Subtle Changes in Speech Mark Pre-symptomatic Huntington’s, Study Finds

Subtle Changes in Speech Mark Pre-symptomatic Huntington’s, Study Finds
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premanifest Huntington's disease

People at a pre-symptomatic, or premanifest, stage of Huntington’s disease (HD) have subtle speech alterations that may be used as a marker to evaluate new therapies intended to stop or slow disease progression before it becomes too debilitating.

The study with that recent research, “Speech in prodromal and symptomatic Huntington’s disease as a model of measuring onset and progression in dominantly inherited neurodegenerative diseases,” was published in the journal Neuroscience & Biobehavioral Reviews.

Huntington’s disease (HD) is a neurodegenerative and genetic disorder characterized by irregular and  uncontrolled movements known as chorea, loss of thinking ability, and psychiatric problems. No treatments are currently available to delay onset or slow its progression.

There is evidence that subtle changes in cognitive and fine motor skills may appear before more debilitating symptoms like chorea emerge and the disease is diagnosed. Such signs of premanifest, or prodromal, disease can show up more than a decade before.

Scientists are trying to find disease-modifying therapies (that could stop or slow disease progression) that specifically target this initial stage of the disease, with the hope to prevent further deterioration of patients’ condition.

However, such approaches are possible only with the aid of sensitive and reliable markers, early traceable, to tell if an experimental treatment under investigation in clinical trials is effectively preventing disease worsening or not.

One such potential marker is speech alteration. Most people with Huntington’s disease develop slurred or slow speech (dysarthria) and speech changes are one of the earliest indicators of disease onset.

This suggests that subtle speech impairments could be a “potential marker of disease trajectory and/or treatment response,” the researchers wrote.

Yet, little is known about how speech deficits evolve though disease course, how they relate to neurodegeneration in the brain, and their clinical implications.

Researchers reviewed the available literature and performed a meta-analysis of studies reporting the characteristics of speech in people with HD.

A total of 12 studies were reviewed, which included data from 575 participants: 180 HD, 87 premanifest HD and 308 healthy controls. Nine of the studies were included in the meta-analysis, in which data were combined to find average trends in speech changes.

Findings revealed that patients at a premanifest stage of HD had subtle, but real, deficits in speech. They produced significantly fewer single syllables per second, a slower sound repetition rate, and had an inconsistent syllabic pace, compared to healthy controls.

As a whole, alterations were marked by reduced speech agility, impaired vocal cord control (a reduced ability to maintain amplitude or loudness during vowel production) and varied speech timing. Through the course of disease, all speech features gradually deteriorated.

“Articulation agility and speech rate appear to be the most promising speech markers in premanifest individuals,” the researchers wrote.

However, pinpointing the specific speech marks that distinguish people with premanifest HD from healthy individuals remains unclear, in part due to the lack of neuroimaging studies that could help draw a link between speech changes and brain degeneration.

In addition, methodologies and speech findings varied across studies, which made it difficult to rely on definitive conclusions.

“Stronger evidence is needed to establish the sensitivity and reliability of speech markers in detecting pathophysiological changes in [premanifest] HD and evaluating the effectiveness of pharmacological therapy,” the researchers wrote.

“Nonetheless, the non-invasive and easy to acquire nature of speech measures, along with their precision and resulting high degree of sensitivity, may yield new outcomes that will be useful in observational studies and clinical trials in HD,” they concluded.

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