Friday, 18 January 2019

Great Debates

While there are many great debates happening this week in the UK, perhaps the most interesting happened at today’s biannual meeting of the Association of British Neurologists Movement Disorders Special Interest Group, held in the beautiful Oxford Town Hall. The opening session of the meeting was a debate between two giants of the international Parkinson’s world: Professor Donald Grosset from Glasgow, and Professor Ron Postuma from Montreal.

The topic they were debating was “Should research focus on prodromal disease prevention or improving symptomatic therapies?” Professor Grosset set out the reasons for focussing on better treatments in the complex phase of the disease – when the treatments that we have either fail to work or side effects become increasingly troublesome and diffucult to manage. He also pointed out the near-total lack of well-proven treatments for many of the non-motor aspects of Parkinson’s (a point we have laboured in previous blog posts here). He suggested that detection of the prodromal stage was hit-and-miss and that the best case scenario was that trials in this group would costs hundreds of millions of pounds which would be better served investing in treatments for people with definite Parkinson’s.

Ron Postuma countered his argument and opened with the metaphor central to preventive medicine: people are falling over a waterfall and nearly drowning in the pool below. A man is pulling them out one by one and calls to a bystander to help. The bystander walks away, but returns at the top of the waterfall to stop people from falling down in the first place. Although  this metaphor may seem simplistic, it highlights the importance of focussing on the earliest stages. He went on to simplify the drug treatment of established Parkinson’s as “playing with neurotransmitters” – and no matter how successful one might be at doing that, there is an underlying progression of brain death. To deal with that means to effect a change before disease causing cascade of events has become unstoppable – i.e. in the earliest (prodromal) stages. Finally, he highlighted the seismic changes that have occurred in medicine in the last two generations. Penicillin used to be so expensive that patients given penicillin had their urine collected, the excreted penicillin extracted and given back to the patients to make each vial go further. Wards for women with infected wombs after miscarriages who would almost inevitably succumb to their infections closed within weeks. The AIDS wards that were in most hospitals in the 70s and 80s were empty just a few years after HIV medication started being used. New treatments for advanced cancer have changed the landscape for some of these diseases (including nilotonib which is currently being trialed in Parkinson’s), and the last two years has brought these game-changing experiences to neurological diseases with drugs such as Nucinercin – effectively curing an incurable genetic condition that killed children in their first few years. The message, he said, was clear – things we now take for granted were once hard and very expensive, and for Parkinson’s there is change on the horizon.

The rest of the meeting continued with many other fascinating and useful talks from some of the leaders of British neurology, and has offered many insights and ideas that we at Predict-PD can use to help bring us closer to a robust identificaiton of prodromal Prkinson’s and therefore, another step closer to a cure.


Tuesday, 15 January 2019

PLAIN ENGLISH: Gout and the risk of Parkinson's disease in older adults

First blog post of the year from me and, after feedback from literally everyone, I will be making a concerted effort to make them easy (easier) to understand. I can't get rid of the science I'm afraid... after all this is a research blog. But I (and we) can make bigger efforts to keep the focus on predicting Parkinson's, the PREDICT-PD study ( and related projects. 

The reason this blog was started was to help researchers, patients and the public understand how we use and weigh emerging research, which in turn informs our approach to our work on Parkinson's.

Take this study as an example... it looked at health insurance claims data from the USA over a 6 year period. The researchers looked at the link between claims for gout and subsequent claims for Parkinson's. They observed that, compared to people that made claims for other illnesses, people that claimed for gout were more likely to claim for Parkinson's in subsequent years. This in turn offers a weak suggestion that gout might be in some way linked with a higher risk of Parkinson's. However... we also know that this is only part of a much bigger story.

The biggest determinant of gout is the amount of a chemical in the blood known as uric acid. Generally speaking, people with higher levels of uric acid are more likely to have gout. It has also been noted on multiple occasions that people with Parkinson's tend to have lower levels of uric acid (both after diagnosis and in the years before)... which in turn has led to strategies to try and boost uric acid levels to treat Parkinson's (without introducing gout). 

So how does that make any sense at all?? High uric acid is associated with an increase in gout, gout is associated with an increase of Parkinson's, but Parkinson's is associated with low uric acid levels...?? We seem to be going in circles. 

