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

Yen-Chun Fan,Chia-Chi Chou,Chyi-Huey Bai,Kuo-Liong Chien,Bagas Suryo Bintoro

doi:10.1186/s12979-022-00265-0

Abstract

BackgroundChronic 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).MethodsA 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.ResultsDuring 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.ConclusionsA 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.

Highlights

Chronic inflammation might play a major role in the pathogenesis linking diabetes mellitus (DM) to cognition
During 32,926.90 person-years, 106 persons developed all-cause dementia (ACD) in up to eight years of follow-up. These participants were classified into four categories, including both hs-CRP and HbA1c levels above the 66th percentile (756 subjects), only high-sensitivity C-reactive protein (hsCRP) levels above the 66th percentile (682 subjects), only HbA1c levels above the 66th percentile (772 subjects), and neither hs-CRP nor HbA1c levels above the 66th percentile (1903 subjects)
During the 8 years of follow-up, subjects with high levels of both hs-CRP and HbA1c, individuals with a high level of only hs-CRP, and those with a high level of HbA1c were associated with a higher risk of developing ACD than those with no high levels

Summary

Introduction

Chronic inflammation might play a major role in the pathogenesis linking diabetes mellitus (DM) to cognition. The etiology of neurodegenerative diseases is multifactorial and is attributable to several major risk factors, [1] including hypertension, diabetes mellitus (DM), high cholesterol, obesity, physical inactivity, smoking, and depression [2,3,4]. These predictors contributing to the development of dementia could be modified through healthy lifestyle behaviors [5]. Chronic low-grade inflammation, measured using levels of high-sensitivity C-reactive protein (hsCRP), was associated with early stage β-amyloid accumulation, resulting in neuroinflammation in brain regions [12]

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