Objective To analyze the relationships of lipoprotein a , von willebrand factor (vWF) and intercellular adhesion molecule-1 (ICAM-1) with the severity of vascular cognitive impairment in patients with ischemic cerebral small vessel disease (CSVD). Methods A retrospective analysis was performed on 110 patients with ischemic CSVD admitted to our hospital from January to December 2019. According to their mini-mental state examination (MMSE) and Wechsler adult intelligence scale (WAIS) scores, they were divided into cognitive impairment group (CSVD-1 group, n=59; MMSE≤26 points, WAIS≤69 points) and normal cognitive group (CSVD-2 group, n=51; MMSE＞26 points, WAIS＞69 points). Another 50 healthy subjects taking physical examination during the same period served as the control group. Lp(a) level was detected by immunoturbidimetry, and the levels of vWF and ICAM-1 were detected by enzyme-linked immunofluorescence assay. The relationship of the 3 indicators and cognitive impairment in ischemic CSVD patients was analyzed. SPSS statistics 25.0 was used for statistical analysis. According to data types, ANOVA was used for inter-group comparison, and LSD-t test was used for further pairwise comparison. Logistic regression was used to analyze the risk factors of cognitive impairment in CSVD patients. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive values of Lp(a) and ICAM-1 levels in the CSVD patients. Results Compared with the control group, the levels of TC, Lp(a), vWF and ICAM-1 were significantly increased, and the level of high-density lipoprotein cholesterol (HDL-C) was significantly decreased in the CSVD-1 and CSVD-2 groups (P<0.05). Compared with the CSVD-2 group, the levels of TC, Lp(a) and ICAM-1 were significantly increased, and the level of HDL-C was significantly decreased in the CSVD-1 group (P<0.05). However, the difference in the vWF level was not significant (P>0.05). Binary logistic regression analysis showed that Lp(a) (OR=1.872,95%CI 1.406-2.492; P=0.008) and ICAM-1 (OR=1.115,95%CI 1.031-1.206; P=0.002) were independent risk factors for cognitive impairment in CSVD patients. When the cut-point values of Lp(a) and ICAM-1 for predicting CSVD risk factors were 30.89 mg/dl and 300.25 μg/L, respectively, the combined detection of the 2 indicators had the highest predictive value (area under the ROC curve=0.930, P=0.000). Conclusion Lp(a) and ICAM-1 are closely associated with vascular cognitive impairment, and their combined detection has higher predictive value in patients with CSVD.