The different subtypes of Parkinson’s
Parkinson’s is different for everyone — but did you know there are also different subtypes of the condition? It’s an idea that has been around for a few years now, so what progress has been made towards diagnosing different subtypes of Parkinson’s?
- Parkinson’s itself is now regarded as an umbrella term for several conditions that have different symptoms and progression rates.
- Being able to identify these subtypes would improve the use of treatments we have today, and also speed up the search for new and better treatments and a cure.
- Researchers have been trying to categorise different combinations of symptoms into subtypes and to find out which subtypes progress faster or slower than average.
Are there types of Parkinson’s?
Over the last decade, it has become apparent that the way we currently diagnose Parkinson’s as a single condition is an oversimplification. This is likely impacting both the quality of care people with Parkinson’s receive, as well as research into new and better treatments.
When we consider how Parkinson’s affects people so differently, the idea that there might be many subtypes of the condition shouldn’t come as a shock. It’s clear that not everyone has the same symptoms, as Martin writes about in his blog:
Parkinson’s itself is likely an umbrella term for several subtypes of the condition. We could consider the future of Parkinson’s diagnosis to follow a similar path to say breast cancer, which is no longer seen as a single condition but a collection of conditions that happen to occur in the same area of the body but have different causes and respond differently to treatments.
So researchers are now investing time and energy in trying to unpick these different subtypes in Parkinson’s — research that will hopefully give people answers to some really important questions, such as:
- What’s the best type of therapy for me?
- What symptoms will I develop? and,
- How fast will my Parkinson’s progress?
Progress in subtyping Parkinson’s
To find out how far we have come, we have to look back at developments that have been made into subtyping Parkinson’s.
The Oxford Parkinson’s Disease Centre
We started writing about this topic in 2015, at the time there were a few papers detailing small scale studies about how Parkinson’s affects people differently, but it was clear that more data was needed.
Fortunately, Parkinson’s UK had recently renewed a grant from the Oxford Parkinson’s Disease Centre to support the world-leading Discovery project. This included a study led by Dr Michele Hu with over 1,400 participants with and without Parkinson’s that might shed more light on the subtyping situation.
“We’ve discovered that there are differences between men and women who have Parkinson’s. Men are more likely to experience problems with memory, postural hypotension (dizziness on standing) and sleep problems. While women tend to experience more problems with posture and balance.
“Even more excitingly, we think that we are beginning to be able to separate the people with Parkinson’s in our study into distinct groups based on their symptoms and how the condition is progressing.”
— Dr Michele Hu, University of Oxford (2015)
It was a study that might open the door to separating Parkinson’s out into groups. Something that, if it were made possible, could improve not only how we treat Parkinson’s today but would also play a vital role in developing and testing new treatments that may slow or stop the condition.
Different types of symptoms
One of the first attempts to separate Parkinson’s into different subtypes based on symptoms experienced came from the Oxford Parkinson’s Disease Centre a couple of years later. In a condition where every individual is different, this pioneering study had discovered 5 potential subtypes by analysing both the movement (motor) and non-movement (non-motor) symptoms that 769 people with Parkinson’s experienced. You can read about these types in a previous blog.
In the discussion of this paper, the researchers were keen to point out that they didn’t yet know if these subtypes would predict the progression and types of symptoms people would develop. However, other studies were starting to publish the first information about what symptoms may be linked to faster progression of Parkinson’s.
One such study was lead by a Canadian team and analysed data from 113 people with Parkinson’s. In this study, the researchers suggested that early symptoms of mild cognitive impairment, blood-pressure related dizziness on standing, and REM-sleep behaviour disorder may identify a subgroup of people with a more rapidly progressing condition.
Using subtypes to predict the progression of Parkinson’s
Over the course of the next couple of years several more studies were published that further explored the ability to use the subtypes of Parkinson’s to predict the progression of Parkinson’s. Here are the highlights from a few of them:
1. Tracking Parkinson’s joins forces with the Oxford Parkinson’s Disease Centre
In 2018, Tracking Parkinson’s was the largest, in-depth study of the condition ever attempted, a title it still holds to this date. The project had been running for 5 years and had data from 2,600 participants (people with Parkinson’s and their siblings) across 70 hospitals in the UK.
Using sophisticated data analysis on the types of motor and non-motor symptoms people had when joining the research studies, the teams identified 4 possible subtypes (or ‘clusters’) of Parkinson’s:
Subtype I: Prominent tremor on one side, an average level of non-motor symptoms and responding poorly to levodopa.
Subtype II: Mild motor and non-motor symptoms.
Subtype III: Severe movement symptoms, poor psychological well-being and poor sleep.
Subtype IIII: Symmetrical motor symptoms (meaning that they are equally affected on both sides of the body), poor sense of smell, low blood pressure, memory problems and responding poorly to levodopa .
— Adapted from “Developing and validating Parkinson’s disease subtypes and their motor and cognitive progression” (2018)
And for the first time, researchers linked these subtypes to progression rates. Those in the last subtype were likely to experience the fastest progression of their symptoms, while the middle two progressed at an average rate, and those in the first seemed to have the slowest progressing form of the condition.
2. Italian researchers also find subtypes are linked to progression
In the same year, another smaller study was published that identified three main subtypes of Parkinson’s based on the main motor symptom that people experienced.
Subtype I: Predominant tremor.
Subtype II: Mixed motor symptoms, with no prevailing motor features.
Subtype II: Stiffness or inflexibility of the muscles, or balance or walking difficulties as their main symptoms.
