International Journal of Neurorehabilitation

White Matter Hyperintensities and their Location in Alzheimer's Disease

Abstract

Reinhold Schmidt, Anna Damulina and Lukas Pirpamer

White matter hyperintensities (WMH) are areas of hyperintense signal within cerebral white matter which can be identified on T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scans. WMH are common in older individuals and in patients with small vessel disease-related ischemic brain injury. Increased WMH were also reported in patients with Alzheimer’s disease (AD). Whether WMH can be a sign of early AD or the result of the pathophysiological mechanisms of AD is yet unclear. By its localization, all the white matter abnormalities can be divided into periventricular and deep WMH. Here we review the differences between periventricular and deep WMH in terms of pathophysiology, etiology and the neuroimaging characteristics in normal subjects and AD patients. Neuroimaging studies distinguish regional patterns in the WMH distribution between healthy aging controls and AD patients. Previous studies using different approaches have reported the prevalence of periventricular WMH in AD. Similar results were demonstrated in our recent study using lesion probability mapping in AD patients and age-matched controls. These results highlight the important etiological role of periventricular white matter damage in the pathogenesis of AD. It has been suggested that white matter lesions may disrupt cholinergic long projection fibers, thus confirming the possible contribution of WMH to the pathogenesis of cognitive decline in AD. It is possible that the effect of periventricular white matter abnormalities on cognitive function is typical for the early AD stages before cortical neurodegeneration begins to prevail over the relatively subtle effects of periventricular white matter damage in patients with dementia. The pathogenesis of the WMH spatial distribution in AD and their connection with cognitive impairment requires further research using new imaging techniques.