Development, validation and application of a new fornix template for studies of aging and preclinical Alzheimer's disease

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

doi:10.1016/j.nicl.2016.11.024

Development, validation and application of a new fornix template for studies of aging and preclinical Alzheimer's disease

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

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

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.

Original language	English
Pages (from-to)	106-115
Number of pages	10
Journal	NeuroImage: Clinical
Volume	13
DOIs	https://doi.org/10.1016/j.nicl.2016.11.024
State	Published - 2017

Bibliographical note

Publisher Copyright:
© 2016

Funding

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. The content is solely the responsibility of the authors and does not necessarily represent the official views of these granting agencies. The authors thank Beverly Meacham for conducting some of the MRI scans.

Funders	Funder number
National Institutes of Health (NIH)	P30AG10124, RO1AG033036, U01AG24904
National Institute on Aging	P30AG028383, P01AG030128
National Center for Advancing Translational Sciences (NCATS)	UL1TR001998, TL1TR000115

Keywords

Aging
Aβ amyloid
Diffusion tensor imaging
Fornix
Tau

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Neurology
Clinical Neurology
Cognitive Neuroscience

Access to Document

10.1016/j.nicl.2016.11.024

Cite this

Brown, C. A., Johnson, N. F., Anderson-Mooney, A. J., Jicha, G. A., Shaw, L. M., Trojanowski, J. Q., Van Eldik, L. J., Schmitt, F. A., Smith, C. D., & Gold, B. T. (2017). Development, validation and application of a new fornix template for studies of aging and preclinical Alzheimer's disease. NeuroImage: Clinical, 13, 106-115. https://doi.org/10.1016/j.nicl.2016.11.024

@article{089cda881338466c890d4db5e0029433,

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 (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.",

keywords = "Aging, Aβ amyloid, Diffusion tensor imaging, Fornix, Tau",

author = "Brown, \{Christopher A.\} and Johnson, \{Nathan F.\} and Anderson-Mooney, \{Amelia J.\} and Jicha, \{Gregory A.\} and Shaw, \{Leslie M.\} and Trojanowski, \{John Q.\} and \{Van Eldik\}, \{Linda J.\} and Schmitt, \{Frederick A.\} and Smith, \{Charles D.\} and Gold, \{Brian T.\}",

note = "Publisher Copyright: {\textcopyright} 2016",

year = "2017",

doi = "10.1016/j.nicl.2016.11.024",

language = "English",

volume = "13",

pages = "106--115",

}

TY - JOUR

T1 - Development, validation and application of a new fornix template for studies of aging and preclinical Alzheimer's disease

AU - Brown, Christopher A.

AU - Johnson, Nathan F.

AU - Anderson-Mooney, Amelia J.

AU - Jicha, Gregory A.

AU - Shaw, Leslie M.

AU - Trojanowski, John Q.

AU - Van Eldik, Linda J.

AU - Schmitt, Frederick A.

AU - Smith, Charles D.

AU - Gold, Brian T.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Aging

KW - Aβ amyloid

KW - Diffusion tensor imaging

KW - Fornix

KW - Tau

UR - https://www.scopus.com/pages/publications/85007008991

UR - https://www.scopus.com/inward/citedby.url?scp=85007008991&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2016.11.024

DO - 10.1016/j.nicl.2016.11.024

M3 - Article

C2 - 27942453

AN - SCOPUS:85007008991

SN - 2213-1582

VL - 13

SP - 106

EP - 115

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

ER -

Development, validation and application of a new fornix template for studies of aging and preclinical Alzheimer's disease

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this