Friedreich’s Ataxia Cognitive Loss Linked to Abnormalities in Non-movement-related Brain Areas

Friedreich’s ataxia patients’ cognitive decline is linked to changes in brain networks — but the changes go beyond the movement-related cerebellum and spinal cord neuron degeneration associated with the disease, a study suggests.

The findings led the research team to suggest that Friedreich’s ataxia is a multisystem disorder. The implication is that research into the disease needs to be broadened to include other brain abnormalities.

The study, “Cognition in Friedreich’s ataxia: a behavioral and multimodal imaging study,” was published in the journal Annals of Clinical and Translational Neurology.

Although research on cognitive problems in Friedreich’s ataxia has been done, few studies have attempted to understand how cognition — a feature linked to the brain’s cortex — relates to the degeneration of movement-related neurons.

To examine this, researchers at RWTH Aachen University in Germany recruited 22 patients with Friedreich’s ataxia and 22 healthy controls.

The study started with neurocognitive assessments of the patients. The tests showed the disease had not affected patients’ general cognition. Rather, patients had problems with social cognition and working memory.

When researchers gave patients two versions of a verbal fluency task, the patients performed worse than controls, however.

There were two parts to the verbal fluency task. The semantic verbal fluency test required a participant to do a quick verbal listing of words in a category — in this case food. In the phonemic fluency part, participants listed words starting with the letters A and F.

Researchers were unable to establish a link between worse performance on the tasks and speech difficulties. But they did make an association between reduced phonemic fluency and longer disease duration.

The team then asked 15 participants in each group to perform the verbal fluency task while their brains were scanned with two types of magnetic resonance imaging (MRI). Measurements revealed that certain brain connections were abnormally active in the Friedreich’s patients. In particular, the team noted that parts of the cerebellum and cortex seemed to become activated together.

They also observed that the larger the tissue loss in certain areas of the brain, the more abnormal activation there was in other regions, suggesting that the changes in brain function were caused by neurodegeneration.

That prompted the team to underscore the importance of investigating brain structure and function beyond areas known to be associated with Friedreich’s ataxia neuronal damage.

“Our findings emphasize the need for multimodal investigations into brain structure–function relationships to unravel the complex neuronal interactions in this multisystem disorder. In addition to structural MRI, functional imaging data hold valuable information for a more comprehensive understanding of neural dynamics in FRDA,” the authors concluded.