Evaluation of Peripheral Inflammatory Activity in Different Types of Dementia

Yıl 2024, Cilt: 8 Sayı: 1, 20 - 25, 30.04.2024

Esra Erkoç Ataoğlu

https://doi.org/10.30565/medalanya.1422120

Öz

Aim: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by pathophysiological processes involving neuroinflammation, neurodegeneration, and synaptic dysfunction. Vascular dementia (VaD) stands as the second most prevalent form among all dementia types, sharing common pathophysiological mechanisms with AD, such as vascular oxidative stress and chronic inflammation.The neutrophil-to-lymphocyte ratio (NLR) is considered a simple, noninvasive, and widely available clinical marker of inflammation. The aim of this study is to investigate the potential differences between these two different types of dementia in terms of NLR values.

Materials and Methods:The data of patients diagnosed with AD or VaD and healthy controls who applied to a University Hospital Neurology outpatient clinic were retrospectively examined, and the groups were analyzed with statistical methods in terms of NLR levels.

Results: A total of 39 AD, 32 VaD, and 30 healthy controls were enrolled in the study. Hemogram analyses revealed significantly elevated NLR values in both the AD and VaD groups compared to the healthy control group (p = .001, p = .001, respectively). AD and VaD groups demonstrated no significant difference in NLR (p = .787).Additionally, as a result of regression analyses, it was determined that age and NLR were independent variables associated with the presence of dementia.

Conclusions:NLR values are at higher levels in AD and VaD patient groups compared to healthy controls. Our results support the role of peripheral inflammation in the pathogenesis of VaD, as in AD. Additional studies are needed on potential inflammatory biomarkers of VaD.

Anahtar Kelimeler

alzheimer's disease, vascular dementia, NLR, neuroinflammation

Farklı Demans Tiplerinde Periferik İnflamatuar Aktivitenin Değerlendirilmesi

Öz

Amaç: Alzheimer hastalığı (AH), nöroinflamasyon, nörodejenerasyon ve sinaptik işlev bozukluğu gibi karmaşık patofizyolojik süreçlerle karakterize kronik bir nörodejeneratif hastalıktır. Vasküler demans (VaD), tüm demans türleri arasında ikinci en yaygın form olup, vasküler oksidatif stres ve kronik inflamasyon gibi AH ile ortak patofizyolojik mekanizmalara sahiptir. Nötrofil-lenfosit oranı (NLR), inflamasyonun basit, invaziv olmayan ve yaygın olarak kullanılabilen bir klinik belirleyicisi olarak kabul edilmektedir. Bu çalışmanın amacı, NLR değerleri açısından, bu iki farklı demans tipi arasındaki potansiyel farkları araştırmaktır.

Hastalar ve Yöntem: Bir Üniversite Hastanesi Nöroloji polikliniğine başvuran, AH veya VaD tanısı alan hastaların ve sağlıklı kontrollerin verileri retrospektif olarak incelenerek, gruplar NLR düzeyleri açısından istatistiksel yöntemlerle analiz edilmiştir.

Bulgular: Çalışmaya toplamda 39 AH hastası, 32 VaD hastası ve 30 sağlıklı kontrol dahil edildi. Hemogram analizleri, AH ve VaD gruplarında NLR değerlerinin sağlıklı kontrol grubuna kıyasla anlamlı bir şekilde yüksek olduğunu ortaya koydu (sırasıyla p = .001, p = .001). AH ve VaD grupları arasında NLR'de anlamlı bir fark saptanmadı (p = .787). Ayrıca, regresyon analizleri sonucunda, yaş ve NLR'nin demans varlığı ile ilişkili bağımsız değişkenler olduğu belirlendi.

Sonuç: NLR değerleri, AH ve VaD hasta gruplarında sağlıklı kontrollere göre yüksek seviyelerdedir. Sonuçlarımız, VaD patogenezinde de, AH'de olduğu gibi periferik inflamasyonun rolünü desteklemektedir. VaD'nin potansiyel inflamatuar biyobelirteçleri konusunda ek çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

