Impact of White Matter Changes on Clinical Manifestation of Alzheimer’s Disease

Abstract

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. (Stroke. 2000;31:2182-2188.)

The correlation between white-matter microstructure and the complexity of spontaneous brain activity: A difussion tensor imaging-MEG study

“…For instance, LZC scores were significantly lower in Alzheimer's disease Gómez, et al 2006) and this fact was accompanied by an exaggerated reduction of patients' complexity scores with age, as compared to controls (Fernández et al 2010). The reduction of LZC scores was attributed to the well-known disconnection syndrome in Alzheimer's disease and the consequent connectivity impairment observed in these patients (Bozzali et al 2002;Hirono et al 2000;Stam et al 2007). …”

A fully automated method for quantifying and localizing white matter hyperintensities on MR images

“…Some methods automatically or semi-automatically segment the WMHs on FLAIR images by defining a cut-off threshold on the images. For example, 3.5 standard deviations (SD) of the intensity value of the normal WM has been used as the lower intensity threshold for WMH segmentation (Hirono, et al 2000). The histogram of the FLAIR image has been used in a regression model to decide on a cut-off intensity threshold, with the pixels above the threshold classified as WMHs (Jack, et al 2001).…”

“…Another method uses the mean and standard deviations of the gray matter, white matter and CSF to estimate the intensity threshold for WMH, in which a probability map is used to favor the most likely WM regions (Wen and Sachdev 2004). These methods use only a single intensity threshold to segment the WMHs for the whole brain or for each slice of the brain images, which may misclassify some non-WMHs as WMHs, since some gray matter demonstrates signal intensity above the threshold (Hirono, et al 2000), and also the image intensity inhomogeneities may be problematic. To exclude the misclassified voxels, a manually outlined mask of WMHs with surrounding WM, GM and CSF has been used as WMH mask in Hirono's paper, while in Wen's paper a WM probability map (MNI 152 brains) has been used to favor the most likely WM regions.…”

MRI Biomarkers of Vascular Damage and Atrophy Predicting Mortality in a Memory Clinic Population

“…10,11 The relation between MRI markers of vascular disease and cognitive function is less clear; however, some studies suggest an association 12,13 but others fail to do so. 10,14 Less is known about the value of MRI in predicting survival in memory clinic patients. A limited number of studies found a correlation between imaging markers and an increased risk of mortality, and only 1 of those studies 4 was conducted in a dementia population, using CT rather than MRI.…”