title: Strategic lacunes and their relationship to cognitive impairment in cerebral small vessel disease.
abstract: OBJECTIVE
  Lacunes are an important disease feature of cerebral small vessel disease (SVD) but their relationship to cognitive impairment is not fully understood. To investigate this we determined (1) the relationship between lacune count and total lacune volume with cognition, (2) the spatial distribution of lacunes and the cognitive impact of lacune location, and (3) the whole brain anatomical covariance associated with these strategically located regions of lacune damage.
  
  
  METHODS
  One hundred and twenty one patients with symptomatic lacunar stroke and radiological leukoaraiosis were recruited and multimodal MRI and neuropsychological data acquired. Lacunes were mapped semi-automatically and their volume calculated. Lacune location was automatically determined by projection onto atlases, including an atlas which segments the thalamus based on its connectivity to the cortex. Lacune locations were correlated with neuropsychological results. Voxel based morphometry was used to create anatomical covariance maps for these 'strategic' regions.
  
  
  RESULTS
  Lacune number and lacune volume were positively associated with worse executive function (number p < 0.001; volume p < 0.001) and processing speed (number p < 0.001; volume p < 0.001). Thalamic lacunes, particularly those in regions with connectivity to the prefrontal cortex, were associated with impaired processing speed (Bonferroni corrected p = 0.016). Regions of associated anatomical covariance included the medial prefrontal, orbitofrontal, anterior insular cortex and the striatum.
  
  
  CONCLUSIONS
  Lacunes are important predictors of cognitive impairment in SVD. We highlight the importance of spatial distribution, particularly of anteromedial thalamic lacunes which are associated with impaired information processing speed and may mediate cognitive impairment via disruption of connectivity to the prefrontal cortex.
authors.affiliation: Neurosciences Research Centre, St George's University of London, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Benjamin
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.affiliation: Neurosciences Research Centre, St George's University of London, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Lambert
authors.affiliation: Neurosciences Research Centre, St George's University of London, UK.
authors.forename: Bhavini
authors.initials: B
authors.lastname: Patel
authors.affiliation: Neurosciences Research Centre, St George's University of London, UK.
authors.forename: Ai Wern
authors.initials: AW
authors.lastname: Chung
authors.affiliation: Atkinson Morley Regional Neuroscience Centre, St George's NHS Healthcare Trust, London, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: MacKinnon
authors.affiliation: King's College Institute of Psychiatry, London, UK.
authors.forename: Robin G
authors.initials: RG
authors.lastname: Morris
authors.affiliation: Neurosciences Research Centre, St George's University of London, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Barrick
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D049292:Leukoaraiosis / Q000150:complications*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D013223:Statistics as Topic; D059409:Stroke, Lacunar / Q000150:complications*
keywords: Cognitive Impairment; Lacunes; Small vessel disease