Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-beta in Cognitively Normal Individuals

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-beta(1-42) (A(beta 1-42)) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal A beta(1-42) change in cognitively normal (CN) subjects. The interaction of WMH and A beta(1-42) on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer's Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in A beta(1-42) over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and A beta(1-42)beta(1-42) on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 A beta(1-42) (p = 0.008) and two-year change in A beta(1-42) (p = 0.006). Interaction between higherWMHand lower A beta 1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal A beta(1-42) change in CN. The interaction between higher WMH and lower A beta(1-42) was associated with poorer memory. Since SVD is associated with longitudinal A beta(1-42) pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer's disease.