title: Trajectory of white matter hyperintensity burden preceding mild cognitive impairment.
abstract: OBJECTIVE
  To determine the time of acceleration in white matter hyperintensity (WMH) burden, a common indicator of cerebrovascular pathology, in relation to conversion to mild cognitive impairment (MCI) in the elderly.
  
  
  METHODS
  A total of 181 cognitively intact elderly volunteers from the longitudinal, prospective, Oregon Brain Aging Study underwent yearly evaluations, including brain MRI, and cognitive testing. MRIs were analyzed for imaging markers of neurodegeneration: WMH and ventricular CSF (vCSF) volumes. The time before MCI, when the changes in WMH and vCSF burden accelerate, was assessed using a mixed-effects model with a change point for subjects who developed MCI during follow-up.
  
  
  RESULTS
  During a follow-up duration of up to 19.6 years, 134 subjects converted to MCI. Acceleration in %WMH volume increase occurred 10.6 years before MCI onset. On average, the annual rate of change in %WMH increased an additional 3.3% after the change point. Acceleration in %vCSF volume increase occurred 3.7 years before the onset of MCI. Out of 63 subjects who converted to MCI and had autopsy, only 28.5% had Alzheimer disease (AD) as the sole etiology of their dementia, while almost just as many (24%) had both AD and significant ischemic cerebrovascular disease present.
  
  
  CONCLUSIONS
  Acceleration in WMH burden, a common indicator of cerebrovascular disease in the elderly, is a pathologic change that emerges early in the presymptomatic phase leading to MCI. Longitudinal changes in WMH may thus be useful in determining those at risk for cognitive impairment and for planning strategies for introducing disease-modifying therapies prior to dementia onset.
authors: Department of Neurology, Oregon Health & Science University, Portland, OR, USA. silbertl@ohsu.edu
authors: Lisa C
authors: LC
authors: Silbert
authors: Hiroko H
authors: HH
authors: Dodge
authors: Louie G
authors: LG
authors: Perkins
authors: Lena
authors: L
authors: Sherbakov
authors: David
authors: D
authors: Lahna
authors: Deniz
authors: D
authors: Erten-Lyons
authors: Randall
authors: R
authors: Woltjer
authors: Lynne
authors: L
authors: Shinto
authors: Jeffrey A
authors: JA
authors: Kaye
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology*; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D015577:Geriatric Assessment / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D059906:Neuroimaging / Q000379:methods; D013997:Time Factors