Cardiovascular Risk as a Moderator of the Relationship Between Plasma Alzheimer Disease Biomarkers and Cognitive Status.
Kancheva AK., Lyall DM., Tsvetanov KA., Kancheva IK., Mavromati K., Koychev I., Tari B., Garcia DJ., Hughes L., Wardlaw JM., Quinn TJ.
BACKGROUND: Plasma biomarkers may aid Alzheimer disease (AD) diagnosis and prognosis. Cardiovascular risk contributes to cognitive decline in AD, but whether it modifies the relationship between plasma biomarkers and cognitive status has not been assessed in a large multisite cohort. We aimed to explore if cardiovascular risk moderates plasma AD biomarkers' relationship with cognitive status. METHODS: We included cognitively normal (n=301) participants and participants with mild cognitive impairment or probable AD (n=444) from the Bio-Hermes-001 study. Cardiovascular risk was quantified using the Atherosclerotic Cardiovascular Disease risk calculator. Logistic regression analyzed associations of cardiovascular risk and plasma biomarkers (amyloid beta 42/amyloid beta 40, phosphorylated tau [p-tau]181, p-tau217, apoE4 [apolipoprotein E]) with cognitive status. Moderation by cardiovascular risk was tested in each model. RESULTS: We included 745 participants (mean age=72.3 years; 423 [56.8%] female). Plasma biomarkers and cardiovascular risk were independently associated with cognitive status across models; the strongest association was with p-tau217 (odds ratio [OR], 2.33 [95% CI, 1.89-2.9]; P<0.001). Cardiovascular risk moderated only the relationships of p-tau181 and p-tau217 with cognitive status (P<0.05). CONCLUSIONS: Plasma AD biomarkers and cardiovascular risk were independently associated with cognitive status, with cardiovascular risk moderating the p-tau181 and p-tau217 cognitive status relationships. If certain plasma biomarkers and cardiovascular risk independently contribute to dementia risk, cardiovascular risk assessment should complement other biomarker evaluations in cognitive screening. Results should be interpreted with caution as associations might be primarily driven by age and sex. Future research including education and genetic risk is needed to clarify the studied relationships.