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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Association of Neutrophil-Lymphocyte Ratio with Mild Cognitive Impairment in Elderly Chinese Adults: A Case-control Study

Author(s): Peilin An, Xuan Zhou, Yue Du, Jiangang Zhao, Aili Song, Huan Liu, Fei Ma and Guowei Huang*

Volume 16, Issue 14, 2019

Page: [1309 - 1315] Pages: 7

DOI: 10.2174/1567205017666200103110521

Price: $65


Background: Inflammation plays a significant role in the pathophysiology of cognitive impairment in previous studies. Neutrophil-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation.

Objectives: The aim of this study was to investigate the association between NLR and mild cognitive impairment (MCI), and further to explore the diagnostic potential of the inflammatory markers NLR for the diagnosis of MCI in elderly Chinese individuals.

Methods: 186 MCI subjects and 153 subjects with normal cognitive function were evaluated consecutively in this study. Neutrophil (NEUT) count and Lymphocyte (LYM) count were measured in fasting blood samples. The NLR was calculated by dividing the absolute NEUT count by the absolute LYM count. Multivariable logistic regression was used to evaluate the potential association between NLR and MCI. NLR for predicting MCI was analyzed using Receiver Operating Characteristic (ROC) curve analysis.

Results: The NLR of MCI group was significantly higher than that of subjects with normal cognitive function (2.39 ± 0.55 vs. 1.94 ± 0.51, P < 0.001). Logistic regression analysis showed that higher NLR was an independent risk factor for MCI (OR: 4.549, 95% CI: 2.623-7.889, P < 0.001). ROC analysis suggested that the optimum NLR cut-off point for MCI was 2.07 with 73.66% sensitivity, 69.28% specificity, 74.48% Positive Predictive Values (PPV) and 68.36% negative predictive values (NPV). Subjects with NLR ≥ 2.07 showed higher risk relative to NLR < 2.07 (OR: 5.933, 95% CI: 3.467-10.155, P < 0.001).

Conclusion: The elevated NLR is significantly associated with increased risk of MCI. In particular, NLR level higher than the threshold of 2.07 was significantly associated with the probability of MCI.

Keywords: Neutrophil-lymphocyte ratio, mild cognitive impairment, systemic inflammation, cut-off value, elderly, casecontrol study.

