Journal of Neurology

, 255:1302

First online:

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

  • E. C. W. van StraatenAffiliated withDept. of Neurology and Alzheimer Center, VU Medical Center Email author 
  • , D. HarveyAffiliated withDivision of Biostatistics, Dept. of Public Health Sciences, University of California at Davis
  • , P. ScheltensAffiliated withDept. of Neurology and Alzheimer Center, VU Medical Center
  • , F. BarkhofAffiliated withDept. of Radiology, VU University Medical Center
  • , R. C. PetersenAffiliated withDept. of Neurology, Mayo Clinic
  • , L. J. ThalAffiliated withDept. of Neurology and Alzheimer Center, VU Medical Center
  • , C. R. JackJr.Affiliated withDept. of Radiology, Mayo Clinic
  • , C. DeCarliAffiliated withDept. of Neurology and Imaging of Dementia and Aging (IDeA) Laboratory, Center for Neuroscience, University of California at Davis
  • , for the members of the Alzheimer’s Disease Cooperative Study Group*

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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