Deterioration in a small region of the brain called the locus coeruleus is associated with apathy and more severe cognitive problems in people with Parkinson’s disease, according to a new study.
The study, “7T MRI locus coeruleus integrity is linked to apathy and cognition in parkinsonian disorderswas published in Movement disorders.
Parkinson’s disease is caused by the death and dysfunction of brain cells that make a signaling molecule called dopamine. Treatments for Parkinson’s disease that aim to increase dopamine levels (eg, levodopa) are generally effective in managing motor symptoms, but less effective for non-motor complications.
A growing body of evidence suggests that dysfunction of another brain signaling molecule, called norepinephrine, plays a role in the development of non-motor symptoms of Parkinson’s disease. This molecule is produced in a small region of the brain called the locus coeruleus (LC).
“Norepinephrine 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 – meaning ‘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,” James Rowe, PhD , a professor at the University of Cambridge in England, and co-author of the study, said in a press release.
Previous research using donated brains has indicated that the LC atrophies (shrinks) in people with Parkinson’s disease or a related neurodegenerative disorder called progressive supranuclear palsy (PSP). Here, the scientists wanted to examine whether degeneration in this small region of the brain is associated with the severity of symptoms in people with Parkinson’s disease or PSP.
Magnetic resonance imaging (MRI) is a technology commonly used to image the brain in living humans; it works by using strong magnets to detect water molecules in the body. The resolution of an MRI scanner is based on the strength of its magnet, measured in teslas (T).
Most MRI scanners used in hospitals are 1.5T or 3T. These can provide resolution down to about the size of a grain of rice. But this is not enough to reliably measure the LC.
“The locus coeruleus is a devil to see on a normal CT scan. Even good hospital scanners just can’t see it very well,” Rowe said. “And if you can’t measure it, you can’t determine how two people differ: who has more, who has less?”
Here, scientists used MRI scanners with stronger magnets – 7T. These allow a finer resolution of about 0.08 square millimeters, or about the size of a grain of sand.
“We’ve wanted MRI scanners to be good enough to do this for some time,” Rowe said.
The researchers analyzed LC size in 25 people with nonfamilial Parkinson’s disease, 14 people with probable PSP, and 24 people with no known health conditions (controls). All groups had slightly more men than women, and the average age was in the mid-sixties. LC size did not vary significantly by sex or age.
Compared to controls, there was significant LC degeneration in the brains of people with Parkinson’s disease or PSP, with the most pronounced changes usually seen in PSP.
Further analyzes in both groups showed that greater LC degeneration was associated with more severe scores related to apathy and cognitive problems. Scientists have proposed that drugs to stimulate norepinephrine signaling may help relieve these non-motor symptoms in people with more LC degeneration.
“Cognitive decline and disturbances in goal-directed behavior, including the co-occurrence of apathy and impulsivity, are common in both [Parkinson’s] and PSP,” the researchers wrote. “The link we showed between LC integrity and these non-motor symptoms supports the rationale for noradrenergic therapies in some patients.”
“Not all patients with PSP or Parkinson’s disease will benefit from norepinephrine-stimulating drugs. They are more likely to benefit people with damaged locus coeruleus – and the greater the damage, the more likely they are to benefit,” said Rong Ye, PhD, Cambridge postdoctoral fellow and lead author of the paper. ‘study.
The team noted that identifying patients with LC degeneration will require more powerful MRI scanners than those currently available in most clinics.
“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 which patients to give the treatment to,” Ye said. “In the long run, this will prove more cost-effective than giving norepinephrine boosters to patients who ultimately see no benefit.”