Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities

Abstract

AbstractBackgroundWhite matter injury had been mostly considered a result of chronic ischemia caused by cerebral small vessel disease. However, recent studies reported that white matter degeneration could also be an important pathophysiological feature in Alzheimer’s disease (AD). This study aimed to identify the relationship between AD biomarkers, particularly amyloid‐beta (Aβ) and tau deposition, with white matter hyperintensities (WMHs) representing cerebral white matter injury.MethodA total 456 older adults aging from 55 to 90 years including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aβ deposition, [18F] AV‐1451 PET for measuring tau deposition, and MRI scans with fluid‐attenuated inversion recovery image for measuring WMH volume. For PET scans, standard uptake value ratio (SUVR) was used for the analyses; combined regions of hemispheric white matter, inferior cerebellum and pons were used as the reference region when obtaining SUVRs. The relationships between Aβ or tau deposition and WMH volume were examined using multiple regression analysis. In this analysis, baseline Aβ or tau were used as independent variables, and baseline as well as change of WMH volume over 2 years were used as dependent variables.ResultBaseline Aβ deposition levels had significant positive association with longitudinal change of WMH volume over 2 years (β = 0.238, p = 0.009), but not with WMH volume at baseline. Baseline tau was not related with any of WMH volume at baseline and longitudinal change of WMH volume over 2 years. We also found significant interaction effect between baseline Aβ deposition level and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aβ deposition was associated with increase of WMH volume over 2 years in female (β = 0.427, p = 0.001), but not in male.ConclusionOur findings suggest that Aβ deposition, but not tau, accelerates cerebral white matter injury, particularly in female.