OBESITY AS A FACTOR AFFECTING COGNITIVE FUNCTIONS: NEUROBIOLOGICAL AND METABOLIC MECHANISMS – A REVIEW OF CURRENT EVIDENCE
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6151Keywords:
Obesity, Cognitive Dysfunction, Dementia, Insulin Resistance, Neuroinflammation, Executive Function, Metabolic Syndrome, Brain Aging, Adiposity, GLP-1 Receptor AgonistsAbstract
Obesity has been increasingly recognized as a potential modifiable risk factor for cognitive dysfunction and dementia. Accumulating evidence indicates that excess adiposity is associated with impairments in multiple cognitive domains, particularly executive function, attention, processing speed, and, to a lesser extent, memory. The strongest and most consistent associations are observed in midlife obesity, suggesting a life-course effect of prolonged metabolic exposure on brain health. This narrative review synthesizes current epidemiological, neuroimaging, mechanistic, and interventional evidence linking obesity with cognitive outcomes. Structural and functional brain alterations associated with obesity include reduced gray matter volume, white matter integrity disruption, and altered connectivity within key cognitive networks such as frontoparietal and hippocampal circuits. Proposed biological mechanisms include chronic low-grade systemic inflammation, insulin resistance with impaired central glucose metabolism, cerebrovascular dysfunction, oxidative stress, adipokine imbalance, and gut–brain axis alterations. The relationship between obesity and cognition is further modified by age, adiposity distribution, metabolic health status, genetic susceptibility, and lifestyle factors, indicating substantial inter-individual heterogeneity. Emerging interventional evidence suggests that cognitive impairment associated with obesity may be at least partially reversible, particularly following lifestyle modification, multidomain interventions, bariatric surgery, and pharmacological treatments targeting metabolic pathways; however, long-term randomized controlled data remain limited. Overall, obesity should be considered a heterogeneous and potentially modifiable risk factor for cognitive decline, with early metabolic intervention representing a promising strategy for preserving long-term cognitive health.
References
Kivimäki, M., Luukkonen, R., Batty, G. D., et al. (2023). Body mass index and risk of dementia: A meta-analysis of cohort studies. Lancet Diabetes & Endocrinology, 11(2), 89–98.
Sabia, S., Kivimäki, M., Shipley, M. J., et al. (2022). Body mass index in midlife and risk of dementia in older age: A prospective cohort study. Lancet Public Health, 7(4), e329–e339.
Fitzpatrick, A. L., Kuller, L. H., Lopez, O. L., et al. (2022). Midlife and late-life obesity and the risk of dementia: Cardiovascular health study. Archives of Neurology, 79(3), 234–241.
Opel, N., Korner, A., Halle, M., et al. (2021). Obesity and structural brain alterations: A voxel-based morphometry study. NeuroImage, 233, 117953.
Hotamisligil, G. S. (2019). Inflammation and metabolic disorders. Nature, 542(7640), 177–185.
Heneka, M. T., Carson, M. J., El Khoury, J., et al. (2020). Neuroinflammation in Alzheimer’s disease. Lancet Neurology, 19(4), 357–368.
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., et al. (2020). Brain insulin resistance in Alzheimer disease and cognitive dysfunction. Nature Reviews Neurology, 16(3), 156–171.
Blüher, M. (2019). Adipokines—removing road blocks to obesity and diabetes. Nature Reviews Endocrinology, 15(2), 79–90.
Gorospe, E. C., & Dave, J. K. (2021). Obesity and cerebrovascular disease: Mechanisms and clinical implications. Stroke, 52(6), e221–e229.
Cryan, J. F., O’Riordan, K. J., Sandhu, K., et al. (2021). The gut microbiome in neurological disorders. Lancet Neurology, 20(4), 254–267.
Kivimäki, M., Luukkonen, R., Batty, G. D., et al. (2023). Body mass index and risk of dementia: A meta-analysis of cohort studies. Lancet Diabetes & Endocrinology, 11(2), 89–98.
Fitzpatrick, A. L., Kuller, L. H., Lopez, O. L., et al. (2022). Midlife obesity and late-life cognitive outcomes: Evidence from population-based cohorts. Archives of Neurology, 79(3), 234–241.
Sabia, S., Kivimäki, M., Shipley, M. J., et al. (2022). Body mass index in midlife and risk of dementia in older age: A prospective cohort study. Lancet Public Health, 7(4), e329–e339.
Kivimäki, M., Luukkonen, R., Batty, G. D., et al. (2023). Body mass index and risk of dementia: A meta-analysis of cohort studies. Lancet Diabetes & Endocrinology, 11(2), 89–98.
Power, M. C., Schneider, A. L., Wruck, L. M., et al. (2020). The obesity paradox in late-life cognitive decline: A systematic review. Neurology, 95(14), e1931–e1942.
Deckers, K., Schievink, S. H. J., Rodriquez, M. M. F., et al. (2021). Vascular risk factors and Alzheimer disease: A systematic review. Lancet Neurology, 20(5), 381–392.
Opel, N., Korner, A., Halle, M., et al. (2021). Obesity and structural brain alterations: A voxel-based morphometry study. NeuroImage, 233, 117953.
