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: www.predictpd.com

RNR

Non-motor features of PD... new report from the HPFS

Here we see evidence to support the fact that it you have a combination of smell loss, probable REM sleep behaviour disorder and constipation, you are more likely to have Parkinson's... this is not surprising because we have seen this in lots of other studies but it is nice to see it all brought together in one study.

The comments are as follows... odds ratios (ORs) in this context are a little bit meaningless. How does one interpret an odds ratio of 160, let alone an OR of 1323 other than to say it looks like a lot?? By comparison, if you look at ORs between an established risk factor (such as smoking) and disease outcome (such as lung cancer), the ORs are between 20-40. It is not a criticism of the approach; in PREDICT-PD we too have traditionally modelled ORs. However, we rank an individual's OR against the ORs of everyone else in the cohort, meaning that, whilst not their literal risk, it is correct in relation to all other participants in the cohort.   

The combination of the three factors has a positive predictive value of 35% - meaning that if you have all three together there is a 35% chance of you having a diagnosis of PD. Long story short... these three non-motor features, in combination, still look like some of the most useful for recognising PD... either in those that have a diagnosis or who are in the prodromal phase...

- Alastair Noyce

https://jnnp.bmj.com/content/early/2018/08/03/jnnp-2018-318275.long

Substantia nigra fractional anisotropy changes confirm the PD at-risk status of patients with idiopathic smell loss

In my opinion idiopathic anosmics are an under-researched group (PARS study aside). It is good to see others taking a particular interest in them... at PREDICT-PD we are very in interested in idiopathic anosmia and are about to start reassessing the people that we have recruited with unexplained smell loss. Particularly interesting that there are MRI differences between the groups....

Parkinsonism Relat Disord. 2018 Feb 17. pii: S1353-8020(18)30076-2. doi: 10.1016/j.parkreldis.2018.02.026. [Epub ahead of print]
Haehner A, Schöpf V, Loureiro A, Linn J, Reichmann H, Hummel T, Kitzler HH.

INTRODUCTION: Individuals with unexplained smell loss constitute an at-risk population for the development of Parkinson's disease (PD). Currently, no specific MRI patterns are known for early PD diagnosis. In this study, we measured the fractional anisotropy (FA) in the substantia nigra (SN) in PD patients, in patients with idiopathic smell loss, and in healthy controls.

METHODS: All subjects underwent extensive olfactory testing and MR imaging data were obtained to explore SN diffusion characteristics. The SN regions were manually identified by two independent raters on the individual imaging data.

RESULTS: FA measurements in the SN revealed significant group differences, with reduced values clearly distinguishing PD patients and patients with idiopathic smell loss from healthy controls.

CONCLUSION: These findings indicate a reduced intrinsic integrity of the SN in PD at-risk subjects and support the risk status of patients with idiopathic smell loss.