Negative correlation between serum pyruvate kinase M2 and cognitive function in patients with cerebral small vessel disease

Abstract

Objective: Cerebral small vessel disease (CSVD) is one of the main contributing factors to vascular cognitive impairment (VCI), with an increasing incidence rate. However, the genesis of CSVD cognitive impairment remains unknown. Inflammation and metabolic disorders are considered important pathogenesis of CSVD. In addition to acting as the key regulator of aerobic glycolysis, pyruvate kinase muscle isozyme 2 (PKM2) is a proinflammatory mediator transcriptional activator that can promote an inflammatory response. This study explored whether serum PKM2 is associated with cognitive impairment in CSVD patients.

Methods: The demographic data, history of risk factors, laboratory data, and cognitive function scale assessment of 219 CSVD patients were analyzed, and the correlation between the CSVD clinical data and neuroimaging parameters with serum PKM2 was further explored. The serum PKM2 level was determined by enzyme-linked immunosorbent assay using the collected serum samples. Insulin resistance (IR) was assessed with reference to the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). HOMA-IR was calculated using the formula HOMA-IR = fasting plasma glucose (FPG, mmol/L) × fasting insulin (FINS, μU/mL)/22.5. A binomial logistic regression model was referred to infer the risk factors for VCI, and the ability of serum PKM2 to diagnose VCI was assessed by using a ROC curve.

Results: Serum PKM2 level was positively correlated with HOMA-IR (r = 0.206, P = 0.002), negatively correlated with MMSE and MOCA on the cognitive scale in CSVD patients, and higher in CSVD patients with white matter hyperintensities (WMH) (P < 0.001). When compared with patients without cognitive impairment, the serum PKM2 levels were elevated in cases with suspected dementia, mild dementia, mild to moderate dementia, and moderate to severe dementia, and the differences were statistically significant (P < 0.05). Serum PKM2 levels were correlated with cognitive screening test scores in CSVD.

Conclusion: The present findings indicated that the serum PKM2 level was positively correlated with HOMA-IR, WMH, and enlarged perivascular spaces and negatively correlated with cognitive function in CSVD patients.

Keywords: CSVD—Insulin resistance—Vascular cognitive impairment; PKM2—White matter hyperintensities; Pyruvate kinase muscle isozyme 2; VCI; WMH—Cerebral small-vessel disease.