Chemotherapy-related cognitive dysfunction: current animal studies and future directions

Cancer survivors treated with chemotherapy frequently complain about impairment of cognitive functions including attention and memory. While the contribution of factors like psychological distress, anxiety or fatigue to this "chemobrain" syndrome has been discussed, studies in rodents have demonstrated the toxicity of various chemotherapeutic substances to the adult central nervous system. In humans, structural brain imaging has revealed both reduced gray and white matter volume and decreased white matter integrity related to chemotherapeutic treatment. Studies of brain function have found alterations in brain activation patterns during different types of tasks. Nevertheless, further clinical research using prospective designs in larger samples is required to better understand the relationship between chemotherapy and cognitive deficits. Variables that need to be considered more systematically include drug dose, genetic variations, and psychological factors. Assessing both electroencephalographic and hemodynamic responses during tasks at different stages of the processing hierarchy and at di erent di culty levels should help in pinpointing the cortical processes a ected by chemotherapy.

show abstract

“…Additional evidence for this notion has been provided by an increasing number of animal studies using behavioral paradigms [15,16].…”

Section: Manymentioning

confidence: 99%

Challenges in research on the neural basis of „chemobrain”

Kaiser

Dietrich

2014

Translational Neuroscience

View full text Add to dashboard Cite

show abstract

“…Although the increased BCNU concentration can improve therapeutic outcome [13], it also has toxic effects on neurogenesis and cognitive function [15,16]. One of the advantages of resveratrol is its non-toxicity to normal cells, including glial cells and neurons, at effective anti-cancer doses [17].…”

Section: Introductionmentioning

confidence: 99%

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Shu

Wang

et al. 2015

Neurotherapeutics

View full text Add to dashboard Cite

Resveratrol possesses anti-tumor activities against central nervous system (CNS) tumors in vitro but has not yet been used clinically due to its low bioavailability, particularly in the CNS. This study thus aimed to elucidate brain bioavailability of trans-resveratrol by monitoring brain concentrations and dwell times following administration of resveratrol through intragastric, intraperitoneal, external carotid artery/ ECA and intrathecal routes. In parallel, we evaluated the biological responses of rat RG2 glioblastoma cells as well as RG2-formed rat intracranial glioblastomas treated with resveratrol via intrathecal administration. The results revealed that resveratrol was detected in rat brains except when administered systemically. Intrathecal administration of reseveratrol led to abundant apoptotic foci and increased staining of the autophagy proteins, LC-3 and Beclin-1 and shrinkage of the intracranial tumors. In conclusion, the BBB penetrability of resveratrol is remarkably increased by intracthecal administration. Regular short-term resveratrol treatments suppress growth and enhance autophagic and apoptotic activities of rat RG2 glioblastoma cells in vitro and in vivo. Therefore, intrathecal administration of resveratrol could be an optimal intervention approach in the adjuvant management of brain malignancies.

show abstract

“…However, besides well known immediate side effects, such as nausea, chemotherapy has also been associated with long-term negative consequences, such as cardiovascular disease [2] and the potential neurotoxicity of chemotherapy [3,4] through possible disturbance of various mechanisms including apoptosis and suppressed neurogenesis [5].…”

mentioning

confidence: 99%

“…the optimization of the dosing of chemotherapy regimens by minimizing their harm while maintaining treatment efficacy [5], knowledge of the impact of such neurotoxic effects on patients' functioning in everyday life including their vocational careers [10,11], and adoption of cognitive rehabilitation interventions in routine clinical practice [12]. Furthermore, from a neuro-epidemiological perspective, it is important to examine whether treatment with chemotherapy in (late) adulthood accelerates cognitive decline and increases the risk of dementia.…”

mentioning

confidence: 99%

Neurocognitive function of lymphoma patients after treatment with chemotherapy

2016

View full text Add to dashboard Cite

Background: Chemotherapy has been shown to cause brain changes and to compromise cognitive function in cancer survivors. Knowledge about this matter is of vital importance for good clinical practice and insights into neurological aging. However, most studies have been conducted among breast cancer patients. Less is known about the effects of chemotherapy on the cognitive function of lymphoma patients. Material and method: We studied patients with non-Hodgkin or Hodgkin lymphoma who had been treated with standard dose chemotherapy or with supplementary high dose chemotherapy when standard dose chemotherapy had been unsuccessful. Age-and sex-matched relatives and friends were invited to participate as control participants. All participants underwent a cognitive examination with a battery of validated neuropsychological tests. Results: Matching of patients with control participants was found to be successful. Regression analysis did not reveal worse cognitive functioning of patients (N ¼ 106) compared to matched controls (N ¼ 53) on the overall group level (All Bonferroni-Holm corrected p-values >0.05). However, a subgroup of 16% of patients had deviant performance according to a chance-corrected criterion based on Ingraham and Aiken's probability curves, i.e. 1.5 standard deviations below the norm on three of 14 tests. Exploratory analyses showed that this subgroup of patients was lower educated and had lower estimated premorbid intelligence. Conclusion: Chemotherapy may compromise the function of the brain in a subgroup of lymphoma patients. We hypothesize protection of the brain by 'cognitive or brain reserve' as a possible explanation.

show abstract

Chemotherapy-related cognitive dysfunction: current animal studies and future directions

Cited by 122 publications

References 82 publications

Challenges in research on the neural basis of „chemobrain”

Challenges in research on the neural basis of „chemobrain”

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Neurocognitive function of lymphoma patients after treatment with chemotherapy

Contact Info

Product

Resources

About