What Causes Parkinson Disease?
What Causes Parkinson Disease?
Medscape: Have there been any dietary associations with PD, positive or negative?
Dr. Tanner: Yes. My colleague Freya Kamel just reported that polyunsaturated fatty acids (including omega-3 fatty acids found in fish and certain plant and seed oils) are associated with a lower risk for PD. These counteract oxidative stress, one of the mechanisms that's thought to be critical in the pathogenesis of PD. So, certain environmental factors can have a positive effect as well; these are important to identify, because they're an easy recommendation. It's too bad flaxseed is not so palatable!
Other people have looked at the Mediterranean diet and found it fairly beneficial in Alzheimer disease, and one report shows the same in PD. Also, diets that are high in certain antioxidants and diets that tend to increase the level of the strong antioxidant uric acid are associated with a lower risk for PD. Conversely, dairy products or diets high in animal fats were associated with greater risk for PD.
Medscape:Beyond potential dietary recommendations, what advice do you have for community neurologists or primary care providers in terms of minimizing risk? Are there genetic tests available that you would recommend for at-risk patients?
Dr. Tanner: Genetic testing for PD is a little controversial at this point. There are a few genes that are more common, and some people might want to be tested for them, such as people with a strong family history of PD. But in that case, I strongly advise the involvement of a genetic counselor, because in most cases having a mutation associated with PD does not necessarily mean that the individual will ever develop PD.
For example, mutations in the LRRK2 gene can account for a significant number of PD cases in certain populations – Mediterranean, Ashkenazi Jew, and North African. So here you might say that there could be some justification, particularly in familial PD but also maybe even in nonfamilial, to test for mutations in the LRRK2 gene.
But whenever you do this, it's not just the individual being tested that you're concerned about, but also the family. Patients have to seriously think about how to address this with their family members, particularly if some members of the family don't want to know their own genetic status.
And it's particularly important, because this gene is not fully penetrant -- so having the gene does not necessarily mean that you will definitely develop PD. Just being able to know that you have a mutation might not be so good.
On the other hand, some people do want to know. People who know that their genotype may put them at risk for PD may be motivated to live healthier lifestyles. In this case -- as we touched on -- there are a few recommendations you can make as a clinician that are probably good things to do. And even if they're not completely accepted as being beneficial in PD, they're probably good things to do anyway: for example, exercising and eating a healthy diet.
We do not at this point have a treatment that has been demonstrated to alter the course of PD. Throughout my career, we've been trying to develop one, but we still don't have one. Having one would certainly change the game, and we'd potentially be able intervene early. Having an effective way to delay or prevent PD might make many people more interested in knowing whether they carry a risk mutation.
As I mentioned in my talk, we're not quite sure whether the treatments we have are not good enough to alter the disease, or whether most cases of PD have progressed so far by the time we see them that the current treatments are ineffective. Throughout most of my career, we have been interested in identifying people at risk for PD at the very earliest point.
I believe that we will be able to prevent PD with new understandings and ways of identifying people at risk, possibly through biomarkers. I envision a screening approach comprising several different ways of identifying someone who might be at risk for disease. For example, persons with loss of olfactory function, or those with REM sleep behavior disorder or a specific mutation, might be identified at the first level of risk. Then you'll bump them to the next level of testing -- maybe dopamine transporter imaging, or maybe a biomarker test -- and if they look like they might be at risk on the basis of these tests, you can monitor more closely. Of course, if we had an effective intervention, that would be the time to use it -- before the parkinsonian symptoms have developed. So in the future, when people of a certain age get screened for colon or breast cancer, we could also screen them for neurologic diseases, such as PD.
Medscape:So at this point, even if your patient was found to be predisposed to PD on the basis of a genetic test or has been exposed to known environmental risk factors, for now clinicians should focus on lifestyle advice?
Dr. Tanner: For now. But there is one other analysis we did in the study of farmers and their wives, which was to look at who wore personal protective equipment. Some wore respirators, and some just gloves that were impervious and a coverall. People who used protective equipment and washed off after spills did not have an increased risk for PD. So I think the basic, healthy living, common-sense approaches are very important.
Medscape:And this seems like something primary care physicians should be aware of?
Dr. Tanner: That's right. If you are a primary care physician in a farming region, it would be worthwhile to have this talk with your patients. And the same goes for those who work in industrial settings with potential solvent exposures.
