Journal of Neurology

, 255:1302 | Cite as

Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia

  • E. C. W. van Straaten
  • D. Harvey
  • P. Scheltens
  • F. Barkhof
  • R. C. Petersen
  • L. J. Thal
  • C. R. JackJr.
  • C. DeCarli
  • for the members of the Alzheimer’s Disease Cooperative Study Group*



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.


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.


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.


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.

Key words

Alzheimer’s disease MCI (mild cognitive impairment) MRI cerebrovascular disease 


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Copyright information

© Springer 2008

Authors and Affiliations

  • E. C. W. van Straaten
    • 1
  • D. Harvey
    • 2
  • P. Scheltens
    • 1
  • F. Barkhof
    • 3
  • R. C. Petersen
    • 4
  • L. J. Thal
    • 1
  • C. R. JackJr.
    • 5
  • C. DeCarli
    • 6
  • for the members of the Alzheimer’s Disease Cooperative Study Group*
  1. 1.Dept. of Neurology and Alzheimer CenterVU Medical CenterAmsterdamThe Netherlands
  2. 2.Division of Biostatistics, Dept. of Public Health SciencesUniversity of California at DavisCaliforniaUSA
  3. 3.Dept. of RadiologyVU University Medical CenterAmsterdamThe Netherlands
  4. 4.Dept. of NeurologyMayo ClinicRochesterUSA
  5. 5.Dept. of RadiologyMayo ClinicRochesterUSA
  6. 6.Dept. of Neurology and Imaging of Dementia and Aging (IDeA) LaboratoryCenter for Neuroscience, University of California at DavisCaliforniaUSA

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