But what if the explanation is simple... what if Parkinson's disease consumes uric acid and makes it look like low levels of uric acid are causing Parkinson's, when in fact it is the other way around? There have been similar examples in cancer where vitamin E was noted to be low in people that had prostate cancer, leading to the suggestion of supplementing vitamin E to reduce cancer. Instead the cancer rates appeared to increase... so it wasn't that low vitamin E was causing cancer... it was cancer consuming vitamin E and supplementing vitamin E only added more fuel to the fire.

If for some reason Parkinson's consumes uric acid, then gout may actually increase the risk of being diagnosed with Parkinson's and strategies to boost uric acid to treat or protect against Parkinson's may not lead to benefit and have the opposite effect...

Of course, this is speculation and certainly not the final say on the matter. Further research will likely reveal the truth over time...

- Alastair Noyce

BMC Neurol. 2019 Jan 5;19(1):4. doi: 10.1186/s12883-018-1234-x.
Singh JA, Cleveland JD.

BACKGROUND: In the presence of limited available data, our objective was to assess the association of gout with the risk of incident Parkinson's disease (PD) in adults 65 years or older.

METHODS: We used the 5% random sample of Medicare claims data from 2006 to 2012 to examine the association of gout with incident PD. The multivariable Cox regression model adjusted for demographics, comorbidity, and common cardiovascular disease and gout medications. We calculated hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses adjusted for comorbidity categorically, or individually and for additional cardiovascular comorbidities.

RESULTS: In a cohort study, 1.72 million Medicare beneficiaries were eligible. The mean age was 75 years (standard deviation [SD], 7.6), 58% were female, 86% were White and 37% had Charlson-Romano comorbidity index score of ≥2. We found that 22,636 people developed incident PD, 1129 with gout and 21,507 without gout. The respective crude incidence rates of incident PD were 3.7 vs. 2.2 per 1000 person-years. We found that gout was associated with 1.14-times higher hazard ratio (95% CI, 1.07, 1.21) of PD in the main analysis; findings were confirmed in sensitivity analyses. We noted that the risk differed slightly by age; ages 65-75, 75-85 and > 85 had hazard ratios of incident PD with gout of 1.27 (95% CI, 1.16, 1.39), 1.07 (95% CI, 0.97, 1.16) and 0.97 (95% CI, 0.79, 1.20), respectively, but no gender or race differences were noted.

CONCLUSIONS: Gout was associated with a higher risk of incident PD in older adults, with the risk being significant in the age group 65-75 years. Future studies need to assess the mechanisms of this increased risk.

Monday, 14 January 2019

The hard miles

Happy new year to you all. I hope you have had a good start to the year.

2018 was a busy year for us. In this map, we have highlighted all the participants we have visited at their homes. The red markers are our participants with idiopathic anosmia (smell loss) and the blue markers are regular members of the Predict-PD study. Between us we have travelled literally thousands of miles.

The information we have collected will be vital in helping to define the 'prodromal phase' of Parkinson's, and potentially identifying key features that might allow identification of early Parkinson's. This will be vital in getting the right people into trials of potentially disease modifying treatments.

This study is funded by Parkinson's UK. Many of us in the research team are also movement disorders neurologists and see people with Parkinson's in clinic, and we see the benefits that Parkinson's UK also provide to individuals and even at a national policy level. I am running the 2019 Virgin Money London Marathon for Parkinson's UK, and training is going well. This weekend the charity held a 'preparation day' for its runners in the London and Brighton marathons. I had the wonderful opportunity to spend a few minutes telling them about the world-leading research we are doing at Predict-PD, and encouraging them to tell all their friends and family age 60-80 years about the study. It was very special to share the study with a group of such motivated and interested people, and showcase the work that we do. They were a mix of men and women of all ages, some of whom are running their first marathon (having never run 5km before), others are running their 30th full marathon this year. Some had relatives or friends with Parkinson's, others had Parkinson's themselves - all had a deep connection with the condition. I wish them all the best of luck with their training and look forward to seeing them at the finish line on the 28th April.

Because this post is getting perilously close to having no stats, here are some of mine since starting my training programme on Christmas day:
Total miles: 114.26
Total time running:  15 hours 8 minutes
Total calories burned: 11,206

2019 is another year of progress - please help us by encouraging everyone you know, age 60-80 to go to and take part!


Monday, 24 December 2018

A few personal thoughts to round the year off.

