White Matter Changes in Patients with Alzheimer’s Disease and Associated Factors

Yi-Hui Kao,Chun-Hung Chen,Yuan-Han Yang,Mei-Chuan Chou

doi:10.3390/jcm8020167

Abstract

Alzheimer’s disease (AD) is traditionally thought of as a neurodegenerative disease. Recent evidence shows that beta amyloid-independent vascular changes and beta amyloid-dependent neuronal dysfunction both equally influence the disease, leading to loss of structural and functional connectivity. White matter changes (WMCs) in the brain are commonly observed in dementia patients. The effect of vascular factors on WMCs and the relationship between WMCs and severity of AD in patients remain to be clarified. We recruited 501 clinically diagnosed probable AD patients with a series of comprehensive neuropsychological tests and brain imaging. The WMCs in cerebral CT or MRI were rated using both the modified Fazekas scale and the combined CT-MRI age related WMC (ARWMC) rating scale. Periventricular WMCs were observed in 79.4% of the patients and deep WMCs were also seen in 48.7% of the patients. WMC scores were significantly higher in the advanced dementia stage in periventricular WMCs (p = 0.001) and total ARWMCs (p < 0.001). Age and disease severity were both independently associated with WMCs score, particularly in the total, frontal and parieto-occipital areas. Vascular factors including hypertension, diabetes mellitus, and gender were not significantly associated with WMCs. In conclusion, both age and severity of dementia were significantly associated with WMCs in AD patients. These associations highlight future research targets.

Highlights

Alzheimer’s disease (AD) is widely accepted to be a disease of the cerebral gray matter
age related WMC (ARWMC), total score 0.249 (−0.448–1.726) 0.000 *(0.065–0.199) 0.007 *(0.387–2.489) 0.148 (−1.837–0.277) 0.249 (−0.502–1.931). Both periventricular and deep White matter changes (WMCs) are common in Taiwanese AD patients
Our study indicates that the frontal areas have the most WMCs followed by the parieto-occipital areas, which is similar to reports in western AD patients [18]

Summary

Introduction

Alzheimer’s disease (AD) is widely accepted to be a disease of the cerebral gray matter. Several pathological changes have been noted in the white matter, including the loss of axons, oligodendrocytes and reactive astrocytosis [2], dilation of the perivascular space, and failure of drainage of interstitial fluid secondary to deposition of beta-amyloid AD. Vascular insufficiency [3] and Wallerian degeneration of fiber tracts caused by neuronal loss in cortical associative areas [4] have been related to the pathogenesis of WM changes in AD. White matter changes (WMCs) have been reported to be associated with a decline in motor function in speed and fine motor coordination, and with many diseases including AD [2,5,6], vascular dementia, dementia with Lewy bodies, and psychiatric disorders [5]. WMCs were once considered to be benign and not related to dementia [7] as they are frequently present in the brain images of healthy aging

Methods

Results

Conclusion