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United States Department of Agriculture

Agricultural Research Service

Research Project: LIPOPROTEINS AND NUTRITION Title: C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study

Authors
item Mooijaart, Simon P. -
item Sattar, Naveed -
item Trompet, Stella -
item Polisecki, Eliana -
item DE Craen, Anton J. M. -
item Schaefer, Ernst J. -
item Jahn, Sabine E. -
item Van Himbergen, Thomas -
item Welsh, Paul -
item Ford, Ian -
item Stott, David J. -
item Westendorp, Rudi G. J. -

Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 29, 2011
Publication Date: September 7, 2011
Citation: Mooijaart, S., Sattar, N., Trompet, S., Polisecki, E., De Craen, A., Schaefer, E., Jahn, S., Van Himbergen, T., Welsh, P., Ford, I., Stott, D., Westendorp, R. 2011. C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study. PLoS One. 6(9):e23890.

Interpretive Summary: C reactive protein (CRP) is a protein made in the liver in response to infection and illness. High levels in the bloodstream have been associated with an increased risk of developing cardiovascular disease and dementia. Our goal was to determine if the association was true for cognitive decline in the elderly. CRP levels were associated with poorer performance over time in various measures of cognitive function, but these associations were not nearly as strong as those observed for apoE phenotype (a genetic variant of the protein apoE). Nevertheless the data do indicate that elevated levels of CRP can be used as a marker of increased risk of cognitive decline with aging, but genetic variation at the CRP locus are not associated with such variation. Our data are of interest to people trying to prevent and/or treat the cognitive decline that often accompanies the aging process.

Technical Abstract: 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. 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 less than 0.001), but not with the immediate and delayed Picture Learning Test (PLT; both P greater than 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 greater than 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 less than 0.007). In comparison to strong associations of apolipoprotein E with cognitive measures, associations of CRP haplotypes with such measures were inconsistent. In conclusion 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 do 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

Last Modified: 12/26/2014
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