AAN 2026 | The unique characteristics of early-onset PD and the impact of autonomic dysfunction

Early onset, Parkinson’s disease is a group of different disorders. I’m using this term, group of different disorders, because it’s true. This group of people share common findings, tremor, stiffness, rigidity, slowness, all the features of Parkinson’s disease. But in reality, they are not necessarily having the same pathological mechanism behind the development of the disease and this is an important aspect because the only commonality between early onset Parkinson’s and late onset Parkinson’s, the typical Parkinson’s we are in our 70s or 80s, is that the reduction of the level of dopamine that is lower than expected. Early onset population are obviously younger, we’re talking about people that are 50 years and below, so people that are still very active, people that have a lot to do in their life, people that are able to function and they may have work and a family, they are young and active. But they have some features that are kind of unique, and they differentiate quite a lot with Parkinson’s disease, the regular Parkinson’s disease, so to speak. Why is this important? Because with some of our studies, we have been identifying a number of factors that seem to change the way early-onset Parkinson’s disease progresses and manifests. We know that insomnia, like a problem with falling asleep, has been a preceding factor for early-onset Parkinson’s disease. We know that anxiety and depression can precede this phenomenon of the symptoms of Parkinson’s disease, this phenomenon for many years. What was not clear was whether autonomic dysfunction, in the sense of constipation, bladder dysfunction, and erectile dysfunction in men or vaginal dryness in women, orthostatic hypotension, whether these symptoms that are mainstay symptoms in late-onset Parkinson’s disease, whether they had a role also in early-onset Parkinson’s. And not to our surprise, but we have identified that there’s a group of patients with early-onset Parkinson’s disease that if this group of patients develops constipation, severe constipation, meaning that they are not able to go to the restroom, they take a lot of laxatives, they have major issues in the activity they’re living in, in going to the restroom to pass bowels, they seem to be having not as good a prognosis. In other words, people with constipation preceding the onset of early onset Parkinson’s and also developing constipation right after the disease has been diagnosed seem to be associated with a much more severe, faster prognosis compared to people that do not have that. That’s important, not just for the knowledge. First, constipation is a very bothersome symptom. Sometimes people say even more bothersome than the tremor itself or the stiffness itself. Most important is that if you’re able to improve the component, if you’re able to improve constipation, there’s a risk and there’s a chance that we can also maybe improve the symptoms of Parkinson’s. So improving the gut health, in other words, can potentially improve also the brain health. I want to clarify a point, though. Gut health, brain health seem to be two different things. We’re still talking about the nervous system here. The gut problem is because the nervous system, the little fibers within the bowel, are not working very well, that’s the reason why they’re not two separate things altogether. So this study opened a number of potential future developments that I think are very exciting, including potentially specific targeted populations that are more severe compared to others, specific target symptoms such as constipation and bowel disorders, or in general, autonomic dysfunction. But interestingly, it’s also shedding light on the fact that, again, early onset Parkinson’s disease is different than late onset Parkinson’s disease. Not everyone has the same, not everyone be as the same.

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