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

Dept. of Neurology and Alzheimer Center, VU Medical Center, De Boelelaan 1117, 7057, 1007 MB, Amsterdam, The Netherlands.
Journal of Neurology (Impact Factor: 3.38). 10/2008; 255(9):1302-8. DOI: 10.1007/s00415-008-0874-y
Source: PubMed


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.


Available from: Ph Scheltens
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    • "All MRI were acquired on 1.5 T scanners and the sequences were modified to suit differences in machine manufacturers and operating systems. Qualitative rating scales were applied, which, by their simplicity, are relatively insensitive to measures at multiple sites [41]. In addition, all data were analyzed by a single rater (C.D.), who was blind to all clinical and genetic data, to reduce interrater variance [42]. "
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