Do White Matter Changes Have Clinical Significance in Alzheimer’s Disease?

Abstract

Background: Although white matter changes visible with MRI are generally considered to result from ischemia, it has become clear that these changes also appear in patients with Alzheimer’s disease (AD). However, their significance in AD is unknown. Objective: We evaluated the clinical significance of white matter changes in AD. Methods: Ninety-six AD patients (79.4 ± 5.92 years old) and 48 age-matched control subjects (80.0 ± 7.03 years old) participated in the study. Three neuroradiologists assessed the degree of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) using a modified Fazekas’ rating scale. We examined whether there was a difference in the severity and the histogram pattern of the white matter changes, or in vascular factors (hypertension, diabetes mellitus, and ischemic heart disease) between the two groups. We also analyzed the association between the severity of the white matter changes and the degree of dementia (MMSE score and disease duration). Results: There were no differences in the vascular factors between AD and control subjects. The degree of PVH in AD was severe compared with that in the control subjects. In histograms of the number of subjects with each degree of PVH severity, the distribution of AD patients had peaks at both the low and intermediate degrees of PVH, while most of the controls had a low degree of PVH. There was no difference in the degree or the histogram pattern of DWMH between the two groups. The severity of white matter changes was not associated with severity of dementia in AD. Conclusions: Although PVH might have several causative factors, and may have some clinical significance, the change itself does not contribute to the progression of AD.

Do Lesions Involving the Cortical Cholinergic Pathways Help or Hinder Efficacy of Donepezil in Patients with Alzheimer’s Disease?

“…In line with previous theories [18][19][20][21][22] , the present study confirmed that the cognitive function of AD patients at baseline was mostly unaffected by MR lesions, including those on the cholinergic pathways, or hippocampal size. Among them, WMH showed a tendency to be associated with lower CDT scores ( ␤ = -0.52, p = 0.06).…”

“…White matter hyperintensities (WMH) are associated with slow psychomotor speed [10][11][12] , depression [13][14][15] and sometimes memory impairment [16,17] , but not with the severity of AD [18][19][20][21][22] .…”

Alzheimer’s Disease: Role of Size and Location of White Matter Changes in Determining Cognitive Deficits

“…These negative results could be due to poor investigation of cognitive skills specifically subserved by frontal-subcortical circuits [15,16] and to the methodology adopted in rating WMC that disregards the role of cortical atrophy [49] as well as the location of WMC lesions [15,35] . A study paying attention to just lobar distribution of white matter lesions displayed a relationship between frontal WMC volumes and Category Fluency in a small sample of AD cases [17] .…”

“…More recently, AD has been proposed as a clinical syndrome with two radiological expressions, with and without small vessel disease [14] . However, data on the frequency [2] and clinical relevance of WMCs in AD are still controversial and lack evidence of a specifi c effect of WMCs on global measures of mental impairment [15] , even when the location of the lesions has been considered [16] . A survey focused on WMCs in healthy aging and vascular dementia/AD patients detected a relationship between frontal WMC volumes and verbal category fl uency just in a small subgroup of AD cases [17] .…”

Diffusion Tensor Imaging of Normal-Appearing White Matter in Mild Cognitive Impairment and Early Alzheimer Disease: Preliminary Evidence of Axonal Degeneration in the Temporal Lobe

“…[1][2][3] Although neuroimaging and pathoanatomic studies have confirmed both macroscopic and microscopic white matter changes in patients with AD and MCI, controversy exists regarding the clinical relevance of these changes and the mechanisms underlying them. [4][5][6][7] By taking advantage of the anisotropic nature of water diffusion in biologic tissues, the diffusion tensor imaging (DTI) technique provides increased sensitivity for detecting ultrastructural abnormalities of white matter in vivo. 8 This is true even in regions that appear normal on traditional MR imaging sequences (so called normal-appearing white matter [NAWM]).…”