Rubenstein E, Hartley S, Bishop L. Epidemiology of dementia and Alzheimer disease in individuals with down syndrome. JAMA Neurol 2019.
[] [PMID: 31657825]
Sanford AM. Mild cognitive impairment. Clin Geriatr Med 33(3): 325-37. (2017)
[] [PMID: 28689566]
Behrman S, Valkanova V, Allan CL. Diagnosing and managing mild cognitive impairment 261(1804): 17-20. (2017)
Alzheimer’s Association. 2015 Alzheimer’s disease facts and figures. Alzheimers Dement 11(3): 332-84. (2015)
[] [PMID: 25984581]
Morris JC. Revised criteria for mild cognitive impairment may compromise the diagnosis of Alzheimer disease dementia. Arch Neurol 69(6): 700-8. (2012)
[] [PMID: 22312163]
Bettcher BM, Fitch R, Wynn MJ, Lalli MA, Elofson J, Jastrzab L, et al. MCP-1 and eotaxin-1 selectively and negatively associate with memory in MCI and Alzheimer’s disease dementia phenotypes. Alzheimers Dement (Amst) 3: 91-7. (2016)
[] [PMID: 27453930]
Moyse E, Haddad M, Benlabiod C, Ramassamy C, Krantic S. Common pathological mechanisms and risk factors for Alzheimer’s disease and type-2 diabetes: focus on inflammation. Curr Alzheimer Res 2019; 16(11): 986-1006.
[] [PMID: 31692443]
Lathe R, Sapronova A, Kotelevtsev Y. Atherosclerosis and Alzheimer--diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr 14: 36. (2014)
[] [PMID: 24656052]
de Oliveira FF, de Almeida SS, Chen ES, Smith MC, Naffah-Mazzacoratti MDG, Bertolucci PHF. Lifetime risk factors for functional and cognitive outcomes in patients with Alzheimer’s disease. J Alzheimers Dis 65(4): 1283-99. (2018)
[] [PMID: 30149448]
Paouri E, Georgopoulos S. Systemic and CNS inflammation crosstalk: implications for Alzheimer’s disease. Curr Alzheimer Res 16(6): 559-74. (2019)
[] [PMID: 30907316]
Magalhães CA, Ferreira CN, Loures CMG, Fraga VG, Chaves AC, Oliveira ACR, et al. Leptin, hsCRP, TNF-α and IL-6 levels from normal aging to dementia: relationship with cognitive and functional status. J Clin Neurosci 56: 150-5. (2018)
[] [PMID: 30150062]
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 14(4): 388-405. (2015)
[] [PMID: 25792098]
Bettcher BM, Kramer JH. Inflammation and clinical presentation in neurodegenerative disease: a volatile relationship. Neurocase 19(2): 182-200. (2013)
[] [PMID: 22515699]
Popp J, Oikonomidi A, Tautvydaitė D, Dayon L, Bacher M, Migliavacca E, et al. Markers of neuroinflammation associated with Alzheimer’s disease pathology in older adults. Brain Behav Immun 62: 203-11. (2017)
[] [PMID: 28161476]
Kuyumcu ME, Yesil Y, Oztürk ZA, Kizilarslanoğlu C, Etgül S, Halil M, et al. The evaluation of neutrophil-lymphocyte ratio in Alzheimer’s disease. Dement Geriatr Cogn Disord 34(2): 69-74. (2012)
[] [PMID: 22922667]
Halazun HJ, Mergeche JL, Mallon KA, Connolly ES, Heyer EJ. Neutrophil-lymphocyte ratio as a predictor of cognitive dysfunction in carotid endarterectomy patients. J Vasc Surg 59(3): 768-73. (2014)
[] [PMID: 24571940]
Malhotra K, Goyal N, Chang JJ, Broce M, Pandhi A, Kerro A, et al. Differential leukocyte counts on admission predict outcomes in patients with acute ischaemic stroke treated with intravenous thrombolysis. Eur J Neurol 25(12): 1417-24. (2018)
[] [PMID: 29953701]
Zhang J, Ren Q, Song Y, He M, Zeng Y, Liu Z, et al. Prognostic role of neutrophil-lymphocyte ratio in patients with acute ischemic stroke. Medicine (Baltimore) 96(45) e8624 (2017)
[] [PMID: 29137097]
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 256(3): 183-94. (2004)
[] [PMID: 15324362]
Ritchie K, Artero S, Touchon J. Classification criteria for mild cognitive impairment: a population-based validation study. Neurology 56(1): 37-42. (2001)
[] [PMID: 11148233]
Perneczky R, Pohl C, Sorg C, Hartmann J, Komossa K, Alexopoulos P, et al. Complex activities of daily living in mild cognitive impairment: conceptual and diagnostic issues. Age Ageing 35(3): 240-5. (2006)
[] [PMID: 16513677]
Biggerstaff BJ. Comparing diagnostic tests: a simple graphic using likelihood ratios. Stat Med 19(5): 649-63. (2000)
[<649:AID-SIM371>3.0.CO;2-H] [PMID: 10700737]
