White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults

• Published in: Neurobiology of aging 2014-10, Vol.35 (10), p.2263-2271
• Main Authors: Gold, Brian T, Zhu, Zude, Brown, Christopher A, Andersen, Anders H, LaDu, Mary Jo, Tai, Leon, Jicha, Greg A, Kryscio, Richard J, Estus, Steven, Nelson, Peter T, Scheff, Steve W, Abner, Erin, Schmitt, Frederick A, Van Eldik, Linda J, Smith, Charles D
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Aging - pathology; Aging - psychology; Alzheimer Disease - cerebrospinal fluid; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers - cerebrospinal fluid; Cognition - physiology; CSF; Diffusion Magnetic Resonance Imaging; DTI; Female; Fornix, Brain - pathology; Hippocampus - pathology; Humans; Internal Medicine; Male; Neurology; Normal older adults; Organ Size; Peptide Fragments - cerebrospinal fluid; Preclinical AD; tau Proteins - cerebrospinal fluid; White matter; White Matter - pathology
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2014.04.030

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.