title: C-reactive protein and genetic variants and cognitive decline in old age: the PROSPER study.
abstract: BACKGROUND
  Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline.
  
  
  RESULTS
  Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial, with 5680 participants with a mean age of 75 years, we examined associations of CRP levels and its genetic determinants with cognitive performance and decline over 3.2 years mean follow-up. Higher plasma CRP concentrations were associated with poorer baseline performance on the Stroop test (P = 0.001) and Letter Digit Tests (P<0.001), but not with the immediate and delayed Picture Learning Test (PLT; both P>0.5). In the prospective analyses, higher CRP concentrations associated with increased rate of decline in the immediate PLT (P = 0.016), but not in other cognitive tests (all p>0.11). Adjustment for prevalent cardiovascular risk factors and disease did not change the baseline associations nor associations with cognitive decline during follow-up. Four haplotypes of CRP were used and, compared to the common haplotype, carrierships associated strongly with levels of CRP (all P<0.007). In comparison to strong associations of apolipoprotein E with cognitive measures, associations of CRP haplotypes with such measures were inconsistent.
  
  
  CONCLUSIONS
  Plasma CRP concentrations associate with cognitive performance in part through pathways independent of (risk factors for) cardiovascular disease. However, lifelong exposure to higher CRP levels does not associate with poorer cognitive performance in old age. The current data weaken the argument for a causal role of CRP in cognitive performance, but further study is warranted to draw definitive conclusions.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. s.p.mooijaart@lumc.nl
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.forename: Eliana
authors.initials: E
authors.lastname: Polisecki
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: Sabine E
authors.initials: SE
authors.lastname: Jahn
authors.forename: Thomas
authors.initials: T
authors.lastname: van Himbergen
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D003072:Cognition Disorders / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D002097:C-Reactive Protein