Parkinson's disease
Open accessAbstract
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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Non-motor symptoms remain poorly responsive to current PD treatments despite being present from early prodromal PD and contributing significantly to overall disease burden.
“Strikingly, non-motor symptoms remain poorly responsive to current PD treatments despite being present from early prodromal PD and contributing significantly to overall disease burden [36].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [36]
The Clinical spectrum section says non-motor features can appear among early symptoms and contribute substantially to disability. Non-pharmacological interventions says many PD features respond inadequately to optimal pharmacotherapy, and Treatment of non-motor manifestations notes that some symptoms worsen with dopaminergic medication. The broader claim that non-motor symptoms remain poorly responsive to current PD treatments is not established: the paper also describes other pharmacological and non-pharmacological strategies. (LLM, conf=0.84)
Experimental — accuracy not yet measuredClinical practice guidelines recommend non-pharmacological lifestyle approaches including physical activity, stress management, and social support to provide additional symptomatic relief for patients with Parkinson's disease.
“Clinical practice guidelines support resilience training and exercise for patients with Parkinson’s disease (PD).”
From A randomized clinical trial of mindfulness meditation versus exercise in Parkinson’s disease during social unrest (2023) · cites this paper as [1]
The Physiotherapy section says aerobic exercise has symptomatic benefits for people with Parkinson’s disease and notes a relevant physiotherapy guideline. The paper also supports non-pharmacological care, but the passages do not establish that clinical guidelines recommend resilience training, stress management, or social support for additional symptomatic relief. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCNS diseases include neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as traumatic brain injuries and spinal cord injuries.
“The diseases encompass various severe conditions, including neurodegenerative disorders like Alzheimer’s disease (AD) [3, 4] and Parkinson’s disease (PD) [5, 6], as well as traumatic brain injuries (TBI) [7] and spinal cord injuries (SCI) [8].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [5]
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- Authors
- Bloem, B. R., Okun, M. S., & Klein, C.
- Affiliations
- Radboud University Nijmegen (NL)
- University of Florida Health (US)
- University Hospital Schleswig-Holstein (DE)
- Corresponding author
- Bloem, Bastiaan R
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 397
- Issue
- 10291
- Pages
- 2284-2303
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W4206481149
- Cited by
- 3,920
- References
- 159
- Citations by year
- 2026: 878 · 2025: 1098 · 2024: 901 · 2023: 607 · 2022: 364 · 2021: 72
- FWCI
- 62.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft
- Parkinson's Foundation (FOR2488)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, neurodegeneration, genetic risk variants, monogenic Parkinson's disease, non-motor symptoms, levodopa, disease-modifying therapy, multidisciplinary care, non-pharmacological treatment, diagnosis, prodromal period
- MeSH terms
- Antiparkinson Agents, Humans, Levodopa, Parkinson Disease, Time Factors, Tremor, Disease Management, Prodromal Symptoms
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