Mild Parkinsonian Signs in a Community Population

One question that many of the PREDICT-PD participants ask me is “I am slower than I used to be, does it mean that I am getting Parkinson’s?”

I am interested in the early motor phases of Parkinson’s disease. They are subtle in appearance and usually start before the classical symptoms of Parkinson’s arise, which are slowness of movement, stiffness and tremor. 

When studying subtle abnormalities it is important to know the full range of normal amongst older people. It can be difficult to establish the boundaries between what is normal and abnormal, especially at very early stages of Parkinson’s and in older people.

What it is known is that mild parkinsonian signs or subtle motor symptoms are quite common in the elderly population (ranging from 15% to 50%). The question of whether their presence occurs as part of normal aging or as the result of neurodegeneration has not been clearly answered. 

Here I share a paper that tries to address the issue mentioned above. 

https://www.ncbi.nlm.nih.gov/pubmed/32310187?dopt=Abstract

Abstract.

Background: Mild parkinsonian signs (MPS) are common in the older adult and associated with a wide range of adverse health outcomes. There is limited data on the prevalence of MPS and its significance.

Objective: To determine the prevalence of MPS in the community ambulant population and to evaluate the relationship of MPS with prodromal features of Parkinson’s disease (PD) and cognition.

Methods: This cross-sectional community-based study involved participants aged ≥50 years. Parkinsonian signs were assessed using the modified Unified Parkinson’s Disease Rating Scale (mUPDRS) and cognition using the Montreal Cognitive Assessment (MoCA). Premotor symptoms of PD were screened using a self-reported questionnaire. Linear regression was used to assess the association of MPS with premotor symptoms of PD and cognitive impairment.

Results: Of 392 eligible participants, MPS was present in 105 (26.8%). Mean age of participants with MPS was 68.8 +/- 6.9 years and without MPS was 66.1 +/- 5.9 years (p < 0.001). Multivariate analysis revealed that MoCA scores were significantly lower in the MPS group (b= –0.152, 95% CI = –0.009, –0.138, p < 0.05). A significant correlation between the presence of REM sleep behavior disorder (RBD) and total MPS scores (b= 0.107, 95% CI = 0.053, 1.490, p < 0.05) was also found. Neither vascular risk factors nor other premotor symptoms were significantly associated with MPS.

Conclusion: MPS is common and closely related to cognitive impairment and increasing age. Presence of RBD is predictive of higher MPS scores. This study highlights the necessity of other investigations or sensitive risk markers to identify subjects at future risk of PD.

The main purpose was to know how frequent subtle motor symptoms were in an elderly community without Parkinson´s and evaluate if these features were associated with a loss of cognitive abilities or other features known to be part of the early phase of Parkinson’s including reduced sense of smell, constipation, depression and sleep disturbances. 

To do that, participants were evaluated with motor and memory tasks as well as answering a self-reported questionnaire about the other symptoms mentioned. 

The authors found that one quarter of the group had subtle movement symptoms and this proportion increased with age, with 3 out of 10 people older than 75 having some kind of movement abnormalities. It is important to note that none of these symptoms were strong enough to make the diagnosis of Parkinson’s. They also found that cognitive and motor symptoms were highly associated.

We can extract several conclusions from these results. It is undeniable that once we get older our movement becomes slower and clumsier. The point here is when these motor symptoms occur together with mild memory problems it could mean that some neurodegenerative condition apart from simple aging is occurring.  

In order to these findings be more convincing, we would need to know how many of these people ended up having Parkinson’s or other conditions like Alzheimer’s over time. This was not reported in the study and so further studies are needed.

Cristina Simonet

Patients’ views on the ethical challenges of early PD detection

I read this paper this morning and thought it represented an important step forward in our understanding of this delicate issue

https://n.neurology.org/content/early/2020/04/14/WNL.0000000000009400

Many of us are working on risk factors of Parkinson's and early identification strategies, but what do patients with PD think about finding out they were at risk before the point of diagnosis? Here the authors surveyed >100 patients with PD and found interesting results. 

