Association between the neutrophil-to-lymphocyte ratio and cognitive impairment: a meta-analysis of observational studies

Kuo-Chuan Hung; Chien-Cheng Liu; Jheng-Yan Wu; Chun-Ning Ho; Ming-Chung Lin; Chung-Hsi Hsing; I-Wen Chen

doi:10.3389/fendo.2023.1265637

Association between the neutrophil-to-lymphocyte ratio and cognitive impairment: a meta-analysis of observational studies

Front Endocrinol (Lausanne). 2023 Nov 28:14:1265637. doi: 10.3389/fendo.2023.1265637. eCollection 2023.

Authors

Kuo-Chuan Hung^{1

2}, Chien-Cheng Liu^{3

4

5}, Jheng-Yan Wu⁶, Chun-Ning Ho², Ming-Chung Lin², Chung-Hsi Hsing^{2

7}, I-Wen Chen⁸

Affiliations

¹ School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
² Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan.
³ Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
⁴ Department of Nursing, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
⁵ School of Medicine, I-Shou University, Kaohsiung, Taiwan.
⁶ Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan.
⁷ Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
⁸ Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan, Taiwan.

Abstract

Background: Systemic inflammation is one of the underlying mechanisms of cognitive impairment. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a systemic inflammation indicator. This meta-analysis aimed to evaluate the association between high NLR and cognitive impairment (CI) risk.

Method: A comprehensive systematic search was conducted to identify eligible studies published until May 30, 2023. The reference group comprised patients with the lowest NLR level, whereas the exposure group comprised those with the highest NLR level. The main outcome was to examine the relationship between NLR and CI risk. The secondary outcome included the association between patient characteristics or comorbidities and CI risk.

Results: This meta-analysis included 11 studies published between 2018 and 2023, involving 10,357 patients. Patients with CI had a higher NLR than those without (mean difference=0.35, 95% confidence interval [CI]: 0.26-0.44, p < 00001, I^{2 =} 86%). Consistently, pooled results revealed an association between high NLR and CI risk (odds ratio [OR]=2.53, 95% CI:1.67-3.82, p<0.0001, I^{2 =} 84%). Furthermore, aging (mean difference =4.31 years, 95% CI:2.83-5.8, p < 0.00001, I^{2 =} 92%), diabetes (OR=1.59, 95% CI:1.35-1.88, p < 0.00001, I^{2 =} 66%), and hypertension (OR=1.36, 95% CI:1.19-1.57, p < 0.00001, I^{2 =} 0%) were significant risk factors for CI. However, no significant associations were observed between CI and male gender (OR = 0.84, 95% CI:0.64-1.11, p = 0.22, I^{2 =} 81%), body mass index (mean = -0.32 kg/m², 95% CI: -0.82, 0.18, p = 0.2, I^{2 =} 82%), alcohol consumption (OR = 1.11, 95% CI:0.95-1.3, p = 1.35, I^{2 =} 0%), and smoking (OR = 0.99, 95% CI:0.87-1.13, p = 0.86, I^{2 =} 0%). Meta-regression found that diabetes and hypertension, but not age, significantly moderated the association between NLR and CI.

Conclusion: This meta-analysis showed a significant association between high NLR and increased CI risk. Moreover, meta-regression identified diabetes and hypertension, but not age, as significant moderating factors in the relationship between NLR and CI. To validate and strengthen these findings, further large-scale studies are required.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023430384, identifier CRD42023430384.

Keywords: age; cognitive impairment; meta-analysis; mild cognitive impairment; neutrophil-to-lymphocyte ratio.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Cognitive Dysfunction* / epidemiology
Cognitive Dysfunction* / etiology
Diabetes Mellitus*
Humans
Hypertension*
Inflammation
Lymphocyte Count
Lymphocytes
Male
Neutrophils
Observational Studies as Topic

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Chi Mei Medical Center, Tainan, Taiwan (grant number: CMOR11203).