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

Article type: Research Article

Authors: Al-Janabi, Omar M.^{a; b; 1} | Brown, Christopher A.^{c; 1} | Bahrani, Ahmed A.^{a; d} | Abner, Erin L.^{a; e} | Barber, Justin M.^a | Gold, Brian T.^{a; c} | Goldstein, Larry B.^f | Murphy, Ronan R.^{a; f} | Nelson, Peter T.^{a; g} | Johnson, Nathan F.^h | Shaw, Leslie M.ⁱ | Smith, Charles D.^{a; f} | Trojanowski, John Q.ⁱ | Wilcock, Donna M.^{a; j} | Jicha, Gregory A.^{a; b; f; *}

Affiliations: [a] Sanders-Brown Center on Aging, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [b] Departments of Behavioral Science, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [c] Departments of Neuroscience, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [d] Departments of Biomedical Engineering, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [e] Departments of Epidemiology and Biostatistics, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [f] Departments of Neurology, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [g] Departments of Pathology, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [h] Departments of Rehabilitation Science, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [j] Departments of Physiology, University of Kentucky Colleges of Medicine, Public Health, Health Sciences and Engineering Lexington, KY, USA | [i] Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, 800 South Limestone St, Lexington, KY 40536-0230, USA. Tel.: +1 859 323 5550; Fax: +1 859 257 3819; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

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 Aβ1-42 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 Aβ1-42 levels were each associated with white matter hyperintensities (WMH). Also, CSF Aβ1-42 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 Aβ1-42 on WMH volume, but no significant HTN×CSF Aβ1-42 interaction. Furthermore, voxelwise analyses showed unique patterns of WM alteration associated with hypertension and CSF Aβ1-42. Conclusion:Associations of HTN and lower CSF Aβ1-42 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.

Keywords: Alzheimer’s disease, Aβ_1-42 , hypertension, white matter alteration

DOI: 10.3233/JAD-180663

Journal: Journal of Alzheimer's Disease, vol. 66, no. 3, pp. 1095-1104, 2018