Development, Validation and Application of a New Fornix Template for Studies of Aging and Preclinical Alzheimer's Disease

Authors

Christopher A. Brown, University of KentuckyFollow
Nathan F. Johnson, University of KentuckyFollow
Amelia J. Anderson-Mooney, University of Kentucky
Gregory A. Jicha, University of KentuckyFollow
Leslie M. Shaw, University of Pennsylvania
John Q. Trojanowski, University of Pennsylvania
Linda J. Van Eldik, University of KentuckyFollow
Frederick A. Schmitt, University of KentuckyFollow
Charles D. Smith, University of KentuckyFollow
Brian T. Gold, University of KentuckyFollow

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 (Aβ₄₂ and the t-tau/Aβ₄₂ ratio) 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.

Document Type

Article

Publication Date

11-25-2016

Notes/Citation Information

Published in NeuroImage: Clinical, v. 13, p. 106-115.

© 2016 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.nicl.2016.11.024

Funding Information

This study was supported by the National Institute on Aging and National Center for Advancing Translational Sciences of the National Institutes of Health (grant numbers RO1AG033036, P30AG028383, P01AG030128, TL1TR000115). In addition, JQT is supported by P30AG10124 and U01AG24904, and LMS is supported by U01AG24904.

Repository Citation

Brown, Christopher A.; Johnson, Nathan F.; Anderson-Mooney, Amelia J.; Jicha, Gregory A.; Shaw, Leslie M.; Trojanowski, John Q.; Van Eldik, Linda J.; Schmitt, Frederick A.; Smith, Charles D.; and Gold, Brian T., "Development, Validation and Application of a New Fornix Template for Studies of Aging and Preclinical Alzheimer's Disease" (2016). Physical Therapy Faculty Publications. 69.
https://uknowledge.uky.edu/rehabsci_facpub/69