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Treatment hope for cognitive symptoms in Parkinson's disease

Tuesday May 17th 2022

Ultra-powerful 7T MRI scanners could help to identify those patients with conditions such as Parkinson's disease who would benefit from new treatments for cognitive symptoms that were previously untreatable, British researchers report today.

Although individuals with Parkinson's disease and progressive supranuclear palsy (PSP), a related disorder, are often treated with drugs such as L-DOPA, which compensate for the severe loss of dopamine, they have little effect on non-motor symptoms.

Now, focus is shifting to noradrenaline, a chemical that plays a critical role in brain functions including attention and arousal, thinking and motivation.

A study last year by Professor James Rowe from the Department of Clinical Neurosciences at the University of Cambridge, and his team found that some people with PSP had lost as much as 90% of the noradrenaline-producing locus coeruleus.

For this study, they wanted to establish if they could study this tiny region of the brain could be studied in patients who are still alive.

They measured changes in the brains of people with Parkinson's disease, PSP, and individuals in good health, with a new ultra-high strength 7T MRI scanner at the Wolfson Brain Imaging Centre.

Normal MRI scanners do not have the resolution to measure the region in living patients, but the new 7T scanners have ultra-strong magnetic fields and can provide resolution at the size of a grain of sand.

The scanners enabled the team to examine the locus coeruleus of the study participants and confirm that the greater the level of damage found in this region resulted in more severe symptoms of apathy, which also led to poorer performance in cognitive tests.

Writing in *Movement Disorders*, they say their findings could offer renewed hope for treatments for these symptoms because some drugs that boost noradrenaline have already been through clinical trials for other conditions and are safe and well tolerated.

In PSP, it is believed damage to the locus coeruleus is caused by a build-up of the junk protein tau. When noradrenaline breaks down, changes are triggered in the tau protein, leading to its accumulation. This then damages the same cells that produce noradrenaline. A similar situation may occur in Parkinson's disease.

Professor Rowe and colleagues are now leading a clinical trial at Cambridge University Hospitals NHS Foundation Trust to see if these drugs alleviate symptoms in PSP.

Joint first author of the study Dr Rong Ye from the Department of Clinical Neurosciences at the University of Cambridge said: "Not every PSP or Parkinson's patient is going to benefit from noradrenaline-boosting drugs. They're more likely to benefit those people with damage to their locus coeruleus - and the greater the damage, the more benefit they're likely to see.

"The ultra-powerful 7T scanner may help us identify those patients who we think will benefit the most. 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. In the long term, this will prove more cost-effective than giving noradrenaline boosters to patients who ultimately would see no benefit."

Ye R, O'Callaghan, C Rua C et al. Locus Coeruleus Integrity from 7T MRI Relates to Apathy and Cognition in Parkinsonian Disorders. *Movement Disorders* 17 May 2022; DOI: 10.1002/MDS.29072

Tags: Brain & Neurology | UK News

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