Parkinson's disease, multiple sclerosis, ALS: behind the rising case numbers, distinct dynamics

Parkinson's disease, multiple sclerosis, and motor neuron diseases (MND, a category mainly comprising amyotrophic lateral sclerosis) are progressive chronic conditions that affect the central nervous system and cause motor disability that weighs heavily on patients' quality of life. Their prevalence—the total number of people living with the disease—is rising worldwide[1].

This observation, taken on its own, is not very informative. A rise in prevalence can be driven by patients living longer, by more people falling ill in response to environmental exposures or behavioral changes, or simply by population aging—neurodegenerative diseases being more common in older adults.

To untangle these threads, Octave Guinebretière, an epidemiologist at Pitié-Salpêtrière Hospital and former doctoral researcher at the Paris Brain Institute, Thomas Nedelec, a researcher in the ARAMIS team, and their colleagues drew on two of the world's most comprehensive national health databases—the French National Health Data System (SNDS), which covers 99% of the population, and the Swedish national health registers, in operation since the 1960s. Their study spans nearly two decades (2001-2016 in Sweden, 2009-2022 in France) and several hundred thousand patients.

“Although there are differences between these databases, which we account for in our analysis, they are highly comparable. Both countries have high-performing, centralized healthcare systems with universal coverage. These administrative health databases allow us to describe population health in a satisfactory way, drawing on data from reimbursable care”, Octave Guinebretière explains.

The researchers' first finding confirms existing epidemiological data: between 2003 and 2022, the prevalence of Parkinson's disease rose by 1.4% per year, multiple sclerosis by 2.9%, and motor neuron diseases by 2.8%. How is this possible?

Multiple sclerosis: patients are living longer with the disease

A deeper analysis shows that the substantial rise in multiple sclerosis (MS) prevalence reflects an increase in life expectancy at diagnosis. Patients have gained 2.35 months per calendar year, while the incidence of the disease—the number of new cases diagnosed each year—has remained roughly stable over the period.

“In short, we are diagnosing roughly as many MS cases today as twenty years ago. But patients are living significantly longer thanks to better clinical management and therapies that can alter the trajectory of the disease—such as immunosuppressive and immunomodulatory treatments—whose arsenal has expanded considerably”, Thomas Nedelec adds.

The challenge now is to support a growing number of patients and offer them the best possible quality of life, including in old age.

ALS: several hypotheses behind the rise in new cases

In contrast, the researchers report a real rise in the incidence of amyotrophic lateral sclerosis (ALS) and other motor neuron diseases[2]: the number of new cases is increasing by 1.8% per year.

“56% of this rise is explained by population aging. Although ALS can occur at any age, it more commonly affects older adults, with an average age at diagnosis of 70. We are not currently able to put forward other explanations with certainty, although we suspect that improved awareness of the disease has also led to better case detection”, Octave Guinebretière says.

Because ALS is unevenly distributed geographically, with regional clusters, environmental or lifestyle factors may also contribute—to a lesser extent—to the rising incidence.

Parkinson's: a more modest rise, and a surprise

In the case of Parkinson's disease, the epidemiological picture is more complex. Prevalence is rising more slowly than for the other two diseases, and once population aging is accounted for, incidence is actually declining slightly (−1.4% per year).

“Several decades ago, a significant rise in the prevalence of Parkinson's disease was observed, largely linked to improvements in the management of the disease and of its cardiovascular comorbidities: patients were living longer. Today, that beneficial effect is plateauing, especially as life expectancy is also slowing in the general population. The rise in prevalence is therefore more modest”, Thomas Nedelec explains.

The decline in incidence, meanwhile, could be due to a favorable shift in exposure to certain established risk factors, such as pesticides or industrial degreasing solvents.

But the team also made a more unexpected finding: life expectancy at Parkinson's diagnosis, which had improved between 2003 and 2013, declined by 1.20 months per year between 2013 and 2022.

“It is possible that we are observing here, at least in part, an effect of the COVID-19 pandemic, whose mortality was highest among older patients with comorbidities. Indeed, in Parkinson's disease, the average age at diagnosis is 75”, he adds.

To find out more, we will need to wait until new data—collected several years after the pandemic—can be analyzed and compared with data from countries where COVID had a less severe impact on the population and the healthcare system.

Toward a European map of neurodegenerative diseases

While the study clearly shows that the rising number of cases of these three neurodegenerative diseases is not the result of a surge in risk factors and does not warrant a public-health alarm, the researchers still lack comparative data across territories to explain certain trends.

They observe, for example, a north-south gradient in multiple sclerosis: the further from the equator, the more common the disease. This effect is already well documented in the literature, although its cause remains unknown. The most widely proposed hypothesis is that exposure to sunlight, which enables vitamin D synthesis to a greater or lesser extent, may influence the risk of developing the disease—but this remains uncertain.

“Our algorithms are now robust enough to envisage drawing up a Europe-wide map of neurodegenerative diseases, in order to better detect and understand their risk factors. Beyond Sweden, we are already developing collaborations with Denmark and Germany”, Thomas Nedelec says.

The researchers hope that their future work, accelerated by the build-out of a European Health Data Space (EHDS), will generate new knowledge to inform public policy—always with the hope of seeing encouraging epidemiological trends emerge thanks to future innovative treatments.

[1] Steinmetz J. et al. Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet Neurology, 2024.

[2] For convenience, we use “ALS” here as shorthand for the broader category of motor neuron diseases (MND). Around 90% of cases identified as MND in administrative health databases correspond to ALS.