title: White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults.
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 (Aβ(42) and Aβ(42)/p-Tau(181)) 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 Aβ(42)/p-Tau(181) 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.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA. Electronic address: brian.gold@uky.edu.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Gold
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Zude
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Brown
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Andersen
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois, Chicago, IL, USA.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: LaDu
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois, Chicago, IL, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Tai
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Jicha
authors.affiliation: Department of Statistics, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Estus
authors.affiliation: Department of Pathology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Steve W
authors.initials: SW
authors.lastname: Scheff
authors.affiliation: Department of Epidemiology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Abner
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Eldik
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology* / Q000523:psychology*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003071:Cognition / Q000502:physiology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D020712:Fornix, Brain / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D009929:Organ Size; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D066127:White Matter / Q000473:pathology*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: CSF; DTI; Normal older adults; Preclinical AD; White matter