期刊
JOURNAL OF INVESTIGATIVE MEDICINE
卷 62, 期 7, 页码 927-933出版社
BMJ PUBLISHING GROUP
DOI: 10.1097/JIM.0000000000000102
关键词
diffusion tensor imaging; Alzheimer disease; mild cognitive impairment; fractional anisotropy; axial diffusivity; radial diffusivity; cholinergic pathway
资金
- VA Special Fellowships in Advanced Geriatrics
- National Institutes of Health [NIH]
- ADNI (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BioClinica, Inc
- Biogen Idec, Inc
- Bristol-Myers Squibb Company
- Eisai, Inc
- Elan Pharmaceuticals, Inc
- Eli Lilly and Company
- F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc
- GE Healthcare
- Innogenetics, NV
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Medpace, Inc
- Merck Co, Inc
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer, Inc
- Piramal Imaging
- Servier
- Synarc, Inc
- Canadian Institutes of Health Research
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.
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