Peripheral high levels of CRP predict progression from normal cognition to dementia: A systematic review and meta-analysis

Objective: Several cross-sectional studies have demonstrated a relationship between inflammation and dementia. Uncertainty exists over the ability of C-reactive protein (CRP), one of the most investigated markers of inflam-mation, to predict the progression of normal cognition to dementia. A systematic review and meta-analysis were performed to assess whether high peripheral levels of CRP are associated with cognitive impairment and whether CRP is a risk factor for predicting progression from normal cognition to cognitive decline or dementia.Methods: Literature published before November 2022 was retrieved from PubMed, Embase, and Web of Science. Prospective cohort studies that employed recognized evaluation instruments to assess global cognitive function or used accepted diagnostic criteria to ascertain dementia were selected. Subgroup analysis was conducted on specific cognitive domains and causes of dementia (i.e., Alzheimer's disease and vascular dementia). Odds ratios (ORs) and hazard ratios (HRs) were extracted and merged to facilitate data analysis. A random-effects model was used for the meta-analysis and a descriptive analysis of the data that could not be merged was conducted.Results: A total of 13 articles (14 cohort studies) were included for meta-analysis and six articles were included for descriptive analysis. The results showed that high CRP levels were not related to future cognitive decline (OR = 1.115; 95 % CI: 0.830-1.497; p = 0.469) but were associated with an increased risk of conversion to dementia. (HR = 1.473; 95 % CI: 1.037-2.090; p = 0.0394). This association persisted after full adjustment for potential covariates, with an OR of 1.044 (95 % CI:0.767-1.421, p = 0.785) for cognitive decline and an HR of 1.429 (95 % CI:1.088-1.876, p = 0.010) for dementia. The subgroup analysis showed that a higher level of CRP was related to a decline in visual-spatial ability (OR = 1.402, 95 % CI: 1.045-1.882, p = 0.024) and the risk of conversion to vascular dementia (total effect size of OR and HR = 2.769, 95 % CI: 1.586-4.83, p = 0.000). Conclusions: Higher CRP levels as an indicator of chronic systemic inflammation cannot predict future cognitive decline but may indicate a higher risk of conversion to dementia.