title: Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia.
abstract: BACKGROUND
  White matter hyperintensities (WMH) have an effect on cognition and are increased in severity among individuals with amnestic mild cognitive impairment (aMCI). The influence of WMH on progression of aMCI to Alzheimer's disease (AD) is less clear.
  
  
  METHODS
  Data were drawn from a three-year prospective, double blind, placebo controlled clinical trial that examined the effect of donepezil or vitamin E on progression from aMCI to AD. WMH from multiple brain regions were scored on MR images obtained at entry into the trial from a subset of 152 study participants using a standardized visual rating scale. Cox proportional hazards models adjusting for age, education and treatment arm were used to investigate the role of WMH on time to progression.
  
  
  RESULTS
  55 of the 152 (36.2 %) aMCI subjects progressed to AD. Only periventricular hyperintensities (PVH) were related to an increased risk of AD within three years (HR = 1.59, 95 % CI = 1.24 - 2.05, p-value < 0.001). Correcting for medial temporal lobe atrophy or the presence of lacunes did not change statistical significance.
  
  
  CONCLUSIONS
  PVH are associated with an increased risk of progression from aMCI to AD. This suggests that PVH, an MRI finding thought to represent cerebrovascular damage, contributes to AD onset in vulnerable individuals independent of Alzheimer pathology.
authors.affiliation: Dept. of Neurology and Alzheimer Center, VU Medical Center, De Boelelaan 1117, 7057, 1007 MB, Amsterdam, The Netherlands. i.vanstraaten@vumc.nl
authors.forename: Elisabeth C W
authors.initials: EC
authors.lastname: van Straaten
authors.forename: Danielle
authors.initials: D
authors.lastname: Harvey
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Thal
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D000647:Amnesia / Q000188:drug therapy / Q000473:pathology*; D000975:Antioxidants / Q000627:therapeutic use; D001284:Atrophy; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000473:pathology*; D003704:Dementia / Q000188:drug therapy / Q000473:pathology*; D018450:Disease Progression; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007189:Indans / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010880:Piperidines / Q000627:therapeutic use; D011446:Prospective Studies; D013702:Temporal Lobe / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D014810:Vitamin E; D000077265:Donepezil