The prevalence of Parkinson's disease is increasing worldwide, with 12m–17m people expected to be suffering from the condition by 2040, the authors of a three-paper series in The Lancet say.
The authors address the current state of knowledge on the epidemiology of Parkinson’s disease, recent advances in their understanding of its pathogenesis, as well as the latest evidence supporting the optimal medical, surgical and physical treatment.
The prevalence of the disease, the second most common neurodegenerative disorder, is increasing worldwide. Characterised clinically by progressive asymmetric slowness of movement, rigidity, tremor, gait disturbance, and a wide range of non-motor symptoms, its aetiology is multi-factorial, involving both genetic and environmental risk factors.
Despite the growing public health burden, current treatment strategies are focused solely on symptom management, and disease-modifying treatments are urgently needed to help prevent development of the most disabling refractory symptoms, like gait and balance difficulties, cognitive impairment and dementia, and speech and swallowing problems.
Parkinson’s is second only to Alzheimer’s disease in the list of most common neurodegenerative disorders and, with increasing life expectancies and fewer competing causes of death, its prevalence is expected to increase to 12m–17m people by 2040.
Such a rise will require increasing amounts of human and care resources, which will add to the strain already felt by health systems globally.
The issue will be particularly acute in low-income and middle-income countries, where availability of treatments and supporting therapy are lowest; even in high-income countries, both minority ethnic groups and those in rural areas face broader challenges in accessing care.
Difficulties in the diagnosis of Parkinson’s (especially early disease) also hamper effective care, and there is much need for a better understanding of the specific needs of minority ethnic patients, in whom the clinical manifestations and morbidities associated with Parkinson’s are still poorly described.
As detailed in papers 1 and 2 of the series, the pathogenesis of the disease remains largely elusive. The cause is multi-factorial and, although there is consensus among experts that it is an age-related disease, questions regarding the extent to which Parkinson’s can be attributed to external drivers (such as pollutants) do not yet have clear answers.
Insights have been derived from genetics and molecular pathology. Biochemical studies, investigation of transplanted neurons in patients with Parkinson’s, and cell and animal model studies, suggest that abnormal aggregation of α-synuclein and spreading of pathology between the gut, brainstem, and higher brain regions probably underlie the development and progression of the disease.
At a cellular level, abnormal mitochondrial, lysosomal, and endosomal function can be identified in both monogenic and sporadic Parkinson’s, suggesting multiple potential treatment approaches.
Recent work has also highlighted maladaptive immune and inflammatory responses, possibly triggered in the gut, that accelerate the pathogenesis of the disease.
Although there are currently no disease-modifying treatments for Parkinson’s, we now have a solid basis for the development of rational neuro-protective therapies that we hope will halt the progression of this disabling neurological condition.
Paper 3 reviews the latest evidence on the optimal management of the disease.
Ultimately, research needs to aim for treatments that can alter the course of Parkinson’s but, despite growing research funding, major breakthroughs have been few and far between.
A move towards biologically based criteria for its classification is proving controversial, but it is hoped these new criteria can help detect the disease in its early stages, preferably in the prodromal phase, which might also pave the way for further research on disease-modifying therapies.
Meanwhile, clinical studies of new drugs to better treat dyskinesia and other motor symptoms are under way, as are trials covering several known mechanisms of disease in Parkinson’s.
Non-pharmacological approaches, such as robotics to help with gait impairments, and music-based interventions to help manage various non-motor symptoms, also show promise.
Additionally, the potential value of lifestyle interventions to improve control of Parkinson’s symptoms should not be overlooked, particularly regarding physical activity and nutrition, which offer some means to take care out of the clinic and into a patient’s home.
Most health systems worldwide are ill-prepared to deal with the growing population of patients with Parkinson’s. Despite an acute need for better access to specialist care, there is still much to be done in ensuring that essential drugs reach patients.
Data from 2017 show that levodopa and carbidopa – mainstays of Parkinson’s treatment – were consistently available in primary care settings in only 37 of 110 countries (and just three in Africa, and none in southeast Asia).
Informal carers, especially women, remain essential for many patients with Parkinson’s, yet their experiences are often overlooked, and there is little support for caregivers globally.
Tackling stigma against the disease (which can lead to higher rates of depression, comorbidities and mortality in individuals with Parkinson’s) and dispelling the misconception that it is a natural consequence of ageing can be achieved through education and advocacy – not least among healthcare providers, especially to help to improve communication around a diagnosis of the disease.
A disease-modifying treatment to slow, halt and reverse progression of Parkinson’s must be the goal to strive for.
But in the meantime, concluded the authors, improvements in basic and specialist care for patients with Parkinson’s – supporting caregivers, ensuring access to simple medication regimens, and expanding the provision of primary and multidisciplinary care for comorbidities – would make tremendous differences to the care and quality of life for millions of patients worldwide.
The Lancet article – What’s next in Parkinson’s Disease? (Open access)
The Lancet article – The epidemiology of Parkinson's disease (Open access)
The Lancet article – The pathogenesis of Parkinson's disease (Open access)
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