Huntington’s disease is a hereditary neurodegenerative disease caused by a mutation in a gene, which severely affects the cognitive ability of those who suffer from it. Traditionally, the way in which cognitive decline behaves over time in the disease has been considered very homogeneous. However, according to a new study led by Dr. Saül Martínez-Horta, a researcher in the Parkinson’s Disease and Movement Disorders group led by Dr. Jaume Kulisevsky at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, there are at least two distinct patterns of cognitive decline progression in people affected by this disease.
The study, published in the European Journal of Neurology, analyzes data obtained over a 3-year follow-up in over 500 people affected by the disease and participating in the international Enroll-HD study, excluding those cases that presented juvenile or late-onset forms or had clearly established dementia.
“Through a statistical approach, we were able to demonstrate that the trajectory of cognitive decline was very different and that, in practically half of the cases, there was a very aggressive pattern of progression without any differences between the two groups in terms of clinical, demographic or genetic characteristics,” explains Dr. Martínez-Horta.
The authors of the study conclude that the progression of Huntington’s disease varies significantly even among patients with similar characteristics, thus confirming the existence of at least two cognitive phenotypes that differ significantly in terms of the rate of progression. These findings open up new avenues for studying additional mechanisms that contribute to the heterogeneity of Huntington’s disease beyond the known genetic mutation that causes the disease.
“Unlike what the data usually show us, direct contact with affected individuals perfectly illustrates that, despite being a genetically determined disease, cases vary greatly in terms of appearance and progression pattern.”
In addition, the researchers developed a mathematical model that allows them to predict, by observing the behavior of cognitive decline during the first year, which patients will be in the group that progresses rapidly, which is very useful for classifying these individuals before it is evident that they are deteriorating much more.
These findings will be useful for improving prognosis and “anticipating what will happen to these individuals.” This is very useful for improving the design of clinical trials with potential treatments since “if you do not consider that the behavior of the disease will be different, you cannot adequately evaluate the effect of a drug because it is not the same as what you would expect to happen to someone who will remain more or less stable than someone who would actually have to deteriorate a lot.”
Martínez-Horta, S, Perez-Perez, J, Oltra-Cucarella, J, et al. Divergent cognitive trajectories in early stage Huntington’s disease: A 3-year longitudinal study. Eur J Neurol. 2023; 00: 1- 9. doi:10.1111/ene.15806 https://onlinelibrary.wiley.com/doi/10.1111/ene.15806
