Author(s):
Sai S. Dhatrak, Sanjana C. Pardeshi, Aditi A. Avhad, Madhura D. Dhonnar, Mukund M. Pache, Avinash B. Darekar
Email(s):
mukundpache@zohomail.in
DOI:
10.52711/2231-5659.2026.00058 
Address:
Sai S. Dhatrak1, Sanjana C. Pardeshi1, Aditi A. Avhad1, Madhura D. Dhonnar1, Mukund M. Pache1, Avinash B. Darekar2
1Department of Pharmacology, K.V.N. Naik S. P. Sanstha's, Institute of Pharmaceutical Education & Research, Nashik, 422002, Maharashtra, India.
2Principal, K. V. N. Naik S. P. Sanstha's, Institute of Pharmaceutical Education & Research, Nashik, 422 002, Maharashtra, India.
*Corresponding Author
Published In:
Volume - 16,
Issue - 4,
Year - 2026
ABSTRACT:
Chemotherapy-Induced Cognitive Impairment (CICI), colloquially termed “chemo brain,” represents a significant yet often under-recognized complication impacting survivors of breast, lymphoma, colorectal, and paediatric cancers. It is characterized by deficits in memory, attention, and executive function, which may arise during chemotherapy, shortly thereafter, or persist over an extended period. CICI has profound implications for quality of life and long-term survivorship, yet it is frequently confounded by overlapping symptoms such as fatigue, depression, and age-related cognitive decline. This review examines the clinical features, diagnostic challenges, and mechanistic underpinnings of CICI. Key pathophysiological processes include neuroinflammation, oxidative stress, mitochondrial dysfunction, blood-brain barrier disruption, direct neurotoxicity, impaired neurogenesis, and alterations in neurotransmitter and hormonal levels. Preclinical rodent and cellular models have yielded significant insights, although they face limitations in translating findings to human pathologies. Therapeutic strategies encompass pharmacological agents, including anti-inflammatory drugs, antioxidants, SSRIs, cognitive enhancers, and hormonal modulators, alongside behavioural interventions such as exercise, cognitive training, and mindfulness practices. Novel approaches, including stem cell therapy, exosome-based delivery systems, probiotics, and gene editing, are currently under investigation. Despite ongoing clinical trials, progress is impeded by the absence of standardized diagnostic criteria and reliable biomarkers. Future directions emphasize omics-driven personalization, the development of neuroprotective chemotherapy, and cross-disciplinary collaboration. Advancing these areas is critical for enhancing cognitive outcomes and quality of life for cancer survivors.
Cite this article:
Sai S. Dhatrak, Sanjana C. Pardeshi, Aditi A. Avhad, Madhura D. Dhonnar, Mukund M. Pache, Avinash B. Darekar. Chemotherapy-Induced Cognitive Impairment: Mechanisms and Potential Neuroprotective Strategies. Asian Journal of Research in Pharmaceutical Sciences. 2026; 16(4):403-2. doi: 10.52711/2231-5659.2026.00058
Cite(Electronic):
Sai S. Dhatrak, Sanjana C. Pardeshi, Aditi A. Avhad, Madhura D. Dhonnar, Mukund M. Pache, Avinash B. Darekar. Chemotherapy-Induced Cognitive Impairment: Mechanisms and Potential Neuroprotective Strategies. Asian Journal of Research in Pharmaceutical Sciences. 2026; 16(4):403-2. doi: 10.52711/2231-5659.2026.00058 Available on: https://ajpsonline.com/AbstractView.aspx?PID=2026-16-4-11
REFERENCES:
1. Kaur S, Mayanglambam P, Bajwan D, et al. Chemotherapy and its Adverse Effects – A Systematic Review. IJNER. 2022; 399–402; doi: 10.52711/2454-2660.2022.00090.
2. Lal R, Dharavath RN, Chopra K. Nrf2 Signaling Pathway: a Potential Therapeutic Target in Combating Oxidative Stress and Neurotoxicity in Chemotherapy-Induced Cognitive Impairment. Molecular Neurobiology. 2023; 61(2): 593–608; doi: 10.1007/s12035-023-03559-6.
3. Srivastava S, Kumar A. Breast Cancer Survivorship among Indian Women: An Overview. AJNER. 2022; 262–266; doi: 10.52711/2349-2996.2022.00056.
