Cerebral amyloid is associated with greater white-matter hyperintensity accrual in cognitively normal older adults

Abstract

Cross-sectional studies show that elevated cerebral amyloid is associated with greater white-matter hyperintensity (WMH) burden in cognitively normal (CN) older adults. However, the relative time courses of amyloid and WMH accrual are unclear. To address this, we tested the associations between known WMH correlates-age, hypertension, and amyloid-with WMH accrual rate. We used brain magnetic resonance imaging to measure WMH change in 112 CN Alzheimer's Disease Neuroimaging Initiative (GO/2) participants over a 2-year period. A linear mixed effects model assessed baseline cerebrospinal fluid amyloid beta (Aβ) 1-42, hypertension, age, and their interactions, as predictors of greater WMH accrual. Greater amyloid burden was associated with greater WMH accrual over time. Those with hypertension showed a stronger association between greater amyloid burden and WMH accrual rate. Greater age was not significantly associated with greater WMH accrual in this model. Although the direction of the relationship cannot be tested in this model, CN individuals harboring cerebral amyloid had greater accrual of WMH over a 2-year period after accounting for hypertension and age. Impaired amyloid clearance and cerebral small vessel disease may both underlie the more rapid emergence of WM lesions. The role of cerebral amyloid burden in white-matter injury should thus be considered as a relevant factor when WMHs are detected clinically.

Keywords: ADNI; Amyloid; FLAIR; Hypertension; MRI; Normal aging.

Fig. 1

Using parameter estimates from Table 2, estimated trends of WMH volume as a function of years from baseline, are shown for prototype individuals for the following categories: normotensive/negative amyloid (blue, dashed), normotensive/positive amyloid (blue, solid), hypertensive/negative amyloid (red, dashed), and hypertensive/positive amyloid (red, solid). Amyloid positive threshold was CSF Aβ_1–42 < 192 pg/mL; the amyloid level used in these calculations is the mean for each category. For each, the intercept represents a 74-year-old, APOE _ε4 negative male with a high school education, no hyperlipidemia, and average intracranial volume. Abbreviation: WMH, white-matter hyperintensity. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)