Do cardiometabolic risk factors influence amyloid, tau, and neuronal function in APOE4 carriers and non-carriers in Alzheimer's disease trajectory?

Cardiovascular risk could be calculated using Qrisk2. It is suggested that cardiovascular risk factors influence the progression of Alzheimer's disease (AD). However, studies have not specifically evaluated the influence of cardiovascular risk using Qrisk2 on neuropathological progression and AD biomarkers. The aim of the study was to evaluate the influence of cardiovascular risk factors using Qrisk2 on CSF amyloid-β (Aβ) and tau, 18F-AV45-PET, 18F-FDG-PET, MRI, and cognitive measures in APOE4 negative cognitively normal and mild cognitive impairment (MCI) subjects. 614 cognitively normal, early, and late MCI subjects were selected from the ADNI cohort with a 2-year follow-up. CSF Aβ and tau, 18F-AV45-PET, 18F-FDG-PET, MRI, and cognitive measures along with modified Qrisk2 were evaluated. APOE4 non-carrier, high cardiovascular risk sub-group of early and late MCI and cognitively normal subjects, demonstrated worse biomarker and cognitive profile at baseline and during follow up compared to low cardiovascular risk group. Additionally, similar pattern was also observed in APOE4 carriers. We demonstrated that Qrisk2 and APOE4 were independent predictors of biomarker and clinical progression in AD trajectory. High cardiovascular risk is associated with biomarker changes in APOE4 non-carriers in prodromal AD, which may suggest that treatment of cardiovascular risk is an effective prevention strategy even in APOE4 negative subjects and may influence disease progression independent of amyloid pathology. Demonstration of accelerated neuropathological changes in both APOE4 carriers and non-carriers suggest that focusing on modifiable cardiovascular risk factors is an effective preventative strategy while we eagerly waiting for new treatments.