Researchers at the Sant Pau Research Institute (IR Sant Pau) have published a study showing that “brain alterations related to the more aggressive forms of cognitive decline in Parkinson’s disease can be detected years before cognitive impairment manifests.” The research is part of a project funded by the Fundación la Marató de TV3 and led by Dr. Javier Pagonabarraga, researcher of the Parkinson’s Disease Group at IR Sant Pau and neurologist at the Movement Disorders Unit of the Neurology Department at Hospital de Sant Pau. The results open new avenues to anticipate, understand, and intervene in cognitive disorders related to this disease.
Unlike what occurs in other neurodegenerative diseases like Alzheimer’s, not all people with Parkinson’s develop cognitive impairment or dementia. Unfortunately, a significant proportion does, and in some cases, cognitive decline is very aggressive during the early years of the disease.
Currently, it is very difficult to predict which recently diagnosed Parkinson’s patients or those without cognitive problems will develop dementia, but researchers have a clear understanding of the brain and cognitive anomalies that are commonly present in people with Parkinson’s who experience severe cognitive disorders.
“In many cases, when the brain is becoming diseased, neuropsychological evaluation tests and brain imaging techniques do not allow us to see phenomena that are already present. When we detect problems clinically, we know that significant brain damage has already occurred. Therefore, to intervene before the brain damage becomes too extensive, we need to develop techniques that allow us to observe phenomena that are already present in those who will experience a more aggressive form of the disease, but which we cannot yet detect,” explains Dr. Saül Martínez-Horta, researcher of the Parkinson’s Disease Group at IR Sant Pau and neuropsychologist at the Movement Disorders Unit of the Neurology Department at Hospital de Sant Pau.
In this study, researchers focused on newly diagnosed Parkinson’s patients without cognitive problems and followed them for four years. Initially, they measured brain activity using an electroencephalogram (EEG), took brain images using magnetic resonance imaging (MRI), and measured the levels of a blood marker related to neuronal damage known as neurofilament light chain (NfL); in addition, every year they underwent an extensive neuropsychological examination to assess their cognitive state.
The follow-up showed that there are two large groups of patients: one group did not show significant cognitive decline during the first four years, while the other group dramatically worsened after the second year. Interestingly, MRI measures, NfL levels, or cognitive performance during the first visit did not detect differences between these two groups. In other words, these commonly used measures did not anticipate how the patients would progress. However, EEG analyses showed that those who would experience clear cognitive decline two years later already exhibited significant slowing of brain activity in the temporal, parietal, and frontal lobes during the first visit.
According to Dr. Arnau Puig-Davi, researcher of the Parkinson’s Disease Group at IR Sant Pau and neuropsychologist at the Movement Disorders Unit of the Neurology Department at Hospital de Sant Pau, “thanks to resting EEG, we can detect brain anomalies related to changes that already affect patients who will later present clear cognitive decline and dementia, even in the early stages before mild cognitive impairment.”
This study opens new horizons for the early detection of cases that will develop dementia associated with Parkinson’s disease. The results obtained will help researchers better study and understand the mechanisms underlying the cognitive evolution differences observed in Parkinson’s patients. The researchers believe that this discovery could be very useful for early evaluation of treatments aimed at minimizing the risk of developing Parkinson’s-related cognitive impairment.
Arnau Puig-Davi, Saül Martínez-Horta, L., et al. (2024). Prediction of Cognitive Heterogeneity in Parkinson’s Disease: A 4-Year Longitudinal Study Using Clinical, Neuroimaging, Biological and Electrophysiological Biomarkers. Annals of Neurology 2024 Aug 5; 00:1-13 DOI: 10.1002/ana.27035
Project funded by the Fundación la Marató de TV3: “Blood and Neurophysiological Markers of Cognitive Decline Progression in Parkinson’s Disease” (Expedient: 20142910; PI: Dr. Javier Pagonabarraga).
