High sensitivity C-reactive protein and glycated hemoglobin levels as dominant predictors of all-cause dementia: a nationwide population-based cohort study

Background: Chronic inflammation might play a major role in the pathogenesis linking diabetes mellitus (DM) to cognition. In addition, DM might be the main driver of dementia risk. The purpose of the present study was to evaluate whether inflammation, glycation, or both are associated with the risk of developing all-cause dementia (ACD). Methods: A nationwide population-based cohort study was conducted with 4113 participants. The data were obtained from the Taiwanese Survey on Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH) in 2007, which was linked with the Taiwan National Health Insurance Research Database (NHIRD). The markers of inflammation, expressed as hs-CRP, and glycation, presented as HbA1c, were measured. High levels of hs-CRP and HbA1c were defined as values greater than or equal to the 66th percentile. Developed ACD was identified based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Results: During 32,926.90 person-years, 106 individuals developed ACD in up to 8 years of follow-up. The study participants were separated into four categories by the top tertiles of hs-CRP and HbA1c based on the 66th percentile: high levels of both hs-CRP and HbA1c, only high levels of hs-CRP, only high levels of HbA1c, and non-high levels of hs-CRP nor HbA1c. Those who with a high level of only hs-CRP had the higher hazard for developing ACD (adjusted HR = 2.58; 95% CI = 1.29 ~ 5.17; P = 0.007), followed by the group with a high level of only HbA1c (adjusted HR = 2.52; 95% CI = 1.34 ~ 4.74; P = 0.004) and the group with high levels of both hs-CRP and HbA1c (adjusted HR = 2.36; 95% CI = 1.20 ~ 4.62; P = 0.012). Among those aged less than 65 years, hs-CRP was the only significant predictor of ACD risk (P = 0.046), whereas it did not yield any significant result in the elderly. Conclusions: A higher risk of developing ACD was found not only in patients with high levels of inflammation but also high levels of glycated hemoglobin. Future studies should focus on the clinical implementation of hs-CRP or HbA1c to monitor cognitive deficits.