title: C-reactive protein, APOE genotype and longitudinal cognitive change in an older population.
abstract: BACKGROUND
  circulating measures of inflammatory markers, such as C-reactive protein (CRP) have been associated with an increased risk of future cognitive decline. However, the nature of the relationship among the very old (>75 years) is unclear. Cross-sectional evidence suggests that elevated CRP may even be protective in this age group. This study examines these associations longitudinally.
  
  
  METHODS
  logistic regression was used to investigate the association between CRP and drop in cognitive performance (≥3 point change on the Mini-Mental State Examination) over a 4-year period in a population of 266 people, mean age 77 years.
  
  
  RESULTS
  increased levels of CRP were associated with a decreased risk of a drop in cognitive performance; however, this association was only seen in those without an APOE e4 allele [odds ratio of decline per unit increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained consistent after adjustment for cardiovascular confounders (smoking, drinking, MI, stroke, diabetes, education, medication and blood pressure). For those with an e4 allele, the relationship with longitudinal cognitive decline was neither statistically significant nor in a consistent direction after controlling for acute inflammation.
  
  
  CONCLUSIONS
  this study strengthens previous cross-sectional findings and shows elevated levels of CRP to be linked to a decreased risk of longitudinal cognitive decline in the very old. However, as with prior analyses, this was only observed in those not carrying an APOE e4 allele. Future work on larger APOE e4 allele carrying samples is required to determine the nature of the association in this population.
authors.affiliation: Hospital Militar de Área de Brasília, Brasília, Brazil.
authors.forename: Thomas A S
authors.initials: TA
authors.lastname: Lima
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Adler
authors.forename: Thais
authors.initials: T
authors.lastname: Minett
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Matthews
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Marioni
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003071:Cognition; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D018836:Inflammation Mediators; D002097:C-Reactive Protein
keywords: APOE; C-reactive protein; cognitive decline; older people; older population