Parkinson’s Disease and the Gut
Parkinson’s disease is primarily a neurological condition; however, symptoms also manifest outside of the brain itself, including within the gut (gastrointestinal tract). This article aims to provide a simple background to Parkinson’s disease, and some insights into how these GI symptoms may arise and how we can treat them. Increased awareness of these often-overlooked GI issues in Parkinson’s might lead to better understanding of the condition by researchers, as well as improved treatment and quality of life for patients.
Parkinson’s Disease is a Neurodegenerative Condition
Parkinson’s disease is a chronic condition in which neurons within a region of the brain responsible for the control of movement break down and die. These neuronal cells use a chemical called dopamine to communicate with each other. It is this complex dopamine-based communication between neurons that is responsible for control of movement. Death of these neurons is referred to as dopaminergic neurodegeneration, and directly leads to the movement-related symptoms of the condition (motor symptoms). These include tremors, changes in posture, stiffness, and a slowness of movement, also referred to as bradykinesia.1,2
Importantly, and often little appreciated, is the fact that Parkinson’s disease can also affect neurons outside of the brain. Neuronal connections are made throughout the body, and connect all parts of the body to the brain and spinal cord, including to the GI tract. In particular, Parkinson’s interferes with normal communication between the central nervous system, and the esophagus and stomach.3 Parkinson’s can also affect the enteric nervous system, a network of neurons that functions with a considerable level of independence from the brain and central nervous system, and that is highly involved in controlling the intestinal tract and digestion.3,4 By affecting both the central and enteric nervous systems, Parkinson’s disease may give rise to an array of GI symptoms.
Prevalence and Symptoms
In the majority of cases, Parkinson’s disease develops with no directly attributable cause, although age and genetics are factors, while exposure to environmental pollutants might also play a role.5-7 There are more than 6 million people living with Parkinson’s disease around the globe, including approximately 84,000 Canadians 40 years of age and older with either Parkinson’s disease or another form of parkinsonism.8,9 Increasing age is a clear risk factor in the development of Parkinson’s, with diagnosis before 50 years of age generally described as ‘young-onset Parkinson’s disease’ and accounting for only a small proportion of cases.9,10 Over 60 years of age, Parkinson’s affects 1 in every 100 people, increasing to 5 in every 100 over 85 years of age.5 Healthcare and social costs associated with caring for those living with Parkinson’s is expected to increase due to an aging Canadian population.8,11
Symptoms of Parkinson’s disease increase in breadth and severity over time as the condition advances, so Parkinson’s is described as a progressive condition.12 Parkinson’s disease progresses slowly, meaning that those living with the condition may notice only minor symptoms at first and, therefore, go undiagnosed for some time. At present, there is no clinical test for Parkinson’s, so diagnosis is based upon the detection and progression of motor symptoms, both before and after treatment. As symptoms can vary between patients and over time, Parkinson’s disease diagnosis can be difficult to confirm, especially at an early stage of the disease.13
With such a focus placed by physicians and researchers upon the core motor symptoms of the disease, non-motor symptoms of Parkinson’s, including those of the GI tract, can become under-appreciated by the Parkinson’s research and patient communities. This has resulted in patients under-reporting GI symptoms. Researchers estimate that more than half of non-motor symptoms within the Parkinson’s community go un-reported owing to embarrassment, or because patients are unaware that their non-motor and GI problems may even be associated with Parkinson’s disease.14,15 Non-motor symptoms can significantly affect quality of life when left unaddressed, so improving public awareness of the GI symptoms of Parkinson’s disease is of the utmost importance.
