The largest-ever environmental and occupational risk factor survey in PSP was just published. Irene Litvan of UCSD led a group of sites throughout North America with 284 patients and 284 controls who were friends or non-blood relatives of the patients.
The results corroborate the finding of all three previous such studies that lesser educational attainment is more common in people with PSP. Two of those studies were done by me and my colleagues in New Jersey (1988 and 1996) and the other was in France by Vidal et al (2009).
In this new study, the odds ratio for having earned a college degree was 0.585 (95% confidence interval 0.345 to 0.993, p = 0.047). The only other statistically significant result was that people with PSP reported having drunk well water for an average of 11.7 years, while for the controls, the figure was 7.4 years. That p-value after multivariate correction, was 0.032. They showed that these two findings were not correlated to each other in this subject group.
Interestingly, the well-documented tendency in Parkinson’s disease for non-smoking was not observed. In fact, there was a non-significant trend in the opposite direction, with the odds ratio of 1.096 (multivariate corrected p = 0.082) for smoking among the PSP group relative to controls.
So what’s the take-home? We’ve been saying for years that most of the diseases for which we have no clear cause (most cases of cancer, Alzheimer’s, atherosclerosis, schizophrenia, PSP, etc.) are the result of a genetic predisposition and an environmental trigger, with “environment” being broadly defined as anything other than the person’s genome. This study suggests that for PSP, the trigger (or one of the triggers) is something associated with the lifestyles, work places or home neighborhoods of people with lesser education. But the only clue the study provided beyond that is that the trigger may be something in well water. Furthermore, using well water may tend to correlate with other toxic exposures or experiences that the survey did not ask about.
This result may now stimulate researchers to study “environmental” causes of PSP more closely and may induce granting agencies to support such studies. Of course, this search will be guided in part by ongoing genetic studies of PSP: If a variant in a detoxification gene is found to be over-represented in PSP, then perhaps the corresponding toxin is the environmental trigger. If a gene variant that causes over-expression of a gene is found to be over-represented in PSP, then environmental agents that cause a similar effect would immediately become suspect.
Another point, just to make life more complicated: Environmental toxins may not only act directly, as, for example, lead in the drinking water affects childhood brain development. They may also cause epigenetic changes that affect the expression of genes. They may also affect the gut bacteria, the “endobiome,” which itself produces and alters a wide array of compounds, some of which could be pathogenic.
So we’ve got work to do, but Dr. Litvan and colleagues have taken an important step.
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PSP Blog 
My husband does not fit this criterion. He had PSP but was a graduate and taught in a university.
The effect was only a difference between the average years of education in the two groups. There was a lot of overlap, as in any biological effect.
Hi Kathryn, my dear Daddy with PSP is the only person I’ve ever seen do algebra in his HEAD, very intelligent but albeit, without the education to go along with it. How could his lack of extended education cause PSP? What in the world could be the connect there!? Baffling.
Sheila: I think that the connection between lesser education and PSP is that part of the cause of the disease is some toxin in the environment or workplace. On average, people with less education tend to live and/or work in places with more industrial or agricultural toxins. Someone with an extended education can still be exposed to those toxins, but perhaps with a lesser likelihood or intensity. If such a person with the genetic (or other) factors at a greater than average intensity may require only a brief or low-level exposure to the toxin to set off the disease process. Just my theory, but it does conform to the existing facts.
Short Version:
WELL . . . what’s in the well water?
Let’s find out! Let’s test the well water of the 284 participants. Why? (See the Long Version)
Long Version:
WELL WATER DESERVES MORE INVESTIGATION
Per the USGS: “ . . .43 million Americans supplied their own home water and over 99 percent of that water came from groundwater.” (http://water.usgs.gov/edu/gw-well-contamination.html)
An estimated 30 million Americans have rare disease and 43 million Americans have their own water supply and 99% is groundwater? Maybe this is coincidence.
PRIVATE WELL REGULATIONS EXIST . . . or they do NOW
But they didn’t exist when my parents grew up.
“ . . . in 2009, the U.S. Geological Survey (USGS) studied the water quality of over 2,000 private wells to measure the existence and extent of contamination. The study found that about 23 percent of them did have at least one contaminant at a level of potential health concern.” (same reference as above)
In published medical research, I have often heard it’s all about the numbers, the quantity of individuals in the study, i.e., small number of participants equals pure rubbish (someone was desperate to be published). The USGS study was small (only 2,000 wells), but almost 1/4 had contamination levels to potentially affect health! Tip of the iceberg?
PRIVATE WELLS ARE RARELY TESTED BY OWNERS
All of the responsibility for testing relies with owners. Our well was hand-dug & hand-built proudly by my grandfather around 1960 with no formal “professionals” involved. In the late 60s, our well was drilled deeper by an outside drilling agency, but I do not believe any sort of reporting or regulating requirements were in place at that time.
To my knowledge, we NEVER once had our water tested in 50+years.
And I’m confident that if I asked all of the neighbors in the surrounding 30mi radius, the number of private well owners who had their water tested would be staggeringly low.
