Neuroinflammation and Cognitive health in Type 2 Diabetes
Main Article Content
Abstract
This review explores the complex relationship between neuroinflammation and cognitive decline in individuals with Type 2 Diabetes (T2D). There is increasing awareness that cognitive impairment, which can range from mild difficulties to severe dementia, is a significant complication associated with T2D. Extensive research indicates that chronic neuroinflammation plays a critical role in this context, linking metabolic dysfunction with neurodegenerative changes in the brain. The discussion begins with the effects of chronic hyperglycemia, insulin resistance, and metabolic disruptions that contribute to systemic inflammation. This inflammation can be intense enough to breach the blood-brain barrier (BBB), leading to neuroinflammation. The activation of essential immune cells in the brain, such as microglia and astrocytes, is accompanied by a rise in pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α. These inflammatory agents disrupt synaptic function, inhibit neurogenesis, and promote neuronal death, particularly in areas critical for memory and executive functions, such as the hippocampus and prefrontal cortex. As the investigation unfolds, valuable insights are drawn from both preclinical and clinical studies. Animal research highlights the adverse effects of metabolic stress and inflammation on neuronal health, while clinical data correlate elevated inflammatory markers with reduced cognitive performance among individuals with T2D. Neuroimaging studies further support these findings by visually demonstrating microglial activation in regions essential for cognitive function.
Keywords:
Neuroinflammation, Type 2 Diabetes, Cognitive Decline, Insulin Resistance, Synaptic Dysfunction, Neurodegeneration
Article Details
How to Cite
CHOUDHARY, Arbind Kumar.
Neuroinflammation and Cognitive health in Type 2 Diabetes.
Medical Research Archives, [S.l.], v. 13, n. 8, aug. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6866>. Date accessed: 06 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i8.6866.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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5. Valenza S, Paciaroni L, Paolini S, et al. Mild cognitive impairment subtypes and type 2 diabetes in elderly subjects. Journal of Clinical Medicine. 2020;9(7):2055.
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8. Lénárt N, Brough D, Dénes Á. Inflammasomes link vascular disease with neuroinflammation and brain disorders. Journal of Cerebral Blood Flow & Metabolism. 2016;36(10):1668-1685.
9. Gupta M, Pandey S, Rumman M, Singh B, Mahdi AA. Molecular mechanisms underlying hyperglycemia associated cognitive decline. IBRO Neuroscience Reports. 2023;14:57-63.
10. Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nature Reviews Neurology. 2021;17(3):157-172.
11. Kacířová M, Zmeškalová A, Kořínková L, Železná B, Kuneš J, Maletínská L. Inflammation: major denominator of obesity, Type 2 diabetes and Alzheimer’s disease-like pathology? Clinical Science. 2020;134(5):547-570.
12. Macedo RG. The Immune System and Inflammation in Type 2 Diabetes. The Diabetes Textbook: Clinical Principles, Patient Management and Public Health Issues. 2019:145-167.
13. Li C, Wang Y, Xing Y, et al. Regulation of microglia phagocytosis and potential involvement of exercise. Frontiers in Cellular Neuroscience. 2022;16:953534.
14. Rauf A, Badoni H, Abu-Izneid T, et al. Neuroinflammatory markers: key indicators in the pathology of neurodegenerative diseases. Molecules. 2022;27(10):3194.
15. Rao JS, Kellom M, Kim H-W, Rapoport SI, Reese EA. Neuroinflammation and synaptic loss. Neurochemical research. 2012;37:903-910.
16. Sun Y, Koyama Y, Shimada S. Inflammation from peripheral organs to the brain: how does systemic inflammation cause neuroinflammation? Frontiers in aging neuroscience. 2022;14:903455.
17. Khalid M, Petroianu G, Adem A. Advanced glycation end products and diabetes mellitus: mechanisms and perspectives. Biomolecules. 2022;12(4):542.
18. Lee J, Kim SW, Kim K-T. Region-specific characteristics of astrocytes and microglia: a possible involvement in aging and diseases. Cells. 2022;11(12):1902.
19. Zhang T, Ma C, Zhang Z, Zhang H, Hu H. NF‐κB signaling in inflammation and cancer. MedComm. 2021;2(4):618-653.
20. Sullivan M, Fernandez-Aranda F, Camacho-Barcia L, et al. Insulin and disorders of behavioural flexibility. Neuroscience & biobehavioral reviews. 2023;150: 105169.
21. Emma E, Amanda J. Dietary lipids from body to brain. Progress in lipid research. 2022;85:101144.
22. de la Monte SM. Malignant brain aging: the formidable link between dysregulated signaling through mechanistic target of rapamycin pathways and alzheimer’s disease (type 3 diabetes). Journal of Alzheimer’s Disease. 2023;95(4):1301-1337.
23. Lin M-m, Liu N, Qin Z-h, Wang Y. Mitochondrial-derived damage-associated molecular patterns amplify neuroinflammation in neurodegenerative diseases. Acta Pharmacologica Sinica. 2022;43(10):2439-2447.
24. Andersson U, Ottestad W, Tracey KJ. Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19? Molecular Medicine. 2020;26:1-13.
25. Angelova PR. Sources and triggers of oxidative damage in neurodegeneration. Free Radical Biology and Medicine. 2021;173:52-63.
26. Feingold KR, Grunfeld C. Diabetes and dyslipidemia. Diabetes And Cardiovascular Disease. Springer; 2023:425-472.
27. Passarelli M, Machado UF. AGEs-induced and endoplasmic reticulum stress/inflammation-mediated regulation of GLUT4 expression and atherogenesis in diabetes mellitus. Cells. 2021;11(1):104.
