When I first start talking to Joanne Douglas, she speaks slowly but eloquently, with deliberation and confidence. But after ten minutes, I start to notice subtle changes. She repeats some of her words, just a few at first, and then more. Pauses and hesitations creep in. Once-seamless sentences become increasingly marbled by erms and uhs. She sounds tired. After thirty minutes, I know it’s time to wrap up the interview. On any given day, Douglas only has so many words to give, and she has given me plenty.
Douglas has primary progressive aphasia (PPA)—a brain disorder that robs people of their language skills. Unlike other aphasias (language impairments) caused by trauma or stroke, PPA is degenerative: It gets worse, slowly and inexorably. But unlike other degenerative conditions, like Alzheimer’s dementia, it leaves most of a patient’s mental faculties untouched. People can still plan, reason, and multi-task. Their memories stay healthy and their personalities remain unchanged, at least at first.
But their blooming inability to write, read, speak, and comprehend can leave them locked inside their own heads, responsive but unable to respond, thoughtful but unable to share those thoughts. “It can be a truly devastating condition,” says Joseph Duffy from the Mayo Clinic College of Medicine. “It sucks our humanity, or what makes us uniquely human, from us.”
It also affects people earlier than most neurodegenerative conditions—at 60, on average, but as early as 20. For Douglas, the problems began at age 44. It was the summer of 2008, and her health had already taken a pounding. She had recently been diagnosed with breast cancer and would eventually go through a course of radiotherapy and 16 major surgeries. During her treatments, her doctors noticed that she was having trouble understanding them, especially if they said something unexpected or switched topics. Her own speech became halting and difficult. “I would close my eyes to speak and use a lot of hand gestures,” she recalls.
At the time, Douglas was an assistant professor at the University of Alabama at Birmingham, working on ways of delivering gene therapy. “I was using language at a fairly precise level day by day,” she says, “so it was very noticeable to me when my abilities started to decline.” Unable to give lectures, read papers, or write grants, she retired due to disability in December 2009. The next year, she was finally diagnosed with PPA.
Her condition “has progressed steadily and slowly” she says. “And it has had a very significant impact on my daily life. Writing has become very difficult. I can manage to write at a good level for only about 10 minutes, and then I make a lot of spelling errors. I can no longer read a whole scientific paper in one go. And I can really manage one reasonable length conversation a day. Thirty minutes.”
As they tick by and her sentences fray, I hear the last eight years of progressive deterioration play out in a time-lapse.
* * *
In the early 1970s, Marsel Mesulam, a neurologist at Harvard Medical School, noticed that six of his patients had an unusual language disorder. It wasn’t caused by stroke. It was progressive. And it didn’t affect memory. Mesulam described this syndrome in 1982. Shortly after, he gave it a name: PPA.
It’s not a new problem. In 1892, French psychiatrist Paul Sérieux described an intelligent 47-year-old woman who gradually lost the ability to understand words; she likely had what we now call PPA. But this case, and others like it, were quietly forgotten. “When I started in the Mayo Clinic 33 years ago, I had been taught that you couldn’t become aphasic as your only problem because of a neurodegenerative disease,” says Duffy. He saw several patients who didn’t fit that description, “I collected cases and tucked them away. Then, I read Mesulam’s paper.”
“When I first described these patients, there was a flurry of interest but it was considered esoteric. That’s no longer the case,” says Mesulam. “There are now close to 200 publications a year on PPA. Patients are being seen in their thousands in clinics.” Still, a lot of basic information is missing, like how common it is, or whether it’s becoming more common.
Awareness of PPA is also patchy, and many people don’t get diagnosed correctly. Some are told that their problems are all in their heads. Some are diagnosed with stroke. Others are wrongly lumped together with Alzheimer’s disease. The problem is that “many memory assessments are based on language,” says Argye Hillis from Johns Hopkins Medicine. “If you don’t have the word for what happened yesterday or you can’t remember someone’s name, people think you might have a memory problem.”
A correct diagnosis matters, says Duffy, because Alzheimer’s has so much stigma and fatalism attached to it. “And in spite of how devastating PPA can be, one can still perform activities of daily living that don’t involve language,” he says. “I’ve seen many people continue to work.”
To add to the confusion, Alzheimer’s and PPA aren’t totally distinct. Alzheimer’s disease is associated with clumped molecules like amyloid plaques. These same clumps are found in around 40 percent of PPA cases. So PPA is clinically distinct from Alzheimer’s disease, but it can be caused by Alzheimer’s features. It’s what happens when those same clumps hit specific parts of the brain, especially those in the left hemisphere that govern language.
