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Journal of Investigative Medicine:
doi: 10.1097/JIM.0000000000000102
Original Articles

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

Sun, Xiaoyan MD, PhD*†‡§; Salat, David PhD‡∥¶; Upchurch, Kristen MD*‡§; Deason, Rebecca PhD**; Kowall, Neil MD*‡§; Budson, Andrew MD*†‡§

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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.

Copyright © 2014 by The American Federation for Medical Research

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