Relationships among serum C-reactive protein, receptor for advanced glycation products, metabolic dysfunction, and cognitive impairments.

Background: We examined the clinical value of two serum markers of low-grade inflammation, C-reactive protein (CRP) and receptor of advanced glycation products (RAGE), as prognostic indices for cognitive decline.

Methods: Patients with cognitive impairment (n = 377) and controls (n = 66) were examined by blood biochemistry tests, including ELISAs of serum CRP and RAGE, the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), and STEAM 1H-MRS of the left hippocampus and thalamus.

Results: Compared to the control group, the cognitive impairment group was older (63.10 ± 9.70 years vs. 55.09 ± 10.77 years, P = 0.000) and had fewer years of formal education (9.01 ± 4.01 vs. 12.94 ± 3.0, P = 0.000). There were no significant differences in the frequencies of type 2 diabetes, hypertension, or hyperlipidemia between groups. Serum CRP and RAGE were higher in the cognitive impairment group (CRP: 2.08 mg/L, range 1.07 - 3.36 mg/L vs. 0.21 mg/L, range 0.18 - 0.42 mg/L; RAGE: 4.01, range 2.49 - 5.71, vs. 2.28, range 1.84 - 3.03; P < 0.05 for both). In patients with cognitive impairment, there were negative correlations between cognitive function (as measured by MMSE and MoCA) and both CRP and RAGE levels (P < 0.05). Patients over 55 years exhibited a positive correlation between CRP and myo-inositol peak area in the left hippocampus (P < 0.05), while there was no relationship between RAGE and any metabolite (P > 0.05). Multiple linear regression revealed that CRP was influenced by hypertension (P = 0.026) and cognitive impairment (P = 0.042).

Conclusions: Chronic low-grade inflammation is present in patients with cognitive impairment. Serum CRP, RAGE, and left hippocampal myo-inositol may provide prognostic information on cognitive decline.