At Predict-PD Towers we have had a busy and successful year. We have rebuilt the website from scratch, taking the opportunity to really review all the questions in the surveys, and select the very best questions to help us answer our research questions. We have pioneered new techniques that are now included in the website, including an online trailmaking task and making the tap-test even better. We have made excellent progress with the imaging substudy: selecting some high risk and similar low risk controls to see if we can see some of the early changes associated with Parkinson’s using cutting edge MRI techniques. We’ve been travelling the length and breadth of the country seeing many of the participants in our ‘special groups’: people with smell loss, and people with a certain kind of sleep disorder, to conduct physical and cognitive examinations in their own homes. We have grown our team allowing us to do similar in person assessments in the homes of many of our ‘regular’ participants, and now have some specialist statistical and techincal data management help. Most crucially of all, we have launched the second phase of the study, in which we aim to recruit 10,000 new participants aged 60-80 – please spread the word, and encourage as many friends and relatives to head to the website ( and consider taking part. It takes only about 25 minutes and could potentially change the future of Parkinson’s disease.

I also wanted to reflect on the festive period and what advice or suggestions I could make to individuals or families with someone who has Parkinson’s.

Christmas is a time for family and celebration. When someone has Parkinson’s not only can movement be slow, but many non-motor symptoms can make this time of year hard. Depression, apathy and difficulty keeping up with conversations can make participation in family events so much harder. If Parkinson’s affects your family, friends or neighbours, please try and make the effort not to leave them behind. Social and physical exercise are vital to people with Parkinson’s, so make the effort to make that easy. The post-Christmas lunch walk may doesn’t need to be fast, but by making it inclusive you’ll make a real difference.

Another, far less pleasant aspect of this time of year, is flu. Flu continues to be a significant cause of illness and even death, and although there is no magic bullet, for many people it is potentially preventable. The simplest things are the most effective: handwashing with soap and water (especially after using public transport, before eating, and after coughing and sneezing), using disposable tissues (catch it, bin it, kill it), and the flu jab. It is worth busting a few common flu-jab myths: the immunisation does not contain the live virus – therefore you cannot catch the flu from the jab. While the recommended time to have the jab is October – November, flu cases continue to be common all the way through to the end of March, so better late than never. Each year the vaccine covers different strains of the flu, so that is why it is recommended to have it every year. This also means that the vaccine won’t protect you from evey strain  of flu (there are hundreds), but it will protect you from the ones that are likely to be the most common each year. Being otherwise healthy doesn’t protect you: despite running around 50 miles a week and generally enjoying excellent health, I’ve had a grotty end to the year, with the flu, which then predisposed me to pneumonia (and as a responsible health professional, yes I did get the jab in October, but that just means I was unlucky, and would still recommend it). 

We are of course indebted and grateful to Parkinson's UK for the funding that has allowed us to do this research, and for the support they continue to give. I'm looking forward to my first training run on Christmas day for the London Marathon, where I'll be aiming to break both my targets: under 3 hour finishing time and over £2500 for Parkinson's UK ( for those that are interested).

Finally, from the entire team at Predict-PD, we thank you for your interest and participation throughout this year, and wish you and your family a very merry Christmas, and a happy and healthy 2019.


Thursday, 20 December 2018

Gout again.. and is work affected by early Parkinson's?

After my positive blog-post on uric acid a while ago, we have another reminder that unfortunately in research things are often not so simple, especially when moving from observational findings to affecting real-world changes. We are ending the year with another negative trial in Parkinson's - it's recently been announced that the trial of urate-elevating drug Inosine is ending early as the investigators don't believe that the trial will achieve it's stated goal of slowing progression of Parkinson's. Alastair's paper on the causal relationship between urate levels and Parkinson's gave us a hint that uric acid, while associated with reduced risk, may not be directly causing this - so it's still important to understand more about these relationships and it will be instructive to read about the data that has been collected when this is published next year.

Talking of real-world impact, this interesting paper below explored the very real impact of early symptoms of Parkinson's disease on the workforce. At PREDICT-PD we are fascinated by what happens in the years before diagnosis of Parkinson's - a lot has been published on non-motor symptoms such as constipation, depression and sleep disorders - but not much on how this affects specific activities such as work. They looked at patients with Parkinson's who had to take sick leave and compared them to people who had taken sick leave for other reasons. Those with Parkinson's sick leave were more likely in the preceeding 5 years to have taken sick leave for reasons other than Parkinson's and more likely to have taken sick leave for musculoskeletal issues in particular. Given that the study was only able to look at sick-leave episodes exceeding 14 days, it illustrates the significant impact that these symptoms are having on patients in the early disease and even before diagnosis.

