Published Online
on December 8, 2008

A more recent version of this article appeared on March 1, 2009

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Submitted on September 16, 2008
Accepted on September 16, 2008

Understanding White Matter Disease. Imaging-Pathological Correlations in Vascular Cognitive Impairment

Sandra Black MD, FRCP(C)^*; FuQiang Gao MD; and Juan Bilbao MD, FRCP(C)

From the Heart and Stroke Foundation Centre for Stroke Recovery and Departments of Medicine (Neurology) and Neuropathology, Sunnybrook Health Sciences Centre, University of Toronto, Canada.

^* To whom correspondence should be addressed. E-mail: sandra.black{at}sunnybrook.ca.

Abstract—Most strokes are covert and observed incidentally on brain scans, but their presence increases risk of overt stroke and dementia. Amyloid angiopathy, associated with Alzheimer Disease (AD) causes stroke, and when even small strokes coexist with AD, they lower the threshold for dementia. Diffuse ischemic white matter disease impairs executive functioning, information processing speed, and gait. Neuroimaging techniques, such as tissue segmentation, Diffusion Tensor Imaging, MR Spectroscopy, functional MRI and amyloid PET, probe microstructural integrity, molecular biology, and activation patterns, providing new insights into brain-behavior relationships. MR-pathological studies of periventricular hyperintensity (leukoaraiosis) in aging and dementia reveal arteriolar tortuosity, reduced vessel density, and occlusive venous collagenosis which causes venous insufficiency and vasogenic edema. Activated microglia, oligodendroglial apoptosis, clasmatodendritic astrocytosis, and upregulated hypoxia-markers are seen on immunohistochemistry. Further research is needed to understand and treat this chronic subcortical vascular disease, which is epidemic in our aging population.

Key words: silent stroke • white matter hyperintensities • venous collagenosis • tissue segmentation • neuropathology

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