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The last decades have seen increased concern about the possible effects of low to moderate doses of ionizing radiation (IR) exposure on cognitive function. An interdisciplinary group of experts (biologists, epidemiologists, dosimetrists and clinicians) in this field gathered together in the framework of the European MELODI workshop on non-cancer effects of IR to summarise the state of knowledge on the topic and elaborate research recommendations for future studies in this area. Overall, there is evidence of cognitive effects from low IR doses both from biology and epidemiology, though a better characterization of effects and understanding of mechanisms is needed. There is a need to better describe the specific cognitive function or diseases that may be affected by radiation exposure. Such cognitive deficit characterization should consider the human life span, as effects might differ with age at exposure and at outcome assessment. Measurements of biomarkers, including imaging, will likely help our understanding on the mechanism of cognitive-related radiation induced deficit. The identification of loci of individual genetic susceptibility and the study of gene expression may help identify individuals at higher risk. The mechanisms behind the radiation induced cognitive effects are not clear and are likely to involve several biological pathways and different cell types. Well conducted research in large epidemiological cohorts and experimental studies in appropriate animal models are needed to improve the understanding of radiation-induced cognitive effects. Results may then be translated into recommendations for clinical radiation oncology and imaging decision making processes., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The neurodevelopmental effects of high doses of ionizing radiation (IR) in children are well established. To what extent such effects exist at low-to-moderate doses is unclear. Considering the increasing exposure of the general population to low-to-moderate levels of IR, predominantly from diagnostic procedures, the study of these effects has become a priority for radiation protection., Objectives: We conducted a systematic review of the current evidence for possible effects of low-to-moderate IR doses received during gestation, childhood and adolescence on different domains of neurodevelopment., Data Sources: Searches were performed in PubMed, Scopus, EMBASE and Psychinfo on the 6th of June 2017 and repeated in December 2018., Study Eligibility Criteria: We included studies evaluating the association between low-to-moderate IR doses received during gestation, childhood and adolescence, and neurodevelopmental functions., Study Appraisal and Synthesis Methods: Studies were evaluated using the Cochrane Collaboration's risk of bias tool adapted to environmental sciences. A qualitative synthesis was performed., Results: A total of 26 manuscripts were finally selected. Populations analyzed in these publications were exposed to the following sources of IR: atomic bomb (Hiroshima and Nagasaki), diagnostic/therapeutic radiation, and Chernobyl and nuclear weapon testing fallout. There was limited evidence for an association between low-to-moderate doses of IR and a decrease in general cognition and language abilities, that is, a causal interpretation is credible, but chance or confounding cannot not be ruled out with reasonable confidence. Evidence for a possible stronger effect when exposure occurred early in life, in particular, during the fetal period, was inadequate. Evidence for an association between IR and other specific domains, including attention, executive function, memory, processing speed, visual-spatial abilities, motor and socio-emotional development, was inadequate, due to the very limited number of studies found., Limitations, Conclusions, and Implications of Key Findings: Overall, depending on the domain, there was limited to inadequate evidence for an effect of low-to-moderate IR doses on neurodevelopment. Heterogeneity across studies in terms of outcome and exposure assessment hampered any quantitative synthesis and any stronger conclusion. Future research with adequate dosimetry and covering a range of specific neurodevelopmental outcomes would likely contribute to improve the body of evidence., Systematic Review Registration Number: The systematic review protocol was registered in PROSPERO (registration number CRD42018091902)., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)