On a more positive note as we look towards the end of the year and Christmas, we are very pleased that recruitment is ramping up for the next stage of the PREDICT-PD project. We are working towards new publications of our own data in the coming months and we'd like to thank all for their ongoing support. If you or any family members are interested, please do have a look on

Reduced workforce participation 5 years prior to first Parkinson’s disease sick-leave 

Jonathan Timpka, Örjan Dahlström, Armin Spreco, Maria H. Nilsson, Susanne Iwarsson, Toomas Timpka & Per Odin 

Wishing you all the best over the festive season.



Thursday, 6 December 2018

Motivation to exercise

Exercise is known to have many benefits to people with and without Parkinsons. In Parkinsons it is known to improve slowness of movement, balance, mood, memory and quality of life. There is also some evidence that it might slow down the progression of the disease. So we know that exercise is good for people with Parkinsons, but we still aren't sure why.

One of the theories is that exercise might cause more dopamine to be released in the brain. Dopamine is the chemical that people with Parkinsons lack, and that is why giving medications which contain dopamine are an effective treatment for Parkinsons.

In this study from Canada they used a special scan and tracer to measure dopamine release in the brain before and after exercise in Parkinsons patients. They also compared how dopamine release differed between regular exercisers and more 'sedentary' participants.

They found that even before starting any exercise the regular exercisers had a higher level of dopamine in their caudate (the area of the brain associated with Parkinsons) than the sedentary participants. But when they looked at any differences in dopamine levels in other areas of the brain there was no difference between the two groups.

All the participants then had to cycle on an exercise bike for 30 minutes before they were re-scanned. The second scan found that both groups, as expected, had an increase in dopamine release in the brain. Interestingly the regular exercisers had a bigger increase in dopamine release in the brain, suggesting that regular exercisers get an even greater benefit from exercise.

This study could explain why people with Parkinsons notice that their symptoms improve with exercise. It is also possible that exercise could promote nerve cells to survive for longer. However the problem with this study is that it does not provide any evidence as to whether this is a cause or effect of exercise. In other words, does the exercise cause higher levels of dopamine in the brain or do the higher levels of dopamine in the brain make those Parkinsons patients more likely to exercise. Either way, whether you have Parkinsons or you don't, the evidence is overwhelming that moderate exercise is good for your whole body including your brain. So unless you have a compelling reason not to, its a good idea to get and hopefully stay active.

Mov Disord. 2018 Oct 30. doi: 10.1002/mds.27498. [Epub ahead of print]
Habitual exercisers versus sedentary subjects with Parkinson's Disease: Multimodal PET and fMRI study.
Sacheli MA1Murray DK1,2Vafai N3Cherkasova MV1Dinelle K3Shahinfard E1Neilson N1McKenzie J1Schulzer M1Appel-Cresswell S1,2McKeown MJ1,2Sossi V3Jon Stoessl A1,2.
Author information
The benefits of exercise in PD have been linked to enhanced dopamine (DA) transmission in the striatum.
To examine differences in DA release, reward signaling, and clinical features between habitual exercisers and sedentary subjects with PD.
Eight habitual exercisers and 9 sedentary subjects completed [11 C]raclopride PET scans before and after stationary cycling to determine exercise-induced release of endogenous DA in the dorsal striatum. Additionally, functional MRI assessed ventral striatum activation during reward anticipation. All participants completed motor (UPDRS III; finger tapping; and timed-up-and-go) and nonmotor (Beck Depression Inventory; Starkstein Apathy Scale) assessments.
[11 C]Raclopride analysis before and after stationary cycling demonstrated greater DA release in the caudate nuclei of habitual exercisers compared to sedentary subjects (P < 0.05). Habitual exercisers revealed greater activation of ventral striatum during the functional MRI reward task (P < 0.05) and lower apathy (P < 0.05) and bradykinesia (P < 0.05) scores versus sedentary subjects.
Habitual exercise is associated with preservation of motor and nonmotor function, possibly mediated by increased DA release. This study formulates a foundation for prospective, randomized controlled studies

Sunday, 18 November 2018

The prodromes of Parkinson's

Following on nicely from our last post, we are delighted to publicise our latest peer-reviewed publication.