Why would problems only affect those particular regions? No one knows, but there are clues. Mesulam and others have found that PPA patients are more likely to have a family history of dyslexia and other learning disabilities. They suspect that some people have a genetic vulnerability that leaves their language centers particularly prone to plaques and other problems. That same vulnerability could lead to dyslexia in some family members and PPA in others.
Complicating matters, PPA isn’t just one disorder. In 2011, it was formally split into three variants, each of which is associated with different molecular causes, parts of the brain, and symptoms.
The agrammatic variant (which Douglas has) is a problem with producing words. People can remember words but they struggle to speak and to string grammatical sentences together. They can understand single words but find sentences harder.
By contrast, the logopenic variant is a problem with finding words. People might struggle to find the right word, or say a wrong but rhyming word. But they can otherwise speak fluently, albeit hesitantly.
Finally, the semantic variant is a problem with understanding words. People can speak fluently, but their words make no sense together (even though they’re in the right grammatical order). They also have severe comprehension problems. They can understand casual conversation through contextual cues, but they struggle with isolated words.
Hillis is now trying to find more efficient ways of diagnosing these three variants. For example, she asked some patients to match words to pictures, while tracking their eye movements. Those who eventually develop semantic PPA are more likely to flick back and forth between the answers even after they choose the right one. And they do so before their comprehension problems become obvious. “That will help us with prognosis and telling family members what will happen next,” she says. The semantic variant, for example, sometimes leads to agitation and other behavioral changes.
There’s no cure for PPA, but research is underway. The logopenic variant is the one that’s associated with Alzheimer’s pathology, so some patients are taking part in clinical trials for Alzheimer’s drugs. And Hillis and others are trying transcranial direct current stimulation—a technique that used electrodes to apply low electrical currents to the brain. “The idea is to try and get unaffected areas to take over for the affected ones,” she says.
For now, the main treatment is speech therapy. Therapists might ask patients to practice their most impaired skills, whether reading out loud or naming objects. They might offer assistive tools—everything from picture books to point at, or smartphone apps. Mesulamn’s colleagues are also developing an online speech therapy program, so even isolated patients can get some help. None of this will reverse or stall the disorder, but it can be invaluable in helping people to communicate more effectively.
That’s why the right diagnosis matters. If PPA patients are told they have a stroke, their speech therapists may try the wrong strategies and become discouraged when they see no improvements. “They may discharge the patients, saying: I can’t do anything for you,” says Mesulam.
“And there is a lot that can be done.”
* * *
When Joanne Douglas was first diagnosed with PPA, her neurologist noticed that she was speaking softly. She went on an intensive course of breathing exercises that raised her volume to normal levels, and helped others to understand her. As a side effect, she finds speaking easier and rarely stutters. That was the first of many techniques that have helped her to deal with her disorder. She wrote about them in 2014, in a four-page paper that took her five months to complete, in bursts of 20 minutes.
It’s as if she has a daily quota of words—currently around half an hour of talking time, and less for writing. The disorder has progressed to the point when she can’t “have a significant conversation and produce a piece of high-quality writing on the same day.” And once the quota depletes, speech becomes hard and sentences start to look strange. Then, she lapses into silence and puts away any text, allowing herself to rebuild her cognitive resources.
So, Douglas carefully prioritizes when and how to use up her quota. “I’m always looking for quality rather than quantity, making the absolute best use of what I have, and not frittering away my very precious coterie of words,” she tells me. “I try to store up my reserves of language so they’re available for optimum use when I want to. And I spend most of my time alone fairly quietly.”
Preparation is vital. She makes notes before important conversations or meetings, outlining what she wants to say beforehand and preparing relevant words. When starting a conversation, she’ll mentally rehearse key sentences, and she has a stock speech about PPA. She uses voice-recognition software to write, since her writing ability is declining faster than her speech. And she also avoids noisy places like coffee shops and restaurants because background noise seems louder than normal now, and hampers her ability to concentrate (her only request to me was that I interview her from a quiet place).
“And my ability to cook has improved dramatically,” she says.
That’s a common theme. Many PPA patients turn to hobbies that don’t involve language, including music, photography, gardening, woodworking, Sudoku, jigsaw puzzles, sculpting, and even breeding rare birds. “I had a patient who was diagnosed in her sixties and took up oil painting for the first time. She does remarkable pieces,” says Mesulam. “There’s a lot of life in these patients that are intact. An informed approach makes all the difference in the world.”
“My goal is always to be grateful for the abilities I have and use them to the best of what I can,” Douglas tells me. “The diagnosis makes all the difference to how I can approach the disorder.”
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