Chemobrain or Chemo Brain (CRCI): Neuropsychological Foundations and Intervention for Cancer-Related Cognitive Impairment

Valeria Medina, a neuropsychologist at NeuronUP, explains what chemobrain is, which cognitive areas it affects, and how cognitive rehabilitation interventions improve cognition and quality of life.

What is chemobrain and how prevalent is it?

The increase in cancer survival over the past several decades has transformed modern oncology. Advances in early diagnosis, targeted therapies, and treatments have enabled millions of people to overcome the disease. However, alongside these achievements, an unexpected consequence has emerged: persistent cognitive difficulties after treatment. This group of symptoms is colloquially known as chemobrain, and refers to problems with concentration, memory, information processing, or verbal fluency that many patients experience after chemotherapy or other cancer treatments (Mayo Clinic Staff, 2025).

Today, this phenomenon is included within the broader concept of cancer-related cognitive impairment (CRCI) and is a central focus of clinical neuropsychology and psycho-oncology. Far from being an anecdotal phenomenon, it is estimated that between 20% and 75% of people treated with cancer therapies experience some degree of cognitive impairment, even several years after completing treatment (Godaert & Dramé, 2025; Vitali et al., 2017). This impairment affects quality of life, independence, and, in many cases, personal identity by limiting the ability to work, study, or perform activities previously considered routine.

Effects of chemotherapy on the brain: Chemobrain

Causes and mechanisms involved in chemobrain

The origin of chemobrain cannot be attributed to a single factor. Research points to a complex interaction among biological, tumor-related, and emotional mechanisms, although the main factors are chemotherapy, radiation therapy, and/or hormone therapy, which can induce neuroinflammation, alter neurogenesis, and modify synaptic plasticity, affecting key regions such as the hippocampus and prefrontal cortex (Onzi et al., 2022; Li & Caeyenberghs, 2018). 

Likewise, drugs such as anthracyclines, taxanes, and cyclophosphamides, which are widely used in breast cancer, have also been associated with oxidative stress, mitochondrial damage, and changes in white matter connectivity (Onzi et al., 2022). At the same time, the systemic inflammatory response increases proinflammatory cytokines (IL-6, TNF-α, IL-1β), which can cross the blood-brain barrier and affect neuronal communication.

Tumor-related factors may also play a role. Some tumors cause metabolic or endocrine changes capable of modifying brain function even before treatment begins (Kuśmierek et al., 2020).

Moreover, emotional variables such as anxiety, depression, fatigue, or sleep problems significantly modulate cognitive performance. Hermelink (2015) notes that the subjective perception of mental slowness increases during periods of high emotional burden, demonstrating the interdependence between emotion and cognition.

What is important to understand is that these mechanisms converge in the functional disruption of brain networks involved in attention, memory, and executive functions, manifesting very heterogeneously among patients.

Manifestations and cognitive areas affected by chemobrain

As mentioned at the beginning, chemobrain is characterized by a set of difficulties affecting different cognitive domains. The most frequent difficulties are observed in attention, processing speed, episodic memory, and executive functions (Vitali et al., 2017; Kuśmierek et al., 2020). 

Attention is usually the primarily affected function: many patients describe difficulties concentrating, following conversations, or completing activities. After returning to work, the most common complaints are related to sustained attention and performing tasks simultaneously (Klaver et al., 2020). 

On the other hand, working memory and episodic memory are also affected, as are inhibition and cognitive flexibility (Kuśmierek et al., 2020); neuroimaging studies show decreased functional connectivity and patterns of compensatory hyperactivation, resulting in greater cognitive effort and mental fatigue, affecting executive performance (Li & Caeyenberghs, 2018). In breast cancer, these changes may persist for years, especially under conditions of stress or fatigue (Onzi et al., 2022). 

Intervention strategies and cognitive rehabilitation for chemobrain

Addressing chemobrain requires combined interventions: cognitive rehabilitation, cognitive behavioral therapy, attention training, physical exercise, and mindfulness (Chao et al., 2021; Alwi et al., 2021).

Cognitive rehabilitation for chemobrain

Cognitive rehabilitation for chemobrain has not only shown efficacy in improving processes such as working memory, sustained attention, and processing speed, but also contributes to strengthening executive functions, including planning, cognitive flexibility, and decision-making, which are often affected. Strengthening the neural networks involved in these functions facilitates the resumption of work, academic, and household activities, which is essential for restoring a sense of personal independence (Kuśmierek et al., 2020; Jean-Pierre, Johnson-Greene, & Burish, 2014). 

In addition to the cognitive aspect, rehabilitation has a significant effect on the subjective perception of mental clarity; many patients report less of a “foggy” feeling, greater confidence when performing cognitive tasks, and an increasing sense of control over their daily functioning. This impact is accompanied by meaningful emotional benefits, as programs often incorporate psychoeducation, compensatory strategies, and self-regulation training, which help reduce anxiety, frustration, and sadness resulting from the experience of cognitive loss. 

Likewise, systematic work on cognitive skills supports brain plasticity and may increase cognitive reserve, helping compensate for potential future vulnerabilities, especially in patients who continue to undergo treatment or prolonged medical monitoring. 