“Patients also often indicate that their non-motor symptoms are more difficult to manage than their motor problems and may sometimes result in their hospitalization and institutionalization”16
Constipation and Parkinson’s Disease
Constipation is one of the most commonly reported GI symptoms of Parkinson’s disease, affecting 60-80% of patients.17,18 Constipation occurs when movement of material through the GI system slows down. This slowing can result from the direct effects of Parkinson’s disease upon the action of intestinal muscles that would normally act to massage material through the intestines in a wave-like action (peristalsis), or indirectly through side-effects of some medications.19 In severe cases, accounting for approximately 7% of those with a parkinsonism, compromised peristalsis can lead to complete gut blockage resulting in further symptoms such as cramping, abdominal pain, vomiting, and bloating.16
Patients may find that regular exercise along with an increase in fluid and dietary fibre intake can help alleviate their constipation.13,15,20 One of the primary functions of the large intestine is the reabsorption of water; therefore, maintaining levels of hydration can act to soften stools, and aid passage of material through the intestines.17,19-21 Constipation is a common side effect of some classes of drugs used to treat motor symptoms of Parkinson’s disease, particularly anticholinergics.16,21 Therefore, should constipation persist despite some non-drug measures, patients may wish to see their doctor about optimizing the type and dosage of drugs being taken to counteract motor symptoms of the disease. Balancing the dosage and types of anti-Parkinsonian medication being taken may provide an improved trade-off between motor and GI symptoms. Stool softeners such as docusate sodium alone, or in combination with fibre-based bulk-forming agents, can improve movement of food through the intestines, as well as the passing of stools.13,16,20,21
If these treatments do not reduce constipation, then there are a variety of laxative options to consider. Osmotic laxatives encourage bowel movements by drawing water into the bowel from the nearby tissue, thereby softening the stool. Polyethylene glycol (PEG) is an example of a well-tolerated osmotic laxative that the American Academy of Neurology and the International Parkinson and Movement Disorder Society have recommended as an effective and safe treatment for Parkinson’s patients.16,20-22 Lactulose is another osmotic laxative that is relatively mild and is sometimes used to treat chronic constipation. This makes lactulose an attractive alternative, should PEG prove ineffective or unsuitable.15,16,21 Some other classes of osmotic laxative, such as salt preparations, are not intended for long-term use, and may be unsuitable for the routine treatment of Parkinson’s disease GI symptoms, except as a last resort.23 Stimulant laxatives such as bisacodyl increase peristalsis by directly affecting the muscles of the digestive system. However, some physicians harbour concerns that these laxatives may result in the gut becoming dependent on the stimulant laxative for normal activity. As a result, physicians carefully consider stimulant laxatives in the context of chronic conditions such as Parkinson’s disease, but might prescribe them if constipation persists after trying other therapeutic options.13,23 Parkinson Canada notes that while use of certain laxatives are “generally not recommended for extended periods of time, many patients nevertheless require daily laxatives”.21 Ultimately, it is important that patients are aware of the options available to treat their Parkinson’s-associated constipation, as well as the side effects associated with those treatments. In this way, in consultation with their doctor and pharmacist, patients may work toward a treatment regime that is right for them.
Drooling and Swallowing
Up to 80% of those living with a parkinsonism experience drooling (sialorrhea), which makes it among the most common GI symptoms of the disease. However, this figure varies widely among studies.16,24 Drooling can result from over-production of saliva, the over-retention of saliva in the mouth, or a combination of these two factors together. Research suggests that the majority of those with Parkinson’s actually produce less saliva as a result of their condition, and that it is therefore most commonly a result of an impaired ability to swallow.25 Difficulty swallowing (dysphagia) occurs in about 50% of those with parkinsonism, and is a result of bradykinesia, which can reduce control of the tongue and esophagus.16,24-26 A stooped posture that pitches the head forwards and downwards, as well as unintentional mouth opening, may develop as a result of Parkinson’s disease. These features can compound accumulation of saliva in the mouth, and increase the likelihood of drooling developing.24 In extreme cases, excessive drooling can lead to malnutrition, and even the potentially fatal complications of saliva-induced asphyxiation, or aspiration pneumonia, so physicians and patients should address and not overlook this symptom.25–27
There are several non-medication treatments for the associated issues of swallowing and drooling that may be beneficial to those with Parkinson’s. Chewing gum or sucking on hard candy can improve swallowing and reduce drooling.22,28 It is important to choose sugarless products in order to avoid the development of cavities, especially as symptoms of Parkinson’s disease can interfere with dental hygiene practices.29 Speech and position therapies may reduce drooling through improved head posture, strengthening of the tongue, and voluntary airway protection techniques.16,30 Thickening liquid to the consistency of nectar or honey before drinking can make it easier to swallow.13,29 As with the treatment of constipation, the next step to reduce drooling and swallowing problems that result from Parkinson’s disease is to determine, with the aid of a physician, whether it is possible to adjust treatments for motor symptoms that may be contributing to these symptoms. Examples of drugs that can cause drooling are numerous, and include: acetylcholinesterase inhibitors, the antipsychotic quetiapine, and adrenergic receptor agonists.16 In the case of severe drooling, pharmacological solutions do exist, and include injections of botulinum toxin (Botox®) to inhibit saliva production. However, such injections, while thought to be effective, come with some side effects and a lack of significant guidance as to best practice for drug delivery.16,20,31 Side effects can include dry mouth, neck pain, worsened gait, and diarrhea.31 Another option for pharmacological treatment of drooling include anticholinergic drugs such as atropine sulphate, or glycopyrrolate (Robinul®).15,24 Parkinson Canada notes that side effects of these anticholinergic drugs are uncommon at low dose; however, those that can otherwise occur are likely to worsen other GI symptoms associated with the disease. Anticholinergic drugs should be used with caution by patients with Parkinson’s disease, as their side effects include nausea and constipation.16,21
