- 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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