28. Biasizzo M, Kopitar-Jerala N. Interplay between NLRP3 inflammasome and autophagy. Frontiers in Immunology. 2020;11:591803.
29. Shi X, Sun Q, Hou Y, et al. Recognition and maturation of IL-18 by caspase-4 noncanonical inflammasome. Nature. 2023;624(7991):442-450.
30. Wang H, He Y, Sun Z, et al. Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression. Journal of neuroinflammation. 2022;19(1):132.
31. Anita NZ, Zebarth J, Chan B, et al. Inflammatory markers in type 2 diabetes with vs. without cognitive impairment; a systematic review and meta-analysis. Brain, Behavior, and Immunity. 2022;100:55-69.
32. Dyer AH, McKenna L, Batten I, et al. Peripheral inflammation and cognitive performance in middle-aged adults with and without type 2 diabetes: results from the ENBIND study. Frontiers in Aging Neuroscience. 2020;12:605878.
33. Edison P. Neuroinflammation, microglial activation, and glucose metabolism in neurodegenerative diseases. International Review of Neurobiology. 2020;154:325-344.
34. Xu T, Liu J, Li X-r, et al. The mTOR/NF-κB pathway mediates neuroinflammation and synaptic plasticity in diabetic encephalopathy. Molecular neurobiology. 2021;58:3848-3862.
35. Gaggini M, Ndreu R, Michelucci E, Rocchiccioli S, Vassalle C. Ceramides as mediators of oxidative stress and inflammation in cardiometabolic disease. International Journal of Molecular Sciences. 2022;23(5):2719.
36. Boghdadi AG, Teo L, Bourne JA. The neuroprotective role of reactive astrocytes after central nervous system injury. Journal of Neurotrauma. 2020;37(5):681-691.
37. Schönfeld P, Reiser G. How the brain fights fatty acids’ toxicity. Neurochemistry International. 2021;148:105050.
38. Garbuz D, Zatsepina O, Evgen’ev M. Beta amyloid, tau protein, and neuroinflammation: an attempt to integrate different hypotheses of Alzheimer’s disease pathogenesis. Molecular Biology. 2021;55:670-682.
39. Luo A, Xie Z, Wang Y, et al. Type 2 diabetes mellitus-associated cognitive dysfunction: advances in potential mechanisms and therapies. Neuroscience & Biobehavioral Reviews. 2022;137:104642.
40. Soung AL, Davé VA, Garber C, Tycksen ED, Vollmer LL, Klein RS. IL-1 reprogramming of adult neural stem cells limits neurocognitive recovery after viral encephalitis by maintaining a proinflammatory state. Brain, behavior, and immunity. 2022;99:383-396.
41. Wu A, Zhang J. Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis. Journal of Neuroinflammation. 2023;20(1):283.
42. Brown DT, Vickers JC, Stuart KE, Cechova K, Ward DD. The BDNF Val66Met polymorphism modulates resilience of neurological functioning to brain ageing and dementia: a narrative review. Brain Sciences. 2020;10(4):195.
43. Colucci-D’Amato L, Speranza L, Volpicelli F. Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. International journal of molecular sciences. 2020;21(20):7777.
44. Spinelli M, Fusco S, Grassi C. Brain insulin resistance impairs hippocampal plasticity. Vitamins and Hormones. 2020;114:281-306.
45. Di Domenico F, Lanzillotta C. The disturbance of protein synthesis/degradation homeostasis is a common trait of age-related neurodegenerative disorders. Advances in Protein Chemistry and Structural Biology. 2022;132:49-87.
46. Fan CL, Sokolowski HM, Rosenbaum RS, Levine B. What about “space” is important for episodic memory? Wiley Interdisciplinary Reviews: Cognitive Science. 2023;14(3):e1645.
47. Davidson TL, Stevenson RJ. Vulnerability of the Hippocampus to Insults: Links to Blood–Brain Barrier Dysfunction. International Journal of Molecular Sciences. 2024;25(4):1991.
48. Arvanitakis Z, Tatavarthy M, Bennett DA. The relation of diabetes to memory function. Current neurology and neuroscience reports. 2020;20:1-10.
49. Patwardhan M. Gender-Specific Differences in Cognitive Functions and Alzheimer’s Risk in Type 2 Diabetes Mellitus. Adler University; 2021.
50. Cui Y, Tang TY, Lu CQ, Ju S. Insulin resistance and cognitive impairment: evidence from neuroimaging. Journal of Magnetic Resonance Imaging. 2022;56(6):1621-1649.
51. Jorge HMVM. Decision-Making Under Uncertainty: Linking Brain, Behavior and Family Factors in Patients with Type 1 Diabetes. Universidade de Coimbra (Portugal); 2020.
52. Vinciguerra L, Lanza G, Puglisi V, et al. Update on the neurobiology of vascular cognitive impairment: from lab to clinic. International journal of molecular sciences. 2020;21(8):2977.
53. Motevalli S, Salahshour HM, Bailey RP. The mediating role of cognitive flexibility in the relationship between cognitive emotion regulation strategies and mindfulness in patients with type 2 diabetes. Journal of affective disorders. 2023;339:676-682.
54. Mengozzi A, de Ciuceis C, Dell’oro R, et al. The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation. Journal of Hypertension. 2023;41(10):1521-1543.
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