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      Moon, Mars and Minds: Evaluating Parkinson’s disease mortality among U.S. radiation workers and veterans in the million person study of low-dose effects

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          Abstract

          Background

          Radiation is one of the most important stressors related to missions in space beyond Earth’s orbit. Epidemiologic studies of exposed workers have reported elevated rates of Parkinson’s disease. The importance of cognitive dysfunction related to low-dose rate radiation in humans is not defined. A meta-analysis was conducted of six cohorts in the Million Person Study (MPS) of low-dose health effects to learn whether there is consistent evidence that Parkinson’s disease is associated with radiation dose to brain.

          Materials and methods

          The MPS evaluates all causes of death among U.S. radiation workers and veterans, including Parkinson’s disease. Systematic and consistent methods are applied to study all categories of workers including medical radiation workers, industrial radiographers, nuclear power plant workers, atomic veterans, and Manhattan Projects workers at the Los Alamos National Laboratory and at Rocky Flats. Consistent methods for all cohorts are used to estimate organ-specific doses and to obtain vital status and cause of death.

          Results

          The meta-analysis include 6 cohorts within the MPS, consisting of 517,608 workers and 17,219,001 person-years of observation. The mean dose to brain ranged from 6.9 to 47.6 mGy and the maximum dose from 0.76 to 2.7 Gy. Five of the 6 cohorts revealed positive associations with Parkinson’s disease. The overall summary estimate from the meta-analysis was statistically significant based on 1573 deaths due to Parkinson’s disease. The summary excess relative risk at 100 mGy was 0.17 (95% CI: 0.05; 0.29).

          Conclusions

          Parkinson’s disease was positively associated with radiation in the MPS cohorts indicating the need for careful evaluation as to causality in other studies, delineation of possible mechanisms, and assessing possible implications for space travel as well as radiation protection guidance for terrestrial workers.

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          Most cited references61

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          Meta-analysis in clinical trials

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            Regression Models and Life-Tables

            D R Cox (1972)
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              Parkinson's disease

              Parkinson's disease is a recognisable clinical syndrome with a range of causes and clinical presentations. Parkinson's disease represents a fast-growing neurodegenerative condition; the rising prevalence worldwide resembles the many characteristics typically observed during a pandemic, except for an infectious cause. In most populations, 3-5% of Parkinson's disease is explained by genetic causes linked to known Parkinson's disease genes, thus representing monogenic Parkinson's disease, whereas 90 genetic risk variants collectively explain 16-36% of the heritable risk of non-monogenic Parkinson's disease. Additional causal associations include having a relative with Parkinson's disease or tremor, constipation, and being a non-smoker, each at least doubling the risk of Parkinson's disease. The diagnosis is clinically based; ancillary testing is reserved for people with an atypical presentation. Current criteria define Parkinson's disease as the presence of bradykinesia combined with either rest tremor, rigidity, or both. However, the clinical presentation is multifaceted and includes many non-motor symptoms. Prognostic counselling is guided by awareness of disease subtypes. Clinically manifest Parkinson's disease is preceded by a potentially long prodromal period. Presently, establishment of prodromal symptoms has no clinical implications other than symptom suppression, although recognition of prodromal parkinsonism will probably have consequences when disease-modifying treatments become available. Treatment goals vary from person to person, emphasising the need for personalised management. There is no reason to postpone symptomatic treatment in people developing disability due to Parkinson's disease. Levodopa is the most common medication used as first-line therapy. Optimal management should start at diagnosis and requires a multidisciplinary team approach, including a growing repertoire of non-pharmacological interventions. At present, no therapy can slow down or arrest the progression of Parkinson's disease, but informed by new insights in genetic causes and mechanisms of neuronal death, several promising strategies are being tested for disease-modifying potential. With the perspective of people with Parkinson's disease as a so-called red thread throughout this Seminar, we will show how personalised management of Parkinson's disease can be optimised.

                Author and article information

                Contributors
                Journal
                Z Med Phys
                Z Med Phys
                Zeitschrift für Medizinische Physik
                Elsevier
                0939-3889
                1876-4436
                01 August 2023
                February 2024
                01 August 2023
                : 34
                : 1
                : 100-110
                Affiliations
                [a ]Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
                [b ]Department of Physics, University of Zürich, Zürich, Switzerland
                [c ]Vanderbilt University Medical Center’s International Epidemiology Field Station, Rockville, MD, USA
                [d ]DLH Corporation, Durham, NC, USA
                [e ]ORISE Health Studies Program, Oak Ridge Associated Universities, Oak Ridge, TN, USA
                [f ]National Council on Radiation Protection and Measurements, Bethesda, MD, USA
                [g ]Vanderbilt University School of Medicine, Nashville, TN, USA
                Author notes
                [* ]Corresponding author: Lawrence T. Dauer, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. dauerl@ 123456mskcc.org
                Article
                S0939-3889(23)00084-3
                10.1016/j.zemedi.2023.07.002
                10919963
                37537100
                43d58cb9-5414-4e8d-8201-84e3836a95d4
                © 2023 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 May 2023
                : 7 July 2023
                Categories
                Original Paper

                parkinson’s disease,radiation epidemiology,million person study

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