July 16, 2014
Mayo Clinic has a distinguished history in the study and treatment of speech and language pathologies. It was Mayo researcher Frederick L. Darley, Ph.D., who coined the term "apraxia of speech" in 1969 to describe an acquired motor speech disorder characterized by an inability to produce sounds correctly. Apraxia of speech has generally been associated with stroke, and thus sudden onset. Progressive apraxia of speech occurring in neurodegenerative disease has largely been ignored and typically subsumed under aphasia.
Researchers at Mayo Clinic in Rochester, Minnesota, have identified primary progressive apraxia of speech as a distinct entity that can evolve into a movement disorder. "We have recognized patients who do not have any language problem whatsoever. Instead, they have a motor speech disorder — trouble producing sounds correctly. They have it for years, and it worsens over time," says Keith A. Josephs, M.D., a neurologist at Mayo.
The identification of primary progressive apraxia of speech is one of several findings resulting from a National Institutes of Health (NIH) research grant that funds Mayo's work on progressive speech and language disorders (SLDs) and neurodegenerative disease. Mayo's grant, for which Dr. Josephs is the primary investigator, is the only one in the world focusing on apraxia of speech in the context of neurodegenerative cognitive and motor disorders.
Dr. Joseph and fellow researchers have published articles about their findings in Brain, the American Journal of Alzheimer's Disease & Other Dementias, Neurology and the Journal of Neurology.
Diagnosis and treatment implications
The key distinction between primary progressive apraxia of speech and primary progressive aphasia is the patient's ability or inability to communicate. "Patients with apraxia of speech may ultimately become mute because they can't produce sounds. Yet they can communicate by typing or writing," Dr. Josephs says. "The patient who is aphasic has problems finding words or structuring sentences correctly, which affects both spoken and written forms of communication. These patients can't rely on typing or writing to communicate."
Yet primary progressive apraxia of speech is often misdiagnosed. Dr. Josephs cites two patients seen at Mayo who had the condition. One had experienced motor speech problems for several years and been treated for depression and anxiety. The other had been treated with onabotulinumtoxinA (Botox), a therapy for dystonia.
Speech therapy, which is offered at Mayo, doesn't reverse or halt the progression of apraxia. But speech therapy can help muscles adapt to producing better sounds. "Most patients tend to want to speak less because they are embarrassed by the inability to produce sounds correctly. But speech therapy can be beneficial," Dr. Josephs says.
Early sign of neurodegenerative disease
Brain regions involved in primary progressive apraxia of speech
Primary progressive apraxia of speech involves focal abnormality typically in the left brain but sometimes in the right brain.
Mayo researchers have designated the best-known form of apraxia of speech, characterized by distortions in the production of sound, as type 1 apraxia of speech. But type 2, a second type that was first recognized by Joseph R. Duffy, Ph.D., a speech pathologist and researcher at Mayo clinic's campus in Minnesota, may account for as many as 80 percent of cases. In type 2 apraxia of speech, "the speech is very slow, and the segmentation — the breaks between syllables or words — is lengthened and abnormal," Dr. Josephs says.
Imaging of these patients shows focal areas of abnormality, typically in the left brain but sometimes in the right, which are likely due to protein deposits in these areas. Most of the patients with primary progressive apraxia of speech are women older than age 65, although some patients have presented as young as age 40.
"We are surprised by how rapidly they are progressing," Dr. Josephs says. "Within five to six years of experiencing apraxia of speech, the majority of these patients develop a widespread motor parkinsonian disorder with features that resemble those of progressive supranuclear palsy or corticobasal syndrome. The patients might subsequently start to lose coordination of the right hand, or the right leg may start to drag. Two to three years later, they may complain of double vision, trouble walking and falling. Eventually, they're using a wheelchair and unable to communicate because they cannot speak, write or point. Some may even die soon after."
Because amyloid deposits are rare in patients with primary progressive apraxia of speech, Dr. Josephs suspects that the protein responsible for this condition is tau. Mayo researchers will continue investigating that question and others under both the current NIH grant as well as a second NIH grant addressing the evolution of primary progressive apraxia of speech.
"Every patient we have diagnosed with an apraxia of speech in the context of neurodegeneration, and who has died, has had tau in the brain," Dr. Josephs says. "I can't think of another clinical feature that is as predictive for a brain protein as apraxia of speech."
Enrolling patients with apraxia and aphasia
Mayo's NIH grant, which began in 2010, continues to enroll patients with progressive SLDs — both primary progressive aphasia and primary progressive apraxia of speech. Over 48 hours, study participants receive:
- Comprehensive evaluation by a neurologist and a speech and language pathologist
- Neuropsychological testing
- Blood test
- Glucose positron emission tomography (PET) scan
- Pittsburgh compound B (PiB) PET scan, which can detect amyloid in the brain
As many as 10 Mayo specialists confer on each patient's diagnosis.
Other findings to date
Study participants include a high prevalence of teachers. However, Dr. Josephs says there is no evidence that teaching predisposes people to progressive SLDs. Teachers may simply be more attuned to detecting abnormalities in their speech and language and thus likelier to seek treatment.
About 90 percent of patients with logopenic primary progressive aphasia — characterized by impairments in naming — have Alzheimer's disease. Among those who have logopenic progressive aphasia but not Alzheimer's, about half have a genetic mutation.
"The patients who join these studies get a baseline evaluation and diagnosis," Dr. Josephs says. "But everyone wants to know what's going to happen to them in five years. Which patients will become mute? Will they know their spouses? How long will they live? These are the answers we hope to find."
For more information
PIB PET scanning in speech and language-based dementias. Mayo Clinic.
Josephs KA, et al. Characterizing a neurodegenerative syndrome: Primary progressive apraxia of speech. Brain. 2012;135:1522.
Josephs KA, et al. Occupational differences between Alzheimer's and aphasic dementias: Implication for teachers. American Journal of Alzheimer's Disease & Other Dementias. 2013;28:612.
Josephs KA, et al. Syndromes dominated by apraxia of speech show distinct characteristics from agrammatic PPA. Neurology. 2013;81:337.
Josephs KA, et al. Progranulin-associated PiB-negative logopenic primary progressive aphasia. Journal of Neurology. 2014;261:604.