{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T12:01:15Z","timestamp":1784635275098,"version":"3.55.0"},"reference-count":224,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Chemotherapy is a treatment designed to contain or eradicate neoplastic cells; however, patients may experience various treatment-related adverse effects. Chemotherapy-related cognitive impairment (CRCI), clinically referred to as \u201cchemobrain,\u201d is a frequent complication with a duration ranging from months to years, affecting between 17% and 70% of cancer patients. These cognitive deficits not only impair social, educational, and occupational functioning but may also impact survival outcomes, possibly by interfering with medication adherence and health-related behaviors. Emerging evidence has converged on an integrative cascade in which chemotherapy-induced systemic inflammation, intestinal dysbiosis, blood\u2013brain barrier disruption, microglial\/astroglial activation, and impaired hippocampal neurogenesis act in sequence rather than as independent pathways. Underlying pathophysiological mechanisms include neuroinflammation, reduced neurogenesis, loss of dendritic spines, oxidative stress, hormonal changes, epigenetic modifications, and mitochondrial dysfunction. In contrast, repair mechanisms involve complex glial responses, particularly those of astrocytes and microglia. Emerging studies suggest a link between changes in the microbiome and cognitive decline, demonstrating the importance of bidirectional communication in the gut\u2013brain axis. Current research seeks to determine appropriate tests to identify chemobrain. Therefore, several biomarkers, such as GFAP, S100\u03b2, and isoprostanes, have been proposed to assess chemobrain, alongside screening tools such as MoCA, MMSE, and CAB-CF, to evaluate cognitive impairment and enable early detection. Pharmacological candidates\u2014including lithium, fluoxetine, methylphenidate, modafinil, metformin, agomelatine, and melatonin\u2014as well as nutritional and lifestyle interventions such as physical exercise, omega-3 fatty acids, curcumin, probiotics, and traditional Chinese medicine formulations\u2014have been investigated, predominantly in animal models. These remain candidate, not validated, therapies; clinical evidence in CRCI populations is limited, heterogeneous, or absent, and well-powered randomized controlled trials are required before any recommendation can be issued. However, optimal strategies for symptom improvement remain unclear, as various approaches have yielded mixed outcomes. This review provides a comprehensive overview of chemobrain, focusing on its molecular mechanisms, interactions with the gut\u2013brain axis, and potential therapeutic targets to improve the quality of life for cancer survivors.<\/jats:p>","DOI":"10.3390\/brainsci16070765","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:35:52Z","timestamp":1784630152000},"page":"765","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cognitive Impairment Associated with Chemotherapy: Neuroimmunological Interactions, Gut\u2013Brain Axis, and Therapeutic Approaches"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7143-4930","authenticated-orcid":false,"given":"Beatriz Alejandra","family":"Llanes-Cervantes","sequence":"first","affiliation":[{"name":"Licenciatura en Nutrici\u00f3n, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-612X","authenticated-orcid":false,"given":"Jos\u00e9 Alfonso","family":"Cruz-Ramos","sequence":"additional","affiliation":[{"name":"Coordinaci\u00f3n de Investigaci\u00f3n, Instituto Jalisciense de Cancerolog\u00eda, Zapopan 45060, Mexico"},{"name":"Departamento de Cl\u00ednicas M\u00e9dicas, Instituto de Patolog\u00eda Infecciosa y Experimental, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5081-6251","authenticated-orcid":false,"given":"Mar\u00eda Esthela","family":"Bar\u00f3n-C\u00e1rdenas","sequence":"additional","affiliation":[{"name":"Campus Zapopan, Universidad del Valle de M\u00e9xico (UVM), Zapopan 45010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Montserrat","family":"Zepeda-Olmos","sequence":"additional","affiliation":[{"name":"Coordinaci\u00f3n de Investigaci\u00f3n, Instituto Jalisciense de Cancerolog\u00eda, Zapopan 45060, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8397-1720","authenticated-orcid":false,"given":"Sandra","family":"L\u00f3pez-Verd\u00edn","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Odontolog\u00eda, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8876-9511","authenticated-orcid":false,"given":"Jennifer Mariana","family":"Vargas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Doctorado en Microbiolog\u00eda M\u00e9dica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"de la Mora-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n de Desarrollo Institucional, Instituto Jalisciense de Cancerolog\u00eda, Zapopan 45060, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3892\/ijo.2018.4661","article-title":"From Chemotherapy to Biological Therapy: A Review of Novel Concepts to Reduce the Side Effects of Systemic Cancer Treatment (Review)","volume":"54","author":"Schirrmacher","year":"2018","journal-title":"Int. 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