title: Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study.
abstract: OBJECTIVE
  White matter hyperintensities and MRI-defined brain infarcts (BIs) have individually been related to stroke, dementia, and mortality in population-based studies, mainly in older people. Their significance in middle-aged community-dwelling persons and the relative importance of these associations remain unclear. We simultaneously assessed the relation of white matter hyperintensities and BI with incident stroke, mild cognitive impairment, dementia, and mortality in a middle-aged community-based cohort.
  
  
  METHODS
  A total of 2229 Framingham Offspring Study participants aged 62+/-9 years underwent volumetric brain MRI and neuropsychological testing (1999 to 2005). Incident stroke, dementia, and mortality were prospectively ascertained and for 1694 participants in whom a second neuropsychological assessment was performed (2005 to 2007), incident mild cognitive impairment was evaluated. All outcomes were related to white matter hyperintensities volume (WMHV), age-specific extensive WMHV and BI adjusting for age and gender.
  
  
  RESULTS
  Extensive WMHV and BI were associated with an increased risk of stroke (hazard ratio [HR]=2.28, 95% CI: 1.02 to 5.13; HR=2.84, 95% CI: 1.32 to 6.10). WMHV, extensive WMHV, and BI were associated with an increased risk of dementia (HR=2.22, 95% CI: 1.32 to 3.72; HR=3.97, 95% CI: 1.10 to 14.30; HR=6.12, 95% CI: 1.82 to 20.54) independently of vascular risk factors and interim stroke. WMHV and extensive WMHV were associated with incident amnestic mild cognitive impairment in participants aged > or = 60 years only (OR=2.47, 95% CI: 1.31 to 4.66 and OR=1.49, 95% CI: 1.14 to 1.97). WMHV and extensive WMHV were associated with an increased risk of death (HR=1.38, 95% CI: 1.13 to 1.69; HR=2.27, 95% CI: 1.41 to 3.65) independent of vascular risk factors and of interim stroke and dementia.
  
  
  CONCLUSIONS
  In a large community-based sample of middle-aged adults, BI predicted an increased risk of stroke and dementia independent of vascular risk factors. White matter hyperintensities portended an increased risk of stroke, amnestic mild cognitive impairment, dementia, and death independent of vascular risk factors and interim vascular events.
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA. sdebette@bu.edu
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Debette
authors.forename: Alexa
authors.initials: A
authors.lastname: Beiser
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.forename: Jayandra J
authors.initials: JJ
authors.lastname: Himali
authors.forename: Margaret
authors.initials: M
authors.lastname: Kelly-Hayes
authors.forename: Jose R
authors.initials: JR
authors.lastname: Romero
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Kase
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020214:Cerebrovascular Trauma / Q000150:complications / Q000401:mortality / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D003704:Dementia; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000503:physiopathology