Image: Locus coeruleus as seen in 7T MRI scan (Photo courtesy of University of Cambridge)
Both Parkinson’s disease and a related disorder, progressive supranuclear palsy (PSP), are progressive brain diseases that not only affect movement but also damage motivation and cognition. Patients with Parkinson’s disease and PSP are often treated with drugs such as L-DOPA, which compensate for the severe loss of dopamine. But, dopamine treatment does little for many of the non-motor symptoms. Now, ultra-powerful 7T MRI scanners could be used to help identify those patients with Parkinson’s disease and similar conditions most likely to benefit from new treatments for previously-untreatable symptoms.
To understand the causes of cognitive symptoms in Parkinson’s disease and PSP, researchers at the University of Cambridge (Cambridge, UK) used a new ultra-high strength ‘7T’ MRI scanner to measure changes in the brains of people with Parkinson’s disease, PSP, or in good health. 7T refers to the strength of the magnetic field; most MRI scanners tend to be 3T or below. Since dopamine treatment does little for many of the non-motor symptoms, scientists have begun to turn their attention to noradrenaline, a chemical that plays a critical role in brain functions including attention and arousal, thinking and motivation. A study last year examining brains donated to the Cambridge Brain Bank, found that some people with PSP had lost as much as 90% of the noradrenaline-producing locus coeruleus. It is thought that in PSP, damage to the locus coeruleus is caused by a build-up of the junk protein tau. When noradrenaline breaks down, it appears to trigger changes in the tau protein that lead to its build-up. This then damages the same cells that produce noradrenaline, leading to a vicious circle. A similar situation may occur in Parkinson’s disease.
The research team wanted to know how this tiny region could be studied in patients who are still alive. Previous MRI scanners have not had the resolution to measure the region in living patients. While most scanners can show structures at the level of detail of a grain of rice, 7T scanners, which have ultra-strong magnetic fields, can provide resolution at the size of a grain of sand. The scanners allowed the team to examine the locus coeruleus of their subjects and confirm that the greater the level of damage to this region, the more severe their symptoms of apathy and the worse they performed at cognitive tests. The findings offer the hope of new treatments for these symptoms. A number of drugs that boost noradrenaline have already been through clinical trials for other conditions and hence have been shown to be safe and well tolerated. The researchers are now leading a clinical trial to see if these drugs alleviate symptoms in PSP.
“The locus coeruleus is a devil to see on a normal scanner. Even good hospital scanners just can't see it very well,” said Professor James Rowe from the Department of Clinical Neurosciences at the University of Cambridge, who led the study. “And if you can't measure it, you can't work out how two people differ: who's got more, who's got less?”
“The ultra-powerful 7T scanner may help us identify those patients who we think will benefit the most,” added Dr Rong Ye from the Department of Clinical Neurosciences at the University of Cambridge, the study’s joint first author. “This will be important for the success of the clinical trial, and, if the drugs are effective, will mean we know which patients to give the treatment to.”
University of Cambridge