alzheimer hastalığı, vasküler demans, NLR, nöroinflamasyon

Kaynakça

• 1.Mumtaz I, Ayaz MO, Khan MS, Manzoor U, Ganayee MA, Bhat AQ, et al. Clinical relevance of biomarkers, new therapeutic approaches, and role of post-translational modifications in the pathogenesis of Alzheimer's disease. Front Aging Neurosci. 2022;14:977411. doi: 10.3389/fnagi.2022.977411.
• 2. Reitz C, Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol. 2014;88(4):640-51. doi: 10.1016/j.bcp.2013.12.024.
• 3. Chen SH, Bu XL, Jin WS, Shen LL, Wang J, Zhuang ZQ, et al. Altered peripheral profile of blood cells in Alzheimer disease: A hospital-based case-control study. Medicine (Baltimore). 2017;96(21):e6843. doi: 10.1097/MD.0000000000006843.
• 4. Hou JH, Ou YN, Xu W, Zhang PF, Tan L, Yu JT, et al. Association of peripheral immunity with cognition, neuroimaging, and Alzheimer's pathology. Alzheimers Res Ther. 2022;14(1):29. doi: 10.1186/s13195-022-00968-y.
• 5. Huang LT, Zhang CP, Wang YB, Wang JH. Association of Peripheral Blood Cell Profile With Alzheimer's Disease: A Meta-Analysis. Front Aging Neurosci. 2022;14:888946. doi: 10.3389/fnagi.2022.888946.
• 6. Walker KA, Ficek BN, Westbrook R. Understanding the Role of Systemic Inflammation in Alzheimer's Disease. ACS Chem Neurosci. 2019;10(8):3340-2. doi: 10.1021/acschemneuro.9b00333.
• 7. Casoli T, Di Stefano G, Balietti M, Solazzi M, Giorgetti B, Fattoretti P. Peripheral inflammatory biomarkers of Alzheimer's disease: the role of platelets. Biogerontology. 2010;11(5):627-33. doi: 10.1007/s10522-010-9281-8.
• 8. Dong X, Nao J, Shi J, Zheng D. Predictive Value of Routine Peripheral Blood Biomarkers in Alzheimer's Disease. Front Aging Neurosci. 2019;11:332. doi: 10.3389/fnagi.2019.00332.
• 9. Sankowski R, Mader S, Valdes-Ferrer SI. Systemic inflammation and the brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration. Front Cell Neurosci. 2015;9:28. doi: 10.3389/fncel.2015.00028.
• 10. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011;42(9):2672-713. doi: 10.1161/STR.0b013e3182299496.
• 11. Iadecola C, Duering M, Hachinski V, Joutel A, Pendlebury ST, Schneider JA, et al. Vascular Cognitive Impairment and Dementia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019;73(25):3326-44. doi: 10.1016/j.jacc.2019.04.034.
• 12. Engelhardt E, Tocquer C, Andre C, Moreira DM, Okamoto IH, Cavalcanti JLS, et al. Vascular dementia: Diagnostic criteria and supplementary exams. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology. Part I. Dement Neuropsychol. 2011;5(4):251-63. doi: 10.1590/S1980-57642011DN05040003.
• 13. Poh L, Sim WL, Jo DG, Dinh QN, Drummond GR, Sobey CG, et al. The role of inflammasomes in vascular cognitive impairment. Mol Neurodegener. 2022;17(1):4. doi: 10.1186/s13024-021-00506-8.
• 14. Imtiaz F, Shafique K, Mirza SS, Ayoob Z, Vart P, Rao S. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med. 2012;5(1):2. doi: 10.1186/1755-7682-5-2.
• 15. Rembach A, Watt AD, Wilson WJ, Rainey-Smith S, Ellis KA, Rowe CC, et al. An increased neutrophil-lymphocyte ratio in Alzheimer's disease is a function of age and is weakly correlated with neocortical amyloid accumulation. J Neuroimmunol. 2014;273(1-2):65-71. doi: 10.1016/j.jneuroim.2014.05.005.
• 16. Petrone AB, Eisenman RD, Steele KN, Mosmiller LT, Urhie O, Zdilla MJ. Temporal dynamics of peripheral neutrophil and lymphocytes following acute ischemic stroke. Neurol Sci. 2019;40(9):1877-85. doi: 10.1007/s10072-019-03919-y.
• 17. Kuyumcu ME, Yesil Y, Ozturk ZA, Kizilarslanoglu C, Etgul S, Halil M, et al. The evaluation of neutrophil-lymphocyte ratio in Alzheimer's disease. Dement Geriatr Cogn Disord. 2012;34(2):69-74. doi: 10.1159/000341583.
• 18. Kara SP, Altunan B, Unal A. Investigation of the peripheral inflammation (neutrophil-lymphocyte ratio) in two neurodegenerative diseases of the central nervous system. Neurol Sci. 2022;43(3):1799-807. doi: 10.1007/s10072-021-05507-5.
• 19. Kalelioglu T, Yuruyen M, Gultekin G, Yavuzer H, Ozturk Y, Kurt M, et al. Neutrophil and platelet to lymphocyte ratios in people with subjective, mild cognitive impairment and early Alzheimer's disease. Psychogeriatrics. 2017;17(6):506-8. doi: 10.1111/psyg.12260.
• 20. Bulut TY, Şair A. Examination of Neutrophil/Lymphocyte (Nlr), Monocyte/Lymphocyte (Mlr), and Platelet/Lymphocyte (Plr) Ratios between Alzheimer's Disease and Vascular Dementia. Eurasian Journal of Critical Care. 2023;5(3):102-6. doi: 10.55994/ejcc.1394602
• 21. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Jr., Kawas CH, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005.
• 22. Ramos-Cejudo J, Johnson AD, Beiser A, Seshadri S, Salinas J, Berger JS, et al. The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study. Front Aging Neurosci. 2021;13:773984. doi: 10.3389/fnagi.2021.773984.
• 23. Morales I, Guzman-Martinez L, Cerda-Troncoso C, Farias GA, Maccioni RB. Neuroinflammation in the pathogenesis of Alzheimer's disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci. 2014;8:112. doi: 10.3389/fncel.2014.00112.
• 24. Chang R, Yee KL, Sumbria RK. Tumor necrosis factor alpha Inhibition for Alzheimer's Disease. J Cent Nerv Syst Dis. 2017;9:1179573517709278. doi: 10.1177/1179573517709278.
• 25. Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol. 2002;52(2):168-74. doi: 10.1002/ana.10265.
• 26. Mehta NH, Zhou L, Li Y, McIntire LB, Nordvig A, Butler T, et al. Peripheral immune cell imbalance is associated with cortical beta-amyloid deposition and longitudinal cognitive decline. Sci Rep. 2023;13(1):8847. doi: 10.1038/s41598-023-34012-2.
• 27. Zuliani G, Ranzini M, Guerra G, Rossi L, Munari MR, Zurlo A, et al. Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia. J Psychiatr Res. 2007;41(8):686-93. doi: 10.1016/j.jpsychires.2006.02.008.
• 28. Ravaglia G, Forti P, Maioli F, Chiappelli M, Montesi F, Tumini E, et al. Blood inflammatory markers and risk of dementia: The Conselice Study of Brain Aging. Neurobiol Aging. 2007;28(12):1810-20. doi: 10.1016/j.neurobiolaging.2006.08.012.