive symptoms was mediated by negative effects on physical health and cognitive ability.
  
  
  CONCLUSIONS
  Hyperintensities in deep brain structures are associated with depressive symptoms, mediated via impaired physical health and cognitive ability. Participants with higher cognitive ability and better physical health are at lower risk of depressive symptoms.
authors.affiliation: University of Aberdeen, Aberdeen, UK. Electronic address: a.d.murray@abdn.ac.uk.
authors.forename: Alison
authors.initials: A
authors.lastname: Murray
authors.affiliation: University of Aberdeen, Aberdeen, UK. Electronic address: c.mcneil@abdn.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: McNeil
authors.affiliation: University of Aberdeen, Aberdeen, UK. Electronic address: s.salari@abdn.ac.uk.
authors.forename: Sima
authors.initials: S
authors.lastname: Salarirad
authors.affiliation: University of Edinburgh, Edinburgh, UK. Electronic address: iand@staffmail.ed.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Deary
authors.affiliation: University of Aberdeen, Aberdeen, UK. Electronic address: louise.phillips@abdn.ac.uk.
authors.forename: Louise
authors.initials: L
authors.lastname: Phillips
authors.affiliation: University of Aberdeen, Aberdeen, UK. Electronic address: l.j.whalley@abdn.ac.uk.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Whalley
authors.affiliation: NHS Grampian, Aberdeen, UK. Electronic address: r.staff@abdn.ac.uk.
authors.forename: Roger
authors.initials: R
authors.lastname: Staff
mesh_terms: D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000175:diagnosis / Q000473:pathology; D015331:Cohort Studies; D003863:Depression / Q000473:pathology* / Q000523:psychology; D003866:Depressive Disorder / Q000473:pathology / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D012606:Scotland
keywords: Cognition; Cohort; Depression; Frailty; Physical health; White matter hyperintensities