August 15, 2017

Water changes mark Parkinson’s disease progression

At a Glance

  • Scientists developed a new way to detect brain changes caused by Parkinson’s disease.
  • The technique may be useful for assessing the effects of potential treatments. 
Image of a brain scan Scientists discovered that Parkinson’s disease increases the amount of “free” water in a particular brain area. David Vaillancourt, Ph.D., University of Florida.

Parkinson’s disease is caused by the loss of dopamine-producing cells in a brain region called the substantia nigra. The loss of the chemical messenger dopamine can cause involuntary shaking, muscle stiffness, slowed movements, problems with balance, and other symptoms. As the disease gets worse, patients may have difficulty walking, talking, or completing other simple tasks. There is no cure for the disease, but a variety of medications can provide relief from the symptoms.

Clinical studies of therapies for Parkinson’s disease have long relied on observing patients’ symptoms. This approach, however, reveals little about how a treatment affects the underlying brain cells. Measurable biological targets, called biomarkers, would be useful for assessing whether a drug affects the progression of the disease in the brain.

One possible biomarker is the amount of “free” water outside of cells in the brain. A technique called diffusion MRI can distinguish between water contained in brain cells and free water in a region. Previous studies have shown that there’s more free water in the substantia nigra of people with Parkinson’s than those of healthy people.

Using diffusion MRI, a research team led by Dr. David Vaillancourt at the University of Florida in Gainesville recently showed that free water in the substantia nigra increased over the course of one year in people with Parkinson’s disease but not in controls. In their latest work, the group tracked free water in the substantia nigra over a four-year period. The study was supported in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS). Results were published on August 1, 2017, in Brain.

The team analyzed changes in free water over the course of a year in 103 patients with early-stage Parkinson’s disease and 49 controls. They found an increase in free water in the substantia nigra of the Parkinson’s patients compared to controls, confirming the earlier findings. In addition, 46 patients who were tracked for three more years showed further free water increases. Notably, the symptoms of patients with greater free water increases progressed faster than those of the people whose free water stayed the same.

A higher amount of free water in the substantia nigra was also associated with decreased dopamine neuron activity in a nearby brain region. This finding further supports the idea that free water changes reflect progression of Parkinson’s disease. 

“By finding a new way to detect and track how Parkinson’s affects the brain, this study provides an important tool for assessing whether a drug might slow or stop those changes and keep symptoms from getting worse,” said NINDS Program Director Dr. Daofen Chen. The team is now testing this approach to gauge the effect of a potential treatment.

More studies are needed to track changes in free water over longer time periods and in other brain regions.

Related Links

References:  Progression marker of Parkinson’s disease: a 4-year multi-site imaging study. Burciu RG, Ofori E, Archer DB, Wu SS, Pasternak O, McFarland NR, Okun MS, Vaillancourt DE. Brain. 2017 Aug 1;140(8):2183-2192. doi: 10.1093/brain/awx146. PMID:28899020.

Funding: NIH’s National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH), and National Institute of Biomedical Imaging and Bioengineering (NIBIB); and the Parkinson’s Progression Markers Initiative.