Metals and Parkinson's Disease: Mechanisms and Biochemical Processes

Bjørklund, Geir; Stejskal, Věra; Urbina, Mauricio A.; Dadar, Maryam; Chirumbolo, Salvatore; Mutter, Joachim

doi:10.2174/0929867325666171129124616

Cited by 134 publications

(96 citation statements)

References 201 publications

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“…Importantly, no common genetic associations have been found to date between ADHD and PD [43], although future assessment of this possibility is needed. It is noteworthy that while our investigation includes covariate data of subjects to account for potential confounders such as tobacco use and psychotic disorders, there are other potential confounders such as head trauma/brain injuries and environmental toxins that may contribute to the development of both Parkinson's disease and ADHD [44,45]. Again, additional investigation as to the contribution of these factors to our present findings is warranted.…”

Section: Discussionmentioning

confidence: 93%

Increased risk of diseases of the basal ganglia and cerebellum in patients with a history of attention-deficit/hyperactivity disorder

Curtin

Fleckenstein

Keeshin

et al. 2018

Neuropsychopharmacol

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Attention-deficit/hyperactivity disorder (ADHD) is marked by an ongoing pattern of inattention and/or hyperactivity and involves dysregulated dopaminergic pathways. Dopaminergic agents (i.e., amphetamine and methylphenidate) are thus prescribed to treat ADHD. As little is known regarding long-term consequences of either ADHD or its treatment, the objective of this study was to determine if either alters the risk of diseases of the basal ganglia and cerebellum, including Parkinson's disease. Statewide medical records from 1996 to 2016 were retrieved from the Utah Population Database to conduct a retrospective cohort study. Participants included ADHD patients (International Classification of Diseases, 9th revision (ICD-9) diagnosis codes 314.0-314.2, 314.8, 314.9) and 5:1 random sex-matched and age-matched subjects with no ADHD diagnosis history. Both patients and non-ADHD subjects met the following eligibility criteria: (1) no prior diagnosis of Parkinson's disease, secondary parkinsonism, basal ganglia disease, or essential tremor (ICD-9 codes 332.0, 332.1, 333.0, 333.1), (2) born in 1950 or later and age ≥20 years at last follow-up, and (3) no history of substance abuse (illicit drugs or alcohol). Outcomes were measured as time to diagnosis of diseases of the basal ganglia and cerebellum, death, or study-end. A Cox model incorporating a competing risk of death was used to provide hazard ratio estimates. Patients with ADHD (N = 31,769) had a 2.4-fold increased risk of basal ganglia and cerebellum diseases (95% confidence interval (CI): 2.0-3.0; P < 0.0001) compared with 158,790 non-ADHD persons, after controlling for sex and age and adjusting for tobacco use and psychotic conditions. In 4960 ADHD patients prescribed psychostimulants, risk of basal ganglia and cerebellum diseases between ages 21 and 49 years was especially pronounced, at 8.6-fold (95% CI: 4.8-15.6; P < 0001). The association of ADHD patients prescribed psychostimulants with higher risk of diseases of the basal ganglia and cerebellum may reflect a more severe ADHD phenotype rather than a direct association between prescribed stimulant use and basal ganglia or cerebellum disorders. Future studies to assess and stratify patient risk so as to inform treatment are warranted.

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Section: Discussionmentioning

confidence: 93%

Increased risk of diseases of the basal ganglia and cerebellum in patients with a history of attention-deficit/hyperactivity disorder

Curtin

Fleckenstein

Keeshin

et al. 2018

Neuropsychopharmacol

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“…5. Other environmental factors: Environmental risk factors, such as dietary factors, 46,47 metal exposure, 48 and illicit drug use 49 have been associated with parkinsonism and may aid with PD prediction. However, marker definitions are often inconsistent, and predictive effects may not be independent.…”

Section: Promising Candidate Markersmentioning

confidence: 99%

Update of the MDS research criteria for prodromal Parkinson's disease

et al. 2019

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The MDS Research Criteria for Prodromal PD allow the diagnosis of prodromal Parkinson's disease using an evidence‐based conceptual framework, which was designed to be updated as new evidence becomes available. New prospective evidence of predictive values of risk and prodromal markers published since 2015 was reviewed and integrated into the criteria. Many of the predictive values (likelihood ratios, LR) remain unchanged. The positive likelihood ratio notably increase for olfactory loss and decreased for substantia nigra hyperechogenicity. Negative likelihood ratio remained largely unchanged for all markers. New levels of diagnostic certainty for neurogenic and symptomatic orthostatic hypotension have been added, which substantially differ in positive likelihood ratio from the original publication. For intermediate strength genetic variants, their age‐related penetrance is now incorporated in the calculation of the positive likelihood ratio. Moreover, apart from prospective studies, evidence from cross‐sectional case‐control genome‐wide association studies is also considered (given their likely lack of confounding and reverse causation), and to account for the effect of multiple low‐penetrance genetic variants polygenic risk scores are added to the model. Diabetes, global cognitive deficit, physical inactivity, and low plasma urate levels in men enter the criteria as new markers. A web‐based prodromal PD risk calculator allows the calculation of probabilities of prodromal PD for individuals. Several promising candidate markers may improve the diagnostic accuracy of prodromal PD in the future. © 2019 International Parkinson and Movement Disorder Society

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“…Moreover, the binding of copper to ceruloplasmin is reduced in PD patients, leading to an increase in the levels of free copper, associated with oxidative stress and neurodegeneration [67]. Therefore, copper homeostasis alteration plays a role in PD [68]; however, it remains controversial whether this is the primary cause or a secondary consequence of the disease. Moreover, no consensus has been reached on the possibility to modulate copper content to alleviate PD manifestation since some studies suggest that copper level should be lowered while other studies show the opposite.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Current Biomedical Use of Copper Chelation Therapy

Baldari

Rocco

Toietta

2020

IJMS

116

105

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Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson’s syndrome, in neurological and neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.

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Metals and Parkinson's Disease: Mechanisms and Biochemical Processes

Cited by 134 publications

References 201 publications

Increased risk of diseases of the basal ganglia and cerebellum in patients with a history of attention-deficit/hyperactivity disorder

Increased risk of diseases of the basal ganglia and cerebellum in patients with a history of attention-deficit/hyperactivity disorder

Update of the MDS research criteria for prodromal Parkinson's disease

Current Biomedical Use of Copper Chelation Therapy

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