Plasma Lipoprotein-Associated Phospholipase A2 and Superoxide Dismutase are Independent Predicators of Cognitive Impairment in Cerebral Small Vessel Disease Patients: Diagnosis and Assessment

Backgroud: Lipoprotein-associated phospholipase A2 (Lp-PLA2) and superoxide dismutase (SOD) have been linked to vascular/neuro-inflammation and stroke. Using a retrospective design, we investigated whether circulating Lp-PLA2 and SOD in cerebral small vessel disease (CSVD) patients were associated with cognitive impairment (CI). Methods: Eighty-seven CSVD patients were recruited. Plasma Lp-PLA2 and SOD were determined, and cognitive status was measured by the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Multiple linear regressions were used to evaluate the relationship between Lp-PLA2 and SOD and the presence of CI. Ordinal logistic regression and generalized linear models (OLRGLMs) were applied to further confirm whether Lp-PLA2 and SOD are independent risk factors for CI in CVSD. Receiver operating characteristic (ROC) analysis was used to distinguish CSVD patients with CI from those with normal cognition (NC). Findings: Lp-PLA2 and SOD with mild or severe CI were lower than those with NC. We noted positive linear associations of Lp-PLA and SOD with CI in CSVD, independent of LDL-C. OLRGLMs confirmed that Lp-PLA2 and SOD were independent risk factors of CI in CSVD. The ROC for the combination of Lp-PLA and SOD yielded a better accuracy for distinguishing CSVD with mild (area under the curve [AUC]=0.77) and severe CI ([AUC]=0.90) from those with NC than each parameter alone. Interpretation: Lp-PLA2 and SOD are independently associated with CI and useful for the rapid diagnosis and evaluation of CI in CSVD. Lp-PLA2 and SOD are modifiable factors that may be considered as therapeutic targets for preventing CI in CSVD patients. Funding Statement: This work was supported by the National Natural Science Foundation of China, Science and Technology Program of Guangdong of China Natural Science Foundations of Guangdong of China, and Leading Talent in Talents Project Guangdong High-level Personnel of Special Support Program. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was approved by the ethics Human Research Committee at Zhujiang Hospital of Southern Medical University and complied with the principles outlined in the revised Declaration of Helsinki of 1975 and the National Institutes of Health Human Subjects Policies and Guidelines released in 1999. Informed written or verbal consent was obtained from patients and family members.