Serum inflammatory proteins and frontal lobe dysfunction in patients with cardiovascular risk factors

Background:  Recent studies have shown that the levels of circulating inflammatory markers are associated with cognitive decline and cerebral small-vessel disease. Frontal lobe dysfunction is believed to be a relatively characteristic neuropsychological symptom in vascular cognitive impairment caused by cerebral small-vessel disease. The purpose of this study was to investigate whether the levels of serum inflammatory markers are associated with frontal lobe dysfunction, particularly executive dysfunction. Methods:  Between January 2003 and September 2007, 388 patients who had one or more atherosclerotic risk factors and subsequently underwent brain MRI and neuropsychological testing including mini-mental state examination (MMSE), frontal assessment battery (FAB), and modified Stroop test were enrolled in this study. We evaluated the effect of serum levels of inflammatory markers and white matter lesions on frontal lobe function. Results:  The FAB score was negatively correlated with serum inflammatory marker levels (hsCRP; r = −0.170, IL-6; r = −0.143, IL-18; r = −0.175) and white matter lesions. In the modified Stroop test, interference measure was positively correlated with the levels of hsCRP (r = −0.198), and IL-18 (r = −0.152), and white matter lesions. However, the MMSE score was not correlated with either inflammatory marker levels. The association between hsCRP and FAB score or interference measure remained significant when controlling for other confounding factors and MRI findings. Conclusions:  The circulating level of hsCRP is associated with frontal lobe dysfunction in patients with cardiovascular risk factors independent of white matter lesions in brain MRI.