Radiation-Induced Brain Injury: Age Dependency of Neurocognitive Dysfunction Following Radiotherapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
3. Results of Clinical Studies on Humans
3.1. Radiation Effects of Low-to-Moderate Doses on Neurocognitive Development
3.2. Radiation Effects on Neurocognitive Function in Brain Cancer Survivors
3.2.1. Childhood Cancer Survivors
3.2.2. Adulthood Cancer Survivors
3.3. Summary of Clinical Trials in Humans
4. Results of Pre-Clinical Studies in Animal Models
4.1. Elucidating the Mechanisms of Radiation-Induced Brain Injury Using Rodent Models
4.2. Age-Dependent Effects of IR Exposure on Hippocampal Neurogenesis
4.3. Radiation-Induced Neurovascular Damage
4.4. Radiation-Induced Neuroinflammation
4.5. Summary of Preclinical Studies in Rodents
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Reference | Study Population (Location) | Sample Size | Type of Exposure | Age at Exposure | Brain Dose | Outcome | Age at Outcome Measurement |
---|---|---|---|---|---|---|---|
Wood, Johnson et al., 1967 [4] | atomic bomb survivors (Japan) | 183 | γ-rays and neutrons | in-utero | ≤4 Gy | small head size, mental retardation | n.s. |
Otake, Schull; 1984 [2] | atomic bomb survivors (Japan) | n.s. | γ-rays and neutrons | in-utero | ≤4 Gy | forebrain damage, mental retardation | n.s. |
Schull, Otake; 1986 [3] | atomic bomb survivors (Japan) | n.s. | γ-rays and neutrons | in-utero | ≤4 Gy | mental retardation | n.s. |
Otake, Schull; 1991 [9] | atomic bomb survivors (Japan) | 1673 | γ-rays and neutrons | in-utero | 0.6–1.4 Gy | IQ decline, lower school performance | 10–11 years |
Yoshimaru, Otake et al., 1991 [8] | atomic bomb survivors (Japan) | 929 | γ-rays and neutrons | in-utero | ≤4 Gy | lower school performance | n.s. |
Ikenoue, Ikeda et al., 1993 [6] | atomic bomb survivors (Japan) | 929 | γ-rays and neutrons | in-utero | ≤4 Gy | lower school performance | n.s. |
Otake, Schull; 1993 [7] | atomic bomb survivors (Japan) | 1473 | γ-rays and neutrons | in-utero | ≤4 Gy | small head size, mental retardation | 9–19 years |
Yoshimaru, Otake et al., 1995 [8] | atomic bomb survivors (Japan) | 888 | γ-rays and neutrons | in-utero | ≤4 Gy | IQ decline, mental retardation | 15–16 years |
Yamada, Sasaki et al., 2002 [10] | atomic bomb survivors (Japan) | 3113 | γ-rays and neutrons | ≥13 years | ≤4 Gy | no neurocognitive dysfunction | adulthood |
Yamada, Kasagi et al., 2009 [12] | atomic bomb survivors (Japan) | 2286 | γ-rays and neutrons | ≥13 years | ≤4 Gy | no increased risk of neurodegeneration | ≥60 years |
Yamada, Landes et al., 2016 [14] | atomic bomb survivors (Japan) | 1844 | γ-rays and neutrons | ≥13 years | ≤4 Gy | no increased risk of neurodegeneration | 60–80 years |
Yamada, Kato et al., 2021 [13] | atomic bomb survivors (Japan) | 303 | γ-rays and neutrons | in-utero | ≤4 Gy | no increased risk of neurodegeneration | 65–70 years |
Ishihara, Kato et al., 2022 [11] | atomic bomb survivors (Japan) | 469 | γ-rays and neutrons | ≤12 years | ≤4 Gy | no increased risk of neurodegeneration | ≥70 years |
Reference | Study Population | Sample Size | Type of Exposure | Age at Exposure | Brain Dose | Outcome | Age at Outcome Measurement |
---|---|---|---|---|---|---|---|
Albert, Omran et al., 1966 [18] | tinea capitis (New York) | 1908 | X-ray RT | mean: 8 years | mean: 1.3 Gy | mental disorders, psychosis | 21 years |
Ron, Modan et al., 1982 [19] | tinea capitis (Israel) | 10,842 | X-ray RT | range: 1–15 years mean: 7 years | range: 0.7–1.6 Gy mean: 1.5Gy | IQ decline, lower school performance | 24 years |
Hall, Adami et al., 2004 [20] | haemangioma (Sweden) | 2816 | X-ray RT | range: 0–18 months mean: 7 months | range: 0–2.8 Gy mean: 0.02 Gy | neurocognitive dysfunction ≥0.25 Gy | 18 years |
Blomstrand, Holmberg et al., 2014 [21] | haemangioma (Sweden) | 3030 | RT (different IR qualities) | range: 0–18 months median: 5 months | range: 0–1.1 Gy median: 0.02Gy | hippocampus ≥0.2Gy → lower verbal skills | 18 years |
Nordenskjöld, Palme et al., 2015 [22] | maternal X-ray pelvimetry (Sweden) | 1612 | diagnostic X-ray | in-utero | estimated fetal dose: 0.0015 Gy | no effect on school performance | 15 years |
Salonen, Nyman et al., 2018 [23] | CT scan (Sweden) | 147 | diagnostic head CT | range: 6–16 years mean: 11 years | estimated dose 0.03–0.05 Gy | no cognitive dysfunction | 18 years |
