ANOTHER KIND OF MID-LIFE CRISIS
ATYPICAL FORMS OF DEMENTIA SHOWING UP IN YOUNGER PEOPLE ARE OFTEN HARD TO DIAGNOSE
NO ONE KNOWS WHY THESE DISEASES START IN SPECIFIC REGIONS OF THE BRAIN. THESE EARLY ONSET DEMENTIAS ARE FREQUENTLY MISDIAGNOSED OR UNRECOGNIZED. — BRADFORD DICKERSON, NEUROLOGIST AT MASSACHUSETTS GENERAL HOSPITAL
After 20 years of marriage, Laura Prewitt knew this about her husband: He was tender- hearted, fun- loving and never let stress land too long.
But in 2014, Ted Prewitt became less communicative. He lost his social edge and seemed unable to read faces or feelings. He was tired and withdrawn.
“He’s just not the same guy,” she says. “I want him back.”
At 59, the old Ted, the sensitive husband who cried during sad movies, is gone. A scan of Ted’s brain helps explain it: Regions of the right temporal lobe that regulate emotion are getting smaller.
Ted can still do some of the things he has done for decades. Until a few years ago, he ran a construction company. Lately, he’ll see someone he knows but forgets who they are. He sleeps a lot. And he can’t be left alone for too long or his wife may find him trying to eat a battery or a hammer. He’s agitated. He’s always putting things in his mouth.
Ted Prewitt, who has behavioural variant frontotemporal dementia (BVFTD), is one of a growing number of people in midlife diagnosed with an atypical form of dementia.
These are rarer dementias including another frontotemporal variant that leads to language disturbances called primary progressive aphasia; a visual and spatial dementia called posterior cortical atrophy; Lewy body dementia; and early onset Alzheimer’s.
These conditions show up in people in their 50s and 60s, sometimes earlier or later.
Some underlying pathology seen in people with typical Alzheimer’s — amyloid plaque and tau tangles in the brain — is also present in people who have Alzheimer’s at a younger age or atypical dementias.
No treatments are available to slow or stop these diseases. The few drugs that treat symptoms of Alzheimer’s are often prescribed for people with rarer forms of dementia. The drugs may help with some symptoms.
The National Institute on Aging suspects that early onset dementia represents about five per cent of the total number of Alzheimer’s patients.
“There is still limited awareness about early onset dementias. When people come in with cognitive complaints in their 40s or 50s, nobody believes them,” said Liana G. Apostolova, a professor at Indiana University School of Medicine and the Indiana Alzheimer’s Disease Research Center.
She is a co- principal investigator of the Longitudinal Early onset Alzheimer’s Disease Study ( LEADS), enrolling 500 cognitively impaired people between ages 40 and 64 with early onset dementia due to Alzheimer’s.
Apostolova and colleagues published a study in August that looked at dementia in people under 65 and found that the earlier onset of the disease, the more severe the cognitive decline.
“No one knows why these diseases start in specific regions of the brain,” said Bradford Dickerson, a neurologist at Massachusetts General Hospital and co- principal investigator in the LEADS trial. “These early onset dementias are very frequently misdiagnosed or unrecognized.”
His FTD clinic started 12 years ago with just a trickle of patients and now sees about 400 patients a year. He believes the increased numbers are due to increasing awareness, and not likely to increasing rates of the diseases.
Virtually everyone in mid- life with visual or spatial problems, language or behavioural symptoms has been through the wringer in trying to get the right diagnosis.
On one visit at the Memory and Aging Center at the University of California at San Francisco, a young woman stared as time ticked on.
The young mother who had showed such immense joy and love was nowhere to be found, said her husband. She no longer speaks. She is led to the bathroom, to the shower, to the table.
She is only 38.
The culprit is a gene called microtubule associated protein tau, or MAPT. A mutation in the gene causes a buildup of toxic tau proteins that form into tangles and eventually kill neurons.
She is a member of one of about 300 families in two National Institutes of Health-funded studies called ARTFL and LEFFTDS ( now merged into ALLFTD) to gather data on families with rich genetic histories of FTD.
Elizabeth Wheat’s problems began when she was 50. She thought there was a hole in her field of vision.
Ophthalmologists threw out a variety of opinions about what was happening — the most common explanation was macular degeneration. Her doctor advised her to see a neuropsychologist.
The neuropsychologist put seven plastic shapes in front of her and asked her to use them to reproduce a series of geometric drawings. She couldn’t and she was a landscape architect who spent her career drawing from her mind’s eye. She failed all the visual tests that day.
Her husband, Eric Scharf, said she was referred to a neurologist, who concluded: “You’ve got some kind of dementia and I am surprised you are still working. Would you like samples of medications used to treat Alzheimer’s?”
The family continued their search for the right diagnosis and the right doctor. Four years later, Wheat was diagnosed with an atypical dementia, posterior cortical atrophy.
By 2012, at 58, Wheat’s brain could no longer process visual information correctly and her cognitive abilities were fading fast. Her husband and sisters placed her in a memory care facility.
When family came to visit, they often found Wheat standing alone, discussing design ideas with clients visible only to her. In 2015, 10 years after her first symptoms, she entered hospice; she died in February 2017.
As for Ted Prewitt, whose atypical dementia causes abnormal proteins to accumulate in areas of the brain that are important for emotional regulation, decision- making and remembering social information, life had grown much more confined — for him and his family.
His diagnosis came in 2014. For a while, he was apathetic and spent a lot of time in his room. Now he asks to help but often doesn’t know what to do. If you ask him to get a cup, he won’t know what a cup is.
Laura recently found him eating a bar of soap. After he broke a tooth, Laura found a hammer while making his bed. Another day, his mouth was black and she found that he had poured grey paint in a bowl and started drinking it like soup.
“There are times that this disease makes me feel like a terrible person,” she said, “that I just don’t have enough ... patience.”
Recently, Ted asked her, “Do you have kids?” Yes, and she named them.
“Hey, I have two kids with the same names.”
Laura had to laugh.
40 YEARS OF RESEARCH
In the late 1970 s , Marek-marsel Mesulam was asked by his mentor, Norman Geschwind, to start a behavioural neurology unit. They had a shared interest in aphasia patients who are no longer talking or are limited in what they say.
One of the patients was a woman who was having “syntax errors and no articles.” They began collecting other patients with unusual language problems, or aphasia, with no evidence of stroke.
That puzzle was the beginning for Mesulam, now at Northwestern University in Chicago and the director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease.
He is considered the father of language dementias. There are many forms and they fall under an umbrella term called primary progressive aphasia.
There are so many possible things that can go bump in the brain and cause deficits in how we process and use language, he said. People can have word- finding trouble, word usage problems, issues with putting words in the correct order, spelling or word comprehension problems.
Mesulam identified patients who had reduced word output. They had the same abnormal buildup of the Alzheimer’s proteins or FTD proteins in the language areas of the brain. He has described 10 language diseases under primary progressive aphasia.
During the 1980s, the late D. Frank Benson, a neurologist, identified unusual visual and spatial symptoms in patients.
He coined the term “posterior cortical atrophy” to describe people who have problems seeing things right in front of them.
Numbers fly off the page. They have difficulty locating objects in space and judging spatial relationships. They have trouble writing and reading words.
Like all of these neurodegenerative conditions, it is progressive.