Impact of White Matter Changes on Clinical Manifestation of Alzheimer's Disease: A Quantitative Study

Background And Purpose: There have been conflicting results involving the clinical significance of white matter changes in patients with Alzheimer's disease (AD). We studied the association between the volume of white matter hyperintensities (WMHs) on T2-weighted images and cognitive, neurological, and neuropsychiatric symptoms.

Methods: The subjects were 76 AD patients who had WMHs but no obvious cerebrovascular diseases. We quantified the volume of WMHs by using fast-fluid-attenuated inversion recovery images and whole brain atrophy by using 3D spoiled gradient-echo images. Effects of WMHs and brain atrophy on dementia severity, cognitive function, neuropsychiatric disturbances, and neurological findings were examined.

Results: Whole brain atrophy was significantly associated with dementia severity and cognitive disturbances, as well as with grasp reflex and some kinds of neuropsychiatric disturbances. After we controlled for the effects of brain atrophy, duration of symptoms, and demographic factors, we found that WMH volume was not associated with global cognitive disturbances or dementia severity but was significantly associated with urinary incontinence, grasp reflex, and aberrant motor behaviors. Brain atrophy and WMH volume were not significantly correlated either before or after controlling for age, sex, education, and duration of symptoms. WMH volume was associated with hypertension, but brain atrophy was not positively correlated with any vascular risk factors.

Conclusions: Our results support the hypothesis that WMHs in AD patients are superimposed phenomena of vascular origin. WMHs contribute to specific neurological and neuropsychiatric manifestations but not to global cognitive impairment, which is more closely associated with brain atrophy.