Association of Circulating Inflammatory Biomarkers with Early Cognitive Decline in Patients with Alzheimer’s Disease: A Clinical Observational Study
Inflammation and Early Cognitive Decline in Alzheimer’s Disease
DOI:
https://doi.org/10.69750/dmls.03.02.0191Keywords:
Alzheimer’s disease, cognitive decline, inflammation, IL-6, TNF-α, C-reactive protein, biomarkersAbstract
Background: Alzheimer's disease is a progressive neurodegenerative condition whereby the advancement of cognitive decline has a profound effect on the outcome of the patients. There is growing evidence that systemic inflammation plays a role in the pathogenesis of the disease, and inflammatory biomarkers in the blood may be indicators of early neurodegenerative alterations.
Objective: The study aims to evaluate the relationship between circulating inflammatory biomarkers and early cognitive deterioration in patients with Alzheimer's disease.
Methods: This was a clinical observational study done at General Hospital, Lahore, Pakistan, between June 2024 and January 2025. Sixty patients were recruited with early-stage Alzheimer's disease through a consecutive sampling method. The cognitive capability was measured through the terms of the Mini-Mental State Examination (MMSE). Measures of serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were taken with the help of enzyme-linked immunosorbent assays. The data were compared with SPSS version 26, and Pearson correlation and multiple linear analysis were carried out with SPSS.
Results: The mean age of the respondents was 65.8 years ± 7.2 years, and they comprised females. The high levels of IL-6, TNF-α, and CRP were found in the patients with low MMSE scores. There were significant negative correlations among the MMSE scores and IL-6 (r = −0.52, p < 0.001), TNF-α (r = −0.44, p < 0.001), and CRP (r = −0.39, p = 0.002). The strongest independent predictor of cognitive decline was IL-6.
Conclusion: The findings of the circulation of inflammatory biomarkers, especially IL-6, are strongly correlated with the cases of early cognitive decline in Alzheimer's disease and can be useful in identifying and monitoring the disease.
Downloads
References
Abe K, Chiba Y, Hattori S, Tamazawa A, Yoshimi A, Katsuse O, et al. Influence of plasma cytokine levels on the conversion risk from MCI to dementia in the Alzheimer’s disease neuroimaging initiative database. J Neurol Sci. 2020;414:116829. doi:10.1016/j.jns.2020.116829
Bawa KK, Krance SH, Herrmann N, Cogo-Moreira H, Ouk M, Yu D, et al. A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease. J Neuroinflammation. 2020;17(1):84. doi:10.1186/s12974-020-01750-3
Bourgognon JM, Cavanagh J. The role of cytokines in modulating learning and memory and brain plasticity. Brain Neurosci Adv. 2020;4:2398212820979802. doi:10.1177/2398212820979802
Cisbani G, Koppel A, Knezevic D, Suridjan I, Mizrahi R, Bazinet RP. Peripheral cytokine and fatty acid associations with neuroinflammation in AD and aMCI patients: an exploratory study. Brain Behav Immun. 2020. doi:10.1016/j.bbi.2020.02.014
Contreras JA, Aslanyan V, Sweeney MD, Sanders LMJ, Sagare AP, Zlokovic BV, et al. Functional connectivity among brain regions affected in Alzheimer’s disease is associated with CSF TNF-α in APOE4 carriers. Neurobiol Aging. 2020;86:112-122. doi:10.1016/j.neurobiolaging.2019.10.013
Culjak M, Perkovic MN, Uzun S, Strac DS, Erjavec GN, Leko MB, et al. The association between TNF-alpha, IL-1 alpha and IL-10 with Alzheimer’s disease. Curr Alzheimer Res. 2020;17(11):972-984. doi:10.2174/1567205017666201130092427
Gongora-Rivera F, Gonzalez-Aquines A, Ortiz-Jiménez X, de la Garza CM, Salinas-Carmona M. Chemokine profile in Alzheimer’s disease: results from a Mexican population. J Clin Neurosci. 2020;73:159-161. doi:10.1016/j.jocn.2019.12.051
Hazen J, Vistnes M, Barca ML, Eldholm RS, Persson K, Brækhus A, et al. The association between circulating inflammatory markers and the progression of Alzheimer disease in Norwegian memory clinic patients with mild cognitive impairment or dementia. Alzheimer Dis Assoc Disord. 2020;34(1):47-53. doi:10.1097/WAD.0000000000000342
Scarabino D, Peconi M, Broggio E, Gambina G, Maggi E, Armeli F, et al. Relationship between proinflammatory cytokines (IL-1beta, IL-18) and leukocyte telomere length in mild cognitive impairment and Alzheimer’s disease. Exp Gerontol. 2020;136:110945.
