By Jamie Talan
Changes in vision, language or behavior may be the first clues to rare, often misdiagnosed conditions: posterior cortical atrophy (PCA), behavioral frontotemporal dementia (FTD) and primary progressive aphasia (PPA)
Andrew was in his mid-50s with a solid career in healthcare.
He was having difficulty getting projects completed at work.
He was having problems reading and tracking words and
was sure it had something to do with his eyes. But a series of
appointments with ophthalmologists and optometrists came
up empty.
Finally, he consulted with a neurologist who believed
that he had early-onset Alzheimer’s. It didn’t add up. The only
problem was his vision. On a second visit to the neurologist’s
practice, a resident met with Andrew and, after listening to
his story, suggested that he had a condition called posterior
cortical atrophy (PCA). It is a brain disease that affects the
visual and the adjacent visuospatial cortex. He is slower at
seeing things because of his brain, and not his eyes.
Andrew is one of a growing number of people in the
prime of midlife diagnosed with an atypical form of dementia.
Unlike the classic form of Alzheimer’s disease that generally
occurs in older people and affects memory first, these rarer
presentations — posterior cortical atrophy (PCA), behavioral
variant frontotemporal disorder (FTD) and a language disorder
called primary progressive aphasia (PPA) — generally begin in
the 50s and 60s, and sometimes earlier.
No one knows if these conditions are becoming more common or doctors are better at diagnosing them. What is clear is that some of the same underlying pathology seen in Alzheimer’s — amyloid plaques and tau tangles — is present in some of these rare conditions. There are other abnormal proteins, as well.
They muck up how the brain proc-esses information and can cause very different symptoms depending on where these toxic proteins begin accumulating, and where they spread. At present, there are treatments that could slow but not stop the progression of these diseases.
The abnormal protein buildup in PCA begins in the visual and visuospatial centers; behavioral FTD damages the frontal regions that regulate emotion and behavior; and PPA affects the brain’s language centers, leading to word-finding difficulties or difficulty understanding word meaning. No matter what the presentation, virtually everyone in the prime of midlife with these unique symptoms has been through the wringer
trying to get the right diagnosis.
Laura’s husband Ted was in the prime of midlife when he started acting strange. The family would be out for dinner and Ted would walk by a table and reach for a stranger’s plate of fries and eat one. He was a tender-hearted and happy guy who was becoming distant and irritable. He was ultimately diagnosed with behavioral-variant frontotemporal dementia (FTD). Over time, he could no longer manage his job as president of a construction company. The guy who could fix cars and farm equipment grew confused about how to do anything mechanical. As the disease spread, Ted could be found trying to eat a battery or a hammer. He drank paint. He paced and was easily agitated. He no longer understood sense of self and his relationships to others. He lived at home in this limbo world for years. Laura and his grown kids took beautiful care of him until he died in 2024. He was 63.
People with primary progressive aphasia, which is an atypical dementia that affects the language regions of the brain, can have word-finding trouble, word usage problems, issues with putting words in sentences in the correct order, spelling or word comprehension problems. The language problems in this semantic variant reflect neurodegeneration starting in the left anterior temporal lobe. This part of the brain has an important job of assigning meaning to words. As the name implies, people have difficulty with semantics, not how you say something, but the concept behind the word. In the early stages, it involves low-frequency words, such as pedestal, which one doesn’t say often. In later stages, they lose a sense of what the objects are. They can’t name it, and they don’t know what it does.
Dorothy arrived at a neurologist’s office because she could no longer find the right words for anything — she’d say snowing when she meant sewing — but ask her to spell something backward, and she could do it with ease. She no longer could tell you what a spoon is, but she was still able to add numbers. Dorothy’s default word was umbrella. The symptoms generally reflect where the pathology begins to accumulate. Other patients have another form of primary progressive aphasia called non-fluent/agrammatic aphasia. People gradually lose their ability to speak, read, write or understand the grammatical components of language, such as prepositions and verb tenses, but not individual words for objects. There are also problems with speech/sound production.
“No one knows why these diseases start in specific regions of the brain, but there is something that makes them selectively vulnerable in individual people,” said Bradford Dickerson, M.D., a behavioral neurologist at Massachusetts General Hospital who works with atypical dementia patients. “They then spread through brain circuits that are connected to one another. These young- onset dementias may be rare, but they are more common than you might think and are very frequently misdiagnosed or unrecognized.”
“Early-onset dementias have not been well studied and characterized, and we can’t ignore this population,” said Liana G. Apostolova, M.D., a professor of neurology, radiology, and medical and molecular genetics at Indiana University School of Medicine and the Indiana Alzheimer’s Disease Center. “We are trying to improve our understanding of the risk factors and various disease presentations and raise awareness about it.”
ABOUT THE AUTHOR
Jamie Talan’s interest in atypical dementias began during a six-month fellowship at the Memory and Aging Center at the University of California, San Francisco (UCSF), in 2017. A longtime science journalist who spent more than 20 years covering the brain for Newsday, she first encountered a person with posterior cortical atrophy (PCA) while reporting there but met many more during her time at UCSF. After returning home, she launched a support group for people with PCA and developed a lecture series featuring leading experts in the field.