Plain English - Low body mass index and life prognosis in Parkinson's disease

Over the last few years we have seen research that suggests being underweight has a negative or detrimental effect on survival with diseases like Parkinson's. The same has been shown for motor neurone disease and Alzheimer's. Whether this reflects a more aggressive form of the disease, which in itself also affects weight, or whether being a bit heavier makes you a bit more 'robust' to these diseases remains to be seen. 

In this study the authors show something similar. When they looked backwards in time in a large number of patients with Parkinson's, they saw that those that were underweight had survived for a shorter time than those that were normal weight or over weight. We must be cautious in how we interpret the results because they don't necessarily suggest that being heavier is better and indeed obesity causes an increase in heart and vascular disease, diabetes, and cancer. However it does suggest that being underweight and having Parkinson's is not a good idea either. Aiming for a recommended normal weight and BMI (body mass index) appears to offer the best option considering all outcomes. 

The reason I am particularly interested in this study is because last year we published research showing that higher BMI appears to protect you against Parkinson's. The special thing about the analysis that we did was that it assessed the effect that BMI has on Parkinson's (BMI -> Parkinson's) without being affected by the effect that Parkinson's has on BMI (Parkinson's -> BMI). The method we used was called Mendelian randomisation and it is increasingly used to assess whether risk factors cause a disease as opposed to simply being associated.

The relationship between weight and BMI and Parkinson's disease is complicated and is an important area for further study.

- Alastair Noyce

Parkinsonism Relat Disord. 2018 May 15. pii: S1353-8020(18)30241-4. doi: 10.1016/j.parkreldis.2018.05.011. [Epub ahead of print]
Park K, Oeda T, Kohsaka M, Tomita S, Umemura A, Sawada H.

https://www.prd-journal.com/article/S1353-8020(18)30241-4/fulltext

INTRODUCTION: Patients with Parkinson's disease (PD) frequently lose weight, even in the early stages of the disease. Our objective was to clarify the association between low body mass index (BMI) and life prognosis in PD.

METHODS: We conducted a retrospective cohort study of 651 PD patients (380 females), with a primary endpoint of survival. Because of sex differences in BMI, male and female data were separated. We compared survival times between underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) patients and calculated hazard ratios (HRs) adjusted for other relevant factors. To investigate the semi-quantitative relationship between relative risk of death and BMI, we divided patients into lower, middle, and upper thirds of BMI and calculated the HRs of the lower and upper thirds, with reference to the middle third.

RESULTS: Seventy-nine patients (41 females) died over a mean (standard deviation) observation period of 39 (26) months. Underweight patients had poorer life prognosis than non-underweight patients and the difference was larger in males than in females (adjusted HR 3.8 (95% confidence interval 1.9-7.9) in males and 1.8 (0.9-3.5) in females). In males, the relationship between survival and BMI was much poorer in the bottom third and slightly poorer in the top third compared with the middle third. In females, the higher the BMI, the better the survival prognosis; however, the difference was not statistically significant.

CONCLUSION: Low BMI had a significant impact on the life prognosis of PD patients, especially males.

Public Engagement

I had the great honour and privilege to be asked to speak to the Parkinson’s UK Barnet and Brent Branch last night. This was the second time I have had this opportunity to meet and engage with a wonderful group of people.

At PREDICT-PD we are working tirelessly to understand more of the ‘prodromal’, ‘premotor’ or ‘prediagnostic’ stage of Parkinson’s [these are all largely interchangeable terms for the period where Parkinson’s is present in the brain and causing mild, often non-motor symptoms]. However, there is little public or academic conversation about the public ‘appetite’ for moving the point of diagnosis from where it currently sits.

After a brief introduction to the topic, I sat back down, and picked up my notebook and invited the group to engage in a conversation and share some of their thoughts and experiences. I was humbled by the honesty and candour shown by many people with Parkinson’s and their family members.

