Lipoprotein-associated phospholipase A2 is associated with risk of dementia

Objective: High levels of the inflammatory marker lipoprotein-associated phospholipase A2 (Lp-PLA2) have been proposed to be a predictor of coronary heart disease and stroke. Because both inflammation and vascular disease are associated with dementia, the objective of the present study was to examine the association between Lp-PLA2 and the risk of dementia. Methods: Within the Rotterdam Study, a population-based prospective cohort study, we performed a case-cohort study. Of the 6,713 participants at risk for dementia, a random sample of 1,742 individuals was drawn. During follow-up (mean, 5.7 years), 302 incident dementia cases were identified. Cox proportional hazard models were used to estimate the association of Lp-PLA2 and dementia. Results: We found that subjects with higher levels of Lp-PLA2 had an increased risk of dementia. Compared with the first quartile of Lp-PLA2, age- and sex-adjusted hazard ratios (HRs; 95% confidence interval [CI]) for dementia for the second, third, and fourth quartiles were 1.19 (0.78-1.81), 1.15 (0.74-1.79), and 1.56 (1.03-2.37), respectively (p value for trend 0.04). Additional adjustment for cardiovascular and inflammatory factors did not change the estimates. Interpretation: This is the first study to our knowledge that shows that Lp-PLA2 is associated with the risk of dementia independent of cardiovascular and inflammatory factors and provides evidence for a potential role of Lp-PLA2 in identifying subjects at risk for dementia.

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