Study identifies early risk factors for progressive supranuclear palsy

Q: What challenges or unmet needs make this study important?

Progressive supranuclear palsy, or PSP, is a rare brain disease that causes problems with balance, eye movements and thinking. Civil rights leader Jesse Jackson recently passed away after living with the disease for more than a decade. Most individuals with PSP, like Jackson, are initially misdiagnosed with Parkinson's disease, and correct diagnosis can be delayed by several years.

Until now, scientists have known very little about what raises a person's chances of getting PSP, so there was a significant need for a large study that tracked healthy people over time to look for early clues.

Q: What central question(s) were you investigating?

We set out with a straightforward question: What are the risk factors for developing PSP? We looked at factors like where people lived, what medical conditions they had and what medications they took, as well as their drinking/smoking habits and diet. All of this information was collected before anyone in the study had overt symptoms of PSP.

We also wanted to know how early these warning signs could be spotted, which would tell us how long the disease might quietly build before symptoms become noticeable.

Q: What methods or approach did you use?

Using data from the UK Biobank-a large health study that followed more than 500,000 adults in the United Kingdom for close to 20 years-we found 240 people who were later diagnosed with PSP. We compared their health habits, medical histories and living environments to those of their healthy counterparts using a careful, step-by-step statistical method that tested many possible risk factors. We also checked how far back in time each risk factor could be detected to ensure we were finding true early warning signs, rather than symptoms of PSP that had already started.

Q: What did you find?

We found five clear risk factors for PSP. Depression and delirium (temporary confusion due to an acute medical illness such as a urinary tract infection) diagnosed years before PSP stood out the most. Depression was linked to higher risk as far back as 10 years before diagnosis, and delirium at least five years before. Gut problems like irritable bowel syndrome were also associated with elevated risk. Finally, heavy drinking was associated with increased risk compared to moderate drinking, as was being overweight.

One of the most surprising findings was that people who had been diagnosed with cancer were about half as likely to develop PSP, a pattern also seen in Parkinson's and Alzheimer's disease. It was also interesting to discover that smoking, diet, air pollution and pesticide exposure did not appear to affect PSP risk.

Q: What are the real-world implications, particularly for patients?

PSP may silently develop for 10 years or more before the well-known symptoms, like falls and trouble with eye movements, show up. If clinicians recognize that depression, confusion episodes and gut issues could be early signs of PSP rather than unrelated problems, they may be able to arrive at the right diagnosis sooner. Identifying people in this early, silent stage of disease could open the door to enrolling them in clinical trials for new treatments at a point when those treatments are most likely to help.

Q: Were you surprised by any of the findings?

The link between cancer and lower PSP risk really stood out to our research team. It fits an emerging idea in science that cancer is a disease of cells growing out of control, while brain diseases like PSP involve cells dying too soon. These two processes may work in opposite directions, almost like two ends of a seesaw.

We were also struck by the fact that depression showed up as a warning sign a full 10 years before PSP diagnosis. That tells us the disease may stealthily affect brain circuits involved in mood long before anyone notices problems with movement or balance. It pushes us to look for ways to detect PSP during this hidden early phase, when future treatments could potentially make the biggest impact.