Some clear themes came out of our conversation:

• ·     Receiving a diagnosis of Parkinson’s is a pivotal moment in a person’s life. As clinicians, the way we offer the diagnosis has a deep and lasting impact that will be remembered, not only by the individual, but by their family for decades. I heard some wonderful stories of good practice, where clinicians had taken their time, been thorough and provided a supportive and accurate diagnosis. Others unfortunately had not been so lucky, and had the diagnosis changed many times or left totally unsupported after a brusque diagnosis. I could only apologise for these experiences. I did also reiterate that Parkinson’s is a clinical diagnosis, with no perfect test in life, and the evidence suggests that even the best experts get the diagnosis wrong 15% of the time.
• ·     So many people last night spoke of the power that comes with acknowledging Parkinson’s, not only to themselves, but to others around them. Telling the ‘tutter’ behind you in the queue at the supermarket that you can’t ‘hurry up’ because you have Parkinson’s changes the shopping trip from being an ordeal to a much more pleasant affair. 
• ·     Family members (and individuals with Parkinson’s) are often relieved by the diagnosis – at last an explanation for all those symptoms, and “at least it wasn’t something else”
• ·     When we discussed the benefits and problems with moving the diagnosis earlier in the disease process, there were not many good things to hear. Too many people suffer at workwith changes to their jobs, reduced hours or even face unemployment as a result of the diagnosis. Others struggle to come to terms with the diagnosis for some time and suffer psychologically, which could be worse if there were fewer symptoms to make it ‘real’.
• ·     However, many saw a positive aspect to learning the diagnosis earlier. This would offer an opportunity start engaging with exercise which has been shown robustly in research and very definitely in the community last night to have a profoundly positive impact on mood, thinking, movement and quality of life. It would also help people make appropriate life decisions, especially regarding work, pension, travel: living the life you want to live regardless of the Parkinson’s.
• ·     When I asked similar questions but in the context of available treatments that change the course of the condition, the group was unanimous: tell us as early as possible!

We left the meeting on a really positive note. There is much excitement in the academic community about how close we are to having truly disease modifying options in Parkinson’s. The road is long, and we still have much work to do: but we’re getting there. I’m delighted that the group last night shared my optimism and excitement.

I was also delighted to share with them (and you, dear reader) this link to Parkinson's TV - an English language version of the amazing Dutch videos created by Prof Bas Bloem's Parkinson'sNET in the Netherlands. Another example of real partnership between people with Parkinson's, researchers and clinicians - answering the questions you have, as well as some that you didn't know you wanted to have!

RNR

Plain English - BDNF variant is associated with milder motor symptom severity in early-stage Parkinson's disease

Single nucleotide polymorphisms (also known as SNPs) describe common genetic variation and can be used to tag regions across the human genome. When SNPs tag regions near to known genes they can help give clues as to how that gene might affect a given disease.   

It is interesting that variation at this SNP (called rs6265) is associated with slower progression in Parkinson's disease because it is near to the BDNF gene whose protein product influences the growth of nerve cells. The very same SNP (rs6265) is also associated with an number of the protective factors for Parkinson's such as smoking, body mass index and coffee consumption...

Coincidence... probably not...

- Alastair Noyce

Parkinsonism Relat Disord. 2018 May 9. pii: S1353-8020(18)30232-3. doi: 10.1016/j.parkreldis.2018.05.003. [Epub ahead of print]

Fischer DL, Auinger P, Goudreau JL, Paumier KL, Cole-Strauss A, Kemp CJ, Lipton JW, Sortwell CE.

INTRODUCTION: Parkinson's disease (PD) progression is heterogeneous. Variants in PD-related genes may alter disease progression or severity. We examined if the single nucleotide variant rs6265 in the gene BDNF alters clinical phenotype in early-stage, unmedicated PD.

METHODS: A retrospective analysis was conducted using data collected in the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) study. DNA samples (n = 217) were genotyped for the BDNF rs6265 variant, and the primary endpoint was time to initiate levodopa. The Parkinson's Progression Markers Initiative (PPMI) was used for validation (n = 383).

