Cardiovascular Risk Burden in Relation to Dementia and Brain Structural and Metabolic Imaging Markers

Abstract

Background: The roles of cardiovascular disease (CVD) and dementia genetic predisposition in the association of cardiovascular risk burden with dementia need to be elucidated. Relevant evidence regarding the brain structural and metabolic pathways underlying this association is scarce. Methods: We conducted a prospective cohort study among 354,654 participants free of baseline CVD and dementia (2006-2010, mean age 56.4 years) within UK Biobank (UKB); brain MRI measurement was available for 15,104 participants since 2014. Cardiovascular risk burden was evaluated by baseline Framingham General Cardiovascular Risk Score (FGCRS); polygenic risk score (PRS) was constructed from common Alzheimer’s disease (AD) variants. Incident dementia was identified from hospital inpatient and death register data. The associations of cardiovascular risk burden with brain glucose uptake indices were evaluated cross-sectionally among 304 individuals free of CVD and cancer with 18F-FDG PET/CT scan measurement in a hospital-based study in China. Findings: During a median 12.0-year follow-up, 3,998 all-cause dementia cases were identified in UKB. Higher FGCRS was associated with increased all-cause dementia risk after controlling for demographic, major lifestyle, clinical factors, and PRS. The corresponding ORs (95% CIs) across increasing FGCRS tertiles were1.00 (ref), 1.10 (0.98, 1.23), and 1.26 (1.12, 1.41) (Ptrend 0.05). Regarding the joint association of FGCRS and PRS with all-cause dementia, we observed an 83% (95% CI: 47%, 128%) higher risk comparing the high-high vs. low-low category. For standardized brain volumes, higher FGCRS was associated with greater white matter hyperintensities (log-transformed), and smaller grey matter volume and cortical volume. FGCRS was inversely associated with the glucose uptake level in all brain lobes and total grey matter. Interpretation: Higher cardiovascular risk burden was associated with higher dementia risk and neurodegeneration-related brain volumes and lower glucose uptake in brain. The association of cardiovascular risk burden with all-cause dementia was partially mediated by CVD onset and independent of dementia genetic risk. Funding: National Key Research and Development Plan of China, Zhejiang University Education Foundation Global Partnership Fund, National Science Fund for Excellent Young Scholars, and Talent Introduction Programme of Chinese Academy of Sciences. Declaration of Interest: None to declare. Ethical Approval: This study received ethical approval from the North West Multi-center Research Ethics Committee (REC reference: 16/NW/0274).