Affiliations: Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Correspondence:
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Correspondence to: Professor Winnie Chiu Wing Chu, Room 27026, G/F, Treatment Block & Children Wards, Department of Imaging & Interventional Radiology, Prince of Wales Hospital, Shatin, Hong Kong SAR, China. Tel.: +86 852 35052299; E-mail: winniechu@cuhk.edu.hk.
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abstract: Background:Diagnosis of Alzheimer’s disease (AD) was recently shifted from clinical to biological construct to reflect underlying neuropathological status, where amyloid deposition designated patients to the Alzheimer’s continuum, and additional tau positivity represented AD. Objective:To investigate white matter (WM) alteration in the brain of patients in the Alzheimer’s continuum. Methods:A total of 236 subjects across the clinical and biological spectra of AD were included and stratified by normal/abnormal (–/+) amyloid (A) and tau (T) status based on positron emission tomography results, yielding five groups: A–T–cognitively normal (CN), A+T–CN, A+T+ CN, A+T+ mild cognitive impairment, and A+T+ AD. WM alteration was measured by diffusion tensor imaging (DTI). Group differences, correlation of DTI measures with amyloid and tau, and diagnostic performance of such measures were evaluated. Results:Compared with A–T–CN, widespread WM alteration was observed in the Alzheimer’s continuum, including hippocampal cingulum (CGH), cingulum of the cingulate gyrus, and uncinate fasciculus. Diffusion changes measured by regional mean fractional anisotropy (FA) in the bilateral CGH were first detected in the A+T+ CN group and associated with tau burden in the Alzheimer’s continuum (p < 0.001). For discrimination between A+T+ CN and A–T–CN groups, CGH FA achieved accuracy, sensitivity, and specificity of 74%, 58%, and 78% for right CGH and 57%, 83%, and 47% respectively for left CGH. Conclusion:WM alteration is widespread in the Alzheimer’s continuum. Diffusion alteration in CGH occurred early and was correlated with tau pathology, thus may be a promising biomarker in preclinical AD.
Keywords: Alzheimer’s disease, amyloid-β, diffusion tensor imaging, hippocampal cingulum, tau
