Default mode network as a potential biomarker of chemotherapy-related brain injury

Kesler, Shelli R.

doi:10.1016/j.neurobiolaging.2014.03.036

Cited by 87 publications

(78 citation statements)

References 130 publications

(173 reference statements)

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“…Functional MRI studies established that DMN is more vulnerable to disease and effects of Table 1. Mean values of the volumes of different brain parts before and 6 months after chemotherapy calculated using coronal MRI chemotherapy in breast cancer patients [13]. Our study also revealed hippocampal volume loss on MRI 6 months after cancer treatment.…”

Section: Discussionsupporting

confidence: 54%

“…It stores memories and it is also able to recall them [8].In cancer patients several studies reported various cognitive impairments called chemobrain [4,[9][10][11]. Chemobrain was mostly studied and proved in patients who received treatment for breast cancer [6,[11][12][13][14]. In a study with 39 breast cancer patients a decline in concentration and memory in 28% of patients was shown [15].…”

Section: Discussionmentioning

confidence: 99%

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Hippocampal volume reduction after chemotherapy assessed by brain MRI: a cause of chemobrain in cancer patients

Herek¹,

Dogu²,

Özdemir³

et al. 2017

Pau Med J

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Purpose:Cancer treatment (chemotherapy) affects various neural parts of the brain which results in cognitive impairments as problems in working memory, concentration, speed of processing and responding, and speech. This condition is called "chemobrain". The aim of this study is to establish whether any change exists in the volume of certain brain parts before and after chemotherapy that might play a role in chemobrain by means of magnetic resonance imaging (MRI). Materials and methods: Eleven patients with various cancers underwent cranial MRI before and after chemotherapy. 3-dimensional reconstruction from coronal 2 dimensional images were obtained by SURFDriver program. Volume calculations of cerebrum, cerebellum, ventricles, right and left hippocampus were done by Cavalieri method. Results:According to measurements there was a statistically significant difference only in the volumes of right and left hippocampus before and after chemotherapy (p<0.05). The volumes of the hippocampus on both sides decreased after chemotherapy. Conclusion:This study revealed significant volume changes in the hippocampus of cancer patients after chemotherapy. We suggest that this volume reduction in hippocampal regions might be the explanation of chemobrain seen in cancer patient during and after chemotherapy.Pam Med J 2017;10(3):222-226 Keywords:Cognitive impairment, neoplasms, drug therapy, magnetic resonance imaging. ÖzetAmaç:Kanser tedavisi (kemoterapi) beyinin çeşitli nöral parçalarını etkileyerek hafıza, konsantrasyon, işleme ve karşılık verme hızı ve konuşma gibi alanlarda bilişsel bozukluklara neden olur. Bu duruma "kemobeyin" adı verilir. Bu çalışmanın amacı manyetik rezonans görüntüleme (MRG) aracılığıyla kemoterapi öncesi ve sonrası bazı beyin kısımlarında kemobeyin oluşmasına neden olabilecek herhangi bir hacim değişikliği olup olmadığını ortaya koymaktır. Gereç ve yöntem:Farklı kanser tanıları olan 11 hastaya kemoterapi öncesi ve sonrası kraniyal MRG tetkiki yapıldı. Koronal 2-boyutlu görüntülerden SURFDriver programı kullanılarak 3-boyutlu rekonstrüksiyonlar elde edildi. Serebrum, serebellum, ventriküller, sağ ve sol hipokampüsün hacim ölçümleri Cavalieri yöntemi kullanılarak elde edildi. Bulgular:Ölçümler sonucunda kemoterapi öncesi ve sonrası sadece hipokampüs hacimlerinde anlamlı farklılık vardı (p<0.05). Her iki tarafta da hipokampüs hacimlerinde kemoterapi sonrası azalma görüldü Sonuç:Bu çalışma kemoterapi sonrası kanser hastalarının hipokampüs bölgelerinde anlamlı hacim değişikliği olduğunu ortaya koymaktadır. Kemoterapi sırasında ve sonrasında kanser hastalarında görülen kemobeyinin nedeninin hipokampüs bölgelerindeki bu hacimsel azalmaya bağlı olduğunu düşünmekteyiz. Tıp Derg 2017;10(3):222-226 Anahtar sözcükler:Bilişsel bozukluk, neoplaziler, ilaç tedavisi, manyetik rezonans görüntüleme. Pam 223Pamukkale Tıp Dergisi 2017;10(3):222-226 Herek ve ark.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Hippocampal volume reduction after chemotherapy assessed by brain MRI: a cause of chemobrain in cancer patients

