title: Lipoprotein-associated phospholipase A2 and risk of dementia in the Cardiovascular Health Study.
abstract: OBJECTIVE
  To evaluate associations between Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with risk of dementia and its subtypes.
  
  
  METHODS
  Analysis 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.
  
  
  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 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).
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA. Electronic address: fitzpal@u.washington.edu.
authors.forename: Annette L
authors.initials: AL
authors.lastname: Fitzpatrick
authors.affiliation: WW Epidemiology, GlaxoSmithKline, Research Triangle Park, NC and Upper Merion, PA, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Irizarry
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA; Department of Pathology, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Department of Pathology, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Chi
authors.affiliation: WW Epidemiology, GlaxoSmithKline, Research Triangle Park, NC and Upper Merion, PA, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Koro
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology; D003704:Dementia / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D012306:Risk; D012307:Risk Factors
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase
keywords: Alzheimer's disease; Cardiovascular risk factors; Dementia; Lp-PLA(2)