Our prospective study recruited a group of acute ischemic patients and investigated relationship between serum periostin concentrations and cognitive function status. We found that higher serum periostin levels were associated with an increased risk of PSCI at 3 months. Furthermore, this association was independent for demographic characteristics, vascular risk factors and stroke severity. Hence, periostin in serum might represent a novel prognostic biomarker of PSCI.
Reported frequency of PSCI is ranges widely from 10–82% [2, 3]. The discrepancy of PSCI incidence may be mainly attributed to differences in race, age, educational status, diagnostic criteria, and study methods. Most studies have assessed cognitive function at 3 months after a stroke using cross-sectional design [21–25], whereas some studies have adopted longitudinal designs [3, 26]. Several diagnostic tools have been applied to investigate the presence of PSCI, such as National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN), Mini-Mental State Examination (MMSE), and MoCA. In studies performed among populations of white dominance, the prevalence of 3-month cognitive impairment after ischemic stroke ranges from 24–39% according to the MMSE, while the prevalence in the same population is up to 96% using a battery of neuropsychological tests [24, 26]. However, in studies using a total MoCA score < 26 as the definition of PSCI, the prevalence of PSCI approximates to 50% [22, 23]. In the present study, we adopted a total MoCA score < 25 as the definition of PSCI because this cutoff had a good sensitivity (77%) and specificity (83%) for mild cognitive impairment . We observed that PSCI occurred in 54.9% of patients, which is similar to the findings of other observational studies that have used the same diagnostic criteria [20, 24].
Periostin is a secreted extracellular matrix protein that plays an important role in tissue repair, oncology, cardiovascular and central nervous systems, and in various inflammatory settings and diseases . Previous studies found that increased periostin levels were associated with clinical severity and poor prognosis in patients with ischemic stroke , intracerebral hemorrhage , and aneurysmal subarachnoid hemorrhage . Our study extended the current knowledge about the role of periostin in cerebrovascular diseases as it confirmed a positive relationship between circulating periostin concentrations and cognitive impairment after stroke. Both of clinical studies showed that periostin may play a crucial role in pathologic process after brain tissue injury.
According to the results from animal experiment, periostin 2 (splicing variant of periostin) was overexpressed at 24 hours after transient middle cerebral artery occlusion model. Exogenously injection of periostin 2 could reduce infarct volume . Periostin has also been reported to promote neural stem cell proliferation and differentiation after hypoxic-ischemic injury. Intracerebroventricular administration of periostin was shown to significantly improve spatial learning and memory, indicating that periostin may alleviate cognitive deficits . Periostin continued to be expressed up to 4 weeks after cerebral ischemia in various cells, such as astrocytes, microglia, and neuronal progenitor cells . Therefore, the increase in circulating periostin levels might occur to repair the brain tissue and improve cognitive function after ischemic stroke. On the contrary, other studies demonstrated a detrimental effect of periostin [28, 29]. Anti-periostin antibody improved post-subarachnoid hemorrhage neurobehavior, brain edema, and blood-brain barrier disruption. Recombinant-periostin significantly aggravated early brain injury . Furthermore, the inhibition of periostin expression may improve cardiac systolic ejection function and animal survival rate . Thus, researchers have not reached a consensus on the net effect of periostin. However, this mechanism warrants to be verified in future studies. Further studies are needed to detect the precise mechanisms underlying the association between elevated circulating periostin concentrations and cognitive impairment after ischemic stroke.
There were several limitations that should be addressed in this study. First, all 315 ischemic stroke patients in our study were prospective recruited from a tertiary referral hospital, so it is difficult to generalize from the results of this study. Second, patients with a history of cognitive impairment or a severe condition after stroke, whowere unable to complete psychological assessment, were excluded from the study. This selection bias would probably reduce the power of study. Third, serum periostin levels were only measured at one time point after admission, which may lead to some misclassification of exposure. Furthermore, multiple factors may influence the accuracy of a single neuropsychological test in the diagnosis of PSCI, including educational status, physiological condition, and sensitivity or specificity of the test itself. The combined application of other evaluation tests in addition to MoCA, such as NINDS-CSN and MMSE, could improve the accuracy of the diagnosis. Therefore, the interpretation of our results should be cautious, and further multi-center studies with larger sample sizes are needed to validate our findings.
In summary, our study provided preliminary data showing that increased serum perostin concentrations at baseline were independently associated with increased risk of PSCI among ischemic stroke patients. Further preclinical studies are warranted to investigate the underlying pathogenesis as well as targeted interventions in PSCI prevention and treatment.