Advice to Patients
Medscape: Have there been any dietary associations with PD, positive or negative?
Dr. Tanner: Yes. My colleague Freya Kamel just reported that polyunsaturated fatty acids (including omega-3 fatty acids found in fish and certain plant and seed oils) are associated with a lower risk for PD. These counteract oxidative stress, one of the mechanisms that's thought to be critical in the pathogenesis of PD. So, certain environmental factors can have a positive effect as well; these are important to identify, because they're an easy recommendation. It's too bad flaxseed is not so palatable!
Other people have looked at the Mediterranean diet and found it fairly beneficial in Alzheimer disease, and one report shows the same in PD. Also, diets that are high in certain antioxidants and diets that tend to increase the level of the strong antioxidant uric acid are associated with a lower risk for PD. Conversely, dairy products or diets high in animal fats were associated with greater risk for PD.
Medscape:Beyond potential dietary recommendations, what advice do you have for community neurologists or primary care providers in terms of minimizing risk? Are there genetic tests available that you would recommend for at-risk patients?
Dr. Tanner: Genetic testing for PD is a little controversial at this point. There are a few genes that are more common, and some people might want to be tested for them, such as people with a strong family history of PD. But in that case, I strongly advise the involvement of a genetic counselor, because in most cases having a mutation associated with PD does not necessarily mean that the individual will ever develop PD.
For example, mutations in the LRRK2 gene can account for a significant number of PD cases in certain populations – Mediterranean, Ashkenazi Jew, and North African. So here you might say that there could be some justification, particularly in familial PD but also maybe even in nonfamilial, to test for mutations in the LRRK2 gene.
But whenever you do this, it's not just the individual being tested that you're concerned about, but also the family. Patients have to seriously think about how to address this with their family members, particularly if some members of the family don't want to know their own genetic status.
And it's particularly important, because this gene is not fully penetrant -- so having the gene does not necessarily mean that you will definitely develop PD. Just being able to know that you have a mutation might not be so good.
On the other hand, some people do want to know. People who know that their genotype may put them at risk for PD may be motivated to live healthier lifestyles. In this case -- as we touched on -- there are a few recommendations you can make as a clinician that are probably good things to do. And even if they're not completely accepted as being beneficial in PD, they're probably good things to do anyway: for example, exercising and eating a healthy diet.
We do not at this point have a treatment that has been demonstrated to alter the course of PD. Throughout my career, we've been trying to develop one, but we still don't have one. Having one would certainly change the game, and we'd potentially be able intervene early. Having an effective way to delay or prevent PD might make many people more interested in knowing whether they carry a risk mutation.
As I mentioned in my talk, we're not quite sure whether the treatments we have are not good enough to alter the disease, or whether most cases of PD have progressed so far by the time we see them that the current treatments are ineffective. Throughout most of my career, we have been interested in identifying people at risk for PD at the very earliest point.
I believe that we will be able to prevent PD with new understandings and ways of identifying people at risk, possibly through biomarkers. I envision a screening approach comprising several different ways of identifying someone who might be at risk for disease. For example, persons with loss of olfactory function, or those with REM sleep behavior disorder or a specific mutation, might be identified at the first level of risk. Then you'll bump them to the next level of testing -- maybe dopamine transporter imaging, or maybe a biomarker test -- and if they look like they might be at risk on the basis of these tests, you can monitor more closely. Of course, if we had an effective intervention, that would be the time to use it -- before the parkinsonian symptoms have developed. So in the future, when people of a certain age get screened for colon or breast cancer, we could also screen them for neurologic diseases, such as PD.
Medscape:So at this point, even if your patient was found to be predisposed to PD on the basis of a genetic test or has been exposed to known environmental risk factors, for now clinicians should focus on lifestyle advice?
Dr. Tanner: For now. But there is one other analysis we did in the study of farmers and their wives, which was to look at who wore personal protective equipment. Some wore respirators, and some just gloves that were impervious and a coverall. People who used protective equipment and washed off after spills did not have an increased risk for PD. So I think the basic, healthy living, common-sense approaches are very important.
Medscape:And this seems like something primary care physicians should be aware of?
Dr. Tanner: That's right. If you are a primary care physician in a farming region, it would be worthwhile to have this talk with your patients. And the same goes for those who work in industrial settings with potential solvent exposures.
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