Highlights
- Parkinson’s disease is the fastest growing neurological disorder, impacting over 11.8 million globally.
- Innovative treatments and improved diagnostics offer hope for better management and quality of life.
Summary and Overview
Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by loss of dopamine-producing neurons, causing motor symptoms like tremor, rigidity, and bradykinesia, alongside non-motor issues such as cognitive decline and mood disturbances. It is the fastest growing neurological disorder globally, with cases rising about 60% from 1990 to 2021, reaching approximately 11.8 million. The disease results from a combination of genetic and environmental factors, with age, male sex, and pesticide exposure as key risks. PD pathology involves alpha-synuclein protein aggregation (Lewy bodies), neuroinflammation, and mitochondrial dysfunction. Diagnosis is clinical but increasingly supported by imaging and emerging biomarkers. Treatments focus on symptomatic management with dopamine replacement and novel agents like tavapadon, while disease-modifying therapies targeting alpha-synuclein and genetic mutations are in development. Multidisciplinary, patient-centered care and community support are vital for improving quality of life, amid ongoing challenges in access and awareness.
Causes, Risk Factors, and Pathophysiology
PD arises from genetic (10–20% of cases) and environmental factors, with age and male sex as significant risks. Pesticide exposure, notably linked since the discovery of MPTP’s effects, along with rural living, farming, and well water consumption, increases PD risk. Other exposures include manganese dust and head injuries. Approximately 20% of PD cases could be prevented by avoiding high pesticide exposure. Pathophysiologically, PD is characterized by dopaminergic neuron loss in the substantia nigra and alpha-synuclein aggregation into Lewy bodies, leading to neuronal dysfunction, mitochondrial impairment, and neuroinflammation. Genetic mutations such as in GBA and LRRK2 genes contribute to disease mechanisms and are targets for emerging therapies. PD also affects other neurotransmitter systems, causing non-motor symptoms.
Symptoms and Diagnosis
PD symptoms include motor signs—resting tremor, bradykinesia, rigidity, and postural instability—and diverse non-motor symptoms like cognitive decline, autonomic dysfunction, sleep disturbances, and mood disorders. Non-motor symptoms often precede motor signs and can be more debilitating. Diagnosis is clinical, based on motor features per Movement Disorder Society criteria, supported by imaging (MRI, DaTscan) to exclude other conditions. Emerging blood-based biomarkers and molecular tests aim to enable earlier, more accurate diagnosis. Tools like the Non-Motor Symptoms Scale (NMSS) assist in assessing symptom burden.
Treatment
Treatment includes symptomatic therapies and disease-modifying approaches. Levodopa remains the most effective symptomatic treatment, with new agents like tavapadon targeting D1 dopamine receptors showing promise. Non-pharmacological interventions and deep brain stimulation complement drug therapy. Disease-modifying therapies under development focus on reducing alpha-synuclein aggregation (immunotherapies), inhibiting LRRK2 mutations, enhancing glucocerebrosidase activity (ambroxol), and gene therapy (AAV2-GDNF) to protect neurons and slow progression.
Management, Daily Living, and Support
Patient-centered, multidisciplinary care is essential due to PD’s complex motor and non-motor symptoms. Care models increasingly shift services to community and home settings to improve accessibility, as exemplified by Singapore’s community programs. Daily living is significantly impacted by motor impairments and cognitive decline, affecting self-care, social interaction, and emotional well-being. Assessment tools like the PD-AID and ChulaPD ADL questionnaires help evaluate functional limitations. Support networks, including local groups and online communities such as the Parkinson’s Buddy Network and PatientsLikeMe, provide emotional and practical assistance, enhancing quality of life.
Research and Future Directions
Research focuses on understanding PD mechanisms and developing therapies beyond symptom relief. Gene therapies like AAV2-GDNF aim for durable neuroprotection. Immunotherapies target alpha-synuclein clearance, while enzyme modulators such as ambroxol and LRRK2 inhibitors enter advanced trials. Cell therapies and GLP-1 receptor agonists show potential in early studies. Advances in biomarkers, including exosome-related genes and imaging, support early diagnosis and monitoring. Large-scale collaborative trials, such as the EJS ACT-PD study, accelerate therapeutic development.
Impact and Public Awareness
PD’s growing prevalence imposes substantial economic and healthcare burdens—estimated at $52 billion annually in the U.S.—and affects patients’ daily functioning and quality of life. Access to specialized care varies regionally, with delays in diagnosis and treatment especially in underserved areas. Social support through patient groups and community resources is crucial. Public awareness has been enhanced by notable individuals sharing their diagnoses and community engagement efforts, which help reduce stigma and inform research priorities despite challenges in communicating complex risk factors.
The content is provided by Avery Redwood, Scopewires
