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

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. Prospective. Research clinic and in-home visits. 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. CRP levels were divided into three groups according to the assay detection limit: undetectable (< 0.5 mg/dL), detectable (0.5-0.7 mg/dL), and elevated (>= 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. 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). 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.