— Adapted from “Psychiatric profile of motor subtypes of de novo drug‐naïve Parkinson’s disease patients” (2018)
The team also linked the subtypes with different progression rates, with those in subtype III usually showing a faster progression and were more likely to develop memory problems and dementia. While those in subtype I, the progression was slower and people were less likely to develop memory problems, visual hallucinations, and depression.
3. Further support from a US based study
In 2019, data from 446 newly diagnosed people with Parkinson’s participating in the Parkinson’s Progression Markers Initiative (PPMI) was published.
The study identified 3 subtypes of Parkinson’s with some similarities to the previous example.
Subtype I: Mild baseline, moderate motor progression — 43.1% of the participants. Characterised by moderate progression of motor symptoms but less likely to experience memory and thinking problems.
Subtype II: Moderate baseline, mild progression — 22.9% of the participants. Characterised by slow progression of motor and non-motor symptoms.
Subtype III: Severe baseline, rapid progression — 33.9% of the participants. Characterised by rapid progression of both motor and non-motor symptoms.
— Adapted from “Data-Driven Subtyping of Parkinson’s Disease Using Longitudinal Clinical Records: A Cohort Study” (2019)
The main conclusion from this paper was that the progression rates in this study did not necessarily associate with how severe a person’s symptoms were on entering the study. They also suggested that the progression rate of non-motor symptoms is not necessarily correlated with the progression rate of motor symptoms.
From subtypes to better treatments
With the identification of different subtypes of Parkinson’s progressing, researchers at UCL wanted to find out if they could use donated tissue from the Parkinson’s UK Brian Bank to retrospectively subtype Parkinson’s. They wanted to look at the early symptoms of Parkinson's to see if it could predict how Parkinson’s would progress.
The team analysed the medical records from 111 patients whose brains arrived at the Brain Bank between 2009 and 2017. They discovered that separating people into three subtypes could predict how the condition progressed.
The subtypes they used were:
- ‘mild-motor predominant’ — often diagnosed in the mid-50s those in this category had less severe symptoms and a slower rate of progression.
- ‘diffuse malignant’ — the more severe type of Parkinson’s often diagnosed later in life (on average 70.3 years) that was faster progressing and more likely to develop complications such as dementia.
Talking about the study to Neurology Today, Thomas T. Warner, MD, PhD, director of the Reta Lila Weston Institute at UCL Institute of Neurology, said:
“This analysis suggests that we may be able to use this type of classification to help guide treatment, as well as help patients better understand their disease course.”
More data = more success
With researchers seeing the potential of these subtypes to change the way to treat and manage Parkinson’s, it is clear why this is a growing area of research. But, we do not yet have a definitive set of subtypes for Parkinson’s. One of the reasons for this, is the complexity of the condition and the way it fluctuates hour to hour, and day to day.
Even back in 2015, it was clear that simply collecting detailed information when people visited the clinic wasn’t going to be good enough to truly understand Parkinson’s.
“Parkinson’s is a fluctuating condition, so how can I really know how it affects the individual throughout the day and between visits? And how can I really know how if the treatment I prescribe is right for that individual?…
“…We’re going to be asking some participants in the Discovery study to take one of our mobile phones home with them and complete the tests at different times over the course of a week. This will give us vital information about how their Parkinson’s affects them from day-to-day which we’ve never really had access to before.”
— Dr Michele Hu, University of Oxford (2015)
And that’s what Michele’s team have been doing for nearly 5 years, and they are starting to find very interesting things from this data. They believe, using technology, will greatly enhance the ability to separate Parkinson’s into different subtypes. It will also help the detection of subtypes associated with the development of symptoms which impact greatly on quality of life, such as problems with balance and falls. This could lead to better management of such symptoms, where people could be identified earlier to receive physiotherapy to improve balance and muscle strength to decrease the risk of falling.
Over the last few years, researchers have attempted to come up with a classification system for Parkinson’s based on the types and severity of motor symptoms and the presence of other non-motor symptoms at diagnosis. There are now a handful of classification systems that have been proposed but few neurologists rely on them in discussions about what their patients may expect.
This is because there are still some subtle but important differences between the results from individual studies, leading to questions about how accurate they might be and whether they should be used soon after the diagnosis of Parkinson’s. More research is still required to better define exactly what the different subtypes are, to develop tests that can differentiate between them, and to confirm how this impacts on progression of Parkinson’s and the types of symptoms people may later develop. It is hard to tell how long this might take.
But perhaps more importantly, more research is needed to better understand why there are different types of Parkinson’s in the first place. Understanding what is happening to those precious brain cells could potentially lead us to more personalised treatments that have the potential to stop Parkinson’s in its tracks.
Subtyping people with Parkinson’s may be the first step towards this much more important goal. After all, once we know what’s going wrong it becomes much easier to design strategies to fix the problem.
We know there are many problems that impact on the brain cells affected by Parkinson’s — faulty batteries, rubbish recycling and chemical stresses to name a few — and this adds to the complexity of the condition as it may not be the same issues playing the lead role in the different subtypes of Parkinson’s. Identifying the trigger, the original domino that fell and started a cascade of issues that ultimately leads to the loss of brain cells, could be the difference between success and failure in clinical trials of treatments that aim to slow the progression of Parkinson’s.
So while subtyping Parkinson’s may help people better understand their condition and access more tailored treatments, the potential to develop and test treatments that are designed to stop the problems instead of masking them is immense. And with the progress into subtyping that has been made in the last 5 year, it is clear that this is one area of research we should be keeping an eye on.