Ultra-powerful brain scans offer hope for treating cognitive symptoms of Parkinson’s disease

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Ultra-powerful 7T MRI scanners could be used to help identify patients with Parkinson’s disease and similar conditions most likely to benefit from new treatments for previously incurable symptoms, scientists say.

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. These latter symptoms can have a major impact on a patient’s outcome, affecting survival and overall well-being, as well as stress and costs for families.

To understand the causes of these cognitive symptoms, researchers from the University of Cambridge used a new ultra-high resistance “7T” MRI scanner at the Wolfson Brain Imaging Center to measure changes in the brains of people with Alzheimer’s disease. Parkinson, PSP, or healthy. health. 7T refers to the strength of the magnetic field; most MRI scanners tend to be 3T or less.

The results are published today in the journal Movement disorders.

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 doesn’t do much for many non-motor symptoms. That’s why scientists have started looking at norepinephrine, a chemical that plays a vital role in brain functions, including attention and wakefulness, thinking, and motivation.

Professor James Rowe from the University of Cambridge’s Department of Clinical Neuroscience, who led the study, said: “Noradrenaline is very important for brain function. All of our brain’s supply comes from a tiny region at the back of the brain called the locus coeruleus – which means “the blue spot” It’s a bit like two short spaghetti sticks half an inch long: it’s thin, it’s small , and it’s hidden at the very base of the brain in the brainstem.”

A study last year by Professor Rowe’s team, looking at brains donated to the Cambridge Brain Bank, found that some people with PSP had lost up to 90% of the norepinephrine-producing locus coeruleus.

The question the team wanted to answer was: how could this tiny region be studied in patients who are still alive? Previous MRI scans lacked the resolution to measure the region in living patients.

“The locus coeruleus is a devil to see on a normal CT scan,” Prof Rowe said. “Even good hospital scanners just can’t see it very well. And if you can’t measure it, you can’t determine how two people differ: who has more, who has less? We wanted to MRI scanners will be good enough to do that for a while.”

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 the size of a grain of sand. The scans allowed the team to examine their subjects’ locus coeruleus and confirm that the greater the level of damage in this region, the more severe their symptoms of apathy and the lower their performance on cognitive tests.

The findings offer hope for new treatments for these symptoms. A number of drugs that boost norepinephrine have already been tested in clinical trials for other conditions and have therefore been shown to be safe and well tolerated. Professor Rowe and his colleagues are currently conducting a clinical trial at Cambridge University Hospitals NHS Foundation Trust to see if these drugs improve the symptoms of PSP.

Dr Rong Ye from the University of Cambridge’s Department of Clinical Neuroscience, co-lead author of the study, said: “Not all patients with PSP or Parkinson’s will benefit from norepinephrine-stimulating drugs. They are more likely to benefit people with damage to their locus coeruleus – and the greater the damage, the more likely they are to benefit.

“The ultra-powerful 7T scanner can help us identify the patients we think will benefit the most. This will be important for the success of the clinical trial and, if the drugs are effective, it will mean that we will know at what giving patients the long term will prove more cost effective than giving norepinephrine boosters to patients who ultimately see no benefit.

It is thought that in PSP, damage to the locus coeruleus is caused by a buildup of the unwanted tau protein. When norepinephrine breaks down, it seems to trigger changes in tau protein that lead to its buildup. This then damages the same cells that produce norepinephrine, leading to a vicious cycle. A similar situation can occur in Parkinson’s disease

The research was supported by Parkinson’s UK, Cambridge Center for Parkinson-Plus, China Scholarship Council, Australian National Health and Medical Research Council, Fitzwilliam College, Association of British Neurologists, Patrick Berthoud Charitable Trust, Medical Research Council, James S. McDonnell Foundation, Wellcome Trust and the NIHR Cambridge Biomedical Research Centre.

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