title: The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults.
abstract: OBJECTIVE
  To assess the association of MRI white matter hyperintensities (WMHI) with cognitive performance, cerebral structure, and cerebral metabolism in 51 healthy individuals aged 19 to 91 years without cerebrovascular risk factors.
  
  
  BACKGROUND
  Abnormal white matter signals have been associated with brain atrophy, reduced cerebral blood flow, focal neurologic signs, gait disorder, and poorer neuropsychological test performance. Most studies of WMHI, however, include subjects with hypertension or other identifiable causes of cerebrovascular disease that may have an independent effect on brain structure and function. To assess brain changes associated with WMHI independent of cerebrovascular risk factors, we determined WMHI volume, brain volume, cerebral metabolism, and cognitive performance for a group of subjects free of medical illness. Regional cerebral metabolism and cognitive domains were also assessed to evaluate the possible role of frontal lobe dysfunction in subjects with WMHI.
  
  
  METHODS
  Cross-sectional study of 51 very healthy subjects aged 19 to 91 years.
  
  
  METHODS
  WMHI, brain, and CSF volumes were determined by MRI segmentation. Neuropsychological tests were employed to assess multiple cognitive domains. Brain metabolism was determined from 18-fluoro-2-deoxy-D-glucose PET. Multivariate relations were tested with stepwise linear regression. Models included the potential confounders of age and education where appropriate.
  
  
  RESULTS
  The distribution of WMHI volume was bimodal, with five subjects having WMHI volumes beyond three SDs from the normally distributed population. A WMHI volume of greater than 0.5% of intracranial volume was considered abnormal. Within the multivariate models, WMHI volumes were significantly predictive of increased ventricular volume, reduced brain volume, and reduced cognitive scores. Subjects with greater than 0.5% WMHI volume also had significantly lower frontal lobe metabolism, significantly higher systolic blood pressure, significantly larger ventricular volume, and significantly lower scores on frontal lobe-mediated neuropsychological tests than age-matched controls.
  
  
  CONCLUSIONS
  WMHI volume is associated with structural and functional brain changes even within a group of very healthy individuals. WMHI is associated with poorer frontal lobe cognitive function and, when severe, is accompanied by significantly reduced frontal lobe metabolism. Subjects with large WMHI volumes have significantly higher systolic blood pressure, brain atrophy, reduced cerebral metabolism, and lower scores on tests of frontal lobe function than age-matched controls. Large amounts of WMHI are, therefore, pathologic and may be related to elevated systolic blood pressure even when it is within the normal age-related range.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: C
authors.initials: C
authors.lastname: DeCarli
authors.forename: D G
authors.initials: DG
authors.lastname: Murphy
authors.forename: M
authors.initials: M
authors.lastname: Tranh
authors.forename: C L
authors.initials: CL
authors.lastname: Grady
authors.forename: J V
authors.initials: JV
authors.lastname: Haxby
authors.forename: J A
authors.initials: JA
authors.lastname: Gillette
authors.forename: J A
authors.initials: JA
authors.lastname: Salerno
authors.forename: A
authors.initials: A
authors.lastname: Gonzales-Aviles
authors.forename: B
authors.initials: B
authors.lastname: Horwitz
authors.forename: S I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012016:Reference Values; D012044:Regression Analysis; D014055:Tomography, Emission-Computed
chemical_list: D005947:Glucose