A horse from our own stable: In memory of Tom Isaacs

We are delighted that one of our reviews has been published by the European Journal of Neuroscience: The Prodromes of Parkinson's.

This article is part of a special edition dedicated to the memory of Tom Isaacs. He was a shining light in the Parkinson's community. Having Parkinson's himself, he grew frustrated with the slow progress of research, and set up his own charity - The Cure Parkinson's Trust. The aim of the Cure Parkinson's Trust is to slow, halt or cure Parkinson's and only fund research that has the potential to do that. Tom's vision in creating and leading the Trust has changed the landscape of Parkinson's research and we are getting closer to achieving his dream. 

We are honoured to have been part of this evidence-based memorial to Tom. In this article we highlight the evidence of the stage before Parkinson's symptoms lead to a positive diagnosis - the prodromal phase. We look in particular at people with smell loss, individuals who have a particular sleep disorder (Rapid Eye Movement Sleep Behavioural Disorder) and some genetic causes of Parkinson's. 

It is increasingly clear that Parkinson's is an umbrella term for different sub-types of the pathology - in a group of people with Parkinson's, very few will have exactly the same features as each other. Even tremor - what most people think is the quintessential feature of Parkinson's, is totally absent in some individuals. Therefore, it stands to reason that there are different prodromal phases too. This is work that we are currently exploring, especially with our work with people with smell loss and with this sleep disorder. We hope to find out what are the markers that separate these groups, and what might shape the kind of Parkinson's that different people get.

The article is open access, thanks to the generous support of Parkinson's UK and can be found here.

Housekeeping

Dear reader, 

Unfortunately we've been targeted by a spam bot. We have deleted over 2000 spam messages and we apologise if we have inadvertently deleted any of your genuine messages in the process.

We have also changed the settings to reduce the amount of spam messages that are displayed.

Thank you for your understanding.

Please can we take this opportunity to thank you for your participation in our research, and if you know anyone who is age 60-80, lives in the UK and doesn't have Parkinson's, please encourage them to take part in the study at www.predictpd.com

Predict-PD

A scan to predict dementia?

We know that Parkinson's is caused by damage to a small area at the base of the brain known as the Substantia Nigra, which contains cells that produce the chemical messenger dopamine. However, this is not the entire picture, and we believe that other brain structures and chemicals may be involved in causing the variety of different symptoms we see in patients. 

One of the key questions for us in predicting what might happen to patients in the future is whether there is damage that can be found at an early stage, before patients start having problems.  A recent study used hundreds of MRI scans from people with Parkinson's to look at another small structure deep in the brain, named the Nucleus Basalis of Meynert. This is shown in the MRI image below.

Nucleus Basalis of Meynert

When this team looked at many different brain structures, it was only the size of this part of the brain that could predict whether patients would go on to develop problems with thinking and processing information. This ties in with other work showing this part of the brain plays a key role in different types of dementia as well as our knowledge that a drug which targets the main chemical found in this part of the brain, acetylcholine, is effective in Parkinson's Disease with dementia. 

As researchers continue to put together these kinds of findings, we can develop increasingly accurate ways to predict disease and ultimately ensure that the right people have access to treatments at the earliest stages. 

If you're interested in reading more, here is the link to the article https://academic.oup.com/brain/article/141/5/1501/4944714 

-Anna

 

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.

RNR

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 (predictpd.com) 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.

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 www.predictpd.com and take part!

RNR