Hot Topic: Pesticides and Parkinson's Disease 1

[00:00:31] Dr. Daniela Berg: Hi, Tiago. It's great to be with you here.

[00:00:34] Prof. Tiago Outeiro: Thank you. We, we appreciate. So on this important topic, I would like to first ask you what is the situation in terms of the numbers of people affected by Parkinson's disease, just in general? 

[00:00:47] Dr. Daniela Berg: In general, and really globally, we need to say the numbers are increasing. They're quite heavily increasing. The exact numbers from 1990 to 2021 actually [00:01:00] witnessed a global increase for about 60 percent. which means that at the moment about 11. 8 million individuals affected by Parkinson's disease.

This is really a great number and in fact Parkinson's disease is the fastest growing neurological disorder worldwide. So, yeah, numbers are increasing. No question.

[00:01:22] Prof. Tiago Outeiro: yeah. So that's, that's something we need to take seriously and I think sometimes governments and responsible authorities. Don't see it in this way because, you know, we lived the pandemic recently, so everyone knows what an infectious disease can do, but in these diseases, we end up thinking about them a bit differently.

So should we think about this as a pandemic, like some of our colleagues are, are claiming are we living a, a Parkinson's disease pandemic?

[00:01:52] Dr. Daniela Berg: Well, you're right. The term pandemic has really been introduced for Parkinson's disease in 2017. And I think [00:02:00] there are many aspects about PD that make this term useful. The main aspect is probably that politics and also the population gets more aware of the problem, but personally I need to say I don't mind how it's called.

We need to move. I think this is the important issue. We need to understand what's happening. We need to understand the contributing factors. We need to translate what we understand. To the public that they understand what they can do in with regard to primary prevention, secondary prevention, all these issues.

So, yeah, whether you call it pandemic or not, because I know there's quite a discussion. About using this word or not, we should get moving.

[00:02:41] Prof. Tiago Outeiro: Yeah. And so about the etiology of Parkinson's, we know that genetics accounts for only about 15 percent of PD cases. So what other factors are known to increase the risk for developing Parkinson's?

[00:02:55] Dr. Daniela Berg: You're right. Genetics is not the major issue. And in [00:03:00] fact, we need to say one important factors, of course, aging. I mean, people in our modern societies are getting older and thus are more likely to develop diseases that are more prevalent with increasing age. So this is, of course, Parkinson's disease. But the increase in PD prevalence is much more than expected in view of our aging societies.

And what we realize is that there's an increased evidence of changes in lifestyle. So for example, there's less physical activity in many, many populations all over the world. There are Changes in nutritional habits with a negative effect on microbiome and many metabolic pathways.

So there are many factors contributing and of course there are environmental factors. The exact contribution of course is difficult to quantify but all these aspects do play a role.

[00:03:50] Prof. Tiago Outeiro: And in light of What we know about the connection between pesticides and Parkinson's or the environment and Parkinson's more generally, and then [00:04:00] pesticides and Parkinson's in particular what we know about what these pesticides are and how people are getting exposed to them.

[00:04:10] Dr. Daniela Berg: It's accepted that pesticides do play a role. There are different attitudes towards this topic, but I think it's accepted. And maybe we should first kind of define what pesticides are, because this is a really huge group. So that includes insecticides, fungicides, herbicides. It's a really different groups of Substances, and they are used, and this is what you've just asked, they are used, of course, occupationally.

For example, in agriculture, forestry, landscape management, but also non occupationally. I think this is something we also need to take into consideration. For example, With frequent intake of contaminated water or food. So we need to consider that too. And the exposure is in generally, primarily by [00:05:00] inhalation or skin contact.

But as just mentioned, can also be ingestion of food or water. So you asked about Different kinds of pesticides that may be involved. And this is also difficult to disentangle because there are so many. And there's of course also often a co contamination, so it's only one pesticide, but several that are, that people are exposed to.

In 2023, actually, there was a very nice paper in Nature Communications that identified 53 different pesticides that upon exposure have an association with Parkinson's disease. So 53 different pesticides, so this is quite a number. And of course we cannot kind of understand for each single pesticide the exact relation, but there are some pesticides I think our community, the MDS community, is well aware of and should also [00:06:00] understand more about the details. Historically, I think the whole story regarding pesticides started with understanding that paraquat, this is a frequently used pesticide, is very similar in structure to MPTP. And in the early 1980s, It was reported that after the injection of MPTP intervenous of drug addicts that people develop Parkinson's disease.

And because of the similarity one started realizing that paraquat has a similar influence on the nervous system. And thus may. be associated with Parkinson's disease. And then many, many studies followed. So MPTP is of course an animal model now for Parkinson's disease 

another example is Rotenone, which is also used for animal models in Parkinson's disease and is still used as a, as a pesticide in some parts of the world. And this is [00:07:00] Actually an animal model in using alpha synuclein aggregation, for example, I mean, there are also case control studies showing that there's an increased risk of Parkinson's disease when exposed to Rotenone. And another example is the herbicide Glyphosate. This is actually herbicide which has been heavily debated in the European Union because they need to say to the great disapproval for us neurologists. Its marketing authorization has just been re approved, so you may have heard that. So Glyphosate is also one of the pesticides known to be associated with Parkinson's disease.

And then there are other groups like the organochlorines, like the dieldrin, organophosphates like chlorpyrifos and, and others so lots and lots of different ones. But in general, as we just said there are many and the global use has also increased. So when we look at the last [00:08:00] decade, we know that.

Well, it increased by nearly 50 percent compared to the early 1990s. So we have an increase in Parkinson's disease. We have an increase in pesticide usage. So, these associations we've just talked about need to be better understood.

[00:08:21] Prof. Tiago Outeiro: Yeah. And so given that this generalized use of these different pesticides are there. Certain parts in the world where the effect is more obvious, where you know that, you know, in this particular part of the world they use such and such pesticide and there we see a greater increase in the incidence of Parkinson's.

Is there something like that or we still don't know?

[00:08:48] Dr. Daniela Berg: Yeah, this is an interesting question because reports vary and this is because studies are so different, especially the case report the um, studies on occupational [00:09:00] exposure, and so on. They are all very different in design. But I think an interesting aspect that touches how much the events is already arising and what can be done is that, for example, in France, Parkinson's disease is already seen as an occupational disease, especially in farmers working in vineyards because the exposure there is quite high.

And here in Germany, for example, the Medical Expert Advisory Board for Occupational Diseases at the Federal Ministry of Labor and Social Affairs has recommended just at the end of last year, a new occupational disease with the proposed name Parkinson's syndrome caused by pesticides. So even here in Germany people see there's this association and the approval for recognizing Parkinson's syndrome caused by pesticides.

Pesticides as occupational disease is expected in autumn this year. So, in, in these countries, in these European countries, it's already being acknowledged. We [00:10:00] know that in many countries, especially when the safety conditions are not well followed, that people are more exposed and then that there is a increase.

These are often low and middle income countries, one needs to say. The problem really is that there is this lead time between exposure and the development of Parkinson's disease. So the countries that have just started to use even more of the pesticides to get better crops they will face the problems in the coming years.

[00:10:36] Prof. Tiago Outeiro: Yeah, and do we understand in general how the pesticides may increase our risk for Parkinson's?

[00:10:45] Dr. Daniela Berg: Yeah, I mean, this is also a very important question. Of course, one needs to say that the mode of action varies in different pesticides, but there are mechanisms that most of the pesticides [00:11:00] associated with PD have in common. These include, for example, that they lead to oxidative stress via free radicals, and thus, of course, to neurodegeneration.

Also, most of them induce mitochondrial dysfunction and neural inflammation. And it's important to realize that some of the pesticides, for example, Paraquat and also Rotenone, can cross the blood brain barrier. So it's not only that they are at the skin, or maybe in a lung via inhalation, but they really cross the blood brain barrier.

And they, it's been shown that they cause selective dopaminergic toxicity. And also important, some, and again, Paraquat, I've mentioned that already, can be named as an example, can directly promote the formation of alpha synuclein aggregation. So yes, the mode of action is understood. In many, and there are many [00:12:00] who have the same modes of action in common, so I think one knows what we need to do, reduce especially these aspects.

[00:12:10] Prof. Tiago Outeiro: Yeah. And in terms of the risk, are there ways for quantifying the risk? So if someone is exposed to a certain pesticide for a number of years, are there tools for quantifying this risk or is this still not easy to do?

[00:12:25] Dr. Daniela Berg: It's as far as I know, not easy because the studies we currently have are so different. I mean of course in animal models it's not so much of a problem, but in the population based studies, in the case control studies, in the cohort studies, they all have a different design that makes it difficult. In Germany, when people worked on this new recommendation for seeing Parkinson's disease as an occupational disease, the whole literature was, of course, screened. And what we saw here in Germany is that the odds [00:13:00] ratios do differ. They are there. They are related to Parkinson's disease, but they do differ.

One review, for example reported a 5 percent and 11 percent augmented risk after 5 and 10 years of pesticide exposure, respectively. For many of the pesticides. So there are these kind of summaries one one finds in the review, but the exact quantification is still difficult. And this is something we need to work on.

[00:13:26] Prof. Tiago Outeiro: And the final question is okay, we know there is a connection. We know there's several of these pesticides. Increase the risk. And we want, of course, governments to act based on the information we have. So, how do you see that we can act as a community to convince governments to take this issue actually seriously?

Because it is a very serious problem affecting the world. millions of people like you told us in the beginning and Therefore we we we need to act together to [00:14:00] to really convince the decision makers that That this is not something to be taken lightly. So What do you think we can do?

[00:14:08] Dr. Daniela Berg: You're absolutely right. We need to convince governments. And the first thing that really needs to be done is we need to make sure that the current evidence is recognized. So although we still lack some evidence, the evidence we have needs to be seen, needs to be recognized. And of course, it needs to be recognized by the public, because the public, I think, is a very strong instrument to move.

I mean, if the public says, well, we don't want to be exposed to the pesticides in such a way, then of course there's something happening. And of course, with all our Our papers with many campaign slots can be done and we just need to move according to the possibilities we have in our respective countries.

So the first point is the current evidence really needs to be seen, needs to be taken by us as scientists, by us as movement disorder specialists, by us [00:15:00] as doctors, and we need to make sure that it's recognized. there are specific steps we can call for. For example, we can say, well, we need a proper labeling and safety instructions of pesticides.

So we really need to make sure that people understand what it means to, to have a pesticide. they are working with or they are related with non occupationally, for example, in their own garden or whatsoever. And we also need a very clear education on hygiene habits and very important, I think this is something we also need to approach politics for, is we need to make sure that all have access to proper safety equipment.

This is not a case in many, many countries, one needs to say. So this is what we can do with all the data we have. And then, of course, we need to provide even more convincing data, I think, especially with regard to human data. And for that, I think it would be good if we as a [00:16:00] scientific community and the MDS Community, really seek a multidisciplinary approach.

For example, we work together with epidemiologists, toxicologists, statisticians, to really have good studies, global studies to better understand what's happening. And again, these data need to be translated to the public and the politicians. And, but maybe last very important question, we always need, as Thread alluded to that we always need to take this whole issue globally.

There are these arbitrary regional differences with regard to quantitative limits on pesticide protection measures, I already alluded to that. And, and this is very, very different in different regions of the world. And we need common rules regarding regulatory control. regarding transparency reporting.

So this is all essential. And finally, and I think this is important because what I realized when I talked to farmers regarding [00:17:00] pesticides, some don't want to tell that they're using pesticides because they need it for their living. And this is absolutely clear and this is even more. In low and middle income countries.

So what we need to urge our governments is that they invest in replacement strategies. There are these replacement strategies, but we need to invest in those. To have a replacement for the pesticides that are currently on the market.

[00:17:29] Prof. Tiago Outeiro: Wonderful. No, I think these are all important thoughts and of course we can also talk about these things in the podcast like we are doing now. I think that this is also a way of, you know advertising the, the problem. And, and hopefully to, to get this information to reach many people around the world that they can talk about this also locally.

 And hopefully also reach their local governments and, and act upon this, this information. So Daniela it was great to have you [00:18:00] on the podcast. Thank you so much for talking to us about this important topic. It was a pleasure.

[00:18:05] Dr. Daniela Berg: Thank you. It was a pleasure for me. Thank you. And you're absolutely right. Maybe I may add that for all who are hearing this podcast, please take it seriously. Please bring this important news to others.

[00:18:19] Prof. Tiago Outeiro: Thank you. So we have just interviewed Professor Daniela Berg on the relationship between pesticides and Parkinson's disease. I thank you all for listening, and I invite you to join us again in our upcoming podcasts.