Objective To evaluate associations between Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with risk of dementia and its subtypes. disease (CVD) and risk factors inflammation markers and apolipoprotein E (APOE) genotype. Results Each 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 CPI-613 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). Interpretation These data support Lp-PLA2 as a risk factor for dementia impartial of CVD and its risk factors. Further study is required to clarify the CPI-613 role of Lp-PLA2-related mechanisms in dementia subtypes. ε4 alleles. Hazard ratios (HR) 95 confidence intervals (CI) and CPI-613 p-values as well as p-for-trend across quartiles were presented for all those associations. Assessments of interactions between Lp-PLA2 mass and activity with age gender and presence of the ε4 allele were conducted to determine effect modification with these variables. We also completed generalized additive models to test for nonlinearity of the associations between the Lp-PLA2 measures and dementia outcomes. The Statistical Package for the Social Sciences version 16.0 and STATA version 11.1 were used to analyze data for CPI-613 this study. RESULTS There were 3 320 CHS participants with measurements of both dementia and Lp-PLA2 mass and 3 315 with both dementia and Lp-PLA2 activity. A total of 470 cases of incident dementia 241 AD (without VaD) 146 mixed dementia (AD and VaD) and 61 VaD (without AD) had both Lp-PLA2 mass and activity measured. Twenty-two cases of other dementia subtypes (including Parkinson’s disease dementia and Lewy-body dementia) were included in incident dementia analysis; in models of AD or VaD these cases were censored at time of dementia onset. Both biomarkers were normally distributed with a mean of 341 (SD 117) ng/ml and 39.4 (SD 13.0) nmol/min/mL for Lp-PLA2 mass and activity respectively. Mean baseline age was 71.9 years (SD 4.8) 59 were female and 85% were Caucasian. A number of bivariate relationships were found in common with both Lp-PLA2 mass (Table 1) and activity (Table 2) including gender race education common and internal IMT total cholesterol LDL and trigycerides. CVD risk factors related to Lp-PLA2 mass but not activity included age BMI and use of any lipid-lowering medication. Variables related to Lp-PLA2 activity but not mass were prevalence of diabetes and hypertension CRP and presence of the ε4 allele. Use of tobacco alcohol baseline history of stroke and IL-6 did not differ by Lp-PLA2 mass or activity. Table 1 Selected characteristics of study participants by quartile of Lp-PLA2 mass in 3 320 participants of the Cardiovascular Health Study Table 2 Selected characteristics of study participants by quartile of Lp-PLA2 CPI-613 activity in 3 315 participants of the Cardiovascular Health Study. A significant association was found between Lp-PLA2 mass and incidence of dementia (Table 3). For each standard deviation of Lp-PLA2 mass measured as a continuous variable risk of dementia was increased 12% when adjusted for demographics (HR: 1.12 95 CI: 1.03-1.22). The relationship remained when adjustments were made for CVD risk factors (HR: 1.14 95 CI: 1.04-1.26) and for number of ε4 alleles (HR: 1.11 95 CI: 1.00-1.24). When categorized into quartiles risk of dementia was Rabbit Polyclonal to CLCN4. increased by about 50% in the highest quartile relative to the lowest quartile in all models (i.e. HR: 1.49 95 CI: 1.08-2.06 in the fully adjusted model). Associations between continuous measures of Lp-PLA2 mass and dementia subtypes were CPI-613 similar to those found with dementia with point estimates between 1.11 and 1.24 and mostly of borderline significance. In the fully adjusted model participants in the highest quartile of Lp-PLA2 mass (>404 ng/ml) were at a two-fold increased risk.