title: Development, validation and application of a new fornix template for studies of aging and preclinical Alzheimer's disease.
abstract: We developed a merged younger-older adult template of the fornix and demonstrated its utility for studies of aging and preclinical Alzheimer's disease (AD). In Experiment 1, probabilistic tractography was used to reconstruct the fornix in younger and older adults and successful streamlines were then averaged to create a merged template in standard space. The new template includes the majority of the fornix from the hippocampal formation to the subcallosal region and the thalamus/hypothalamus. In Experiment 2, the merged template was validated as an appropriate measure for studies of aging, with comparisons against manual tracing measures indicating identical spatial coverage in younger and older adult groups. In Experiment 3, the merged template was found to outperform age-specific templates in measures of sensitivity and specificity computed on diffusion tensor imaging data of an independent participant cohort. In Experiment 4, relevance to preclinical AD was demonstrated via associations between fractional anisotropy within the new fornix template and cerebrospinal fluid markers of AD pathology (Aβ42and the t-tau/Aβ42ratio) in a third independent cohort of cognitively normal older adults. Our new template provides an appropriate measure for use in future studies seeking to characterize microstructural alterations in the fornix associated with aging and preclinical AD.
authors.affiliation: Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Brown
authors.affiliation: Department of Rehabilitation Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: Nathan F
authors.initials: NF
authors.lastname: Johnson
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: Amelia J
authors.initials: AJ
authors.lastname: Anderson-Mooney
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.affiliation: Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Neuroscience, 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; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Psychiatry, University of Kentucky, Lexington, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, 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
authors.affiliation: Department of Neuroscience, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Gold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid / Q000473:pathology*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D020712:Fornix, Brain / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D008875:Middle Aged; D062706:Prodromal Symptoms; D055815:Young Adult
keywords: Aging; Aβ amyloid; Diffusion tensor imaging; Fornix; Tau