Predictive value of circulating inflammatory biomarkers for early-onset post-stroke cognitive impairment: a prospective cohort study

 

This prediction doesn't get survivors recovered, does it? So useless research!

You're fired!

Predictive value of circulating inflammatory biomarkers for early-onset post-stroke cognitive impairment: a prospective cohort study

Weiquan Huang^1†Libin Liao^1†Qian Liu²Rongchao Ma¹Wentong Hu¹Yuan Dai^3*Luna Wang^3*Dujuan Sha^1,2,3,4*

• ¹Department of General Practice, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
• ²Department of General Practice, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, China
• ³Department of General Practice, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
• ⁴Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China

Introduction: Stroke ranks as the second leading cause of mortality and the third leading cause of disability globally. Post-stroke cognitive impairment (PSCI) is a prevalent complication following acute ischemic stroke, imposing substantial burdens on patients, families, and society. This study aimed to explore the potential of circulating immune-inflammatory markers as predictors of PSCI.

Methods: Conducted as a prospective observational cohort study from June 2023 to August 2024 at the Affiliated Drum Tower Hospital, Medical School of Nanjing University, it included patients experiencing their first acute ischemic stroke within 72 h of symptom onset. Cognitive assessments were conducted 7 to 10 days post-stroke using the Montreal Cognitive Assessment (MoCA), with scores below 23 indicating PSCI.

Results: A total of 146 patients meeting the inclusion criteria were recruited, with 71 patients exhibiting PSCI during the acute phase of stroke. Compared to patients in the post-stroke no cognitive impairment (PSNCI) group, those with PSCI demonstrated significantly elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR), globulin-to-lymphocyte ratio (GLR), and C-reactive protein-to-lymphocyte ratio (CLR), while the lymphocyte-to-monocyte ratio (LMR) was notably reduced (all p < 0.05). Both univariate and multivariate logistic regression analyses identified GLR as independently associated with PSCI. After adjusting for common clinical variables, the odds ratio (OR) for the highest tertile of GLR compared to the lowest was 6.20 (95% CI, 2.10–18.33; p = 0.001). The optimal GLR cutoff was 18.22, with a sensitivity of 62.0%, specificity of 78.7%, and an area under curve (AUC) of 0.726.

Conclusion: This study indicates that elevated circulating GLR levels during the acute phase post-stroke onset are an independent risk factor for early-onset PSCI, even after adjusting for clinically relevant variables.

1 Introduction

Stroke is the second leading cause of death and the third leading cause of disability in the world (1). Depending on the etiology and pathogenesis, stroke can be classified as ischemic stroke or hemorrhagic stroke. Of these, ischemic stroke is the most common type, accounting for approximately 87% of all stroke patients (2). Post-stroke cognitive impairment (PSCI) is one of the most common complications of acute ischemic stroke, with a prevalence ranging from 15% to 70%, depending on the clinical features and stroke severity (3), which imposes a heavy burden on the patient, family, and society. PSCI includes cognitive impairment that occurs within 3 to 6 months after stroke and is clinically characterized by persistent impairment in one or more core cognitive domains, such as attention, memory, executive function, language, and visuospatial ability, and is associated with a significantly increased risk of death, disability, and depression up to 5 years after the onset of the stroke (4). Common risk factors for PSCI are advanced age, low education, hypertension, diabetes mellitus, atrial fibrillation, smoking, family history, sedentary lifestyle, stroke subtype, and stroke severity (5–7).

The diagnosis of PSCI is usually based on clinical assessment, neuropsychological evaluation, and neuroimaging (8, 9). The Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) are the most widely used cognitive tests for PSCI research. Factors such as the patient’s education degree, evaluation by different personnel, and the selection of different scales can affect the assessment results; these two tools are mainly applied to neurodegenerative diseases and have low sensitivity in detecting PSCI, which can lead to the underdiagnosis of PSCI (10). Computer tomography (CT) remains the standard imaging modality in clinical practice due to its advantages over magnetic resonance imaging (MRI) in terms of speed, cost, and fewer contraindications (11). MRI brain scans are generally more helpful in dementia assessment and are considered the “gold standard” for neuroimaging-based assessment (12). However, if neuroimaging is to be combined with clinical characterization as the primary diagnostic support for PSCI, it is essential to have experienced imaging physicians and to perform high-quality scans to obtain accurate information.

Therefore, blood biomarkers hold promising potential due to their availability, low invasiveness, objectivity, and cost-effectiveness.(Biomarkers don't get you recovered, do they? So why the fuck are you researching biomarkers?) An increasing number of research studies have shown that blood biomarkers play an important role in the occurrence and development of PSCI. There are currently no precise blood biomarkers for PSCI risk prediction and early diagnosis at home and abroad. Acute cerebral ischemia releases damage-associated molecular patterns that trigger brain intrinsic immune cells (microglia) and recruit peripheral innate immune cells, including neutrophils and monocytes/macrophages for infiltration, leading to exacerbated ischemic injury (13). Meanwhile, cerebral ischemia releases harmful substances, especially necrotic cellular debris, which triggers an inflammatory cascade in the immune system, leading to subsequent repair processes and tissue damage (14). Imbalanced expression of pro- and anti-inflammatory cytokines in the brain activates cerebral microvessels and disrupts the blood–brain barrier, exacerbating neurological dysfunction and ultimately leading to cognitive impairment and dementia (15, 16). Studies have shown a strong correlation between the immune response in the acute phase of stroke and long-term cognitive function (17). A recent study found that the neutrophil-to-lymphocyte ratio (NLR) during the acute phase of ischemic stroke was independently correlated with PSCI at 3 months post-stroke (18), which is consistent with the findings of several other studies (19, 20). Therefore, the immune-inflammatory response plays a significant role in the pathogenic process of PSCI. Peripheral blood cell counts and biochemical indices are among the most accessible laboratory indices in the clinic. In this study, peripheral blood lymphocyte count was combined with neutrophil count, monocyte count, serum globulin, and C-reactive protein (CRP) to investigate the predictive value of the NLR, lymphocyte-to-monocyte ratio (LMR), globulin-to-lymphocyte ratio (GLR), and C-reactive protein-to-lymphocyte ratio (CLR) in early-onset PSCI.

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