C-reactive protein levels and risk of disabling dementia with and without stroke in Japanese: The Circulatory Risk in Communities Study (CIRCS)


      • We examined the association between hs-CRP levels and risk of disabling dementia.
      • First study to provide a positive association in Japanese population.
      • Elevated hs-CRP increased dementia risk in individuals with history of stroke.
      • Elevated hs-CRP did not increase dementia risk in those without history of stroke.



      Studies have shown that elevated high-sensitivity C-reactive protein (hs-CRP) predicts stroke, which is a risk factor for dementia. It remains, however, unclear whether hs-CRP increases risk of dementia.


      A prospective nested case–control study of Japanese 40–69 years of age was conducted using frozen serum samples collected from approximately 7531men and women who participated in cardiovascular risk surveys from 1984 to 1994 in one community and 1989–1995 in another community under the Circulatory Risk in Communities Study (CIRCS). Two control subjects per case were matched by sex, age, community, and year of serum storage. The hs-CRP was measured using a latex particle-enhanced immunonephelometric assay.


      Between 1999 and 2013, we identified 275 disabling dementia cases (96 cases with history of stroke and 179 without it). There was a positive association between hs-CRP levels and risk of dementia with history of stroke. No significant association was observed between hs-CRP levels and risk of dementia without history of stroke. After adjustment for hypertension, diabetes and other confounding variables, the positive association remained statistically significant. The multivariable odds ratios associated with 1-SD increment of log hs-CRP were 1.02 (0.87–1.20) for total dementia, 1.35 (1.02–1.79) for dementia with history of stroke, and 0.89 (0.72–1.10) for dementia without history of stroke.


      Elevated hs-CRP levels were associated with increased risk of disabling dementia in individuals with history of stroke but not in those without it.


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