Associations of plasma brain-derived neurotrophic factor (BDNF) and Val66Met polymorphism (rs6265) with long-term cancer-related cognitive impairment in survivors of breast cancer

Yap, Ning Yi; Tan, Nichole Yue Ting; Tan, Chia Jie; Loh, Kiley Wei-Jen; Ng, Raymond; Ho, Han Kiat; Chan, Alexandre

doi:10.1007/s10549-020-05807-y

Cited by 20 publications

(26 citation statements)

References 38 publications

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“…We postulated that the effects of chronic chemotherapy on BDNF expression could persist long after the completion of chemotherapy and in cancer survivors, resulting in the long-term CRCI [14]. In our past clinical studies [3,12,45], we consistently observed a statistically significant decrease in plasma BDNF levels at 6 and 12 weeks after breast cancer patients were treated with ADR and cyclophosphamide (ADR-CYP). This association between reduced BDNF and the higher risk of cognitive decline was still evident at 24 months post-treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies have suggested that brain-derived neurotrophic factor (BDNF) is linked with a positive impact on cognition in patients with cancer [3][4][5][6][7]. BDNF exerts a number of neuro-modulatory effects on the CNS and the neurosensory, endocrine, and immune systems, and BDNF is also associated with neuronal repair and survival, dendritic and axonal growth, and long-term potentiation.…”

Section: Introductionmentioning

confidence: 99%

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BDNF Augmentation Using Riluzole Reverses Doxorubicin-Induced Decline in Cognitive Function and Neurogenesis

et al. 2023

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Cancer-related cognitive impairment (CRCI) considerably affects the quality of life of millions of cancer survivors. Brain-derived neurotrophic factor (BDNF) has been shown to promote survival, differentiation, and maintenance of in vivo dentate neurogenesis, and chemotherapy induces a plethora of physiological and cellular alterations, including a decline in neurogenesis and increased neuroinflammation linked with cognitive impairments. In our clinical studies, breast cancer patients treated with doxorubicin (Adriamycin®, ADR) experienced a significant reduction in the blood levels of BDNF that was associated with a higher risk of CRCI. Our past rodent studies in CRCI have also shown a significant reduction in dentate neurogenesis accompanied by cognitive impairment. In this study, using a female mouse model of ADR-induced cognitive decline, we tested the impact of riluzole (RZ), an orally active BDNF-enhancing medication that is FDA-approved for amyotrophic lateral sclerosis. ADR-treated mice receiving RZ in the drinking water for 1 month showed significant improvements in hippocampal-dependent learning and memory function (spatial recognition), fear extinction memory consolidation, and reduced anxiety-like behavior. RZ prevented chemotherapy-induced reductions of BDNF levels in the hippocampus. Importantly, RZ mitigated chemotherapy-induced loss of newly born, immature neurons, dentate neurogenesis, and neuroinflammation. In conclusion, this data provides pre-clinical evidence for a translationally feasible approach to enhance the neuroprotective effects of RZ treatment to prevent CRCI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BDNF Augmentation Using Riluzole Reverses Doxorubicin-Induced Decline in Cognitive Function and Neurogenesis

et al. 2023

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“…Others claimed that the use of tests with fewer practice effects or specific selection of testing intervals mitigated practice effects. Complementarily, some researchers provided the percentage of subjects with significant decline as determined by a reliable change index to separate true from practice effects 29,47–49 . Studies with control groups corrected for practice effects by statistically testing the difference in test results from control groups or by generating normative data using control groups, 34,39 thus providing a more robust evidence of the effect of CTX on OCF.…”

