July 31, 2017Neurology
According to a study published in the journal Brain (26 July 2017), a new method was discovered to observe the brain changes caused by Parkinson's disease (PD). In PD, the dopamine-producing cells in the substantia nigra are destroyed. The new method suggests that fluid changes in a specific brain area could provide a way to track that damage. The study showed that a greater free water increase in the substantia nigra was associated with a decrease in dopamine neuron activity in one of these nearby regions, supporting the idea that free water changes are related to disease progression.
For the study, a form of MRI was used that differentiates between water contained in brain cells and free water outside of the cells. The study focused on the substantia nigra, a brain structure where PD kills neurons that use the chemical dopamine to communicate with other cells. The results showed that the amount of free water in that brain area stayed the same over the course of a year in healthy individuals, but increased in early-stage PD patients during that period and increased further over the next three years. This confirmed and expanded on a prior study by the same group that measured free water over just one year. The new findings also revealed the increase in free water was linked to worsening symptoms. The authors used a scale to evaluate patient's movement problems, with Stage One on the scale being the least severe and Stage Five being the most advanced. Results showed that patients who moved up a stage on the scale during the four years of the study, had a greater free water increase than patients who remained at the same stage, suggesting the change reflected PD's-related damage to neurons.
The study's results suggest that the MRI-based free water measurement could be used in PD clinical trials as a surrogate marker, in that if a treatment slows or stops the increase in free water, it might be evidence that the drug is slowing the progressive loss of dopamine neurons. The study used data from the Parkinson's Progression Markers Initiative (PPMI), a large study sponsored by the Michael J. Fox Foundation that has been collecting information on recently diagnosed PD patients from over 30 different U.S. and international sites. The fact that the authors found similar patterns in patients at every location boosted their confidence in the results because, like the PPMI, clinical trials must collect data from many sites using numerous different MRI machines.
The authors speculated that the free water approach could make clinical trials less expensive by reducing the number of participants they would need to enroll. As a result, there is an ongoing clinical trial to validate the use of free water to gauge the effect of a potential PD treatment. At the same time, the authors are attempting to develop computer programs that will make free water analysis faster and easier. Clearly, future studies are needed to track changes in free water over longer time spans and in other brain regions and to determine what causes them.