Researchers at a Parkinson’s Foundation Center of Excellence have found that a brain MRI that uses a special protocol can track changes that occur as Parkinson’s disease (PD) progresses. This biomarker could be used in clinical trials, as an objective way to monitor whether the therapies being tested are effective. The study appears in the August 2017 issue of Brain.
Doctors currently diagnose PD based on a person’s symptoms – slowness, stiffness, tremor and balance difficulties. But these symptoms, and the rate at which they progress, differ from person to person. And there is no blood test, or biomarker, to definitively diagnose PD or objectively monitor underlying biological changes as PD progresses. Currently, a brain MRI may be ordered to rule out other conditions, but cannot diagnose PD or monitor its progression.
In earlier research, scientists led by David Vaillancourt, Ph.D., at the University of Florida in Gainesville – a Parkinson’s Foundation Center of Excellence, used a brain scanning technique called diffusion MRI to detect changes that happen only in the brains of people with PD. The scans showed an increase in “free” water – water outside of brain cells – in a part of the brain called the substantia nigra.
For the new study, Dr. Vaillancourt and coworkers confirmed this finding and expanded on it by analyzing data from study participants at 10 Parkinson’s clinics in the US and Europe, who were enrolled in the Parkinson’s Progression Markers Initiative. In their analysis they included 103 people with newly diagnosed PD, who were not taking any medication when they first enrolled, and 49 healthy volunteers. Doctors evaluated all participants using standard PD rating scales, and all received diffusion MRI brain scans, at the beginning of the study and after one year. A subset of the participants with PD were followed for up to four years.
- In participants who were newly diagnosed with PD, free water increased in the brain’s substantia nigra over the course of one year.
- In individuals who did not have PD, there was no change in free water.
- In people with PD who had brain scans for up to four years, the amount of free water in the substantia nigra steadily increased.
- In people whose scans showed increases in free water in the substantia nigra over one to two years, PD symptoms worsened over four years.
What Does It Mean?
Brain MRI machines are readily available nationwide. Currently, in the diagnosis of PD, a MRI may be used to rule other conditions, such as strokes or hydrocephalus. However, this study (and previous work from this group) suggest that applying different protocols to the MRI imaging may be more useful in PD.
Specifically, researchers find that using an MRI machine, they can reliably measure changes in the region of the brain affected by PD (the substantia nigra) as a marker for PD progression. An important strength of this study is that it involved people with PD from different hospitals in many different countries who received repeated brain scans, allowing the researchers to track brain changes due to PD.
The research is an important step toward being able to objectively test the effects of potential new therapies on PD progression. For example, if researchers were testing a drug designed to slow PD progression, this brain scan could monitor its effects and, in the process, perhaps shorten the length of clinical trials. MRI, in contrast to observing whether PD symptoms improve with medications, may also be able to track PD progression independent of medication usage.
In addition, the study found that the increase in the free water measurement over one year’s time predicted a person’s four year progression of PD motor symptoms, as evaluated using the standard Hoehn and Yahr scale. The result suggests if a therapy could prevent free water from increasing soon after a Parkinson’s diagnosis, then it might control long-term progression of the disease.
Reference: Burciu R, Ofori E, Archer DB, et al. (2017). Progression Marker of Parkinson’s Disease: A 4-Year Multi-Site Imaging Study. Brain 140: 2083-2092, DOI 10.1093/brain/awx146