Vascular contribution to the preclinical Alzheimer’s disease pathological changes: Insights from the EPAD cohort

Background The role of cardiovascular risk factors and cerebral small vessel disease (CSVD) on the sequences of Alzheimer’s Disease (AD) pathological events remains to be determined. Method We included 1592 non‐demented participants from EPAD‐LCS (Table‐1). Linear models were used to study associations between the Framingham score (FRS) and CSF‐Aß1‐42; CSVD indices (visual assessment for perivascular spaces [PVS] in the basal ganglia [BG] and centrum‐semiovale [CS], periventricular and deep white matter hyperintensities [WMHs], presence of lobar or deep cerebral microbleeds [CMBs], and lacunes, and quantification of global and lobar WMH volumes) and Aß1‐42 and p‐Tau181, including an interaction between CSVD indices and Aß1‐42 for the latter. Hippocampal volumes (HCV) were quantified using LEAP. Structural equation models (SEM) were used to assess the association between clinical variables as described in Figure‐1. Models were corrected for age, sex, site and multiple comparisons. Result Higher FRS scores were associated with lower CSF Aß1‐42 (ß = ‐0.18; p