Nausea, Vomiting, and Gastroparesis
Nausea and vomiting are reported by many Parkinson’s patients, and may be the result of dopamine-based treatments aimed at alleviating motor symptoms.32 These symptoms can occur as the enteric nervous system of the GI tract, like the central nervous system, makes use of dopamine as a means of communication between neurons.33 Identical receptors for dopamine can be found in the GI tract as in the brain, and these play an important role in the movement of material through the intestinal tract.34 Nausea and vomiting can result from dopamine receptors within the gut interacting with Parkinson’s treatments, such as levodopa, that are intended to act upon dopamine receptors in the brain. These symptoms can alleviate over time; however, in cases of severe reaction to levodopa therapy, adjustments to treatment made in conjunction with a physician may be necessary. Such adjustments can include changes to dosage, or simply how such medication is taken, for example, by taking medication with a meal.21
Another reason that nausea and vomiting may develop is as a result of severely delayed gastric emptying, also known as gastroparesis. Gastroparesis might present as a GI complication of Parkinson’s and is observed in more than 70% of patients at some point.16,29 The symptoms of delayed gastric emptying include nausea, vomiting, feeling full after only a small amount of food (early satiety), and a feeling of persistence of food in the stomach (postprandial fullness), which can lead to weight loss, malnutrition, and dehydration.29,35
There are very few safe and proven treatment options available for gastroparesis. Lifestyle changes, such as having smaller, more frequent, low-fat meals with plenty of water may help to minimize symptoms. Similarly, walking after meals, and regular exercise, may also help manage symptoms.16,20 One of the few drugs known to be effective for the treatment of gastroparesis is domperidone. Domperidone works by blocking the dopamine receptors of the GI tract and, as it is unable to enter the brain, domperidone does not affect Parkinson’s motor symptoms or levodopa treatment.16,21,36 However, recent evidence has shown that while effective at treating gastroparesis, domperidone poses a risk of serious heart problems including cardiac arrhythmia and sudden cardiac death in certain circumstances.37,38 Domperidone is not a legally marketed drug for human consumption in the United States, and is only available with a prescription in Canada. Unfortunately, metoclopramide, another dopamine blocking drug available for the treatment of gastroparesis and for nausea, is not appropriate for the treatment of Parkinson’s disease. Unlike domperidone, metoclopramide is able to cross into the brain where it can interfere with dopamine-based treatments such as levodopa and worsen motor symptoms.16,21
Considering GI and Non-Motor Symptoms in the Treatment and Research of Parkinson’s Disease
GI symptoms have a significant influence on the quality of life of those living with Parkinson’s, and can reduce the effectiveness of medications such as levodopa. As an example, drooling and difficulty swallowing can result in difficulty taking oral prescriptions. Similarly, gastroparesis can result in changes in response to levodopa treatment by affecting absorption of the drug into the blood stream, and, therefore, into the brain.20,29,39-41 The result of this can be more severe motor-fluctuations in patients, as is also seen in those with other GI conditions that can decrease levodopa absorption, such as small intestinal bacterial overgrowth, or infection with Helicobacter pylori.42 The significance of this is that through appropriate treatment of non-motor and GI symptoms of Parkinson’s disease, there is potential for patients to also experience improvement in their response to treatment for motor-symptoms, for a broad improvement in quality of life.
Non-motor symptoms of Parkinson’s are now becoming an integral focus of many scientists who study the disease. In part, this is due to the observation that GI symptoms such as constipation, as well as mood, sleep, and smell disorders, are commonly experienced by patients before the better-appreciated motor symptoms of the disease become evident.43-46 Scientists hope that such ‘premotor’ symptoms will allow detection of Parkinson’s at an earlier stage. This is important, as such findings may open the door to research into treatments that can halt the progression of the disease before it can affect the brain. Recent clinical evidence even suggests that the degenerative processes of Parkinson’s disease observed in the brain may actually originate in the gut, and only spread to the central nervous system through the brain-gut axis as the disease progresses.29,47-50
Ultimately, Parkinson’s disease is a condition that has been defined and diagnosed based upon motor symptoms that indicate the degeneration of dopaminergic neurons in the brain. It is natural that some within the Parkinson’s community could consider non-motor symptoms of the disease to be of less significance than motor symptoms. For those living with the condition, it is important to appreciate that gastrointestinal symptoms being experienced may relate to their Parkinson’s disease, and should not be neglected when speaking to their doctor. For the Parkinson’s research community, an improved appreciation of the importance of GI symptoms of Parkinson’s disease is improving our understanding of the condition, and has the potential to improve treatment for patients both now, and into the future.