Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-β_1-42 and Hypertension

Authors

Omar M. Al-Janabi, University of KentuckyFollow
Christopher A. Brown, University of Kentucky
Ahmed A. Bahrani, University of KentuckyFollow
Erin L. Abner, University of KentuckyFollow
Justin M. Barber, University of KentuckyFollow
Brian T. Gold, University of KentuckyFollow
Larry B. Goldstein, University of KentuckyFollow
Richard R. Murphy, University of KentuckyFollow
Peter T. Nelson, University of KentuckyFollow
Nathan F. Johnson, University of KentuckyFollow
Leslie M. Shaw, University of Kentucky
Charles D. Smith, University of Kentucky
John Q. Trojanowski, University of Pennsylvania
Donna M. Wilcock, University of KentuckyFollow
Gregory A. Jicha, University of KentuckyFollow

Abstract

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess WM macro- and microstructural properties. Linear regression analyses were used to assess the relationships among WM alterations, cerebrovascular disease risk, and AD pathology. Voxelwise analyses were performed to examine spatial patterns of WM alteration associated with each pathology.

RESULTS: HTN and CSF Aβ_1-42 levels were each associated with white matter hyperintensities (WMH). Also, CSF Aβ_1-42 levels were associated with alterations in normal appearing white matter fractional anisotropy (NAWM-FA), whereas HTN was marginally associated with alterations in NAWM-FA. Linear regression analyses demonstrated significant main effects of HTN and CSF Aβ_1-42 on WMH volume, but no significant HTN×CSF Aβ_1-42 interaction. Furthermore, voxelwise analyses showed unique patterns of WM alteration associated with hypertension and CSF Aβ_1-42.

CONCLUSION: Associations of HTN and lower CSF Aβ_1-42 with WM alteration were statistically and spatially distinct, suggesting independent rather than synergistic effects. Considering such spatial distributions may improve diagnostic accuracy to address each underlying pathology.

Document Type

Article

Publication Date

11-23-2018

Notes/Citation Information

Published in Journal of Alzheimer's Disease, vol. 66, no. 3.

© 2018 The Authors.

The copyright holder has granted the permission for posting the article here.

The document available for download is the authors' post-peer-review final draft of the article.

Digital Object Identifier (DOI)

https://doi.org/10.3233/JAD-180663

Funding Information

This study was funded by NIH P30 AG028383, UH2 NS100606, NR014189, and R01 AG042419.

Repository Citation

Al-Janabi, Omar M.; Brown, Christopher A.; Bahrani, Ahmed A.; Abner, Erin L.; Barber, Justin M.; Gold, Brian T.; Goldstein, Larry B.; Murphy, Richard R.; Nelson, Peter T.; Johnson, Nathan F.; Shaw, Leslie M.; Smith, Charles D.; Trojanowski, John Q.; Wilcock, Donna M.; and Jicha, Gregory A., "Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-β_1-42 and Hypertension" (2018). Sanders-Brown Center on Aging Faculty Publications. 142.
https://uknowledge.uky.edu/sbcoa_facpub/142