High Levels of Serum C‐Reactive Protein Are Associated with Greater Risk of All‐Cause Mortality, but Not Dementia, in the Oldest‐Old: Results from The 90+ Study

OBJECTIVES: To evaluate whether high levels of C-reactive protein (CRP) in serum are associated with greater risk of all-cause dementia or mortality in the oldest-old. DESIGN: Prospective. SETTING: Research clinic and in-home visits. PARTICIPANTS: Population-based sample of adults (N=227; aged 93.9+/-2.8) from The 90+ Study, a longitudinal cohort study of people aged 90 and older. MEASUREMENTS: CRP levels were divided into three groups according to the assay detection limit: undetectable ( or =0.8 mg/dL). Neurological examination was used to determine dementia diagnosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression, and results were stratified according to and apolipoprotein E4 (APOE4) genotype. RESULTS: Subjects with detectable CRP levels had significantly greater risk of mortality (HR=1.7, 95% CI=1.0-2.9), but not dementia (HR=1.2, 95% CI=0.6-2.1), 0.4 to 4.5 years later than subjects with undetectable CRP. The highest relative risk for dementia and mortality was in APOE4 carriers with detectable CRP (dementia HR=4.5, 95% CI=0.9-23.3; mortality HR=5.6, 95% CI=1.0-30.7). CONCLUSION: High levels of CRP are associated with greater risk of mortality in people aged 90 and older, particularly in APOE4 carriers. There was a trend toward greater risk of dementia in APOE4 carriers with high CRP levels, although this relationship did not reach significance. High levels of CRP in the oldest-old represent a risk factor for negative outcomes.