The Interaction Between Vascular Risk Factors, Cerebral Small Vessel Disease, and Amyloid Burden in Older Adults

Background: Cerebral small vessel disease (SVD) and Alzheimer's disease pathology, namely amyloid-beta (A beta) deposition, commonly co-occur. Exactly how they interact remains uncertain. Objective: Using participants from the Alzheimer's Disease Neuroimaging Initiative (n = 216; mean age 73.29 +/- 7.08 years, 91 (42.1%) females), we examined whether the presence of vascular risk factors and/or baseline cerebral SVD was related to a greater burden of A beta cross-sectionally, and at 24 months follow-up. Method: Amyloid burden, assessed using F-18-florbetapir PET, was quantified as the global standardized uptake value ratio (SUVR). Multimodal imaging was used to strengthen the quantification of baseline SVD as a composite variable, which included white matter hyperintensity volume using MRI, and peak width of skeletonized mean diffusivity using diffusion tensor imaging. Structural equation modeling was used to analyze the associations between demographic factors, Apolipoprotein E epsilon 4 carrier status, vascular risk factors, SVD burden and cerebral amyloid. Results: SVD burden had a direct association with A beta burden cross-sectionally (coeff. = 0.229, p = 0.004), and an indirect effect over time (indirect coeff. = 0.235, p = 0.004). Of the vascular risk factors, a history of hypertension (coeff. = 0.094, p = 0.032) and a lower fasting glucose at baseline (coeff. = -0.027, p = 0.014) had a direct effect on A beta burden at 24 months, but only the direct effect of glucose persisted after regularization. Conclusion: While A beta and SVD burden have an association cross-sectionally, SVD does not appear to directly influence the accumulation of A beta longitudinally. Glucose regulation may be an important modifiable risk factor for A beta accrual over time.