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J Investig Med. 2014 Oct;62(7):927-33. doi: 10.1097/JIM.0000000000000102.

Destruction of white matter integrity in patients with mild cognitive impairment and Alzheimer disease.

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From the *Department of Neurology and †Center for Translational Neuroscience, ‡VA Boston Healthcare System, Boston, MA; §Boston University School of Medicine, Boston, MA; ∥Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA; ¶Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA; and **Department of Psychology, Texas State University, San Marcos, TX.



Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD).


The aim of this research was to study the microstructural integrity of white matter in AD in vivo.


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.


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.


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.

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