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

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 A beta(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 micro structural 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 A beta(1-42) levels were each associated with white matter hyperintensities (WMH). Also, CSF A beta(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 A beta(1-42) on WMH volume, but no significant HTNxCSF A beta(1-42) interaction. Furthermore, voxelwise analyses showed unique patterns of WM alteration associated with hypertension and CSF A beta(1-42). Conclusion: Associations of HTN and lower CSF A beta(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.