Section: Resultsmentioning

confidence: 99%

Neuropsychological Effects of Chemotherapy

Kim

Jung

et al. 2022

Cancer Nurs

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BackgroundFindings from longitudinal studies can provide more conclusive evidence as to the impact of chemotherapy on cognitive functioning.ObjectivesThis study aimed to (a) synthesize the evidence from longitudinal studies of the neuropsychological effects associated with chemotherapy in breast cancer patients, (b) identify associated factors, and (c) evaluate methodological issues.MethodsData were extracted from PubMed, EMBASE, CINAHL, PsycINFO, and the Cochrane Library. Inclusion criteria included the original study with the breast cancer sample, validated measure, and at least 1 baseline data point before and after chemotherapy began. Data accrued for sample characteristics, data-collection time points, statistical methods for longitudinal data analysis, outcome measures, and major findings (eg, longitudinal changes in cognitive function).ResultsWe selected 42 articles for this review. The sample sizes ranged from 20 to 610, and most recruited were younger than 70 years. We found a trend across studies—statistically significant objective cognitive function deteriorations in severity and prevalence after initiating chemotherapy compared with a control group or relative to their baseline observations. A subsample, as high as 65%, experienced marked declines in cognitive function after initiating chemotherapy. The memory domain was most affected. The consistently associated factors were education, IQ, and regimen. Major methodological concerns were the measurement—the wide range of neuropsychological tests and a test’s unclear domains.ConclusionChemotherapy affects objective cognitive function in some subsets. The highest-impact time point, mechanisms, and clinical significance of chemotherapy-associated cognitive impairment need additional evidence.Implication for PracticeClinicians must assess and manage cognitive impairment during and after chemotherapy.

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“…BDNF levels may be reflective of synaptic plasticity and neuroprotection in the young and developing brain. 25,26 Interestingly, serum BDNF levels decreased in six of the eight patients for whom measurements were obtained at all three time points. As noted earlier, these six patients had solid tumors requiring intensive chemotherapy.…”

Section: Discussionmentioning

confidence: 95%

“…18,23,24 In addition to neurocognitive testing, biomarkers such as brain-derived neurotrophic factor (BDNF), which previously was demonstrated to correlate with cognitive impairment in studies of breast cancer patients, can be useful in monitoring the impact of cognitive rehabilitation in patients diagnosed with cancer. 25,26 We designed this study to investigate the feasibility of cognitive rehabilitation as a preventative intervention for AYA patients receiving chemotherapy. We hypothesized that it is feasible for newly diagnosed patients, who were undergoing treatment, to successfully engage in a computer-based cognitive training program at least 80% of the goal training time, starting as early as 1 month after the initiation of chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of Cognitive Training to Promote Recovery in Cancer-Related Cognitive Impairment in Adolescent and Young Adult Patients

Gooch

Mehta

John

et al. 2022

Journal of Adolescent and Young Adult Oncology

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Background:Computer-based cognitive rehabilitation programs may help adolescent and young adult (AYA) patients with cancer-related cognitive impairment. This pilot study investigated the feasibility of cognitive rehabilitation as a preventive intervention for AYA patients receiving chemotherapy. Explorative objectives included the correlation of cognitive performance with serum brain-derived neurotrophic factor (BDNF). Methods: This pilot prospective study included English-speaking patients 12-25 years of age with a fist diagnosis of cancer requiring chemotherapy. Participants enrolled in the intervention arm participated in a computer-based neurocognitive training program for 20-30 minutes daily for 16 weeks. Outcome measures, including engagement with and completion of computerized neurocognitive testing and serum BDNF levels, were obtained within the first month following diagnosis, ∼16 and 24 weeks from enrollment.Results: Fourteen of 18 eligible patients provided consent, with 7 patients assigned to each the intervention arm and nonintervention arm. Seventy-one percent of the patients in the intervention arm completed at least 80% of the required activities. Compared to baseline, patients in the nonintervention arm demonstrated higher prevalence of impairment in four of the six cognitive domains (processing speed, visual attention, attention/working memory, and executive function) at the end of the study period. There was a nonstatistically significant reduction of serum BDNF levels over time, which was observed in both intervention and nonintervention arms. Conclusion:This pilot study provides some evidence that it is feasible for AYAs with new cancer diagnoses to receive standardized cognitive rehabilitation. Patients receiving cognitive activities experienced less impairment in numerous cognitive domains.

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Associations of plasma brain-derived neurotrophic factor (BDNF) and Val66Met polymorphism (rs6265) with long-term cancer-related cognitive impairment in survivors of breast cancer

Cited by 20 publications

References 38 publications

BDNF Augmentation Using Riluzole Reverses Doxorubicin-Induced Decline in Cognitive Function and Neurogenesis

BDNF Augmentation Using Riluzole Reverses Doxorubicin-Induced Decline in Cognitive Function and Neurogenesis

Neuropsychological Effects of Chemotherapy

Feasibility of Cognitive Training to Promote Recovery in Cancer-Related Cognitive Impairment in Adolescent and Young Adult Patients

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