Global study identifies markers for the five clinical stages of Parkinson’s disease

From a study that analyzed brain images of more than 2,500 people with Parkinson’s disease in 20 different countries, scientists were able to identify patterns of neurodegeneration and create metrics for each of the five clinical stages of the disease.

The work, published in NPJ Parkinson’s Disease, represents a leap forward in the understanding of the disease. The analysis and volume of data obtained in the study could lead to important developments, not only in terms of diagnostic advances but also in terms of enabling new treatments to be tested and monitored as never before.

It is estimated that approximately 4 million people worldwide have Parkinson’s disease. It is a progressive neurological disease that affects certain structures in the brain, especially those related to movement. The progression of the disease is variable and different from patient to patient, and it can take up to 20 years to go through all the stages. In the initial phase, there are the first signs are tremors, muscle stiffness, and slow movements on only one side of the body. The symptoms then become bilateral. In the final stage, the patient is dependent on a wheelchair to get around, as the stiffness in the legs prevents them from walking.

“Clinical diagnosis, supported by some complementary tests, has been well established for many years. However, for the first time, it has been possible to relate the degree of progression of the disease – the five stages of clinical symptoms – to quantitative changes in brain images,” explains Fernando Cendes, senior researcher at the Brazilian Research Institute for Neuroscience and Neurotechnology (BRAINN) – a FAPESP Research, Innovation and Dissemination Center (RIDC), based at the State University of Campinas (UNICAMP), in the state of São Paulo, Brazil.

BRAINN is one of the institutes that make up the Enigma Consortium, an international network that brings together scientists in imaging genomics, neurology, and psychiatry to understand the structure and function of the brain based on high-resolution magnetic resonance imaging, genetic data, and other information from patients with epilepsy, Parkinson’s, Alzheimer’s, autism, schizophrenia, and other neurodegenerative diseases.

Cendes explains that in Parkinson’s disease, there are changes in the brain structure of the so-called basal ganglia – areas of the brain associated with automatic movement. However, the study demonstrated the existence of progressive changes in other cortical areas that had previously been less involved in the disease.

“We observed that as each stage of the disease progressed, there was a greater degree of atrophy or hypertrophy not only in the movement-related structures but also in other cortical areas. And it’s these combinations of atrophy and hypertrophy that are related to the stage of the disease,” he explains.

“But that’s not all we observed, some of these structures also had differences in shape. They had changed their spatial configuration. Some regions of the thalamus [a structure whose function is to relay information from the senses to the cerebral cortex] had become thicker. Other regions, such as the amygdalae [which play a role in regulating social behavior and emotions] had atrophied,” he notes.

The researcher explains that these changes cannot be seen with the naked eye: “They’re submillimetric measurements. However, with programs and the use of artificial intelligence, it’s possible to identify patterns and, in the future, monitor these changes,” he says.

Push for new treatments

By establishing a metric to quantify brain changes associated with the stages of Parkinson’s disease, the study could have several implications. Starting with supporting better diagnosis. “The morphometric data we obtained with this work are sensitive and reproducible measures that allow us to support clinical diagnosis. With the wealth of data we’ve obtained in this study, it’s possible, with the help of artificial intelligence, to create programs that help the clinic,” he says.

Other developments are in the area of treatment. Currently, Parkinson’s disease has no cure, and only the lack of dopamine – a neurotransmitter that the neurons of Parkinson’s patients stop producing, the absence of which triggers all the brain changes and symptoms – is treated.

Over time, however, the disease is not limited to the basal ganglia but also affects other areas of the brain, and patients tend to experience other non-motor symptoms such as depression, anxiety, sleep disturbances, and cognitive changes such as memory loss and eventually dementia.

“The results of this work provide new ways of monitoring treatments that may be developed in the future. The main objective in relation to the disease has been to find a treatment that stops the neurodegenerative process or at least reduces the speed of its progression. And these measures that we’ve identified are essential for evaluating future therapies, to make sure that they’re working in a global way, not only in the brain areas associated with movement but also in the others that suffer changes,” he points out.

A third impact of the study, which analyzed a large amount of data, is not in the field of medicine but in data science. “It’s a very large cohort with different countries, study groups, stages of the disease, and even types of data. So the innovation of the study is not only in identifying these metrics related to the stages of Parkinson’s disease, but also in all the work related to the data. The whole type of analysis used in the work was a major step forward for further studies using artificial intelligence and on other diseases,” says Cendes.

About FAPESP

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration.