Abstract
One in three people will be diagnosed with cancer during their lifetime. The community of cancer patients is growing, and several common cancers are becoming increasingly chronic; thus, cancer survivorship is an important part of health care. A large body of research indicates that cancer and cancer therapies are associated with cognitive impairment. This research has mainly concentrated on chemotherapy-associated cognitive impairment but, with the arrival of immunotherapies, the focus is expected to widen and the number of studies investigating the potential cognitive effects of these new therapies is rising. Meanwhile, patients with cognitive impairment and their healthcare providers are eagerly awaiting effective approaches to intervene against the cognitive effects of cancer treatment. In this Review, we take stock of the progress that has been made and discuss the steps that need to be taken to accelerate research into the biology underlying cognitive decline following chemotherapy and immunotherapy and to develop restorative and preventive interventions. We also provide recommendations to clinicians on how to best help patients who are currently experiencing cognitive impairment.
Key points
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A growing number of individuals are being confronted with cognitive impairment resulting from non-CNS cancer and its treatment; this impairment has a large effect on occupational, familial and social lives, resulting in diminished quality of life.
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Chemotherapy-induced cognitive impairment is multifactorial: different molecular mechanisms result in blood–brain barrier disruption, inflammation, accelerated cellular senescence and neuronal stem cell abnormalities, all of which lead to cognitive impairment.
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Limited evidence from preclinical and clinical studies suggests that neuroinflammation and activated microglia have an essential role in immunotherapy-related cognitive impairment; future studies of immunotherapy should incorporate cognition endpoints to investigate immunotherapy-related cognitive decline.
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Pharmacological or behaviour-directed interventions with proven effectiveness for prevention or restoration of cognitive problems in patients with non-CNS cancers are lacking; however, preclinical studies on pharmacological mechanism-directed interventions hold some promise.
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To identify successful interventions, adequately designed and powered preclinical and clinical trials are required.
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Prevention and early interventions are likely to be the most effective approaches for maintaining cognitive function; identification of patients at risk of cognitive impairment and development of predictive biomarkers will increase our understanding and facilitate the design of cognitive protection trials.
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S.B.S., A.S.T. and A.C. declare no competing interests as defined by Nature Research, or other interests that might be perceived to influence the interpretation of the article. J.S.W. declares the following research funding, unrelated to the preparation of this manuscript: Bayer, GT Medical Technology, Juno, Novocure, Roche, Vanquish Oncology.
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Netherlands Cancer Institute: https://www.avl.nl/voorbereiding-afspraak/afdelingen-en-centra/centrum-voor-kwaliteit-van-leven-ondersteunende-zorg/cognitieve-problemen-bij-kanker-en-kankerbehandeling/
Glossary
- Neoadjuvant treatment
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Therapy given before primary treatment.
- Micrometastatic disease
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Small numbers of cancer cells that have spread from the primary tumour to other parts of the body and are too few to be detected in a screening or diagnostic test.
- DNA cross-linking agents
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Chemotherapy agents that react with two nucleotides, forming a covalent linkage between them.
- G-quadruplex-targeting drugs
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Chemotherapy drugs that stabilize G-quadruplex DNA, resulting in DNA damage and altered gene expression.
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Schagen, S.B., Tsvetkov, A.S., Compter, A. et al. Cognitive adverse effects of chemotherapy and immunotherapy: are interventions within reach?. Nat Rev Neurol 18, 173–185 (2022). https://doi.org/10.1038/s41582-021-00617-2
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DOI: https://doi.org/10.1038/s41582-021-00617-2