4. Whittaker AL, George RP, O’Malley L. Prevalence of cognitive impairment following chemotherapy treatment for breast cancer: a systematic review and meta-analysis. Scientific Reports. 2022; 12(1); doi: 10.1038/s41598-022-05682-1.
5. Sen A, Kumar K, Khan S, et al. Current Therapy in Cancer: Advances, Challenges, and Future Directions. AJNER. 2024; 77–84; doi: 10.52711/2349-2996.2024.00016.
6. Das A, Nampoothiri M, Kinra M, et al. An Overview on Chemotherapy-induced Cognitive Impairment and Potential Role of Antidepressants. Current Neuropharmacology. 2020; 18(9): 838–851; doi: 10.2174/1570159x18666200221113842.
7. Wang C, Wang L, Wang D, et al. C-phycocyanin Mitigates Cognitive Impairment in Doxorubicin-Induced Chemobrain: Impact on Neuroinflammation, Oxidative Stress, and Brain Mitochondrial and Synaptic Alterations. Neurochemical Research. 2020; 46(2):149–158; doi: 10.1007/s11064-020-03164-2.
8. Ma J, Mseeh F, Jones P, et al. Inhibition of dual leucine zipper kinase prevents chemotherapy-induced peripheral neuropathy and cognitive impairments. Pain. 2021; 162(10): 2599–2612; doi: 10.1097/j.pain.0000000000002256.
9. Daroische R, Hemminghyth MS, Chwiszczuk LJ, et al. Cognitive Impairment After COVID-19-A Review on Objective Test Data. Frontiers in Neurology. 2021; 12; doi: 10.3389/fneur.2021.699582.
10. Fleming B, Edison P, Kenny L. Cognitive impairment after cancer treatment: mechanisms, clinical characterization, and management. BMJ. 2023; 380:e071726; doi: 10.1136/bmj-2022-071726.
11. Hsu Y-H, Hsieh C-C, Hsu Y-T, et al. Subjective and objective cognitive functioning among patients with breast cancer: effects of chemotherapy and mood symptoms. Breast Cancer. 2020; 28(1): 236–245; doi: 10.1007/s12282-020-01168-y.
12. Joly F, Beaumont JL, Correia H, et al. French version of the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog) version 3. Supportive Care in Cancer. 2012; 20(12): 3297–3305; doi: 10.1007/s00520-012-1439-2.
13. Genova HM, Das A, Binder A, et al. Examination of Cognitive Fatigue in Multiple Sclerosis using Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging. PLoS ONE. 2013; 8(11): e78811; doi: 10.1371/journal.pone.0078811.
14. Hojjati SH, Babajani-Feremi A. Seeing beyond the symptoms: biomarkers and brain regions linked to cognitive decline in Alzheimer’s disease. Frontiers in Aging Neuroscience. 2024; 16; doi: 10.3389/fnagi.2024.1356656.
15. Cloutier JM, Al‐Rohil RN, Patel RM, et al. Ancillary Tools for the Diagnosis of CIC ‐Rearranged Sarcoma: A Comprehensive Review. J Cutan Pathol. 2025; 52(4): 324–331; doi: 10.1111/cup.14792.
16. Argyriou AA, Karteri S, Bruna J, et al. Serum neurofilament light chain levels as biomarker of paclitaxel-induced cognitive impairment in patients with breast cancer: a prospective study. Support Care Cancer. 2022; 30(2): 1807–1814; doi: 10.1007/s00520-021-06509-x.
17. Matsos A, Johnston IN. Chemotherapy-induced cognitive impairments: A systematic review of the animal literature. Neuroscience & Biobehavioral Reviews. 2019; 102: 382–399; doi: 10.1016/j.neubiorev.2019.05.001.
18. Briones TL, Woods J. Dysregulation in myelination mediated by persistent neuroinflammation: Possible mechanisms in chemotherapy-related cognitive impairment. Brain, Behavior, and Immunity. 2014; 35: 23–32; doi: 10.1016/j.bbi.2013.07.175.
19. Zhou W, Hu J, Su Q, et al. Luteolin Suppresses Microglia Neuroinflammatory Responses and Relieves Inflammation-Induced Cognitive Impairments. Neurotoxicity Research. 2021; 39(6): 1800–1811; doi: 10.1007/s12640-021-00426-x.
