The interaction between serum cortisol levels and the degree of hippocampal atrophy in elderly patients: An integrative review
DOI:
https://doi.org/10.33448/rsd-v14i10.49691Keywords:
Elderly, Hydrocortisone, Hippocampus.Abstract
The consequences of increased life expectancy imply an increased incidence of chronic and neurodegenerative diseases, particularly Alzheimer's disease, a major public health challenge. Among the associated pathophysiological mechanisms, dysfunction of the hypothalamic-pituitary-adrenal axis and prolonged exposure to high cortisol levels can promote neurotoxic effects in the hippocampus, a brain region crucial for memory and rich in glucocorticoid receptors. This study aimed to investigate, through an integrative review, the relationship between serum cortisol levels and hippocampal atrophy in the elderly, bringing together pathophysiological foundations and empirical evidence, as well as identifying research gaps. The literature search was conducted in PubMed, PsycINFO, SciELO, LILACS, and the Virtual Health Library databases, using specific descriptors and previously defined inclusion and exclusion criteria. The selection process followed stages of screening, reading, and critical analysis, with standardized data extraction. A total of 274 studies were identified, of which 82 were excluded due to duplication and 170 for not meeting the methodological and thematic criteria, leaving only one eligible study. The results reveal a significant scarcity of up-to-date, high-quality research on the topic, despite its global relevance. The integrated analysis indicates that interventions that reduce chronic exposure to cortisol or enhance hippocampal function, such as environmental or physical stimuli, may have a protective effect on brain aging. We conclude that robust longitudinal and experimental investigations are needed to deepen the understanding of this relationship and support preventive strategies for cognitive decline in older adults.
References
Blackmore, D. G., Schaumberg, M. A., Ziaei, M., Belford, S., To, X. V., O’Keeffe, I., Bernard, A., Mitchell, J., Hume, E., Rose, G. L., Shaw, T., York, A., Barth, M., Cooper, E. J., Skinner, T. L., Nasrallah, F., Riek, S., & Bartlett, P. F. (2024). Long-term improvement in hippocampal-dependent learning ability in healthy, aged individuals following high intensity interval training. Aging and Disease. Advance online publication. https://doi.org/10.14336/AD.2024.0203
Brookmeyer, R., Abdalla, N., Kawas, C. H., & Corrada, M. M. (2011). Projections of future dementia prevalence and the value of delaying disease onset. Alzheimer’s & Dementia, 7(1), 1–10. https://doi.org/10.1016/j.jalz.2010.11.002
Chumbley, J. R., Frisston, K. J., et al. (2015). Hippocampal and cerebellar atrophy in patients with Cushing’s disease. Neurosurgical Focus, 39(5), E5. https://pubmed.ncbi.nlm.nih.gov/26646929/
Cotman, C. W., Berchtold, N. C., & Christie, L.-A. (2007). Exercise builds brain health: Key roles of growth factor cascades and inflammation. Trends in Neurosciences, 30(9), 464–472. https://doi.org/10.1016/j.tins.2007.06.011
Da Paz, E. G., Silva, R. S., Souza, M. M. L., Oliveira, L. S. F., & Santos, J. S. S. (2021). Doenças neurodegenerativas em adultos e idosos: um estudo epidemiológico descritivo. Ver Neurocienc, 29, 1–11. https://revistas.faculdadefacit.edu.br/index.php/JNT/article/view/3456/0
Dronse, J., Ohndorf, A., Richter, N., Bischof, G. N., Fassbender, R., Behfar, Q., Gramespacher, H., Dillen, K., Jacobs, H. I. L., Kukolja, J., Fink, G. R., & Onur, O. A. (2023). Serum cortisol is negaively related to hipocampal volume, brain structure, and memory performance in healthy aging and Alzheimer’s disease. Frontiers in Aging Neuroscience, 15, 1154112. https://doi.org/10.3389/fnagi.2023.1154112
Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., & Gage, F. H. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine, 4(11), 1313–1317. https://doi.org/10.1038/3305
Joëls, M., & Baram, T. Z. (2009). The neuro-symphony of stress. Nature Reviews Neuroscience, 10(6), 459–466. https://doi.org/10.1038/nrn2632
Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S. A., & Hudspeth, A. J. (2014). Principles of neural science (5th ed.). McGraw-Hill.
