title: Determinants of white matter hyperintensity burden differ at the extremes of ages of ischemic stroke onset.
abstract: BACKGROUND
  Age is a well-known risk factor for both stroke and increased burden of white matter hyperintensity (WMH), as detected on magnetic resonance imaging (MRI) scans. However, in patients diagnosed with ischemic stroke (IS), WMH volume (WMHv) varies significantly across age groups. We sought to examine the determinants of WMH burden across the ages of stroke onset with the goal to uncover potential age-specific stroke prevention targets.
  
  
  METHODS
  Adult subjects from an ongoing hospital-based cohort study of IS patients with admission brain MRI were categorized as having early (<55 years), late (>75 years), or average (55-75 years) age of stroke onset. WMHv was measured using a previously validated, MRI-based semi-automated method and normalized for linear regression analyses.
  
  
  RESULTS
  Of 1008 IS subjects, 249 had early-onset stroke (24.7%), and 311 had late-onset stroke (30.9%). In multivariable analysis of WMHv using backward stepwise selection, only age (β = .02, P = .018), hypertension (β = .24, P = .049), and history of tobacco use (β = .38, P = .001) were independently associated with WMHv in patients with early-onset stroke, whereas male sex (β = -.30, P = .007), hyperlipidemia (β = -.27, P = .015), and current alcohol use (β = .23, P = .034) were independently associated with WMHv in patients with late-onset stroke.
  
  
  CONCLUSIONS
  History of tobacco use is a strong independent predictor of WMH burden in patients with early-onset stroke, whereas age is no longer associated with WMHv in IS patients older than 75 years of age. These findings suggest that the major risk factors to target for stroke prevention differ across age groups and may be modifiable.
authors.affiliation: Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Cathy R
authors.initials: CR
authors.lastname: Zhang
authors.affiliation: Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cloonan
authors.affiliation: Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Fitzpatrick
authors.affiliation: Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Allison S
authors.initials: AS
authors.lastname: Kanakis
authors.affiliation: Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Ayres
authors.affiliation: Rhode Island Hospital, Providence, Rhode Island.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Furie
authors.affiliation: Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.affiliation: Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: nrost@partners.org.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Rost
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001331:Automation; D001900:Boston / Q000453:epidemiology; D002545:Brain Ischemia / Q000175:diagnosis* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D056784:Leukoencephalopathies / Q000175:diagnosis* / Q000453:epidemiology; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D020521:Stroke / Q000175:diagnosis* / Q000453:epidemiology; D066127:White Matter / Q000473:pathology*
keywords: CT and MRI; Leukoaraiosis; acute cerebral infarction; risk factor; risk factors for stroke; white matter disease