Herek¹,

Dogu²,

Özdemir³

et al. 2017

Pau Med J

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“…Cognitive impairments following breast cancer and its treatments may worsen over time (Wefel, et al, 2010) indicating a persistent or even progressive phenotype. Therefore, cancer and/or its therapies have been theorized to possibly alter or accelerate age-related neurodegeneration (Ahles, 2012; Kesler, 2014; Koppelmans, et al, 2013; Mandelblatt, et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

“…Highly central, “hub” regions participate in a large number of functional interactions and therefore have high metabolic demands (Lord, et al, 2013). These high energy requirements make these regions more vulnerable to age-related reduction of physiologic resources as well as a variety of neuropathologic processes (Crossley, et al, 2014; Kesler, 2014). We have previously demonstrated that hub regions are vulnerable to breast cancer and its treatments (Hosseini and Kesler, 2013).…”

Section: Introductionmentioning

confidence: 99%

Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer

Kesler¹,

Watson²,

Blayney³

2015

Neurobiology of Aging

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107

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Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging (DTI) and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared to 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared to controls, the breast cancer group demonstrated significantly lower fractional anisotropy (FA), altered small-world connectome properties, lower brain network tolerance to systematic region (node) and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology following breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes.

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“…Default mode network includes precuneus, cingulate, medial frontal, middle temporal, and lateral parietal regions as well as the hippocampus and is believed to support implicit learning, monitoring, and allocation of neural resources to various cognitive processes. 22,24,25 The default mode network is an intrinsic functional brain network, meaning that its constituent regions are spontaneously coactive, independent of external stimuli. Such spontaneous, intrinsic connectivity is measured during an extended, task-free “resting” state using fMRI.…”

mentioning

confidence: 99%

Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors

2016

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IMPORTANCE Chemotherapy exposure is a known risk factor for cancer-related cognitive impairments. Anthracycline-based regimens are commonly used chemotherapies that have been shown to be associated with cognitive impairment and brain changes in clinical studies. OBJECTIVE To directly compare the effects of anthracycline and nonanthracycline regimens on cognitive status and functional brain connectivity. DESIGN, SETTING, AND PARTICIPANTS In this observational study, we retrospectively examined cognitive and resting state functional magnetic resonance imaging data acquired from 62 primary breast cancer survivors (mean [SD] age, 54.7 [8.5] years) who were more than 2 years off-therapy, on average. Twenty of these women received anthracycline-based chemotherapy as part of their primary treatment, 19 received nonanthracycline regimens, and 23 did not receive any chemotherapy. Participants were enrolled at a single academic institution (Stanford University) from 2008 to 2014, and the study analyses were performed at this time. MAIN OUTCOMES AND MEASURES Cognitive status was measured using standardized neuropsychological tests, and functional brain connectivity was evaluated using resting state functional magnetic resonance imaging with a focus on the brain’s default mode network. RESULTS The anthracycline group demonstrated significantly lower verbal memory performance including immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001) as well as lower left precuneus connectivity (F = 7.48; P = .001) compared with the other 2 groups. Patient-reported outcomes related to cognitive dysfunction (F = 7.27; P = .002) and psychological distress (F = 5.64; P = .006) were similarly elevated in both chemotherapy groups compared with the non–chemotherapy-treated controls. CONCLUSIONS AND RELEVANCE These results suggest that anthracyclines may have greater negative effects than nonanthracycline regimens on particular cognitive domains and brain network connections. Both anthracycline and nonanthracycline regimens may have nonspecific effects on other cognitive domains as well as certain patient reported outcomes. Further research is needed to identify potential methods for protecting the brain against the effects of various chemotherapeutic agents.

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Default mode network as a potential biomarker of chemotherapy-related brain injury

Cited by 87 publications

References 130 publications

Hippocampal volume reduction after chemotherapy assessed by brain MRI: a cause of chemobrain in cancer patients

Hippocampal volume reduction after chemotherapy assessed by brain MRI: a cause of chemobrain in cancer patients

Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer

Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors

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