Picture a disease that gradually, almost unnoticeably, steals your ability to control your own body movements. That’s a peek into Parkinson’s disease (PD), a progressive neurodegenerative condition initially extensively described by James Parkinson in 18171, 2. It affects millions of people globally, and is the second most prevalent neurodegenerative disease after Alzheimer’s3. At its core, PD primarily involves the relentless neurodegeneration of neurons in one section of the brain named the substantia nigra, the very same cells that are responsible for generating dopamine, an essential chemical messenger for smooth coordinated movement4, 5.
The hallmarks: symptoms of Parkinson’s
Parkinson’s disease often starts subtly, its initial symptoms being easily confused with other diseases, or simply, the aging process. However, as the disease progresses, though, a distinct set of symptoms appears, providing a better picture of its impact on everyday life. These are usually separated into motor and non-motor challenges.
Motor symptoms: the cardinal signs
Although Parkinson’s strikes each person differently, the most familiar aspects are the motor symptoms, which occur due to the death of the brain cells that produce dopamine. These usually consist of:
- Tremor: Typically, the most obvious indication, this is a rhythmic, involuntary shaking that typically starts in a limb when it is at rest6. It often begins on one side of the body.
- Bradykinesia: This refers to a severe slowness, making the simplest activities almost impossibly difficult and exhausting7. Individuals may experience a shuffling gait, trouble initiating movements, or diminished arm swing when walking.
- Rigidity: An ongoing stiffness or lack of flexibility in the limbs and trunk that leads to muscle ache and restricts an individual’s range of motion8.
- Postural instability: Poor balance and coordination that raises the risk of falls and renders easy turns or standing upright difficult9.
Apart from these primary signs, other motor difficulties may evolve, such as diminished or ‘masked’ facial expression, softer speech (hypophonia), trouble swallowing (dysphagia), or handwriting that gets significantly smaller (micrographia)10-13.
Non-motor symptoms
Parkinson’s is not only a movement disorder, however. Most people have a host of non-motor symptoms that may frequently appear years, even decades, prior to developing any movement difficulties. Some of these underlying challenges may sometimes be even more impactful on daily living:
- Olfactory dysfunction: A decreased or absent sense of smell is a frequent and often early sign14.
- Sleep disorders: This usually encompasses REM sleep behavior disorder (RBD), in which individuals actually perform the movements of their dreams15.
- Chronic constipation: A long-standing and frequently neglected gastrointestinal problem16.
- Mood disorders: Depression and anxiety are extremely common, usually manifesting as early as motor symptoms17.
- Cognitive changes: These may be anywhere from mild impaired memory or attention to more substantial impairment and, later on, dementia18.
- Other common non-motor symptoms include chronic pain, debilitating fatigue, and bladder problems19-21.
The brain’s battle: pathophysiology of Parkinson’s
Fundamentally, Parkinson’s is a struggle within the brain itself. It’s a tragic destruction of the critical dopamine-making neurons in the substantia nigra. As they die, the brain’s levels of dopamine take a plunge, disrupting the delicate balance necessary for smooth movement.
A second characteristic feature of Parkinson’s is the occurrence of Lewy bodies and Lewy neurites22. These are abnormal clumps of protein within brain cells. They consist mainly of a sticky, misfolded protein called alpha-synuclein23. Although classically considered as a brain disease, evidence now indicates that this alpha-synuclein misfolding can actually start much earlier, possibly in the gut, majorly influenced by microbial proteins24.
Unraveling the causes and risk factors
For the majority of people with Parkinson’s, the cause is unknown, this is referred to as idiopathic Parkinson’s25. It is thought to be the result of a multifaceted combination of factors.
Genetics contribute in a minority of instances. Certain gene mutations have been identified, especially in familial cases, with certain vulnerabilities increasing risk even in the absence of a specific genetic cause26.
Environmental factors are also being studied. Potential connections include exposure to certain pesticides or prior history of head injury, although these connections are less specific27, 28.
Increasingly, research is indicating the role of emerging biological factors. This includes the gut microbiome, where some studies examine the role of factors such as biofilm-associated proteins from gut microbes in promoting the misfolding of proteins such as alpha-synuclein and affecting disease progression through the gut-brain axis24.
To conclude, age continues to pose the greatest known risk factor, with PD incidence climbing considerably as individuals age29. Although some factors, such as caffeine or exercise, are occasionally proposed to provide a lesser risk, more conclusive research is currently under progress30, 31.
Diagnosing Parkinson’s disease
Diagnosing Parkinson’s isn’t as straightforward as a blood test or confirmatory scan. Rather, it’s principally a clinical diagnosis. This means that physicians exceedingly rely on a complete neurological exam, very closely observing an individual’s typical motor symptoms and taking a complete medical history. A vital first step is, additionally, to exclude other disorders that can mimic Parkinson’s, such as essential tremor or side effects of some medications.
To aid in confirming suspicions and distinguishing the condition, physicians sometimes employ specific imaging. A Dopamine Transporter Scan (DaTscan), for example, can aid in confirming a lack of dopamine-producing brain neurons, which is supportive of a Parkinson’s diagnosis and aids in distinguishing it from other conditions in which the dopamine system is intact32. An MRI of the brain is also usually done, not to diagnose Parkinson’s itself, but to exclude other structural brain disorders that may be producing the same symptoms.
Lastly, one of the strongest clues is an individual’s response to treatment: a notable and favorable improvement in symptoms following levodopa medication is typically strong evidence of a Parkinson’s diagnosis33.
Managing Parkinson’s: treatment and support
It is worth noting that although there is still no cure for Parkinson’s, the treatments available today are extremely successful in controlling symptoms and greatly enhance the quality of life.
Pharmacological interventions are the pillar of treatment. Levodopa is usually regarded as the gold standard, because it acts to increase the level of dopamine in the brain34. Other drugs such as dopamine agonists work by simulating the effect of dopamine, and MAO-B inhibitors by preventing the breakdown of dopamine35, 36. Physicians also prescribe other drugs to specifically treat particular motor difficulties (such as dyskinesia) or non-motor symptoms (such as depression, anxiety, or insomnia), individually tailoring these to each patient to maximize the control of symptoms37.
For certain individuals with advanced PD and severe motor fluctuations, surgical treatments such as deep brain stimulation (DBS) may be considered38. This entails implanting electrodes in certain areas of the brain to control abnormal brain activity.
Aside from medications, non-pharmacologic treatments are also absolutely essential. Physical therapy enhances movement, balance, and walking39. Occupational therapy enhances activities of daily living, while speech therapy tackles voice and swallowing difficulties40, 41. Regular exercise, a well-balanced diet, and adjustments in lifestyle are also central to overall well-being.
Looking to the future, incipient therapies are constantly being explored. Researchers are also studying gene therapies, stem cell therapies, and new approaches that focus on preserving neurons and arresting disease progression42-44. Included in these are promising areas for therapies directed at the gut microbiome to modify the disease process24.
Living with Parkinson’s: a journey of adaptation
Living with Parkinson’s is a process that very frequently calls for adjustment and a strong network of support. Multidisciplinary care by a team of neurologists, therapists, nurses, and social workers can prove worthwhile45. Learning about the illness and joining support groups has the potential to empower the patient and their family to work through difficulties.
The research field of Parkinson’s is extremely active, and every new finding brings with it new hope. Researchers across the globe have been tirelessly working day and night to deepen our knowledge of this multifaceted disease, seeking improved diagnostics, enhanced treatments, and eventually, a cure.