This will come out in a special edition of the European Journal of Neuroscience, dedicated to the memory of Tom Isaacs. Tom was the founder and leader of the Cure Parkinson's Trust - a truly dynamic leader and a real disruptive presence (in all the right ways) within  Parkinson's research. We are honoured to have our names and our ideas as testimonial to him in this way.

It is clear that Parkinson's is more of an umbrella condition than one single entity. For instance, some people have significant tremor, while others have none. Some progress very slowly, and a decade from diagnosis have barely any more symptoms - others progress more quickly. For many Parkinson's affects mainly movement while others have many non-motor symptoms. It is likely (although not yet proven) that these different subtypes of Parkinson's have a different underlying process causing them.

It therefore stands to reason that the earliest phases are also different. In our article we lay out the evidence that Parkinson's that comes from people with a particular kind of sleep disorder (REM sleep behavioural disorder), smell loss, and genetic forms do all look different. The evidence is not bomb-proof, but in Predict-PD we will be able to shed light on both the sleep disorder, smell loss and try and pick apart differences in the general population.

To see the article, please see the journal website. Please also remember to talk to friends and family to read more about the study and sign up themselves:


Friday, 16 November 2018

Do thinking problems develop before Parkinson's?

Many of the blog posts from the PREDICT team have highlighted the fact that Parkinson's affects many more aspects of life than just movement. Whilst the core features are still thought of as slowing down, becoming stiff and developing tremor, problems such as constipation, sleep difficulties and thinking and memory problems are all commonly seen. 

The thinking problems may even be present before diagnosis - testing for specific difficulties could be helpful in the efforts to pick up people at the earliest stages. This research paper used data from a large international study of healthy people who we know are at risk of Parkinson's including people with a sleep disorder strongly related to Parkinson's, people with smell loss and people with genetic mutations associated with Parkinson's.

They found that people with the sleep disorder performed worse on tests of attention and visual function than all the other groups. The groups with smell loss and genetic mutations performed at a similar level across tests and were comparable to people who had already developed Parkinson's. Unfortunately there was no comparison to people without these risk factors, so we can't make any conclusions about whether these groups perform worse than the general population.

I think this finding points to the fact that, just as Parkinson's disease is different in every individual, the route into the disease is also likely to be different. It is also helpful in pointing us towards the specific tests which may be useful in the earliest stages - we have included short tests of attention and memory in the new online PREDICT-PD study and I will be very interested to see how our findings compare to these results.


Cognition among individuals along a spectrum of increased risk for Parkinson's disease.

Chahine LM, Urbe L, Caspell-Garcia C, Aarsland D, Alcalay R, Barone P, Burn D, Espay AJ, Hamilton JL, Hawkins KA, Lasch S, Leverenz JB, Litvan I, Richard I, Siderowf A, Coffey CS, Simuni T, Weintraub D; Parkinson’s Progression Markers Initiative. 

Several characteristics associated with increased risk for Parkinson's disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration. METHODS: Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations)). Inclusion criteria enriched the RBD and hyposmia cohorts, but not the NMC cohort, with individuals with dopamine transporter binding deficit. Baseline neuropsychological performance was compared, and analyses were adjusted for age, sex, education, and depression. RESULTS: The RBD cohort performed significantly worse than the hyposmia and NMC cohorts on Symbol Digit Modality Test (mean (SD) 32.4 (9.16) vs. 41.8 (9.98), p = 0.002 and vs. 45.2 (10.9), p<0.001) and Judgment of Line Orientation (11.3 (2.36) vs.12.9 (1.87), p = 0.004 and vs. 12.9 (1.87), p<0.001). The RBD cohort also performed worse than the hyposmia cohort on the Montreal Cognitive Assessment (25.5 (4.13) vs. 27.3 (1.71), p = 0.02). Hyposmics did not differ from PD or NMC cohorts on any cognitive test score. CONCLUSION: Among individuals across a spectrum of risk for PD, cognitive function is worse among those with the characteristic most strongly associated with future risk of PD or dementia with Lewy bodies, namely RBD.

Wednesday, 14 November 2018

Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson's disease

I love it when something simple yet really effective...