From a global perspective, cognitive rehabilitation promotes more active patient participation in their own care, strengthens coping, and becomes a key component of the multimodal approach to cancer-related cognitive impairment by affecting both quality of life and psychological well-being during and after the cancer journey.

Physical exercise and mindfulness for chemobrain

On the other hand, research has shown that the above, together with regular physical exercise and mindfulness-based interventions, helps improve brain plasticity, emotional well-being, and self-perceived ability, with positive effects on cognitive recovery (Vitali et al., 2017; Chao et al., 2021).

The digitalization of rehabilitation, for example through NeuronUP, makes it possible to expand therapeutic reach, facilitate adherence, and monitor progress in real time.

Conclusion

For chemobrain, cognitive rehabilitation aims to strengthen affected cognitive functions while also supporting the patient in their everyday recovery.

We know that starting intervention as early as possible supports better outcomes and reduces the risk that cancer-related cognitive impairment will become persistent. Therefore, rather than viewing it as optional or something to address later, it is worth including cognitive rehabilitation from the early stages of treatment. This helps preserve independence, mental clarity, self-confidence, and active participation in daily life.

Ultimately, caring for cognitive functioning is not an add-on but an essential part of the cancer journey. Integrating it from the start is a way to ensure that recovery is measured not only in medical terms but also in real quality of life.

References

• Alwi, S., Maisarah, S., Narayanan, V., Che Din, N., & Mohd Taib, N. A. (2021). Cognitive rehabilitation programs for survivors of breast cancer treated with chemotherapy: A systematic review. Rehabilitation Oncology, 39(4), 155–167. https://doi.org/10.1097/01.REO.0000000000000268
• Chao, D., Hale, A., Henry, N. L., Kratz, A. L., & Gabel, N. M. (2021). Cancer-related cognitive impairment or “chemobrain:” Emerging assessments, treatments, and targets for intervention. Current Physical Medicine and Rehabilitation Reports, 9, 108–118. https://doi.org/10.1007/s40141-021-00319-2
• Godaert, L., & Dramé, M. (2025). The chemobrain in breast cancer patients: A systematic review and meta-analysis. Scientific Reports, 15, 35765. https://doi.org/10.1038/s41598-025-95380-5
• Hermelink, K. (2015). Chemotherapy and cognitive function in breast cancer patients: The so-called chemo brain. JNCI Monographs, 2015(51), 67–69. https://doi.org/10.1093/jncimonographs/lgv009
• Klaver, K. M., Duijts, S. F. A., Engelhardt, E. G., Geusgens, C. A. V., Aarts, M. J. B., Ponds, R. W. H. M., van der Beek, A. J., & Schagen, S. B. (2020). Cancer-related cognitive problems at work: Experiences of survivors and professionals. Journal of Cancer Survivorship, 14(2), 168–178. https://doi.org/10.1007/s11764-019-00830-5
• Jean-Pierre, P., Johnson-Greene, D., & Burish, T. G. (2014). Neuropsychological care and rehabilitation of cancer patients with chemobrain: Strategies for evaluation and intervention development. Supportive Care in Cancer, 22(8), 2251–2260. https://doi.org/10.1007/s00520-014-2162-y
• Kuśmierek, M., Jasionowska, J., Maruszewska, P., Kalinka-Warzocha, E., Gałecki, P., Mikołajczyk, I., & Talarowska, M. (2020). The impact of cancer treatment on cognitive efficiency: Chemobrain – does it exist? European Journal of Psychiatry, 34(1), 20–26. https://doi.org/10.1016/j.ejpsy.2019.10.002
• Li, M., & Caeyenberghs, K. (2018). Longitudinal assessment of chemotherapy-induced changes in brain and cognitive functioning: A systematic review. Neuroscience & Biobehavioral Reviews, 92, 304–317. https://doi.org/10.1016/j.neubiorev.2018.05.019
• Mayo Clinic Staff. (2025, March 6). Chemo brain – Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/chemo-brain/symptoms-causes/syc-20351060
• Onzi, G. R., D’Agustini, N., Garcia, S. C., Guterres, S. S., Pohlmann, P. R., Rosa, D. D., & Pohlmann, A. R. (2022). Chemobrain in breast cancer: Mechanisms, clinical manifestations, and potential interventions. Drug Safety, 45(6), 601–621. https://doi.org/10.1007/s40264-022-01182-3
• Vitali, M., Ripamonti, C. I., Roila, F., Proto, C., Signorelli, D., Imbimbo, M., Corrao, G., Brissa, A., Rosaria G., de Braud, F., Garassino, M. C., & Lo Russo, G. (2017). Cognitive impairment and chemotherapy: A brief overview. Critical Reviews in Oncology/Hematology, 118, 7–14. https://doi.org/10.1016/j.critrevonc.2017.08.001

If you enjoyed this article about chemobrain or chemo brain (CRCI): neuropsychological foundations and intervention for cancer-related cognitive impairment, you may also be interested in these NeuronUP articles: