Featuring: M Marsel Mesulam, MD,
Members of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease explain the ins and outs of PPA
Decades before the world learned about Bruce Willis’ aphasia diagnosis, Dr. Marsel Mesulam was pioneering a new field of research on a similar neurological condition: primary progressive aphasia (PPA), a rare, overlooked and underserved syndrome that destroys a person’s language.
Mesulam in the 1980s was running a behavioral neurology unit at Harvard Medical School where he saw patients with dementia — then singularly defined as “having memory loss” — or who had had a stroke, which, at the time, was the only recognized cause of language disturbance. But in 1982, he started seeing individuals who had difficulty with language who hadn’t had a stroke or been diagnosed with dementia. What was causing this language disruption, he wondered?
“That’s when I gave the condition the name of primary progressive aphasia,” said Mesulam, who is now the founder and director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at Northwestern University Feinberg School of Medicine. PPA also is known as Mesulam’s disease.
PPA comes in different forms
Now recognized as one of the major forms of dementia, it is important to note PPA is different from typical Alzheimer’s dementia because PPA doesn’t impact a person’s memory in the early stages and often for several years before the disease spreads to other brain regions. PPA is an early-onset illness, often beginning before the age of 65.
PPA is difficult to diagnose. It requires expert consultation and a team approach to identify, said Sandra Weintraub, a professor of psychiatry and behavioral sciences and neurology at Feinberg and a member of the Mesulam Center.
PPA comes in different forms. Some individuals with PPA can have trouble finding words, much like what a stroke survivor experiences. The speech has many pauses and fillers such as “thing” or “stuff.” The person may have trouble ordering words to form a grammatical sentence. Speech becomes telegraphic, with omission of articles and pronouns. For example, instead of saying, “I can’t find words to express what I want to say,” one of Mesulam’s patients said, “Words in my head and cut up.”
Others speak fluently but don’t understand words. For instance, if you ask a person with PPA to bring an orange from the kitchen, they may say, “Orange? What is that?” or they may return with an apple. It is as if the words belong to a foreign language. Finding names of common objects is particularly difficult, Mesulam said.
People with PPA may be able to drive, perform everyday functions such as banking or shopping, and most can usually still work at the initial stages of disease if their job doesn’t involve speech. For some, they might channel their abilities from other areas of the brain, such as music and painting, said Dr. Borna Bonakdarpour (right), assistant professor of behavioral neurology at Feinberg and a member of the Mesulam Center.
All-virtual speech therapy
The Mesulam Center, based in Chicago, runs an observational research program that flies in participants from more than 30 states across the U.S. and Canada, said Christina Coventry, a senior clinical research associate at Northwestern who manages the program.
Having been continuously funded by the National Institutes of Health for more than a decade, the program is dedicated to improving education and awareness of the disease, helping people better understand the neurobiology behind it and attempting to improve care and provide interventions.
One such intervention is a new, all-virtual, randomized controlled trial for speech therapy intervention for people with PPA focused on maximizing communication and quality of life. To the center’s knowledge, it is the first such trial for PPA said Emily Rogalski, who leads the trial. Rogalski is a professor of psychiatry and behavioral sciences at Feinberg and the associate director of the Mesulam Center.
“People with PPA are distributed but the expertise in the syndrome is not,” Mesulam said. “About three-fourths of our participants come from out of state, as far as New Zealand, because it’s very difficult for them to find expertise locally. Most speech pathologists have never heard of PPA, but instead have expertise in stroke-related aphasia which typically improves over time. To deal with that, we started this online trial to offer something unique.”
So far, the trial has been very positively received and pilot study data showed meaningful gains by persons with PPA, he said.
“The goal of intervention is not necessarily to bring more words but to improve communicative competence and to be more efficient and less anxious when communicating,” Mesulam said. “We also help the spouse or other communication partner learn how to include clues or strategies to spur more effective communication.”
Strong support system is key
Having support from family and friends who understand PPA is critical for those living with the condition, said Darby Morhardt, a research professor at the Mesulam Center. The center’s clinic provides one-of-a-kind care and support for families living with a diagnosis. It has developed and examined the usefulness of care models, support-group approaches and interventions, and it regularly holds specialized educational support conferences for families and professionals.
Another intervention from the center is PPA TeleSavvy, which Morhardt is currently piloting. Funded by the National Institute on Aging and the Emory University Roybal Center, the program supports caregivers across the country on how to best address the unique challenges facing family caregivers of those living with PPA.
Mapping language in the brain
Since Mesulam’s discovery of PPA in the 1980s, he said “the field has exploded.”
“Every year there are hundreds of research papers written on PPA. We’ve learned a huge amount about how to diagnose it and the identity of underlying diseases,” Mesulam said. “On top of that, this has been a remarkable tool for science for understanding the way language is mapped in the human brain.”
The observational research program has helped to define the syndrome and has allowed for the discovery of key insights related to diseases that cause PPA, including risk factors such as dyslexia.
“There are at least six diseases that cause PPA, including atypical forms of Alzheimer’s disease, frontotemporal degeneration with tauopathy, Pick’s disease and three different forms of frontotemporal degeneration with TDP-43 abnormality,” Mesulam said. “Each one at present is incurable. So, the first goal is not only to diagnose the exact underlying diseases but also to be able to treat them.”
His second goal is to study those with PPA even more deeply and to learn more about language in the human brain, “which is the only unique function of the human brain and what makes our brain human,” Mesulam said.
When to be concerned
We all have moments where we can’t remember the name of a person or an object. When should this type of groping for words become a source of concern as a potential symptom of PPA?
“Approach it just like every other disease,” Mesulam said. “If every time you have a little pain in your knees you say, ‘Oh, I have rheumatoid arthritis,’ that’s clearly an overreaction. If you happen to have a slip of the tongue or can’t find the name of a word or a person, that happens, it is not PPA. But if it becomes severe and consistent, look into it.”
This article was originally published in Northwestern Now on April 14, 2022.
M Marsel Mesulam, MD, Director, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Chief of Behavioral Neurology in the Department of Neurology, Ruth Dunbar Davee Professor of Neuroscience, Professor of Neurology (Behavioral Neurology) and Weinberg College of Arts and Sciences
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