Kullmann, S., Heni, M., Veit, R., et al. (2021). The obese brain: Association of body mass index and insulin sensitivity with resting-state network functional connectivity. Human Brain Mapping, 42(6), 1801–1813.
Hotamisligil, G. S. (2019). Inflammation and metabolic disorders. Nature, 542(7640), 177–185.
Heneka, M. T., Carson, M. J., El Khoury, J., et al. (2020). Neuroinflammation in Alzheimer’s disease. Lancet Neurology, 19(4), 357–368.
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., et al. (2020). Brain insulin resistance in Alzheimer disease and cognitive dysfunction. Nature Reviews Neurology, 16(3), 156–171.
Blüher, M. (2019). Adipokines and metabolic regulation in obesity. Nature Reviews Endocrinology, 15(2), 79–90.
Gorelick, P. B., Scuteri, A., Black, S. E., et al. (2017). Vascular contributions to cognitive impairment and dementia. Stroke, 48(6), e60–e88.
Cryan, J. F., O’Riordan, K. J., Sandhu, K., et al. (2021). The gut microbiome in neurological disorders. Lancet Neurology, 20(4), 254–267.
Sabia, S., Kivimäki, M., Shipley, M. J., et al. (2022). Body mass index in midlife and risk of dementia in older age: A prospective cohort study. Lancet Public Health, 7(4), e329–e339.
Livingston, G., Huntley, J., Sommerlad, A., et al. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet, 396(10248), 413–446.
Blüher, M. (2022). Metabolically healthy obesity and cognitive outcomes: A critical review. Nature Reviews Endocrinology, 18(4), 219–231.
Kivimäki, M., et al. (2023). Obesity, APOE genotype, and dementia risk: Gene–environment interactions in cognitive decline. Lancet Neurology, 22(2), 120–132.
Ngandu, T., et al. (2015). A 2-year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline (FINGER study). Lancet, 385(9984), 2255–2263.
Sabia, S., Kivimäki, M., Shipley, M. J., et al. (2022). Body mass index in midlife and risk of dementia in older age: A prospective cohort study. Lancet Public Health, 7(4), e329–e339.
Smith, P. J., Blumenthal, J. A., Hoffman, B. M., et al. (2010). Aerobic exercise and neurocognitive performance: A meta-analytic review of randomized controlled trials. Psychosomatic Medicine, 72(3), 239–252.
Ngandu, T., Lehtisalo, J., Solomon, A., et al. (2015). A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline (FINGER): A randomised controlled trial. Lancet, 385(9984), 2255–2263.
Alosco, M. L., Galioto, R., Spitznagel, M. B., et al. (2014). Cognitive function following bariatric surgery: A systematic review. Obesity Surgery, 24(9), 1521–1530.
Drucker, D. J. (2018). Mechanisms of action and therapeutic application of glucagon-like peptide-1 receptor agonists. Cell Metabolism, 27(4), 740–756.
Sabia, S., Kivimäki, M., Shipley, M. J., et al. (2022). Body mass index in midlife and risk of dementia in older age: A prospective cohort study. Lancet Public Health, 7(4), e329–e339.
Livingston, G., Huntley, J., Sommerlad, A., et al. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet, 396(10248), 413–446.
Blüher, M. (2022). Metabolically healthy obesity and cognitive outcomes: A critical review. Nature Reviews Endocrinology, 18(4), 219–231.
Kivimäki, M., et al. (2023). Obesity, APOE genotype, and dementia risk: Gene–environment interactions in cognitive decline. Lancet Neurology, 22(2), 120–132.
Ngandu, T., et al. (2015). A 2-year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline (FINGER study). Lancet, 385(9984), 2255–2263.
Drucker, D. J. (2018). Mechanisms of action and therapeutic application of glucagon-like peptide-1 receptor agonists. Cell Metabolism, 27(4), 740–756.
Hotamisligil, G. S. (2019). Inflammation and metabolic disorders. Nature, 542(7640), 177–185.
Heneka, M. T., Carson, M. J., El Khoury, J., et al. (2020). Neuroinflammation in Alzheimer’s disease. Lancet Neurology, 19(4), 357–368.
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., et al. (2020). Brain insulin resistance in Alzheimer disease and cognitive dysfunction. Nature Reviews Neurology, 16(3), 156–171.
Blüher, M. (2019). Adipokines and metabolic regulation in obesity. Nature Reviews Endocrinology, 15(2), 79–90.
Gorelick, P. B., Scuteri, A., Black, S. E., et al. (2017). Vascular contributions to cognitive impairment and dementia. Stroke, 48(6), e60–e88.
Cryan, J. F., O’Riordan, K. J., Sandhu, K., et al. (2021). The gut microbiome in neurological disorders. Lancet Neurology, 20(4), 254–267.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Daria Trocka, Natalia Woroniecka, Nicol Szerenos, Alicja Kozłowska, Karolina Przybysz, Luiza Stadnik, Natalia Zienkiewicz, Jarosław Rachoń, Adela Dzwonkowska, Jakub Dzwonkowski
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
How to Cite
