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.