Systemic inflammation as an independent determinant of cognitive decline and cortical atrophy in dementia patients: A cross-sectional analysis

Abstract

Systemic inflammation is increasingly implicated in the pathogenesis of cognitive decline and neurodegeneration. C-reactive protein (CRP), a stable marker of chronic inflammation, may influence cognitive performance and structural brain changes in patients with dementia, particularly in the presence of type 2 diabetes mellitus. To evaluate the association between serum CRP levels and cognitive performance and to examine the relationship between CRP and MRI-based cortical atrophy in patients with dementia. This cross-sectional, hypothesis-driven secondary analysis included 60 patients with clinically diagnosed dementia. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Serum CRP levels were analyzed as both tertiles and continuous variables. MRI-based structural changes were evaluated using medial temporal atrophy and parietal atrophy (Koedam) scores. Pearson correlation and multiple linear regression analyses were performed. Cognitive scores declined across increasing CRP tertiles. The mean MMSE scores were 17.13 ± 6.25, 15.12 ± 5.12, and 11.96 ± 4.27 in low, moderate, and high CRP groups, respectively ( P = 0.009), with similar trends for MoCA ( P = 0.031). CRP correlated negatively with MMSE (r = −0.330, P = 0.008) and MoCA (r = −0.356, P = 0.004). In multivariable regression, CRP remained significantly associated with MMSE scores after adjustment for HbA1c ( β = −0.807, P = 0.022). CRP was significantly associated with greater MTA ( P = 0.046) but not parietal atrophy. Elevated CRP levels were significantly associated with poorer cognitive performance and greater medial temporal lobe atrophy after adjustment for HbA1c.