Destruction of White Matter Integrity in Patients with Mild Cognitive Impairment and Alzheimer Disease

Abstract

Background Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD). Objective The aim of this research was to study the microstructural integrity of white matter in AD in vivo. Methods Global fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer’s Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups. Results Compared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally. Conclusions The radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD.

White Matter Microstructure Improves Stroke Risk Prediction in the General Population

“…31 Indeed, SVD is considered the shared pathology linking stroke with cognitive decline and dementia, including Alzheimer disease. 32 However, more work is needed to fully understand the role of the white matter microstructure in this area of research.…”

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“…32 However, more work is needed to fully understand the role of the white matter microstructure in this area of research.…”

Tract-based analysis of white matter degeneration in Alzheimer’s disease

“…Several studies have used neuroimaging techniques such as volumetric measurements (Salat et al, 1999a, Salat et al, 1999b, Salat et al, 2009) and diffusion tensor imaging (DTI) (Rose et al, 2000, Bozzali et al, 2002, Choi et al, 2005, Bucur et al, 2008, Madden et al, 2009, Salat et al, 2009, Stebbins and Murphy, 2009, Gold et al, 2010, Pievani et al, 2010, Salat et al, 2010, Smith et al, 2010, Douaud et al, 2011, Nir et al, 2012, Nir et al, 2013, Rowley et al, 2013, Lim et al, 2014, Sun et al, 2014) to study WM pathology in AD and show both extensive local and diffuse damage. DTI enables the measurement of several microstructural properties of the WM tissue environment.…”