Lopez OL, Chang Y, Ives DG, Snitz BE, Fitzpatrick AL, Carlson MC, et al. Blood amyloid levels and risk of dementia in the Ginkgo Evaluation of Memory Study (GEMS): a longitudinal analysis. Alzheimers Dement 15(8): 1029-38. (2019)
[] [PMID: 31255494]
Wang J, Qiao F, Shang S, Li P, Chen C, Dang L, et al. Elevation of plasma amyloid-β level is more significant in early stage of cognitive impairment: a population-based cross-sectional study. J Alzheimers Dis 64(1): 61-9. (2018)
[] [PMID: 29865072]
Hilal S, Wolters FJ, Verbeek MM, Vanderstichele H, Ikram MK, Stoops E, et al. Plasma amyloid-β levels, cerebral atrophy and risk of dementia: a population-based study. Alzheimers Res Ther 10(1): 63. (2018)
[] [PMID: 29960604]
Cervellati C, Trentini A, Bosi C, Valacchi G, Morieri ML, Zurlo A, et al. Low-grade systemic inflammation is associated with functional disability in elderly people affected by dementia. Geroscience 40(1): 61-9. (2018)
[] [PMID: 29428983]
van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia 67(3): 280-93. (2012)
[] [PMID: 22321085]
Ohtani R, Nirengi S, Nakamura M, Murase N, Sainouchi M, Kuwata Y, et al. High-Density lipoprotein subclasses and mild cognitive impairment: study of outcome and apolipoproteins in dementia (STOP-Dementia)1. J Alzheimers Dis 66(1): 289-96. (2018)
[] [PMID: 30248050]
Rembach A, Watt AD, Wilson WJ, Rainey-Smith S, Ellis KA, Rowe CC, et al. AIBL Research Group. An increased neutrophil-lymphocyte ratio in Alzheimer’s disease is a function of age and is weakly correlated with neocortical amyloid accumulation. J Neuroimmunol 273(1-2): 65-71. (2014)
[] [PMID: 24907904]
Arima Y, Kamimura D, Sabharwal L, Yamada M, Bando H, Ogura H, et al. Regulation of immune cell infiltration into the CNS by regional neural inputs explained by the gate theory. Mediators Inflamm 2013 898165 (2013)
[] [PMID: 23990699]
Baruch K, Deczkowska A, David E, Castellano JM, Miller O, Kertser A, et al. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science 346(6205): 89-93. (2014)
[] [PMID: 25147279]
Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560): 337-41. (2015)
[] [PMID: 26030524]
Bu XL, Xiang Y, Jin WS, Wang J, Shen LL, Huang ZL, et al. Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies. Mol Psychiatry 23(9): 1948-56. (2018)
[] [PMID: 29086767]
Wendeln AC, Degenhardt K, Kaurani L, Gertig M, Ulas T, Jain G, et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature 556(7701): 332-8. (2018)
[] [PMID: 29643512]
Maitra U, Deng H, Glaros T, Baker B, Capelluto DG, Li Z, et al. Molecular mechanisms responsible for the selective and low-grade induction of proinflammatory mediators in murine macrophages by lipopolysaccharide. J Immunol 189(2): 1014-23. (2012)
[] [PMID: 22706082]
Colton CA, Mott RT, Sharpe H, Xu Q, Van Nostrand WE, Vitek MP. Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. J Neuroinflammation 3: 27. (2006)
[] [PMID: 17005052]
Kyrkanides S, Tallents RH, Miller JN, Olschowka ME, Johnson R, Yang M, et al. Osteoarthritis accelerates and exacerbates Alzheimer’s disease pathology in mice. J Neuroinflammation 8: 112. (2011)
[] [PMID: 21899735]
Ma F, Wu T, Zhao J, Ji L, Song A, Zhang M, et al. Plasma homocysteine and serum folate and vitamin b12 levels in mild cognitive impairment and Alzheimer’s disease: a case-control study. Nutrients 9(7): 725. (2017)
[] [PMID: 28698453]
Kim G, Kim H, Kim KN, Son JI, Kim SY, Tamura T, et al. Relationship of cognitive function with B vitamin status, homocysteine, and tissue factor pathway inhibitor in cognitively impaired elderly: a cross-sectional survey. J Alzheimers Dis 33(3): 853-62. (2013)
[] [PMID: 23042212]
Pierozan P, Biasibetti-Brendler H, Schmitz F, Ferreira F, Netto CA, Wyse ATS. synergistic toxicity of the neurometabolites quinolinic acid and homocysteine in cortical neurons and astrocytes: implications in Alzheimer’s disease. Neurotox Res 34(1): 147-63. (2018)
[] [PMID: 29124681]

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