20. Wang S, Bu Y, Zhang J, et al. Pt–N Coordination Rendering the Chemotherapeutic Agent with Photoactivated ROS Generation and Self-Reporting Cell Uptake. ACS Appl Bio Mater 2023; 6(4):1650–1657; doi: 10.1021/acsabm.3c00100.
21. Wu T, Gong Y, Li Z, et al. Preparation and In Vitro/Vivo Evaluation of Folate-conjugated Pluronic F87-PLGA/TPGS Mixed Nanoparticles for Targeted Drug Delivery. CDD. 2021; 18(10): 1505–1514; doi: 10.2174/1567201818666210412123210.
22. Sekeres MJ, Bradley-Garcia M, Martinez-Canabal A, et al. Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions. International Journal of Molecular Sciences. 2021; 22(23): 12697; doi: 10.3390/ijms222312697.
23. Cao Y, Chen H, Tan Y, et al. Protection of p-Coumaric acid against chronic stress-induced neurobehavioral deficits in mice via activating the PKA-CREB-BDNF pathway. Physiology & Behavior. 2023; 273:114415; doi: 10.1016/j.physbeh.2023.114415.
24. Du J, Jia H, Zhang A, et al. Doxorubicin-Induced Cognitive Impairment: The Mechanistic Insights. Frontiers in Oncology. 2021; 11(5); doi: 10.3389/fonc.2021.673340.
25. Murillo LC, Sutachan JJ, Albarracín SL. An update on neurobiological mechanisms involved in the development of chemotherapy-induced cognitive impairment (CICI). Toxicology Reports. 2023; 10:544–553; doi: 10.1016/j.toxrep.2023.04.015.
26. Schagen SB, Tsvetkov AS, Compter A, et al. Cognitive adverse effects of chemotherapy and immunotherapy: are interventions within reach? Nat Rev Neurol. 2022; 18(3): 173–185; doi: 10.1038/s41582-021-00617-2.
27. Dietrich J, Parsons MW, Santarnecchi E. Exploring Novel Therapeutic Avenues for Chemotherapy-Related Cognitive Impairment. Cancer Research. 2024; 84(13): 2041–2042; doi: 10.1158/0008-5472.CAN-24-1342.
28. Rajizadeh MA, Aminizadeh AH, Esmaeilpour K, et al. Investigating the effects of Citrullus colocynthis on cognitive performance and anxiety-like behaviors in STZ-induced diabetic rats. International Journal of Neuroscience. 2021; 133(4): 343–355; doi: 10.1080/00207454.2021.1916743.
29. D’Isa R, Leocani L, Comi G. Apparatus design and behavioural testing protocol for the evaluation of spatial working memory in mice through the spontaneous alternation T-maze. Scientific Reports. 2021; 11(1) doi: 10.1038/s41598-021-00402-7.
30. Tu Y, Han D, Liu Y, et al. Nicorandil attenuates cognitive impairment after traumatic brain injury via inhibiting oxidative stress and inflammation: Involvement of BDNF and NGF. Brain and Behavior. 2023; 14(1); doi: 10.1002/brb3.3356.
31. Targett IL, Crompton LA, Conway ME, et al. Differentiation of SH-SY5Y neuroblastoma cells using retinoic acid and BDNF: a model for neuronal and synaptic differentiation in neurodegeneration. In Vitro Cellular & Developmental Biology – Animal. 2024; 60(9): 1058–1067; doi: 10.1007/s11626-024-00948-6.
32. Goshi N, Lein PJ, Seker E, et al. A primary neural cell culture model to study neuron, astrocyte, and microglia interactions in neuroinflammation. Journal of Neuroinflammation. 2020; 17(1); doi: 10.1186/s12974-020-01819-z.
33. Yoo KH, Baur JA, Choi J, et al. Nicotinamide Mononucleotide Prevents Cisplatin-Induced Cognitive Impairments. Cancer Research. 2021; 81(13): 3727–3737; doi: 10.1158/0008-5472.can-20-3290.
34. Jiang Z-G, Ghanbari HA, Fuller S, et al. PAN-811 prevents chemotherapy-induced cognitive impairment and preserves neurogenesis in the hippocampus of adult rats. PLOS ONE. 2018; 13(1): e0191866; doi: 10.1371/journal.pone.0191866.
35. Petrakis IL, Ralevski E, Gueorguieva R, et al. Targeting neuroinflammation with minocycline in heavy drinkers. Psychopharmacology. 2019; 236(10): 3013–3021; doi: 10.1007/s00213-019-05205-3.
