The Role of Inflammation, Oxidative Stress, Neuronal Damage, and Endothelial Dysfunction in the Neuropathology of Cognitive Complications in Diabetes: A Moderation and Mediation Analysis
ABSTRACT Objective Cognitive impairment is increasingly recognized as a complication of diabetes, yet the underlying pathology remains unclear. This study aims to investigate the roles of inflammation, oxidative stress, endothelial dysfunction, and neuronal damage in the neuropathology underlying di...
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2025-01-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70225 |
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| author | Betul Sumbul‐Sekerci Ozge Pasin Ezgi Balkan Abdusselam Sekerci |
| author_facet | Betul Sumbul‐Sekerci Ozge Pasin Ezgi Balkan Abdusselam Sekerci |
| author_sort | Betul Sumbul‐Sekerci |
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| description | ABSTRACT Objective Cognitive impairment is increasingly recognized as a complication of diabetes, yet the underlying pathology remains unclear. This study aims to investigate the roles of inflammation, oxidative stress, endothelial dysfunction, and neuronal damage in the neuropathology underlying diabetes related cognitive impairment. Methods This study assessed 183 participants (54 prediabetes, 71 Type 2 diabetes mellitus [T2DM], and 58 controls) for cognitive performance using the Montreal Cognitive Assessment (MoCA). Blood samples were analyzed for interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), malondialdehyde (MDA), VCAM‐1/CD106, and neuron‐specific enolase (NSE) using ELISA. Mediation and moderator analysis methods were used to examine the roles of these biomarkers in diabetes‐related cognitive impairment. Results After adjusting for age, education, and gender, group comparisons revealed significant cognitive impairment in patients with T2DM, particularly in visuospatial functions, naming, language, and memory performance, compared to the control group. The patients with T2DM and prediabetes exhibited similar performance in cognitive functions, except for language. Significant differences in VCAM‐1 and TNF‐α levels were observed; however, these biomarkers did not mediate the effect of T2DM and prediabetes on cognitive functions. Nevertheless, VCAM‐1 was found to moderate abstraction abilities in T2DM. Conclusion Prediabetes represents a transitional stage not only for the pathology of diabetes but also for cognitive complications. Although there were correlations between cognitive performance and various cognitive scores, IL‐6, MDA, NSE, VCAM‐1, and TNF‐α did not play a mediator role in the neuropathology of diabetes‐related cognitive impairment. |
| format | Article |
| id | doaj-art-d3344daac371464cbfcdaaa4c1eeb742 |
| institution | Kabale University |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Brain and Behavior |
| spelling | doaj-art-d3344daac371464cbfcdaaa4c1eeb7422025-01-29T13:36:40ZengWileyBrain and Behavior2162-32792025-01-01151n/an/a10.1002/brb3.70225The Role of Inflammation, Oxidative Stress, Neuronal Damage, and Endothelial Dysfunction in the Neuropathology of Cognitive Complications in Diabetes: A Moderation and Mediation AnalysisBetul Sumbul‐Sekerci0Ozge Pasin1Ezgi Balkan2Abdusselam Sekerci3Department of Clinical Pharmacy, Faculty of Pharmacy Bezmialem Vakıf University Istanbul TurkeyDepartment of Biostatistics Faculty of Medicine Bezmialem Vakıf University Istanbul TurkeyDepartment of Medical Biochemistry Bezmialem Vakif University Istanbul TurkeyDepartment of Internal Medicine, Faculty of Medicine Bezmialem Vakif University Istanbul TurkeyABSTRACT Objective Cognitive impairment is increasingly recognized as a complication of diabetes, yet the underlying pathology remains unclear. This study aims to investigate the roles of inflammation, oxidative stress, endothelial dysfunction, and neuronal damage in the neuropathology underlying diabetes related cognitive impairment. Methods This study assessed 183 participants (54 prediabetes, 71 Type 2 diabetes mellitus [T2DM], and 58 controls) for cognitive performance using the Montreal Cognitive Assessment (MoCA). Blood samples were analyzed for interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), malondialdehyde (MDA), VCAM‐1/CD106, and neuron‐specific enolase (NSE) using ELISA. Mediation and moderator analysis methods were used to examine the roles of these biomarkers in diabetes‐related cognitive impairment. Results After adjusting for age, education, and gender, group comparisons revealed significant cognitive impairment in patients with T2DM, particularly in visuospatial functions, naming, language, and memory performance, compared to the control group. The patients with T2DM and prediabetes exhibited similar performance in cognitive functions, except for language. Significant differences in VCAM‐1 and TNF‐α levels were observed; however, these biomarkers did not mediate the effect of T2DM and prediabetes on cognitive functions. Nevertheless, VCAM‐1 was found to moderate abstraction abilities in T2DM. Conclusion Prediabetes represents a transitional stage not only for the pathology of diabetes but also for cognitive complications. Although there were correlations between cognitive performance and various cognitive scores, IL‐6, MDA, NSE, VCAM‐1, and TNF‐α did not play a mediator role in the neuropathology of diabetes‐related cognitive impairment.https://doi.org/10.1002/brb3.70225cognitive impairmentdiabetesendothelial dysfunctioninflammationneuronal damageoxidative stress |
| spellingShingle | Betul Sumbul‐Sekerci Ozge Pasin Ezgi Balkan Abdusselam Sekerci The Role of Inflammation, Oxidative Stress, Neuronal Damage, and Endothelial Dysfunction in the Neuropathology of Cognitive Complications in Diabetes: A Moderation and Mediation Analysis Brain and Behavior cognitive impairment diabetes endothelial dysfunction inflammation neuronal damage oxidative stress |
| title | The Role of Inflammation, Oxidative Stress, Neuronal Damage, and Endothelial Dysfunction in the Neuropathology of Cognitive Complications in Diabetes: A Moderation and Mediation Analysis |
| title_full | The Role of Inflammation, Oxidative Stress, Neuronal Damage, and Endothelial Dysfunction in the Neuropathology of Cognitive Complications in Diabetes: A Moderation and Mediation Analysis |
| title_fullStr | The Role of Inflammation, Oxidative Stress, Neuronal Damage, and Endothelial Dysfunction in the Neuropathology of Cognitive Complications in Diabetes: A Moderation and Mediation Analysis |
| title_full_unstemmed | The Role of Inflammation, Oxidative Stress, Neuronal Damage, and Endothelial Dysfunction in the Neuropathology of Cognitive Complications in Diabetes: A Moderation and Mediation Analysis |
| title_short | The Role of Inflammation, Oxidative Stress, Neuronal Damage, and Endothelial Dysfunction in the Neuropathology of Cognitive Complications in Diabetes: A Moderation and Mediation Analysis |
| title_sort | role of inflammation oxidative stress neuronal damage and endothelial dysfunction in the neuropathology of cognitive complications in diabetes a moderation and mediation analysis |
| topic | cognitive impairment diabetes endothelial dysfunction inflammation neuronal damage oxidative stress |
| url | https://doi.org/10.1002/brb3.70225 |
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