This BMJ State of the Art Review highlights cognitive impairment as a significant side effect of systemic cancer therapies for non-central nervous system (CNS) cancers, with symptoms often referred to as chemobrain or chemofog. Initially linked to chemotherapy, cognitive decline is now recognized as a consequence of hormone therapy, immunotherapy, and targeted therapies as well. With cancer survival rates increasing, addressing treatment-related cognitive impairment has become urgent due to its profound impact on quality of life. The review discusses how the prevalence of cognitive issues varies widely, with some patients experiencing declines in memory, attention, and processing speed that persist up to 10-20 years post-treatment. Inconsistencies in study methodologies highlight the need for more robust research, particularly beyond breast cancer, to provide a clearer epidemiological understanding of these impairments.
The article explores the underlying mechanisms by which these therapies induce cognitive decline. While each treatment type has unique mechanisms, several shared pathways emerge, including blood-brain barrier (BBB) dysfunction, oxidative stress, neuroinflammation, impaired neurogenesis, and disruptions in neurotransmitter function. For example, chemotherapy may induce oxidative stress, damaging the BBB and allowing neurotoxic substances to enter the brain, while hormone therapies disrupt estrogen signaling, affecting neuroprotective pathways critical to cognition. This interplay between mechanisms highlights the complex pathophysiology of treatment-related cognitive impairment, underscoring the need for targeted interventions based on these distinct but intersecting pathways.
Current management strategies are limited, as no treatments are officially approved for cancer therapy-induced cognitive impairment. The review presents emerging pharmacological and non-drug approaches, including antioxidant and anti-inflammatory agents, neurogenesis-promoting drugs, and cognitive training programs. These strategies offer potential, though further research and clinical trials are essential to evaluate their efficacy. The authors advocate for clinical guidelines that standardize the identification and management of cognitive impairment across cancer therapies. Such guidelines would include routine objective neurocognitive testing, quality of life assessments, and support resources for patients to improve overall care.
In conclusion, the review emphasizes the importance of a systematic approach to monitoring cognitive impairment among cancer survivors, using consistent testing and biomarkers to identify early and subtle cognitive changes. As translational research advances, integrating neurocognitive assessment into routine clinical practice could offer valuable support for cancer survivors and improve long-term quality of life. Looking ahead, further studies on prevalence, effective biomarkers, and tailored therapeutic interventions are necessary to address the ongoing needs of this growing population.
