Lipoprotein-associated phospholipase A2 and risk of dementia in the Cardiovascular Health Study

•LpPLA2 mass and activity were both related to an increased risk of dementia in the Cardiovascular Health Study.•The risk of Alzheimer's dementia was increased two-fold in the highest compared to lowest quartile of Lp-PLA2 mass.•Lp-PLA2 activity doubled the risk of mixed dementia (AD and vascular dementia) in the highest compared to lowest quartile.•These associations were independent of demographics, cardiovascular disease and its risk factors.•These data add to the literature reporting conflicting results of the association between LpPLA2 and dementia.

ObjectiveTo evaluate associations between Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with risk of dementia and its subtypes.MethodsAnalysis were completed on 3320 participants of the Cardiovascular Health Study (CHS), a population-based longitudinal study of community-dwelling adults age ≥65 years followed for an average of 5.4 years. Baseline serum Lp-PLA2 mass was measured using a sandwich enzyme immunoassay and Lp-PLA2 activity utilized a tritiated-platelet activating factor activity assay. Cox proportional hazards regression assessed the relative risk of incident dementia with higher baseline Lp-PLA2 adjusting for demographics, cardiovascular disease (CVD) and risk factors, inflammation markers and apolipoprotein E (APOE) genotype.ResultsEach standard deviation higher Lp-PLA2 mass and activity were related to increased risk of dementia (fully adjusted HR: 1.11 per SD, 95% CI: 1.00-1.24 for mass; HR: 1.12 per SD, 95% CI: 1.00-1.26 for activity). Persons in the highest quartile of Lp-PLA2 mass were 50% more likely to develop dementia than those in the lowest quartile in adjusted models (HR: 1.49; 95% CI: 1.08-2.06). Among dementia subtypes, the risk of AD was increased two-fold in the highest compared to lowest quartile of Lp-PLA2 mass (adjusted HR: 1.98, 95% CI: 1.22-3.21). Results were attenuated in models of mixed dementia and VaD. Lp-PLA2 activity also doubled the risk of mixed dementia in the highest compared to lowest quartile (HR: 2.21, 95% CI: 1.12-4.373).InterpretationThese data support Lp-PLA2 as a risk factor for dementia independent of CVD and its risk factors. Further study is required to clarify the role of Lp-PLA2-related mechanisms in dementia subtypes.