Cognitive impairment resulting from treatment with docetaxel, doxorubicin, and cyclophosphamide

Brown, Taurean; McElroy, Taylor; Simmons, Pilar; Walters, Huddoy; Ntagwabira, Fabio; Wang, Jing; Byrum, Stephanie D.; Allen, Antiño R.

doi:10.1016/j.brainres.2021.147397

Cited by 15 publications

(11 citation statements)

References 54 publications

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“…Consistent with findings reported by Brown et al, proteins such as dynamin-1 and cell-cell junction proteins within the key metabolic and signaling pathways were downregulated and were associated with cognitive dysfunction, as a result of chemotherapy treatment. 77 Furthermore, chemotherapy-induced changes in the junctional and cytoskeletal apparatus of endothelial cells were demonstrated, and these alterations may affect BBB integrity leading to brain dysfunction. 78 This study substantiates a link between EVs and cognitive functioning and represents a starting point for further investigation.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle Proteome of Breast Cancer Patients with and Without Cognitive Impairment Following Anthracycline-based Chemotherapy: An Exploratory Study

Koh

et al. 2021

Biomark�Insights

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Cognitive impairment due to cancer and its therapy is a major concern among cancer patients and survivors. Extracellular vesicle (EVs) composition altered by cancer and chemotherapy may affect neurological processes such as neuroplasticity, potentially impacting the cognitive abilities of cancer patients and survivors. We investigated the EV proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy from longitudinally collected plasma. EVs were cup-shaped and positive for Flotillin-1 and TSG-101. We identified 517 differentially expressed EV proteins between the cognitive impaired and non-impaired groups during and post-chemotherapy. The observed decreased expression of p2X purinoceptor, cofilin-1, ADAM 10, and dynamin-1 in the plasma EVs of the cognitive impaired group may suggest alterations in the mechanisms underlying synaptic plasticity. The reduced expression of tight junction proteins among cognitive-impaired patients may imply weakening of the blood-brain barrier. These EV protein signatures may serve as a fingerprint that underscores the mechanisms underlying cognitive impairment in cancer patients and survivors.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle Proteome of Breast Cancer Patients with and Without Cognitive Impairment Following Anthracycline-based Chemotherapy: An Exploratory Study

Koh

et al. 2021

Biomark�Insights

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“…In this review, we focused on neurogenic disruptions in cell proliferation and cell survival in response to chemotherapy treatment. It is important to note that other pathologies, including microtubule dysfunction, reduced dendritic branching and spine development [ 51 , 238 ], suppressed gliogenesis and mature and precursor oligodendrocytes [ 89 , 101 ], reduced myelination and related white matter degradation [ 239 ], and increased rates of apoptosis [ 89 ] likely contribute to hippocampal neurotoxicity, reduced hippocampal volumes, and hippocampally-mediated cognitive impairment.…”

Section: Limitations and Considerationsmentioning

confidence: 99%

Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions

Sekeres

Bradley-Garcia

Martínez-Canabal

et al. 2021

IJMS

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A wide range of cognitive deficits, including memory loss associated with hippocampal dysfunction, have been widely reported in cancer survivors who received chemotherapy. Changes in both white matter and gray matter volume have been observed following chemotherapy treatment, with reduced volume in the medial temporal lobe thought to be due in part to reductions in hippocampal neurogenesis. Pre-clinical rodent models confirm that common chemotherapeutic agents used to treat various forms of non-CNS cancers reduce rates of hippocampal neurogenesis and impair performance on hippocampally-mediated learning and memory tasks. We review the pre-clinical rodent literature to identify how various chemotherapeutic drugs affect hippocampal neurogenesis and induce cognitive impairment. We also review factors such as physical exercise and environmental stimulation that may protect against chemotherapy-induced neurogenic suppression and hippocampal neurotoxicity. Finally, we review pharmacological interventions that target the hippocampus and are designed to prevent or reduce the cognitive and neurotoxic side effects of chemotherapy.

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“…Preclinical studies have shown that cytostatic drugs and radiation directly impair and damage different cell populations (e. g., neuronal progenitor cells and oligodendrocytes) (18) in the central nervous system (CNS). Clinical investigations, including microscopic and molecular findings, have revealed substantial reductions in gray and white matter volume and integrity (13,(19)(20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Protocol for the Exercise, Cancer and Cognition – The ECCO-Study: A Randomized Controlled Trial of Simultaneous Exercise During Neo-/Adjuvant Chemotherapy in Breast Cancer Patients and Its Effects on Neurocognition

Kiesl

Kuzdas-Sallaberger²,

Fuchs³

et al. 2022

Front. Neurol.

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IntroductionEpidemiological studies show that increased physical activity is linked to a lower risk of breast cancer and mortality. As a result, physical activity can significantly improve patients' quality of life (QOL) both during and after therapy.Many breast cancer patients demonstrate a decrease in cognitive capacity, referred to as the symptom-complex cancer related cognitive impairment (CRCI). Most frequently reported impairments are mild to moderate deficits in processing speed, attention, memory, and executive functions. Cognitive symptoms persist for months or even years, following medical treatment in roughly 35% of afflicted people, impairing everyday functioning, limiting the ability to return to work, and lowering the overall QOL. Recent studies point toward a key role of inflammatory pathways in the CRCI genesis. Attention to physical activity as a potential supportive care option is therefore increasing. However, evidence for the positive effects of exercise on preventing CRCI is still lacking.Patients and MethodsAgainst this background, the prospective, two-arm, 1:1 randomized, controlled trial investigates the influence of first line chemotherapy accompanied by exercise training on preventing CRCI in 126 patients with breast cancer at the local University Hospital. The study will evaluate biomarkers and secondary assessments suspected to be involved in the pathogenesis of CRCI in addition to objective (primary outcome) and subjective cognitive function. CRCI is believed to be connected to either functional and/or morphological hippocampal damage due to chemotherapy. Thus, cerebral magnetic resonance imaging (MRI) and hippocampal volume measurements are performed. Furthermore, a specific neuropsychological test battery for breast cancer patients has been developed to detect early signs of cognitive impairments in patients and to be integrated into practice.DiscussionThis study will explore how a long-term supervised exercise intervention program might prevent CRCI, enables optimization of supportive care and objectifies limits of psychological and physical resilience in breast cancer patients during and after chemotherapy treatment.Trial RegistrationClinicalTrials.gov: Identifier: NCT04789187. Registered on 09 March 2021.

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Cognitive impairment resulting from treatment with docetaxel, doxorubicin, and cyclophosphamide

Cited by 15 publications

References 54 publications

Extracellular Vesicle Proteome of Breast Cancer Patients with and Without Cognitive Impairment Following Anthracycline-based Chemotherapy: An Exploratory Study

Extracellular Vesicle Proteome of Breast Cancer Patients with and Without Cognitive Impairment Following Anthracycline-based Chemotherapy: An Exploratory Study

Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions

Protocol for the Exercise, Cancer and Cognition – The ECCO-Study: A Randomized Controlled Trial of Simultaneous Exercise During Neo-/Adjuvant Chemotherapy in Breast Cancer Patients and Its Effects on Neurocognition

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