Reference | Study Population | Sample Size | Type of Exposure | Age at Exposure | Dose | Outcome | Age at Outcome |
---|---|---|---|---|---|---|---|
Broadbent, Barnes et al., 1981 [39] | medulloblastoma (UK) | 8 | 60Co RT (neuroaxis) | 1–12 years | tumor: 43–50 Gy | mental retardation, younger children (≤2y) more affected | n.s. |
Danoff, Cowchock et al., 1982 [40] | primary brain tumors (USA) | 38 | 60Co RT | 1–16 years | tumor: 40–65 Gy | mental retardation, younger children (≤3y) more affected | n.s. |
Mulhern, Hancock et al., 1992 [42] | primary brain tumors (USA) | 544 | RT (local/ whole brain) | 1–18 years | n.s. | IQ decline, younger children (≤4y) more affected | 1–21 years after RT |
Radcliffe, Bunin et al., 1994 [43] | medulloblastoma | 24 | cranial RT | 1–20 years | n.s. | IQ decline, younger children (≤7y) more affected | 2–4 years after RT |
Skowrońska-Gardas, 1999 [44] | CNS tumors (Poland) | 52 | photon RT (neuroaxis) | 1–3 years | tumor: 50 Gy neuroaxis: 30 Gy | mental retardation, younger children (≤3y) more affected | 5 years after RT |
Edelstein, Spiegler et al., 2011 [41] | medulloblastoma | photon RT | tumor: 50 Gy neuroaxis: 23 Gy | IQ decline, younger children (≤7y) more affected | ≤40 years after RT | ||
Yock, Yeap et al., 2016 [48] | medulloblastoma (USA) | 59 | proton RT (neuroaxis) | 3–21 years | tumor: 54 Gy neuroaxis: 23 Gy | IQ decline, no age-dependent effect | 7 years after RT |
Ventura, Grieco et al., 2018 [47] | primary brain tumors (USA) | 65 | proton RT (local) | 2–17 years | n.s. | IQ decline, no age-dependent effect | 4–18 years after RT |
Tso, Liu et al., 2019 [46] | germ cell tumors (Hong Kong) | 25 | cranial RT | 7–18 years | tumor: 30–54 Gy | IQ decline, no age-dependent effect | 1–12 years after RT |
Stadskleiv, Stensvold et al., 2022 [45] | medulloblastoma (Norway) | 50 | photon RT (neuroaxis) | 5–51 years | tumor: 44–56 Gy | IQ decline, no age-dependent effect | 19 years after RT |
Reference | Study Population | Sample Size | Type of Exposure | Age at Exposure | Brain Dose | Outcome | Age at Outcome Measurement |
---|---|---|---|---|---|---|---|
Meadows, Gordon et al., 1981 [36] | children with ALL (USA) | 41 | WBRT | 2–15 years | 24 Gy, fractionated | IQ decline; younger children more affected | 1–3 years after RT |
Twaddle, Britton et al., 1983 [55] | children with ALL (England) | 23 | WBRT | 1–8 years | 24 Gy, fractionated | IQ decline; younger children more affected | 1–3 years after RT |
Ladavas, Missiroli et al., 1985 [51] | children with ALL (Italy) | 21 | WBRT | 2–9 years | 24 Gy, fractionated | IQ decline; younger children (<5 years) more affected | 1–3 years after RT |
Said, Waters et al., 1989 [54] | children with ALL (Australia) | 106 | WBRT | 1–8 years | 18–24 Gy, fractionated | IQ decline; younger children more affected | 1–13 years after RT |
Chessells, Cox et al., 1990 [49] | children with ALL (England) | 136 | WBRT | 1–12 years | 18–24 Gy, fractionated | IQ decline, younger children (≤2 years) more affected | 1–5 years after RT |
MacLean, Noll et al., 1995 [52] | children with ALL (USA) | 74 | WBRT | 3–7 years | 18 Gy, fractionated | neuropsychological deficits | 1 years after RT |
Iuvone, Mariotti et al., 2002 [50] | children with ALL (Italy) | 21 | WBRT | 1–12 years | 18–24 Gy, fractionated | no age-dependent effect | 4–12 years after RT |
Reinhardt, Thiele et al., 2002 [53] | children with AML (Germany) | 38 | WBRT | 0–18 years | 12–18 Gy, fractionated | learning deficits, younger children more affected | 4–11 years after RT |
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Rübe, C.E.; Raid, S.; Palm, J.; Rübe, C. Radiation-Induced Brain Injury: Age Dependency of Neurocognitive Dysfunction Following Radiotherapy. Cancers 2023, 15, 2999. https://doi.org/10.3390/cancers15112999
Rübe CE, Raid S, Palm J, Rübe C. Radiation-Induced Brain Injury: Age Dependency of Neurocognitive Dysfunction Following Radiotherapy. Cancers. 2023; 15(11):2999. https://doi.org/10.3390/cancers15112999
Chicago/Turabian StyleRübe, Claudia E., Silvia Raid, Jan Palm, and Christian Rübe. 2023. "Radiation-Induced Brain Injury: Age Dependency of Neurocognitive Dysfunction Following Radiotherapy" Cancers 15, no. 11: 2999. https://doi.org/10.3390/cancers15112999