Appearance
Parkinson's disease.
Literature Information
| DOI | 10.1016/S0140-6736(21)00218-X |
|---|---|
| PMID | 33848468 |
| Journal | Lancet (London, England) |
| Publication Year | 2021 |
| Times Cited | 1342 |
| Literature Type | Journal Article, Review |
| ISSN | 0140-6736 |
| Pages | 2284-2303 |
| Issue | 397(10291) |
| Authors | Bastiaan R Bloem, Michael S Okun, Christine Klein |
TL;DR
The paper discusses the rising prevalence of Parkinson's disease, highlighting its multifactorial nature, with 3-5% attributed to genetic causes and various non-genetic risk factors significantly increasing the likelihood of developing the condition. It emphasizes the importance of personalized management strategies and early intervention, while acknowledging the lack of current therapies to slow disease progression, though promising new approaches are under investigation.
Abstract
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.
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Primary Questions Addressed
- What are the most common non-motor symptoms associated with Parkinson's disease, and how do they impact patients' quality of life?
- How does the interplay of genetic and environmental factors contribute to the pathogenesis of Parkinson's disease?
- What recent advancements have been made in the diagnostic criteria for early-stage Parkinson's disease?
- In what ways do different neurotransmitter systems beyond dopamine influence the progression and treatment of Parkinson's disease?
- What are the current research directions aimed at developing therapies that could potentially slow the neurodegenerative process in Parkinson's disease?
Key Findings
1. Research Background and Objectives: Parkinson's disease (PD) is identified as a rapidly increasing neurodegenerative disorder, exhibiting a range of clinical presentations and causes. The purpose of this research is to explore the multifaceted nature of Parkinson's disease, understanding its genetic underpinnings, risk factors, clinical diagnosis criteria, and the implications for treatment strategies. The study seeks to highlight the urgent need for personalized management approaches in light of the rising prevalence of PD, which shares pandemic-like characteristics despite lacking an infectious origin.
2. Key Methods and Findings: The research is primarily based on a review of the existing literature and clinical guidelines regarding Parkinson's disease. It delineates the genetic factors contributing to PD, noting that only 3-5% of cases are attributed to known monogenic causes, while 90 genetic risk variants account for a significant portion of non-monogenic heritable risks. The study identifies various risk factors, such as familial history, specific symptoms (e.g., tremor, constipation), and lifestyle factors (e.g., non-smoking status) that exacerbate the likelihood of developing PD. The clinical diagnosis relies on the presence of bradykinesia alongside additional motor symptoms, but it also acknowledges the importance of recognizing non-motor symptoms. Additionally, it discusses the importance of recognizing prodromal symptoms, which, while currently providing limited clinical implications, could be pivotal in future disease-modifying treatments.
3. Core Conclusions: The study concludes that Parkinson's disease is a complex, heterogeneous disorder requiring personalized treatment strategies. Current symptomatic treatments, primarily using Levodopa, should not be delayed in patients experiencing disability. The research underscores the necessity for a multidisciplinary approach in managing PD, integrating pharmacological and non-pharmacological interventions. Although no current therapies can halt disease progression, ongoing investigations into genetic mechanisms and neuronal death may lead to promising disease-modifying strategies.
4. Research Significance and Impact: This research is significant as it provides a comprehensive understanding of the complexities surrounding Parkinson's disease, emphasizing the importance of early diagnosis and personalized management to improve patient outcomes. By uncovering the genetic and environmental interactions influencing PD, the findings could guide future research directions and therapeutic approaches. The insights gained could facilitate better prognostic counseling, enhance symptom management, and ultimately lead to a more effective response to the growing global challenge posed by Parkinson's disease. Emphasizing the patient perspective, the research advocates for treatment approaches that are tailored to individual needs, which is crucial for optimizing care in this multifaceted condition.
Literatures Citing This Work
- The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson's Disease. - Melissa Vos;Christine Klein - Cells (2021)
- The state of telemedicine for persons with Parkinson's disease. - Robin van den Bergh;Bastiaan R Bloem;Marjan J Meinders;Luc J W Evers - Current opinion in neurology (2021)
- Proteolytic α-Synuclein Cleavage in Health and Disease. - Alexandra Bluhm;Sarah Schrempel;Stephan von Hörsten;Anja Schulze;Steffen Roßner - International journal of molecular sciences (2021)
- Parkinson's Disease in Romania: A Scoping Review. - Elena Cecilia Rosca;Raluca Tudor;Amalia Cornea;Mihaela Simu - Brain sciences (2021)
- Ethical Aspects of Personal Science for Persons with Parkinson's Disease: What Happens When Self-Tracking Goes from Selfcare to Publication? - Sara Riggare;Maria Hägglund;Annelien L Bredenoord;Martijn de Groot;Bastiaan R Bloem - Journal of Parkinson's disease (2021)
- From blood to brain: blood cell-based biomimetic drug delivery systems. - Yong-Jiang Li;Jun-Yong Wu;Jihua Liu;Xiaohan Qiu;Wenjie Xu;Tiantian Tang;Da-Xiong Xiang - Drug delivery (2021)
- Integrated network analysis identifying potential novel drug candidates and targets for Parkinson's disease. - Pusheng Quan;Kai Wang;Shi Yan;Shirong Wen;Chengqun Wei;Xinyu Zhang;Jingwei Cao;Lifen Yao - Scientific reports (2021)
- Moving towards Integrated and Personalized Care in Parkinson's Disease: A Framework Proposal for Training Parkinson Nurses. - Marlena van Munster;Johanne Stümpel;Franziska Thieken;David J Pedrosa;Angelo Antonini;Diane Côté;Margherita Fabbri;Joaquim J Ferreira;Evžen Růžička;David Grimes;Tiago A Mestre - Journal of personalized medicine (2021)
- Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson's Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up. - Diego Santos-García;Teresa de Deus;Carlos Cores;Hector Canfield;Jose M Paz González;Cristina Martínez Miró;Lorena Valdés Aymerich;Ester Suárez;Silvia Jesús;Miquel Aguilar;Pau Pastor;Lluis Planellas;Marina Cosgaya;Juan García Caldentey;Nuria Caballol;Ines Legarda;Jorge Hernández-Vara;Iria Cabo;Lydia López Manzanares;Isabel González Aramburu;Maria A Ávila Rivera;Maria J Catalán;Victor Nogueira;Victor Puente;Julio Dotor;Carmen Borrué;Berta Solano;Maria Álvarez Sauco;Lydia Vela;Sonia Escalante;Esther Cubo;Francisco Carrillo;Juan C Martínez Castrillo;Pilar Sánchez Alonso;Gemma Alonso;Nuria López Ariztegui;Itziar Gastón;Jaime Kulisevsky;Marta Blázquez;Manuel Seijo;Javier Rúiz Martínez;Caridad Valero;Monica Kurtis;Oriol de Fábregues;Jessica Ardura;Ruben Alonso;Carlos Ordás;Luis M López Díaz;Darrian McAfee;Pablo Martinez-Martin;Pablo Mir; Coppadis Study Group - Journal of personalized medicine (2021)
- Probing the Pre-diagnostic Phase of Parkinson's Disease in Population-Based Studies. - Lisanne J Dommershuijsen;Agnita J W Boon;M Kamran Ikram - Frontiers in neurology (2021)
... (1332 more literatures)
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