More than half would not have wanted to know that they were at risk if there was no medical treatment that could be offered prior to diagnosis... but this number dropped to 15% if there were lifestyle changes that one could make to reduce risk.

10% of patients thought disclosure of being high risk should never happen before diagnosis, but about a quarter (23%) thought that such disclosures should be made. The largest proportion of patients thought that it depended on what an individual wants to know. This personal preference is something that we considered in a paper last year focussed on Early vs Timely diagnosis (link here).

These issues are fundamental to arriving at a point where we have early identification strategies, either lifestyle or medical, and a real preventive approach to neurodegenerative disease. There is an awful lot of work that needs to be done and we require 'buy-in' and commitment from patients, the public, primary care, public health, policymakers and research. Our Time Matters initiative launched last year covers the various requirements to make Preventive Neurology a reality, and studies such as the one outlined here are examples of things that will take us further forward...

- Alastair

NEW Research - Is Parkinson's Genetic?? - Penetrance of Parkinson's Disease in LRRK2 Carriers Is Modified by a Polygenic Risk Score.

Here is a nice paper by colleagues from the International PD Genomics Consortium (IPDGC)...
https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27974

One question I frequently get asked is "doctor, please tell me, is it genetic?"... I am instantly caught in conflict between offering swift reassurance because I know what people really mean is "will I pass this on to my children?" OR a providing a rather convoluted explanation along the lines of 'yes in some ways Parkinson's is genetic but because of a whole range of genetic factors affect one's risk of getting Parkinson's just a little bit'.

The truth is that most complex diseases are genetically determined to some extent and Parkinson's is a good example. That doesn't mean that if you have Parkinson's your relatives will definitely also get Parkinson's, but they might be at slightly higher risk. The strength of the genetic factors that they have and the combination of factors adjust the overall risk in individuals. 

This offering from the IPDGC is an example of how different genetic factors combine... 

LRRK2 is the commonest genetic cause of Parkinson's that we know about. Having a mutation in LRRK2 causes Parkinson's in about 30% of carriers in their later years. These mutations have a 50% chance of being passed on to the next generation, who then in turn also have about 30% chance of showing signs of Parkinson's in their later years. What determines the chance of showing signs of Parkinson's? Well at least in part it is likely due to the other genetic risk factors that you have. 

In this paper, the authors show that having other genetic risk factors for Parkinson's (combined in a score) affects how likely carriers of LRRK2 mutations are to show signs of Parkinson's and that on average they tend to show them earlier in life. 

Why is this important? LRRK2 drugs are being tested to see how they might protect people carrying mutations of LRRK2 against getting Parkinson's. It is likely that the combination of other genetic factors that people have will help select groups for trials and might also affect the response to treatment. This kind of research gets a little bit closer to realistic precision medicine for Parkinson's 

Alastair Noyce

NEW Research - Motor complications in Parkinson's disease: 13‐year follow‐up of the CamPaIGN cohort

Back on the blog for the first time in a long time...

This marks another NY resolution to speak and flag more about the research that I/we think is interesting or important in the early identification or prediction of PD. In addition, we like to mention good quality clinical and genetic studies that tell us more about PD in general (not just prediction and early identification). 

First off, the latest from the CAMPAIGN study. CAMPAIGN is one of the most rigorous and thorough long term studies of PD. The team have managed to follow up the people that they recruited with PD for a long, long time in order to help us learn more about the features that emerge over time.

In the present study, they show that eventually motor complications may be inevitable and that current drugs become less effective/predictable over time. Importantly they provide further support for the notion that levodopa replacement itself is not a cause of motor fluctuations and that thoughts about saving levodopa for the future (i.e. not starting after diagnosis) are probably outdated ideas.

Ultimately, whilst the available treatment options are good for most patients, the results here support our ongoing desire to find drugs that delay progression rather than just manage the symptoms...

The link to the study is here and it is open access (👌). The abstract is copied below.
https://onlinelibrary.wiley.com/doi/full/10.1002/mds.27882

Alastair Noyce