36. Pache M, Kedar H, Kond S, et al. Pharmacological Management of Neurodegenerative Disorders: Current and Future Approaches. Int J Sci R Tech. 2025; 2(3): 405–520; doi: 10.5281/ZENODO.15074000.
37. Li X, Feng X, Sun X, et al. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2019. Front Aging Neurosci. 2022; 14: 937486; doi: 10.3389/fnagi.2022.937486.
38. Nasseri S, Hajrasouliha S, Vaseghi S, et al. Interaction effect of crocin and citalopram on memory and locomotor activity in rats: an insight into BDNF and synaptophysin levels in the hippocampus. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2024; 397(9): 6879–6888; doi: 10.1007/s00210-024-03069-9.
39. Jadhav P, Ghuge R, Pache M. Neuropharmacology and Clinical Relevance of Ssris In Anxiety Disorders: From Molecular Targets to Therapeutic Strategies. Int J Sci R Tech. 2025; 2(4): 480–496; doi: 10.5281/ZENODO.15253869.
40. D’Souza MS. Brain and Cognition for Addiction Medicine: From Prevention to Recovery Neural Substrates for Treatment of Psychostimulant-Induced Cognitive Deficits. Frontiers in Psychiatry. 2019; 10(512) doi: 10.3389/fpsyt.2019.00509.
41. Farkas S, Ernszt D, Fazekas CL, et al. Estradiol and Estrogen-like Alternative Therapies in Use: The Importance of the Selective and Non-Classical Actions. Biomedicines. 2022; 10(4): 861; doi: 10.3390/biomedicines10040861.
42. Osborne CK, Fuqua SAW, Zhao H (Holly). Selective estrogen receptor modulators: structure, function, and clinical use. Journal of Clinical Oncology. 2000; 18(17): 3172–3186; doi: 10.1200/jco.2000.18.17.3172.
43. Blankespoor RJ, De Jong BA, Speckens AEM, et al. The Effectiveness of Mindfulness-Based Stress Reduction on Psychological Distress and Cognitive Functioning in Patients with Multiple Sclerosis: a Pilot Study. Mindfulness. 2017; 8(5): 1251–1258; doi: 10.1007/s12671-017-0701-6.
44. Cheng X, Wang J, Gong L, et al. Composition of the Gut Microbiota Associated with the Response to Immunotherapy in Advanced Cancer Patients: A Chinese Real-World Pilot Study. JCM. 2022; 11(18): 5479; doi: 10.3390/jcm11185479.
45. Ben Ezzdine L, Dhahbi W, Dergaa I, et al. Physical activity and neuroplasticity in neurodegenerative disorders: a comprehensive review of exercise interventions, cognitive training, and AI applications. Frontiers in Neuroscience. 2025; 19 doi: 10.3389/fnins.2025.1502417.
46. Russell-Williams J, El Haj M, Perich T, et al. Mindfulness and meditation: treating cognitive impairment and reducing stress in dementia. Reviews in the Neurosciences. 2018; 29(7): 791–804; doi: 10.1515/revneuro-2017-0066.
47. Zhong L, Wang J, Wang P, et al. Neural stem cell-derived exosomes and regeneration: cell-free therapeutic strategies for traumatic brain injury. Stem Cell Research & Therapy. 2023; 14(1); doi: 10.1186/s13287-023-03409-1.
48. Pache MM, Pangavhane RR. Immunotherapy in Autoimmune Diseases: Current Advances and Future Directions. Asian Journal of Pharmaceutical Research. 2025; 15(2): 183–191; doi: 10.52711/2231-5691.2025.00030.
49. Khan SU, Khan MI, Khan MU, et al. Applications of Extracellular Vesicles in Nervous System Disorders: An Overview of Recent Advances. Bioengineering (Basel, Switzerland). 2022; 10(1): 51; doi: 10.3390/bioengineering10010051.
50. Ghule RJ, Jadhav PN, Sanap YN, et al. Tumour-Derived Extracellular Vesicles in Chemotherapy Resistance: Molecular Pathways, Clinical Implications and Therapeutic Opportunities. 2025.
51. Meher AK, Sahu PK, Acharya B. Probiotics: Bridging the interplay of a healthy gut and psychoneurological well‐being. Food Bioengineering. 2024; 3(1): 126–147; doi: 10.1002/fbe2.12081.