Doroszkiewicz J, Kulczynska-Przybik A, Dulewicz M, Borawska R, Krawiec A, Slowik A, et al. The cerebrospinal fluid interleukin 8 (IL-8) concentration in Alzheimer’s disease (AD). Alzheimers Dement. 2021;17 Suppl 5:e051317. doi:10.1002/alz.051317
Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17(3):157-172. doi:10.1038/s41582-020-00435-y
Liang CS, Tsai CL, Lin GY, Lee JT, Lin YK, Chu CS, et al. Better identification of cognitive decline with Interleukin-2 than with amyloid and tau protein biomarkers in amnestic mild cognitive impairment. Front Aging Neurosci. 2021;13:670115. doi:10.3389/fnagi.2021.670115
Mahdavi M, Karima S, Rajaei S, Aghamolaii V, Ghahremani H, Ataei R, et al. Plasma cytokines profile in subjects with Alzheimer’s disease: interleukin 1 alpha as a candidate for target therapy. Galen Med J. 2021;10:e1974. doi:10.31661/gmj.v10i0.1974
Park JK, Lee KJ, Kim JY, Kim H. The association of blood-based inflammatory factors IL-1β, TGF-β and CRP with cognitive function in Alzheimer’s disease and mild cognitive impairment. Psychiatry Investig. 2021;18(1):11-18. doi:10.30773/pi.2020.0205
Rasi Marzabadi L, Sadigh-Eteghad S, Talebi M. Circulating inflammatory cytokine levels correlates with cognitive impairment. Clin Exp Neuroimmunol. 2021;12(1):66-71. doi:10.1111/cen3.12613
Vacinova G, Vejražkova D, Rusina R, Holmerová I, Vaňková H, Jarolímová E, et al. Regulated upon activation, normal T cell expressed and secreted (RANTES) levels in the peripheral blood of patients with Alzheimer’s disease. Neural Regen Res. 2021;16(4):796-800. doi:10.4103/1673-5374.295340
Weston LL, Jiang S, Chisholm D, Jantzie LL, Bhaskar K. Interleukin-10 deficiency exacerbates inflammation-induced tau pathology. J Neuroinflammation. 2021;18(1):161. doi:10.1186/s12974-021-02211-1
Xu L, Dong Q, Zou W, Li H. The MCP-1 A-2518G polymorphism increases the risk of Alzheimer’s disease: a case-control study. Neurosci Lett. 2021;749:135710. doi:10.1016/j.neulet.2021.135710
Fu P, Peng F; Alzheimer’s Disease Neuroimaging Initiative. CSF TNF α levels were associated with conversion from mild cognitive impairment to dementia. PLoS One. 2022;17(10):e0274503. doi:10.1371/journal.pone.0274503
Kipinoinen T, Toppala S, Rinne JO, Viitanen MH, Jula AM, Ekblad LL. Association of midlife inflammatory markers with cognitive performance at 10-year follow-up. Neurology. 2022;99(20):e2294-e2302. doi:10.1212/WNL.0000000000201116
Koca S, Kiris I, Sahin S, Cinar N, Karsidag S, Hanagasi HA, et al. Decreased levels of cytokines implicate altered immune response in plasma of moderate-stage Alzheimer’s disease patients. Neurosci Lett. 2022;786:136799. doi:10.1016/j.neulet.2022.136799
Luo J, le Cessie S, Blauw GJ, Franceschi C, Noordam R, van Heemst D. Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study. Geroscience. 2022;44(4):2259-2270. doi:10.1007/s11357-022-00602-7
Capogna E, Watne LO, Sørensen Ø, Guichelaar CJ, Idland AV, Halaas NB, et al. Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers in cognitively unimpaired older adults. Brain Behav Immun. 2023;113:56-65. doi:10.1016/j.bbi.2023.06.027
Kumar A, Verma A, Chaurasia RN. Vitamin D and inflammatory cytokines association in mild cognitive impaired subjects. Neurosci Lett. 2023;795:137044. doi:10.1016/j.neulet.2022.137044
Zhao Z, Zhang J, Wu Y, Xie M, Tao S, Lv Q, et al. Plasma IL-6 levels and their association with brain health and dementia risk: a population-based cohort study. Brain Behav Immun. 2024;120:430-438. doi:10.1016/j.bbi.2024.06.014
Downloads
PlumX Metrics
Published
Issue
Section
License
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License , which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third-party material in this article are included in the article’s Creative Commons license unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you must obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
How to Cite
