There are two types of Parkinson’s disease, and each may require different treatment, a leading Parkinson’s researcher has found.
It’s long been understood that the disease could start in the nervous system of the gut and spread to the brain via the vagus nerve.
But Per Borghammer, professor and consultant of nuclear medicine at Aarhus University Hospital in Denmark, says there is another way Parkinson’s starts.
Over the last six years, Borghammer has explored this theory.
“Our previous studies support that this gut-start idea could be right. In short, that Parkinson’s starts in the gut and spreads through the brain via the vagus nerve,” he says.
In one Danish study, and a similar Swedish study that later reproduced their results, Borghammer found out that patients who had their vagus nerve cut showed a 50 per cent reduced risk of developing Parkinson’s.
“This finding makes sense, since patients with a surgically severed vagus nerve should be protected against Parkinson’s because the main gut-to-brain spreading highway is no longer there,” he says.
However, the risk reduction was only 50 per cent. This This led him to wonder – what about the other 50 per cent?
Borghammer knew that all Parkinson’s cases probably didn’t start in the gut, because scans show that, in some early-stage Parkinson patients, their nerves to the heart and gut are damaged, but in others they’re not.
“I wanted to design a study that showed that the right way to think about Parkinson’s is that it can start in the gut and move to the brain, but it can also start in the brain and move down through the brain stem into the peripheral nervous system.”
This would mean that, in both group of people, the disease eventually looks the same – but in the early stages it looks completely different.
The motor symptoms of Parkinson’s disease only become apparent when the dopamine system is damaged – which would probably occur much earlier if the disease starts in the brain, not the gut. “The body-first disease seems to be the worst one,” Borghammer says.
“It has the poorest prognosis and these patients have a larger symptom burden than those where it starts in the brain. In body-first patients, you see a lot of early symptoms from the damaged peripheral nervous system.”
Such patients will experience symptoms including constipation, sexual dysfunction and orthostatic hypertension.
And when the disease has advanced far enough it will reach the middle of the brain stem, giving rise to REM sleep behaviour disorder.
“This particular sleep disorder often have a detrimental effect on patients’ quality of life,” Borghammer says.
Normally, when we enter REM sleep, which is when we dream, the body is paralysed. But in the fraction of Parkinson’s patients who develop the sleep disorder, Borghammer says, this paralysis stops working and the person will thrash around in the night.
“We know that patients who get the sleep disorder early will progress through cognitive decline and dementia faster than other patients. We don’t know exactly why, but statistically, that’s a fact.”
In Borghammer’s latest study, he set out to see if there were two types of the disease – a brain-first and body-first.
The first starts in the brain and spreads to the peripheral autonomic nervous system, and the second starts in the peripheral autonomic nervous system and spreads to the brain via the vagus nerve.
In the body-first type of Parkinson’s, he says, the disease damages the heart and gut early, then spreads to the brain stem, where at which time the patient will get the Parkinson’s diagnosis.
“In the brain first subtype, the pathology starts inside the brain, probably most often in the amygdala, where it’s clinically silent and the person doesn’t know there’s anything wrong.
“From there, it spreads in all directions, into the dopamine system, down through the brainstem and eventually into the peripheral nerves, which likely takes five to 10 years.”
It’s too early to know the implications of this, he says, but it’s likely the type types of Parkinson’s should be treated differently.
He urges researchers looking into Parkinson’s to consider these findings.
“If we want to cure the disease, and eventually prevent it, we likely need two different strategies,” he says.
“One tailored to the body-first and one for the brain-first types.”
In recent years there has been a huge increase in studies looking at the gut microbiome.
It’s likely that, if the gut can give someone Parkinson’s, this will result in the body-first type, Borghammer says.
For example, there are several studies currently looking at faecal transplants, which Borghammer guesses will help more in body-first patients of Parkinson’s.
“This is important knowledge, because studies might benefit from including only body-first patients, but that’s not what’s being done. All Parkinson’s patients are put into one big pot.”
But, he says, there needs to be focus on both types of the disease.
If it turns out that certain bacteria in the gut put people at a higher risk of developing Parkinson’s, for example, Borghammer says in an ideal world there would be efforts to ensure people don’t have these bacteria.
But this might only prevent body-first Parkinson’s. Borghammer plans to double the number of patients and repeat the study again on a larger scale, and hopes other researchers will replicate his research in other countries.
“Hopefully the entire field will realise there are these two different types of patients. We’ve shown how they can be identified. If we’re lucky, maybe we can discover the genetic risk factor that predisposes people to the gut-first or brain-first Parkinson’s.”
Lastly, Borghammer clarifies that not all Parkinson’s patients will necessarily fall into one of the two groups, and there could be rare cases that fall outside of these two main categories.