52. Pache MM, Pangavhane RR, Nikam SV, et al. CRISPR-Cas9 in Pharmaceutical Research: Applications, Challenges, Ethical Considerations and Future Directions. Asian Journal of Pharmacy and Technology. 2025.
53. Hort J, Hoerr R, Duning T. Ginkgo biloba Extract EGb 761 in the Treatment of Patients with Mild Neurocognitive Impairment: A Systematic Review. Neuropsychiatric Disease and Treatment. 2023; 19: 647–660; doi: 10.2147/ndt.s401231.
54. Deore A, Kothmire S, Khade A, et al. Efficacy of Standardized Ginkgo biloba Extract in Cognitive Enhancement for Alzheimer’s patients. RJPP. 2025; 219–228; doi: 10.52711/0975-4385.2025.00036.
55. Rapp SR, Klepin HD, King D, et al. Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116). Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2024; 42(21):2546–2557; doi: 10.1200/jco.23.01100.
56. Morris JK, Green ZD, Kemna RE, et al. Biomarker Responses to Acute Exercise and Relationship with Brain Blood Flow. Journal of Alzheimer’s Disease : JAD. 2024; 97(1): 283–292; doi: 10.3233/jad-230766.
57. Conklin HM, Martin-Elbahesh K, Zhang H, et al. Long-Term Efficacy of Computerized Cognitive Training Among Survivors of Childhood Cancer: A Single-Blind Randomized Controlled Trial. Journal of Pediatric Psychology. 2016; 42(2): jsw057; doi: 10.1093/jpepsy/jsw057.
58. Pache MM, Pangavhane RR, Jagtap MN. Cognitive Behavioural Therapy: The Treatment of Insomnia and Depression. Int J Pharm Sci Rev Res. 2024; 84(11): 34–40; doi: 10.47583/ijpsrr.2024.v84i11.005.
59. Rummel NG, Butterfield DA, Bondada S, et al. Chemotherapy-induced cognitive impairment: focus on the intersection of oxidative stress and TNFα. Cellular and Molecular Life Sciences. 2021; 78(19–20): 6533–6540; doi: 10.1007/s00018-021-03925-4.
60. Janel N, Arbones M, Sarazin M, et al. Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer\ text backslashu 2019s disease. Translational Psychiatry. 2017; 7(6):e1154; doi: 10.1038/tp.2017.123.
61. Kesler SR, Petersen ML, Rao V, et al. Functional connectome biotypes of chemotherapy-related cognitive impairment. Journal of Cancer Survivorship : Research and Practice. 2020; 14(4):483–493; doi: 10.1007/s11764-020-00863-1.
62. Argyriou AA, Assimakopoulos K, Iconomou G, et al. Either Called “Chemobrain” or “Chemofog” the Long-Term Chemotherapy-Induced Cognitive Decline in Cancer Survivors Is Real. Journal of Pain and Symptom Management. 2011; 41(1): 126–139; doi: 10.1016/j.jpainsymman.2010.04.021.
63. Liu C, Zong C, Chen S, et al. Machine learning-driven QSAR models for predicting the cytotoxicity of five common microplastics. Toxicology. 2024; 508: 153918; doi: 10.1016/j.tox.2024.153918.
64. Alvarez-Frutos L, Kroemer G, Barriuso D, et al. Multiomics insights on the onset, progression, and metastatic evolution of breast cancer. Frontiers in Oncology. 2023; 13(3) doi: 10.3389/fonc.2023.1292046.
65. Pache M, Bachhav G, Bhamare A, et al. Mapping Drug Responses Through Multi-Omics: A New Era of Bioinformatics in Precision Medicine. Int J Sci R Tech. 2025; 2(8): 319–335; doi: 10.5281/ZENODO.16914606.
66. Yu J, Fu Y, Xu W, et al. Insights into the Pathogenesis and Treatment of Chemotherapy-Induced Neuropathy: A Focus on Oxidative Stress and Neuroinflammation. Current Reviews in Clinical and Experimental Pharmacology. 2025; 20(2): 98–102; doi: 10.2174/0127724328314214240829181006.
67. Doornebosch AJ, Achterberg WP, Smaling HJA. Interprofessional collaboration during multidisciplinary team meetings in geriatric rehabilitation: an observational study. BMC Geriatr. 2025; 25(1): 213; doi: 10.1186/s12877-025-05870-4.