Early Biomarkers For Post-stroke Cognitive Impairment

Background and Purpose:Vascular cognitive impairment (VCI) is a clinical syndrome, from mild cognitive impairment to dementia, caused by cerebrovascular risk factors, the obvious or not obvious cerebrovascular disease. The pathogenesis of post stroke cognitive impairment (PSCI), which is the most common type of VCI, is not clear. So it is difficult to diagnose and treatment early. Increasing evidence shows that VaD and AD share several pathological features. Our previous study indicated that in an Aβ-induced AD mouse model, the alterations in the levels of BACE1, sRAGE, and NEP in the cortex and hippocampus occurred ahead of Aβ accumulation as well as cognitive performance decline. In both experimental stroke models and brain tissue of VaD patients, there are increased levels of BACE1and an accumulation of A β42. NEP, the major Aβ-degrading enzyme that was found to be downregulated in AD, may be altered in VaD. sRAGE, a secreted isoform of the receptor for AGE, may be a marker for VaD and AD. Furthermore, the s4allele of APOE is a well-known risk factor for late-onset AD, and has been recognized as a risk factor for VaD in multiple ethnic groups. The goal of this study was to test our hypothesis that changes in BACE1, sRAGE, NEP, and APOE occurred before cognitive functions could be assessed after stroke.Methods:One hundred fifty-two first-ever stroke patients were recruited within6-72hours after the onset of symptoms and performed CT or MRI on them. Neurological deficits were assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Blood was drawn soon after admission for determining biomarkers. Cognitive status was evaluated by a set of neuropsychological assessments2weeks after stroke. Relationships between the biomarkers and post-stroke cognitive impairment were calculated by Pearson’s correlation coefficient and logistic regression analysis.Results:The152inpatients were divided into the following groups:Stroke, vascular cognitive impairment with no dementia (VCIND), vascular dementia (VaD), and mixed dementia (MD), by cognitive assays. Forty healthy subjects were as controls. The findings indicated that lower soluble receptor for advanced glycation end products (sRAGE), and higher β-secretase enzyme (BACE1) and neprilysin (NEP) were found in the VCIND, VaD, and MD groups relative to the stroke group. In addition, the percentages of s3/s4genotype and ε4allele in the VCIND, VaD, and MD groups were increased as compared to the stroke group. Correlational analysis determined that sRAGE, BACE1, and NEP had significant relationships with the results of neuropsychological assessments. Logistic regression analysis, however, suggested that only sRAGE and BACE1demonstrated significance in the prediction of cognitive impairment after stroke.Conclusions:BACE1and sRAGE may be biomarkers diagnosing post-stroke cognitive impairment.