Cardiovascular Risk as a Moderator of the Relationship of Plasma Alzheimer’s Disease Biomarkers with Cognitive Status

Objectives Plasma biomarkers may assist with diagnosis and prognosis of Alzheimer’s disease and other dementias. Cardiovascular risk is associated with impaired cognitive health, although mechanisms are not completely understood. We sought to explore whether cardiovascular risk moderates the relationship between plasma Alzheimer’s disease biomarkers and cognitive status. Methods We included groups of cognitively normal (n=301) and combined mild cognitive impairment or probable Alzheimer’s disease (n=444), based on clinical assessment, from the Bio-Hermes-001 study. Cardiovascular risk was quantified using the Atherosclerotic CVD (ASCVD) risk calculator. We conducted a series of logistic regression analyses to evaluate the association of cardiovascular risk, each of several Alzheimer’s disease biomarkers (i.e., plasma amyloid beta (Aβ)42/Aβ40, phosphorylated tau (p-tau)181, p-tau217, and circulating levels of apolipoprotein E (ApoE4)), with cognitive status. We tested moderation by cardiovascular risk in each model. Results We included 745 participants (mean age=72.3 years; 423 (56.8%) female) in the analysis. In each model, plasma biomarkers and cardiovascular risk were independently associated with cognitive status; the strongest association was found with p-tau217 (odds ratio (OR)=2.33; 95% confidence intervals (95%CI) [1.89-2.9]; p <0.0001). CVD risk only marginally moderated the relationships between p-tau181 and cognitive status, and between p-tau217 and cognitive status ( p <0.05). Discussion Plasma Alzheimer’s disease biomarkers and cardiovascular risk were independently associated with cognitive status, but cardiovascular risk only marginally moderated the p-tau181- and p-tau217-cognitive status relationships. If plasma biomarkers and CVD risk potentially confer an independent risk of dementia, cardiovascular risk assessment should complement other dementia biomarker assessments in clinical and research cognitive screening.