We are in an era when imaging and laboratory investigations are ever more complex and expensive, and here we have a wonderful study showing that a very simple, cheap and easily-obtained ratio from an MRI scan can be used to accurately diagnose Parkinson's. Importantly the researchers were not satisfied with showing this once and went on to demonstrate similarly impressive results in a separate patient and control group.

Now it is important for other researchers to replicate these findings and to work how far back they go... could it be used to detect people in the pre-symptomatic/pre-diagnostic phase??

Du G, Lewis MM, Sica C, Kong L, Huang X
Ann Neurol 2018 Nov 8

Newer MRI techniques have shown promise in capturing early Parkinson's disease (PD)‐related changes in the substantia nigra pars compacta (SNc), the key pathological loci. Their translational value, however, is hindered by technical complexity and inconsistent results.

A novel yet simple MRI contrast, the T1w/T2w ratio, was used to study 76 PD patients and 70 controls. The T1w/T2w ratio maps were analyzed using both voxel‐based and region‐of‐interest approaches in normalized space. The sensitivity and specificity of the SN T1w/T2w ratio in discriminating between PD and controls also were assessed. In addition, its diagnostic performance was tested in a subgroup of PD patients with disease duration ≤2 years (PDE). A second independent cohort of 73 PD and 49 controls was used for validation.

Compared to controls, PD patients showed a higher T1w/T2w ratio in both the right (cluster size=164 mm3, p<0.0001) and left (cluster size=213 mm3, p<0.0001) midbrain that was located ventrolateral to the red nucleus and corresponded to the SNc. The region‐of‐interest approach confirmed the group difference in the SNc T1w/T2w ratio between PD and controls (p<0.0001). The SNc T1w/T2w ratio had high sensitivity (0.908) and specificity (0.80) to separate PD and controls (AUC=0.926), even for PDE patients (AUC=0.901, sensitivity=0.857, specificity=0.857). These results were validated in the second cohort.

The T1w/T2w ratio can detect PD‐related changes in the SN and may be used as a novel, parsimonious in vivo biomarker for the disease, particularly early stage patients, with high translational value for clinical practice and research.

Friday, 9 November 2018

Why does Parkinson's cause constipation?

When people think of Parkinson's disease they often think of tremors however often people who actually have Parkinson's are more concerned by the symptoms that are not to do with movement and tremors (non-motor symptoms). The commonest of these symptoms are constipation, tiredness, difficulty sleeping, anxiety and needing to pass urine multiple times at night. These symptoms are not always as immediately obvious to people without Parkinson's but they can be extremely troubling. In this blog I want to talk a bit more about constipation and why people with Parkinson's get constipation.

Constipation is when it is more difficult to go for a poo or when the amount of time between opening your bowels increases. Usually your poo will become a lot harder when this happens and sometimes can result in a bloated feeling and pain in your tummy. So the question is how does Parkinson's, a brain disease, affect your bowels in this way?

The answer lies in looking at the large intestine. This is a large pipe near the end of the path from your mouth to your bum (the GI tract). By the time your dinner reaches the large colon it has mainly been digested and had all of the useful vitamins, protein and carbohydrates removed from it. This means that when your dinner reaches the large colon it is made up of waste products (poo) and lots of water; in fact it is so watery at this point that it is completely liquid. The role of the large colon is to turn this liquid into a solid poo and to get the water out of it so that you can stay hydrated. So what changes in Parkinson's disease?

In Parkinson's disease if you measure the amount of time it takes a piece of food to move from the beginning of the large intestine to exiting out of your bum it would take double the amount of time that it would take a healthy person. In other words: poo moves through the large intestine at half the speed if you have Parkinson's. Because the large intestine is so good at draining water from your poo, the poo becomes much drier and harder as the large intestine has double the amount of time to remove as much water as possible. This explains why people with Parkinson's have drier harder poos and subsequently have more constipation.

The large intestine pushes food along it by tensing the muscles around it in a rhythmic way that propels the poo downstream. Like the rest of the body, in Parkinson's, these movements become much slower. The reason for this is not as clear but is probably due to the layer of nerve cells around the gut wall called the enteric nervous system. Studies where they have looked at samples of the gut wall have found build ups of Lewy Bodies (the characteristic thing found in the brain in Parkinson's) also in the gut wall. It is possible that this build up is what also causes the slowness in the gut.

