Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis
Abstract The Bradford Hill model evaluates the causal inference of one variable on another by assessing whether evidence of the suspected causal variable aligns with a set of nine criteria proposed by Bradford Hill, each representing fundamental tenets of a causal relationship. The aim of this study...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-06-01
|
| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-022-00345-4 |
| _version_ | 1827614309194137600 |
|---|---|
| author | Amr H. Abdeen Benjamin G. Trist Kay L. Double |
| author_facet | Amr H. Abdeen Benjamin G. Trist Kay L. Double |
| author_sort | Amr H. Abdeen |
| collection | DOAJ |
| description | Abstract The Bradford Hill model evaluates the causal inference of one variable on another by assessing whether evidence of the suspected causal variable aligns with a set of nine criteria proposed by Bradford Hill, each representing fundamental tenets of a causal relationship. The aim of this study was to use the Bradford Hill model of causation to assess the level of empirical evidence supporting our hypotheses that alterations to iron and copper levels, and iron- and copper-associated proteins and genes, contribute to Parkinson’s disease etiology. We conducted a systematic review of all available articles published to September 2019 in four online databases. 8437 articles matching search criteria were screened for pre-defined inclusion and exclusion criteria. 181 studies met study criteria and were subsequently evaluated for study quality using established quality assessment tools. Studies meeting criteria for moderate to high quality of study design (n = 155) were analyzed according to the Bradford Hill model of causation. Evidence from studies considered of high quality (n = 73) supported a causal role for iron dysregulation in Parkinson’s disease. A causal role for copper dysregulation in Parkinson’s disease was also supported by high quality studies, although substantially fewer studies investigated copper in this disorder (n = 25) compared with iron. The available evidence supports an etiological role for iron and copper dysregulation in Parkinson’s disease, substantiating current clinical trials of therapeutic interventions targeting alterations in brain levels of these metals in Parkinson’s disease. |
| first_indexed | 2024-03-09T08:53:03Z |
| format | Article |
| id | doaj.art-5bcfbed266bc4ea58c4afce7e0cd8331 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-09T08:53:03Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-5bcfbed266bc4ea58c4afce7e0cd83312023-12-02T13:46:17ZengNature Portfolionpj Parkinson's Disease2373-80572022-06-018111110.1038/s41531-022-00345-4Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysisAmr H. Abdeen0Benjamin G. Trist1Kay L. Double2Brain and Mind Centre and School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, CamperdownBrain and Mind Centre and School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, CamperdownBrain and Mind Centre and School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, CamperdownAbstract The Bradford Hill model evaluates the causal inference of one variable on another by assessing whether evidence of the suspected causal variable aligns with a set of nine criteria proposed by Bradford Hill, each representing fundamental tenets of a causal relationship. The aim of this study was to use the Bradford Hill model of causation to assess the level of empirical evidence supporting our hypotheses that alterations to iron and copper levels, and iron- and copper-associated proteins and genes, contribute to Parkinson’s disease etiology. We conducted a systematic review of all available articles published to September 2019 in four online databases. 8437 articles matching search criteria were screened for pre-defined inclusion and exclusion criteria. 181 studies met study criteria and were subsequently evaluated for study quality using established quality assessment tools. Studies meeting criteria for moderate to high quality of study design (n = 155) were analyzed according to the Bradford Hill model of causation. Evidence from studies considered of high quality (n = 73) supported a causal role for iron dysregulation in Parkinson’s disease. A causal role for copper dysregulation in Parkinson’s disease was also supported by high quality studies, although substantially fewer studies investigated copper in this disorder (n = 25) compared with iron. The available evidence supports an etiological role for iron and copper dysregulation in Parkinson’s disease, substantiating current clinical trials of therapeutic interventions targeting alterations in brain levels of these metals in Parkinson’s disease.https://doi.org/10.1038/s41531-022-00345-4 |
| spellingShingle | Amr H. Abdeen Benjamin G. Trist Kay L. Double Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis npj Parkinson's Disease |
| title | Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis |
| title_full | Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis |
| title_fullStr | Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis |
| title_full_unstemmed | Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis |
| title_short | Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis |
| title_sort | empirical evidence for biometal dysregulation in parkinson s disease from a systematic review and bradford hill analysis |
| url | https://doi.org/10.1038/s41531-022-00345-4 |
| work_keys_str_mv | AT amrhabdeen empiricalevidenceforbiometaldysregulationinparkinsonsdiseasefromasystematicreviewandbradfordhillanalysis AT benjamingtrist empiricalevidenceforbiometaldysregulationinparkinsonsdiseasefromasystematicreviewandbradfordhillanalysis AT kayldouble empiricalevidenceforbiometaldysregulationinparkinsonsdiseasefromasystematicreviewandbradfordhillanalysis |