I’m also confident it would be effortless for descendants to take over real estate (w/private wells) without any sort of investigation and/or reporting requirements of the water supply.
The only event where I see regulations to be followed/enforced is when an outside agency gets involved with servicing the well, either through testing or modification.
There is a culture that needs to be acknowledged about people who have grown up with their own private water supply. I think they are completely unaware because having a private well made you a survivor. To question the integrity of your means of survival was never acknowledged. It wasn’t an issue. This type of culture has been passed down through generations.
WELL, WHAT’S IN THE WELL WATER?
Is it time for some cross-discipline collaboration?
Let’s get the well water tested of the 284 participants and see what that reveals! What have we got lose? Nothing ventured, nothing gained.
Yes, there are caveats (contamination now doesn’t necessarily indicate previous contamination), but a proper environmental review and assessment of soil, water, industry, etc can address this and there may be results already available to review.
Since most of the authors of the study are present at universities, it would be fairly easy to reach out to other academic disciplines to get this ball rolling.
Dr. Golbe’s contact would be Rutger’s Research Partner: NJ Water Resources Research Institute (http://njwrri.rutgers.edu/)
Dr. Litvan’s starting point at UC San Diego would be: Research Intelligence Portal (http://blink.ucsd.edu/sponsor/ora/expertise.html) and for University of Kentucky is: KY Water Resources Research Institute (http://www.uky.edu/WaterResources/)
Dr. Lees starting point is: Johns Hopkins Water Institute (http://water.jhu.edu/)
etc.
Thanks to you, Dr. Golbe, & others involved with neurodegeneration. My “thank you” seems paltry in comparison to the efforts put forth by you & other medical researchers. I know that all of you have families & that you sacrifice your time, emotions, and energy for our community.
PLEASE tell your families that we thank them too!
Mother diagnosed w/atypical PSP (Mayo-Rochester) in 2012; died at young at age 74 in 2015, autopsy confirmed CBD (Mayo-Jacksonville).
A study of candidate toxins in the homes, water supplies and soil of patients with PSP (in the cluster) and controls is under way right now. It should take two years.
Hi Dr. Golbe,
Was this study ever completed?
Is there anything interesting to report on it?
Thank you!
Dear Dr. Golbe,
I wanted to bring to your attention a cluster of three men who have all died from PSP in Greencastle, Indiana. My Father died in 2003 and his neighbor died in 2007. Also a man he worked who did not live in the neighborhood died around the same time. This seems unusual for a such a small town. If you are interested please contact me and I can provide the names of these men and perhaps more relevant information. Thank you for your valuable time.
Thank you for your very valuable time.
Omarindeed: Thanks for that report. Major discoveries have come from grass-roots observations like that. But on the face of it, this series of patients isn’t a true cluster. The incidence of new cases of PSP is about 1-2 per 100,000 population per year. Unless the incidence is changing rapidly over time, you’d expect the same number of deaths from PSP each year. Now, you can’t just choose a span of years that conforms to the first and last cases you know of — that biases the analysis in favor of calling it a cluster. Instead, you have to choose a logical, conventional span such as a calendar decade. Let’s choose 2001 to 2010. So in a town of 10,000 population (which is what Greencastle has), you’d expect that over 10 years to have 1-2 deaths from PSP. You know of 3. That’s not sufficiently different from 1 or 2 and could easily be happenstance. But if there are additional cases that you don’t yet know about, then it may be a different story. Keep your ears pricked. Meanwhile, please tell me: Are there any metals-related industries in Greencastle? Any other source of specific toxins?
My ears are pricked. Thank you for
explaining a true cluster. As far as we know Greencastle has no known metal toxins. We are checking with the former mayor to
see if there is any information on toxins.
One more thing that we would like to bring to your attention is that the connection between these men could have something
to do with exposure to bats. We read the article years ago in the New Yorker which talked about Guam and bats. My father was
the DePauw University organist and Mr Sendmeyer helped him maintain the organ. They were in constant contact with bats in the belfry. A Mr. Ben Dean was the church maintenance man and he died before my father of a disease very similar to PSP but my mother cannot remember the name of the disease. Our neighbor Mr. Gaebes bought and renovated houses and encountered many bats while doing so but had no association with the church. When I came to hear you speak at Johns Hopkins in the 90s it was mentioned that some kind of trauma occurred before the onset of PSP in almost all cases. My father poured a toxic commercial drain cleaner in the shower drain and was overcome by the fumes and paramedics had to revive him. This could be the toxic exposure in my father’s case. But we have always been interested in the bat connection. I will be in touch with any new information I receive.
My father has PSP (final stages). He is 67 y/o and has worked all his life designing machines for factories in my hometown (contact with metals). Aside from that, he has always been very handy. Since he was a child. He was also into car mechanics and was able to fix any kind of car issues back in the day. Aside from that, he has suffered most of his life from anger issues. In terms of diet, he used to eat too much salt and sugar. Was a heavy smoker as well, but stopped smoking in 1989. I am very intrigued by this disease and would like to share any information regarding his case in order to help.