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White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults |
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| Authors: | Brian T. Gold Zude Zhu Christopher A. Brown Anders H. Andersen Mary Jo LaDu Leon Tai Greg A. Jicha Richard J. Kryscio Steven Estus Peter T. Nelson Steve W. Scheff Erin Abner Frederick A. Schmitt Linda J. Van Eldik Charles D. Smith |
| Affiliation: | 1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA;2. Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA;3. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA;4. Department of Anatomy and Cell Biology, University of Illinois, Chicago, IL, USA;5. Department of Neurology, University of Kentucky, Lexington, KY, USA;6. Department of Statistics, University of Kentucky, Lexington, KY, USA;g Department of Physiology, University of Kentucky, Lexington, KY, USA;h Department of Pathology, University of Kentucky, Lexington, KY, USA;i Department of Epidemiology, University of Kentucky, Lexington, KY, USA |
| Abstract: | We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ42 and Aβ42/p-Tau181) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF Aβ42/p-Tau181 and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures. |
| Keywords: | Normal older adults CSF White matter DTI Preclinical AD |
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