The relationship between serum PKM2 and SERPINA3 levels and white matter degeneration and cognitive impair-ment in patients with lacunar cerebral infarction

Han Shuang; Wang Jue; Liu Chang; Wang Mingyang

doi:10.3969/j.issn.1671-6450.2026.03.009

Abstract：Objective To investigate the relationship between serum pyruvate kinase M2(PKM2)and serpin family A member 3(SERPINA3)levels and white matter degeneration and cognitive impairment in patients with lacunar cerebral in-farction.Methods A total of 193 patients with lacunar cerebral infarction admitted to the Department of Neurology,the Third Hospital of Heilongjiang Province from May 2020 to May 2025 were selected as the lacunar cerebral infarction group.Ac-cording to the Fazekas score,patients were divided into a subgroup without leukoaraiosis(89 cases)and a subgroup with leu-koaraiosis(104 cases).According to the Montreal Cognitive Assessment(MoCA)score,patients were divided into a normal cognition subgroup(95 cases)and a cognitive impairment subgroup(98 cases).In addition,193 healthy subjects from the same period were randomly selected as the healthy control group.Serum PKM2 and SERPINA3 levels were detected by enzyme-linked immunosorbent assay.Spearman rank correlation analysis was used to analyze the correlation between serum PKM2,SERPINA3 levels and the degree of white matter degeneration and cognitive impairment.Multivariate logistic regression anal-ysis was used to identify factors influencing cognitive impairment in patients with lacunar cerebral infarction.Receiver operat-ing characteristic(ROC)curve analysis was used to evaluate the diagnostic value of serum PKM2 and SERPINA3 levels for cognitive impairment in patients with lacunar cerebral infarction.Results Serum PKM2 and SERPINA3 levels were signifi-cantly higher in the lacunar infarction group than in the healthy control group(t/P=15.776/＜0.001,23.092/＜0.001).With in-creasing severity of white matter degeneration,serum PKM2 and SERPINA3 levels progressively increased across mild,mod-erate,and severe white matter degeneration subgroups(F/P=22.141/＜0.001,52.482/＜0.001).Serum PKM2 and SERPINA3 levels were positively correlated with the degree of white matter degeneration(rs/P=0.621/＜0.001,0.597/＜0.001).Serum PKM2 and SERPINA3 levels were significantly higher in the cognitive impairment subgroup than in the normal cognition sub-group(t/P=10.812/＜0.001,8.986/＜0.001).Serum PKM2 and SERPINA3 levels were positively correlated with the degree of cognitive impairment(rs/P=0.708/＜0.001,0.692/＜0.001).Age,elevated homocysteine(Hcy),white matter degeneration,ele-vated PKM2,and elevated SERPINA3 were independent risk factors for cognitive impairment in patients with lacunar infarc-tion[OR(95％CI)=1.432(1.193-1.718),2.863(1.517-5.403),2.241(1.406-3.573),1.865(1.334-2.607),2.071(1.367-3.138)].The AUCs for PKM2,SERPINA3,and their combination in diagnosing cognitive impairment were 0.802,0.825,and 0.907,respectively.The combined diagnostic value was significantly greater than that of either marker alone(Z/P=2.804/0.001,2.290/0.004).Conclusion Serum PKM2 and SERPINA3 expression is upregulated in patients with lacunar cerebral infarction and is associated with white matter degeneration and cognitive impairment.Early combined detection of these mark-ers may assist in the clinical diagnosis of cognitive impairment.