Laack NN, Brown PD. Cognitive sequelae of brain radiation in adults. Semin Oncol

Division of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Seminars in Oncology (Impact Factor: 3.9). 11/2004; 31(5):702-13. DOI: 10.1053/j.seminoncol.2004.07.013
Source: PubMed


Radiotherapy (RT) is a proven curative and palliative therapeutic tool in the treatment of a wide variety of primary and metastatic brain tumors in adults. Recent advances in multimodality therapy have led to improvement in survival for many cancer patients. As survival has improved, more attention has been directed toward long-term treatment-related morbidity. Specifically, the effect of RT on the long-term cognitive performance of these patients is a major concern. This article reviews the neurocognitive effects of cranial RT on adult patients with brain tumors. Analyses of neurocognitive function are confounded by factors such as surgery, chemotherapy, tumor characteristics, tumor progression, concurrent medical illnesses, neurologic comorbidity, and medications that can contribute to neurocognitive deficits. Risk of deficits after cranial RT is associated with high RT dose, large fraction size, larger field size, and extremes of age at time of treatment. Using modern techniques with moderate total doses (50 to 54 Gy), conformal RT, conventional fractionation, and advanced planning imaging and software, the risks of neurocognitive deficits are quite small and greatly overshadowed by deficits caused by the tumor itself. Further studies need to be undertaken to elucidate the degree and cause of cognitive decline in adult patients undergoing multimodality therapy for cranial tumors.

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    • "Radiotherapy remains the standard treatment for vast majority of high-grade or malignant brain tumors and plays an integral role in treatment of many low-grade and benign primary brain tumors. However, concerns regarding neurocognitive toxicity after radiotherapy in patients with benign or low-grade tumors make the timing of treatment controversial [3]. "
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    ABSTRACT: The goal of this review is to summarize the rationale for and feasibility of hippocampal sparing techniques during brain irradiation. Radiotherapy is the most effective non-surgical treatment of brain tumors and with the improvement in overall survival for these patients over the last few decades, there is an effort to minimize potential adverse effects leading to possible worsening in quality of life, especially worsening of neurocognitive function. The hippocampus and associated limbic system have long been known to be important in memory formation and pre-clinical models show loss of hippocampal stem cells with radiation as well as changes in architecture and function of mature neurons. Cognitive outcomes in clinical studies are beginning to provide evidence of cognitive effects associated with hippocampal dose and the cognitive benefits of hippocampal sparing. Numerous feasibility planning studies support the feasibility of using modern radiotherapy systems for hippocampal sparing during brain irradiation. Although results of the ongoing phase II and phase III studies are needed to confirm the benefit of hippocampal sparing brain radiotherapy on neurocognitive function, it is now technically and dosimetrically feasible to create hippocampal sparing treatment plans with appropriate irradiation of target volumes. The purpose of this review is to provide a brief overview of studies that provide a rationale for hippocampal avoidance and provide summary of published feasibility studies in order to help clinicians prepare for clinical usage of these complex and challenging techniques.
    Full-text · Article · Jun 2014 · Radiation Oncology
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    • "Radiation therapy is commonly used in the treatment of malignant brain tumors, and although effective, the dose that can be administered safely is limited due to potential injury to normal tissues [1], [2], [3], [4]. Radiation injury to the brain can involve multiple regions and a variety of cell/tissue types, leading to variable degrees of motor and cognitive dysfunctions [4]. "
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    ABSTRACT: Radiation therapy of the CNS, even at low doses, can lead to deficits in neurocognitive functions. Reduction in hippocampal neurogenesis is usually, but not always, associated with cognitive deficits resulting from radiation therapy. Generation of reactive oxygen species is considered the main cause of radiation-induced tissue injuries, and elevated levels of oxidative stress persist long after the initial cranial irradiation. Consequently, mutant mice with reduced levels of the mitochondrial antioxidant enzyme, Mn superoxide dismutase (MnSOD or Sod2), are expected to be more sensitive to radiation-induced changes in hippocampal neurogenesis and the related functions. In this study, we showed that MnSOD deficiency led to reduced generation of immature neurons in Sod2-/+ mice even though progenitor cell proliferation was not affected. Compared to irradiated Sod2+/+ mice, which showed cognitive defects and reduced differentiation of newborn cells towards the neuronal lineage, irradiated Sod2-/+ mice showed normal hippocampal-dependent cognitive functions and normal differentiation pattern for newborn neurons and astroglia. However, we also observed a disproportional decrease in newborn neurons in irradiated Sod2-/+ following behavioral studies, suggesting that MnSOD deficiency may render newborn neurons more sensitive to stress from behavioral trainings following cranial irradiation. A positive correlation between normal cognitive functions and normal dendritic spine densities in dentate granule cells was observed. The data suggest that maintenance of synaptic connections, via maintenance of dendritic spines, may be important for normal cognitive functions following cranial irradiation.
    Full-text · Article · Nov 2012 · PLoS ONE
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    • "Whole-brain irradiation (WBI) is essential for the treatment of brain tumours. However, ionizing radiation produces longterm learning and memory deficits, particularly in young children (Monje and Palmer, 2003; Laack and Brown, 2004; Achanta et al., 2009). Although the pathological cascade remains unknown, irradiation-induced cognitive deficits might underlie reduced neurogenesis within the hippocampus , which is important for learning and memory (Crossen et al., 1994; Abayomi, 1996). "
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    ABSTRACT: Background and purpose: Whole-brain irradiation (WBI) therapy produces learning and memory deficits in patients with brain tumours. Although the pathological cascade of cognitive deficits remains unknown, it may involve reduced neurogenesis within the hippocampus. Baicalein is a flavonoid derived from the roots of Huangqin, Scutellaria baicalensis Georgi, and has been shown to have antioxidant effects. Here, we have investigated the protective effects of baicalein on irradiation-induced impairments in hippocampal neurogenesis and cognitive function. Experimental approach: Radioprotective effects of baicalein were evaluated in C17.2 neural progenitor cells and 6-week-old male C57BL/6 mice during hippocampal neurogenesis. Mice were given a single dose of 5 Gy WBI. Changes in hippocampal neurogenesis, oxidative stress and BDNF-pCREB signalling were evaluated. Morris water maze and passive avoidance test were used to assess learning and memory. Key results: Baicalein protected neural progenitor cells against irradiation-induced necrotic cell death. Pretreatment with baicalein attenuated the irradiation-induced impairment of hippocampal neurogenesis by modulating oxidative stress and elevating BDNF-pCREB signalling. Furthermore, baicalein prevented the spatial learning and memory retention deficits follwing WBI. Conclusions and implications: Our findings suggest that baicalein can be viewed as a potential therapeutic agent that protects against the impaired neurogenesis induced by WBI, and its neurocognitive consequences.
    Preview · Article · Aug 2012 · British Journal of Pharmacology
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