Lenze, E. J., Mantella, R. C., Shi, P., Goate, A. M., Nowotny, P., Butters, M. A., Andreescu, C., Thompson, P. A., & Rollman, B. L. (2011). Elevated cortisol in older adults with generalized anxiety disorder is reduced by treatment: a placebo-controlled evaluation of escitalopram. American Journal of Geriatric Psychiatry, 19(5), 482–490. https://doi.org/10.1097/JGP.0b013e3181ec806c
Lucassen, P. J., Fitzsimons, C. P., Salta, E., & Maletic-Savatic, M. (2020). Adult neurogenesis, human after all (again): Classic, optimized, and future approaches. Behavioural Brain Research, 381, 112458. https://doi.org/10.1016/j.bbr.2019.112458
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience, 10(6), 434–445. https://doi.org/10.1038/nrn2639
McEwen, B. S. (2017). Neurobiological and systemic effects of chronic stress. Chronic Stress, 1, 1–11. https://doi.org/10.1177/2470547017692328
McEwen, B. S., & Morrison, J. H. (2013). The brain on stress: Vulnerability and plasticity of the prefrontal cortex over the life course. Neuron, 79(1), 16–29. https://doi.org/10.1016/j.neuron.2013.06.028
Ministério da Saúde. (2024). Relatório nacional sobre a demência estima que cerca de 8,5% da população idosa convive com a doença. Brasília, DF: Ministério da Saúde. Recuperado em setembro de 2024, de https://www.gov.br/saude/pt-br/assuntos/noticias/2024/setembro/relatorio-nacional-sobre-a-demencia-estima-que-cerca-de-8-5-da-populacao-idosa-convive-com-a-doenca
Pereira, A. S. et al. (2018). Metodologia da pesquisa científica. [free ebook]. Santa Maria. Editora da UFSM.
Roever, L., Gomes-Neto, M., Durães, A. R., Reis, P. E. O., Pollo-Flores, P., Silva, R. M. L., & Resende, E. S. (2021). Compreendendo o GRADE: PICO e qualidade dos estudos. Revista da Sociedade Brasileira de Clínica Médica, 19(1), 54–61.
Sapolsky, R. M. (2015). Stress and the brain: Individual variability and the inverted-U. Nature Neuroscience, 18(10), 1344–1346. https://doi.org/10.1038/nn.4109
Schneider, L. R., Pereira, R. P. G., & Ferraz, L. (2020). Prática baseada em evidências e a análise sociocultural na atenção primária. Physis: Revista de Saúde Coletiva, 30(2), e300232. https://www.scielo.br/j/physis/a/kq66hywGnfmM4JtrftJM4ys/
Sirevåg, K., Stavestrand, S. H., Specht, K., Nordhus, I. H., Mohlman, J., Molde, H., Hammar, Å., Halmøy, A., Endal, T. B., Andersson, E., Sjøbø, T., Nordahl, H. M., Thayer, J. F., & Hovland, A. (2025). Diagnostic status moderates the association between verbal memory and left hippocampal volume in older adults with generalised anxiety disorder and healthy controls. Journal of Affective Disorders, 388, 119621. https://doi.org/10.1016/j.jad.2025.119621
Small, S. A., Schobel, S. A., Buxton, R. B., Witter, M. P., & Barnes, C. A. (2011). A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nature Reviews Neuroscience, 12(10), 585–601. https://doi.org/10.1038/nrn3085
Snyder, H. (2019). Literature review as a research methodology: An overview and guidelines. Journal of Business Research, 104, 333-339. https://doi.org/10.1016/j.jbusres.2019.07.039.
White, S., Mauer, R., Lange, C., Klimecki, O., Huijbers, W., Wirth, M., & Alzheimer’s Disease Neuroimaging Initiative. (2023). The effect of plasma cortisol on hippocampal atrophy and clinical progression in mild cognitive impairment. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 15(3), e12463.https://doi.org/10.1002/dad2.12463
World Health Organization. (2025). Dementia: key facts. In Dementia - epidemiology. World Health Organization.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Luiza Helena Santos da Mota e Camanducaia, Carolina Matsuoka Herrera, Andressa Silva Sousa

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
