title: Vascular imaging abnormalities and cognition: mediation by cortical volume in nondemented individuals: atherosclerosis risk in communities-neurocognitive study.
abstract: OBJECTIVE
  The relationships between cerebrovascular lesions visible on imaging and cognition are complex. We explored the possibility that the cerebral cortical volume mediated these relationships.
  
  
  METHODS
  Total of 1906 nondemented participants (59% women; 25% African-American; mean age, 76.6 years) in the Atherosclerosis Risk in Communities (ARIC) study underwent cognitive assessments, risk factor assessments, and quantitative MRI for white matter hyperintensities (WMH) and infarcts. The Freesurfer imaging analysis pipeline was used to determine regional cerebral volumes. We examined the associations of cognitive domain outcomes with cerebral volumes (hippocampus and separate groups of posterior and frontal cortical regions of interest) and cerebrovascular imaging features (presence of large or small cortical/subcortical infarcts and WMH volume). We performed mediation pathway analyses to assess the hypothesis that hippocampal and cortical volumes mediated the associations between cerebrovascular imaging features and cognition.
  
  
  RESULTS
  In unmediated analyses, WMH and infarcts were both associated with worse psychomotor speed/executive function. In mediation analyses, WMH and infarct associations on psychomotor speed/executive function were significantly attenuated, but not abolished, by the inclusion of the posterior cortical regions of interest volume in the models, and the infarcts on psychomotor speed/executive function association were attenuated, but not abolished, by inclusion of the frontal cortical regions of interest volume.
  
  
  CONCLUSIONS
  Both WMH and infarcts were associated with cortical volume, and both lesions were also associated with cognitive performance, implying shared pathophysiological mechanisms. Although cross-sectional, our findings suggest that WMH and infarcts could be proxies for clinically covert processes that directly damage cortical regions. Microinfarcts are 1 candidate for such a clinically covert process.
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.). knopman@mayo.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Michael E
authors.initials: ME
authors.lastname: Griswold
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Seth T
authors.initials: ST
authors.lastname: Lirette
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Gottesman
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Graff-Radford
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Andrea L C
authors.initials: AL
authors.lastname: Schneider
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: B Gwen
authors.initials: BG
authors.lastname: Windham
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Laura H
authors.initials: LH
authors.lastname: Coker
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Marilyn S
authors.initials: MS
authors.lastname: Albert
authors.affiliation: From the Departments of Neurology (D.S.K., J.G.-R.) and Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, MN; Departments of Biostatistics (M.E.G., S.T.L.) and Medicine (B.G.W., T.H.M.), University of Mississippi Medical Center, Jackson, MS; Departments of Neurology (R.F.G., M.S.A.) and Epidemiology (A.R.S., A.L.C.S.), Johns Hopkins University, Baltimore, MD; and Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC (L.H.C.).
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D002561:Cerebrovascular Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D012111:Residence Characteristics; D012307:Risk Factors
keywords: cerebral infarction; cerebral small vessel diseases; cognition; magnetic resonance imaging