NEUROLOGY 2006;67:2192-2198
© 2006 American Academy of Neurology
Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD
M. Yoshita, MD, PhD,
E. Fletcher, PhD,
D. Harvey, PhD,
M. Ortega, BS,
O. Martinez, BS,
D. M. Mungas, PhD,
B. R. Reed, PhD and
C. S. DeCarli, MD
From the Department of Neurology (M.Y., E.F., M.O., O.M., D.M.M., B.R.R., C.S.D.C.), School of Medicine, Division of Biostatistics (D.H.), and Imaging of Dementia and Aging Laboratory (M.Y., E.F., M.O., O.M., C.S.D.C.), Center for Neuroscience, University of California, Davis, and Veterans Administration Northern California Health Care System (D.M.M., B.R.R., C.S.D.C.), Sacramento, CA.
Address correspondence and reprint requests to Dr. M. Yoshita, Department of Neurology and Center for Neuroscience, University of California at Davis, 1544 Newton Ct., Davis, CA 95616; e-mail: myoshita{at}ucdavis.edu.
Objective: To analyze the extent and spatial distribution of white matter hyperintensities (WMH) in brain regions from cognitively normal older individuals (CN) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD).
Methods: We studied 26 mild AD, 28 MCI, and 33 CN. MRI analysis included quantification of WMH volume, nonlinear mapping onto a common anatomic image, and spatial localization of each WMH voxel to create an anatomically precise frequency distribution map. Areas of greatest frequency of WMH from the WMH composite map were used to identify 10 anatomic regions involving periventricular areas and the corpus callosum (CC) for group comparisons.
Results: Total WMH volumes were associated with age, extent of concurrent vascular risk factors, and diagnosis. After correcting for age, total WMH volumes remained significantly associated with diagnosis and extent of vascular risk. Regional WMH analyses revealed significant differences in WMH across regions that also differed significantly according to diagnosis. In post-hoc analyses, significant differences were seen between CN and AD in posterior periventricular regions and the splenium of the CC. MCI subjects had intermediate values at all regions. Repeated measures analysis including vascular risk factors in the model found a significant relationship between periventricular WMH and vascular risk that differed by region, but regional differences according to diagnosis remained significant and there was no interaction between diagnosis and vascular risk.
Conclusions: Differences in white matter hyperintensities (WMH) associated with increasing cognitive impairment appear related to both extent and spatial location. Multiple regression analysis of regional WMH, vascular risk factors, and diagnosis suggest that these spatial differences may result from the additive effects of vascular and degenerative injury. Posterior periventricular and corpus callosum extension of WMH associated with mild cognitive impairment and Alzheimer disease indicate involvement of strategic white matter bundles that may contribute to the cognitive deficits seen with these syndromes.
Supported in part by NIH grants P30 AG10129, R01 AG021028, and R01 AG10220.
Disclosure: The authors report no conflicts of interest.
Received March 24, 2006. Accepted in final form September 13, 2006.
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