It is important to remember that there are many other things that cause constipation other than Parkinson's. There are many medications that can be tried to help improve constipation but some of the simple things that can help are increasing the amount of water you drink or increasing the amount of fibre that you eat, but discuss with your doctor if this is a problem for you.

Curr Treat Options Neurol. 2018 Oct 25;20(12):54. doi: 10.1007/s11940-018-0539-9.
Gastrointestinal Dysfunction in Parkinson's Disease.
Pfeiffer RF
Author information
During the past 25 years, there has been an explosion of information regarding the occurrence of gastrointestinal dysfunction in Parkinson's disease. In this review, the clinical features of gastrointestinal dysfunction in Parkinson's disease will be described and information regarding the potential role of the enteric nervous system and the gut microbiome in the genesis of Parkinson's disease will be addressed.
Recognition is growing regarding the role that gastroparesis and small intestinal dysfunction may play in Parkinson's disease, especially with regard to erratic responses to anti-Parkinson medication. The presence of enteric nervous system involvement in Parkinson's disease is now well established, but whether the enteric nervous system is the starting point for Parkinson's disease pathology remains a source of debate. The potential role of the gut microbiome also is beginning to emerge. Gastrointestinal dysfunction is a prominent nonmotor feature of Parkinson's disease and dysfunction can be found along the entire length of the gastrointestinal tract. The enteric nervous system is clearly involved in Parkinson's disease. Whether it is the initial source of pathology is still a source of controversy. There also is growing recognition of the role that the gut microbiome may play in Parkinson's disease, but much more research is needed to fully assess this aspect of the disorder.

Thursday, 1 November 2018

PLAIN ENGLISH: Does removal of the appendix impact the risk of Parkinson's Disease?

Multiple large news organisations yesterday were reporting the results of a study showing that people who have had appendectomies (surgical removal of the appendix) have a lower chance of developing Parkinson's disease. Its a neat paper which links large amounts of data from medical databases and histology results (looking at tissue under the microscope) on a much smaller number of patients.

First they looked at the Swedish National Patient Registry, a database of 1,698,000 people followed up for 52 years, and identified anyone who had a history of an appendectomy (551,647 people). They then matched these patients to two 'control' patients who had not had appendectomies but were similar in age, sex and geographical to the original patients. They interestingly found that the chance of having Parkinson's disease was 19.3% lower in the participants with appendectomies than the 'control' participants who had not had appendectomies. They also found that the participants who had appendectomies and developed Parkinson's on average developed Parkinson's 1.6 years later than the Parkinson's patients who still had their appendix. Interestingly this effect was not observed in participants who had known genetic mutations causing their Parkinson's suggesting that if the appendix has any effect on the development of Parkinson's it is only in patients whose Parkinson's has an 'environmental' trigger or cause.

This part of the study was not novel or new and previous similar studies have been done and found no association between appendectomy and PD. In a Canadian study they actually found a higher rate of PD in patients who had appendectomies in the past 5 years. So despite the results of this study being very interesting they are not backed up by previous studies.

The novel part of this study is the histological analysis where the researchers analysed the 48 peoples appendixes under the microscope. These participants did not have PD. The appendixes were analysed under the microscope for clumps of protein which have stuck together that we call 'aggregates of α-syneuclein'. These are the key feature of PD that can be found in PD patients brains at autopsy. In other words the misfolded protein that causes PD when it is seen in the brain can be seen in young, healthy peoples appendix. These misfolded proteins were detected in both young and old people.

There are some problems with this study; first is that in large databases it is very difficult to know the accuracy of the Parkinson's diagnosis and previous studies investigating the reliability of this found only a 70.8% chance that it is reliable. They also only examined the appendix under the microscope and did not check any other tissues to compare.

This study does provide some food for thought; at the end of the paper the authors hypothesise that the appendix is the source of the misfolded protein that then spreads through the gut and up the vagus nerve to the brain thereby causing Parkinson's disease. This gut to brain model of the development of Parkinson's disease is often discussed and is a popular research topic at the moment. However the results of this study should still be taken with a pinch of salt because there are a number of large scale similar studies that precede this study that do not come to the same conclusion, that doesn't stop it being interesting though!

Great Debates

While there are many great debates happening this week in the UK, perhaps the most interesting happened at today’s biannual meeting of the ...