RESULTS: The primary endpoint of time to initiate levodopa was associated with a delay in subjects with two copies of the rs6265 minor (Met66) allele (HR: 4.9; 95% CI: 1.3-18.8). Secondary endpoints were not different among genotypes. PPMI subjects with two Met66 alleles demonstrated significantly lower total and part III Movement Disorder Society - United Parkinson's Disease Rating Scale (MDS-UPDRS) scores at baseline, as well as more tremor-related symptoms, but not a delay in initiation of maintenance pharmacotherapy.

CONCLUSIONS: Data from two distinct, unmedicated, early-stage PD cohorts suggest that carrying two copies of the rs6265 Met66 allele (∼4% of the population) is associated with less severity in motor symptoms and potentially a slower rate of progression.

Plain English - Diabetes mellitus and Parkinson disease

This is the first of our new 'Plain English' blogs on Parkinson's research. We are responding to feedback from people who said that they sometimes find it hard to know who the target audience is for our blogs. Some posts are more understandable than others! So from on the Plain English posts will aim to be just that - understandable.

Below there is an abstract from an an article recently published in Neurology journal, in which the authors explore the relationship between diabetes and Parkinson's. Some previous studies have suggested that people with diabetes are at higher risk of being diagnosed with Parkinson's in the future. But the relationship does not end there... diabetes drugs have recently been shown to be effective in reducing the symptoms of Parkinson's and may even slow down the disease. 

In this article the authors show that people with a diagnosis of diabetes have some similarities to people with Parkinson's. The brain scans of people with diabetes looked similar to people with Parkinson's, and so did the levels of certain proteins in their spinal fluid. Furthermore they show that people with both Parkinson's and diabetes, the movement and memory problems tend to progress faster than in those with just Parkinson's on its own.

Interest in the link between Parkinson's and diabetes in increasing, so these types of study are important in helping us to better understand one affects the other.

- Alastair Noyce

Gennaro Pagano, Sotirios Polychronis, Heather Wilson, Beniamino Giordano, Nicola Ferrara, Flavia Niccolini and Marios Politis
Neurology
First published April 6, 2018
DOI: https://doi.org/10.1212/WNL.0000000000005475

http://n.neurology.org/content/90/19/e1654

Objective
To investigate whether diabetes mellitus is associated with Parkinson-like pathology in people without Parkinson disease and to evaluate the effect of diabetes mellitus on markers of Parkinson pathology and clinical progression in drug-naive patients with early-stage Parkinson disease.

Methods
We compared 25 patients with Parkinson disease and diabetes mellitus to 25 without diabetes mellitus, and 14 patients with diabetes mellitus and no Parkinson disease to 14 healthy controls (people with no diabetes mellitus or Parkinson disease). The clinical diagnosis of diabetes mellitus was confirmed by 2 consecutive fasting measurements of serum glucose levels >126 mL/dL. Over a 36-month follow-up period, we then investigated in the population with Parkinson disease whether the presence of diabetes mellitus was associated with faster motor progression or cognitive decline. 

Results
The presence of diabetes mellitus was associated with higher motor scores (p < 0.01), lower striatal dopamine transporter binding (p < 0.05), and higher tau CSF levels (p < 0.05) in patients with Parkinson disease. In patients with diabetes but without Parkinson disease, the presence of diabetes mellitus was associated with lower striatal dopamine transporter binding (p < 0.05) and higher tau (p < 0.05) and α-synuclein (p < 0.05) CSF levels compared to healthy controls. At the Cox survival analysis in the population of patients with Parkinson disease, the presence of diabetes mellitus was associated with faster motor progression (hazard ratio = 4.521, 95% confidence interval = 1.468–13.926; p < 0.01) and cognitive decline (hazard ratio = 9.314, 95% confidence interval = 1.164–74.519; p < 0.05).

Conclusions
Diabetes mellitus may predispose toward a Parkinson-like pathology, and when present in patients with Parkinson disease, can induce a more aggressive phenotype.

Picture from the Shake It Up Australia Foundation 

https://shakeitup.org.au/diabetes-drug-trial-parkinsons/