title: Vascular risk factor burden correlates with cerebrovascular reactivity but not resting state coactivation in the default mode network.
abstract: OBJECTIVE
  White matter hyperintensities (WMH) are prevalent among older adults and are often associated with cognitive decline and increased risk of stroke and dementia. Vascular risk factors (VRFs) are linked to WMH, yet the impact of multiple VRFs on gray matter function is still unclear. The goal of this study was to test for associations between the number of VRFs and cerebrovascular reactivity (CVR) and resting state (RS) coactivation among individuals with WMH.
  
  
  METHODS
  Twenty-nine participants with suspected WMH were grouped based on the number of VRFs (subgroups: 0, 1, or ≥2). CVR and RS coactivation were measured with blood oxygenation level-dependent (BOLD) imaging on a 3T magnetic resonance imaging (MRI) system during hypercapnia and rest, respectively. Default-mode (DMN), sensory-motor, and medial-visual networks, generated using independent component analysis of RS-BOLD, were selected as networks of interest (NOIs). CVR-BOLD was analyzed using two methods: 1) a model-based approach using CO2 traces, and 2) a dual-regression (DR) approach using NOIs as spatial inputs. Average CVR and RS coactivations within NOIs were compared between VRF subgroups. A secondary analysis investigated the correlation between CVR and RS coactivation.
  
  
  RESULTS
  VRF subgroup differences were detected using DR-based CVR in the DMN (F20,2  = 5.17, P = 0.015) but not the model-based CVR nor RS coactivation. DR-based CVR was correlated with RS coactivation in the DMN (r(2)  = 0.28, P = 0.006) but not the sensory-motor nor medial-visual NOIs.
  
  
  CONCLUSIONS
  In individuals with WMH, CVR in the DMN was inversely associated with the number of VRFs and correlated with RS coactivation.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Toronto, Ontario, Canada.|Brain Sciences Research Program, Toronto, Ontario, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Tchistiakova
authors.affiliation: Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Toronto, Ontario, Canada.|Brain Sciences Research Program, Toronto, Ontario, Canada.
authors.forename: David E
authors.initials: DE
authors.lastname: Crane
authors.affiliation: Department of Medical Imaging, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mikulis
authors.affiliation: Department of Psychology, University of Toronto, Toronto, Ontario, Canada.|Rotman Research Institute, Toronto, Ontario, Canada.|Department of Medicine (Psychiatry), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Anderson
authors.affiliation: Rotman Research Institute, Toronto, Ontario, Canada.|Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Carol E
authors.initials: CE
authors.lastname: Greenwood
authors.affiliation: Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Toronto, Ontario, Canada.|Brain Sciences Research Program, Toronto, Ontario, Canada.|Rotman Research Institute, Toronto, Ontario, Canada.|Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Toronto, Ontario, Canada.|Brain Sciences Research Program, Toronto, Ontario, Canada.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: MacIntosh
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D002560:Cerebrovascular Circulation / Q000502:physiology*; D017352:Echo-Planar Imaging; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000150:complications / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D012146:Rest; D012307:Risk Factors; D014652:Vascular Diseases / Q000150:complications / Q000503:physiopathology*
keywords: cerebrovascular reactivity; resting-state coactivation; vascular risk factors