The Association Between Neutrophil-Lymphocyte Ratio and Variability with New-Onset Dementia: A Population-Based Cohort Study

Article type: Research Article

Authors: Chou, Oscar Hou In^{a; b; 1} | Zhou, Jiandong^{a; c; 1} | Li, Lifang^d | Chan, Jeffrey Shi Kai^a | Satti, Danish Iltaf^a | Chou, Vanessa Hou Cheng^a | Wong, Wing Tak^e | Lee, Sharen^a | Cheung, Bernard Man Yung^b | Tse, Gary^{a; f; g} | Chang, Carlin^{b; *} | Liu, Tong^{f; *}

Affiliations: [a] Family Medicine Research Unit, Cardiovascular Analytics Group, Hong Kong, China-UK Collaboration | [b] Department of Medicine, Queen Mary Hospital, Hong Kong, China | [c] Nuffield Department of Medicine, University of Oxford, Oxford, UK | [d] Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom | [e] School of Life Sciences, Chinese University of Hong Kong, Hong Kong, China | [f] Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China | [g] Kent and Medway Medical School, Canterbury, Kent, UK | [h] School of Data Science, City University of Hong Kong, Hong Kong, China

Correspondence: [*] Correspondence to: Dr Carlin Chang, MBChB, MPhil, MRCP, FHKAM, Department of Medicine, Queen Mary Hospital, Hong Kong, China. E-mail: cchang@post.harvard.edu and Dr. Tong Liu, PhD, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China. E-mail: liutongdoc@126.com.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Previous studies identified that neutrophil-to-lymphocyte ratio (NLR) may be a predictor of dementia. However, the associations between NLR and dementia at the population level were less explored. Objective:This retrospective population-based cohort study was designed to identify the associations between NLR and dementia among patients visiting for family medicine consultation in Hong Kong. Methods:The patients were recruited from January 1, 2000, to December 31, 2003, and followed up until December 31, 2019. The demographics, prior comorbidities, medications, and laboratory results were collected. The primary outcomes were Alzheimer’s disease and related dementia and non-Alzheimer’s dementia. Cox regression and restricted cubic spline were applied to identify associations between NLR and dementia. Results:A cohort of 9,760 patients (male: 41.08% ; baseline age median: 70.2; median follow-up duration: 4756.5 days) with complete NLR were included. Multivariable Cox regression identified that patients with NLR >5.44 had higher risks of developing Alzheimer’s disease and related dementia (hazard ratio [HR]: 1.50, 95% Confidence interval [CI]: 1.17–1.93) but not non-Alzheimer’s dementia (HR: 1.33; 95% CI: 0.60–2.95). The restricted cubic splines demonstrated that higher NLR was associated with Alzheimer’s disease and related dementia. The relationship between the NLR variability and dementia was also explored; of all the NLR variability measures, only the coefficient of variation was predictive of non-Alzheimer’s dementia (HR: 4.93; 95% CI: 1.03–23.61). Conclusion:In this population-based cohort, the baseline NLR predicts the risks of developing dementia. Utilizing the baseline NLR during family medicine consultation may help predict the risks of dementia.

Keywords: Alzheimer’s disease, dementia, inflammation, neuro-inflammation, non-Alzheimer’s dementia

DOI: 10.3233/JAD-220111

Journal: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 547-557, 2023