Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-β1-42 and Hypertension

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; Aβ1-42; hypertension; white matter alteration.

Figure 1.. Distinct spatial distribution of white matter hyperintensities related to hypertension and CSF amyloid β_1–42 levels.

The spatial distribution of white matter hyperintensities (WMH) related to hypertension (HTN) (red) and Cerebrospinal fluid amyloid beta 1–42 levels (Aβ_1–42) (green) shows primarily distinct distributions with minimal overlapping areas (blue). WMH associated with HTN occur primarily in deep cortical white matter and along the body of the lateral ventricles. WMH associated with Aβ_1–42 occur primarily near the ventricular horns and the posterior corona radiata. Areas of WMH are displayed on the FMRIB58 FA 1mm³ brain. Contiguous 1mm slices are shown starting from MNI z = 0 at the top left and MNI z = 48 at the bottom right. All images are shown in radiological orientation (anatomical right is on the left side of the image).