Powerful MRI May Help Detect Apathy, Cognitive Problems

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Deterioration in a small brain region called the locus coeruleus is associated with worse apathy and cognitive problems among people with Parkinson’s disease, according to a new study.

The study, “Locus Coeruleus Integrity from 7 T MRI Relates to Apathy and Cognition in Parkinsonian Disorders,” was published in Movement Disorders.

Parkinson’s is caused by the death and dysfunction of brain cells that make a signaling molecule called dopamine. Parkinson’s therapies that aim to boost dopamine levels (e.g., levodopa) are generally effective at managing motor symptoms, but less effective for non-motor complications.

An increasing body of evidence suggests that dysfunction of another brain signaling molecule, called noradrenaline, plays a role in the development of non-motor symptoms in Parkinson’s. This molecule is produced in a small brain region called the locus coeruleus (LC).

“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 sticks of spaghetti half an inch long: it’s thin, it’s small, and it’s tucked away at the very base of the brain in the brain stem,” James Rowe, PhD, a professor at the University of Cambridge in England, and co-author of the study, said in a press release.

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Prior research using donated brains had indicated that the LC atrophies (shrinks) in people with Parkinson’s or a related neurodegenerative disorder called progressive supranuclear palsy (PSP). Here, scientists wanted to examine whether degeneration in this small brain region is associated with symptom severity in people with Parkinson’s or PSP.

Magnetic resonance imaging (MRI) is a technology commonly used to image the brain in living humans; it works by using powerful 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 that isn’t enough to reliably measure the LC.

“The locus coeruleus is a devil to see on a normal scanner. Even good hospital scanners just can’t see it very well,” Rowe said. “And if you can’t measure it, you can’t work out how two people differ: Who’s got more, who’s got less?”

Here, the scientists used MRI scanners with more powerful magnets — 7T. These allow a finer resolution of about 0.08 square millimeters, which is 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 the size of the LC in 25 people with non-familial Parkinson’s, 14 people with probable PSP, and 24 individuals with no known health problems (controls). All the groups had slightly more men than women, and the average age was in the mid-60s. LC size did not significantly vary by sex or age.

Compared to controls, there was significant LC degeneration in the brains of people with Parkinson’s or PSP, with the most pronounced changes generally seen in PSP.

Further analyses in both groups showed that more degeneration in the LC was associated with more severe scores related to apathy and cognitive problems. The scientists proposed that medications intended to boost noradrenaline signaling may help ease these non-motor symptoms in individuals with more LC degeneration.

“Cognitive decline and disorders of goal-directed behavior, including the co-occurrence of both apathy and impulsivity, are common in both [Parkinson’s] and PSP,” the researchers wrote. “The link we have shown between LC integrity and these nonmotor symptoms supports the rationale for noradrenergic therapies in selected patients.”

“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,” said Rong Ye, PhD, a postdoctoral fellow at Cambridge and the study’s lead author.

The team noted that identifying patients with LC degeneration will require more powerful MRI scanners than those currently available at most clinics.

“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,” Ye said. “In the long term, this will prove more cost-effective than giving noradrenaline boosters to patients who ultimately would see no benefit.”