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

Abstract

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.

Biomarkers of chronic inflammation and cognitive decline: A prospective observational study

“… 38 Another population‐based cohort study found that the highest tertile of hs‐CRP (examined only as a categorical variable) was associated with all‐cause dementia at 8 years follow‐up. 39 The relationship was only significant in the subgroup of participants age < 65 years old. 39 This difference related to age was reported in another study specifically looking a diagnosis of AD ( n = 52).…”

“… 39 The relationship was only significant in the subgroup of participants age < 65 years old. 39 This difference related to age was reported in another study specifically looking a diagnosis of AD ( n = 52). 40 There was however no association between hs‐CRP and AD in the overall group, and no cognitive testing was performed as part of the study.…”

“…The study assessed cognition in a largely healthy population, used a cognitive assessment tool devised by the researchers and that relies on recall, and only found a numerically minor difference in the rate of cognitive decline between hs‐CRP quartiles 38 . Another population‐based cohort study found that the highest tertile of hs‐CRP (examined only as a categorical variable) was associated with all‐cause dementia at 8 years follow‐up 39 . The relationship was only significant in the subgroup of participants age < 65 years old 39 .…”

Association of Advanced Lipoprotein Subpopulation Profiles with Insulin Resistance and Inflammation in Patients with Type 2 Diabetes Mellitus

“…It is well-established that combination of hyperglycemia and chronic inflammation is associated with early subclinical carotid atherosclerosis progression and increased risk of new vascular events in diabetic as well as nondiabetic subjects [ 33 , 34 ]. The existing recognized biomarkers hemoglobin A1c (HbA1c) and Hs-CRP are the most clinically useful surrogates for identifying the presence of both insulin resistance and inflammation in T2DM [ 35 ].…”

The Mediating Role of Systemic Inflammation and Moderating Role of Race/Ethnicity in Racialized Disparities in Incident Dementia: A Decomposition Analysis

“…[28][29][30][31][32][33][34][35][36] Some research has shown that non-Hispanic Black women have the highest levels of CRP in comparison to non-Hispanic White women and men, and even non-Hispanic Black men. [37][38][39] Circulating levels of CRP have been associated with higher white matter hyperintensity, 40 Alzheimer's disease, 35 and all-cause dementia, 41 albeit in studies of homogeneous populations that differ from the racial demographic composition of the United States. In a racially diverse population-based study in the United States, elevated serum levels of CRP were associated with two cognitive domains (memory and verbal fluency) at baseline; but not with the rate of cognitive decline.…”