Rare form of dementia eats away at personality and language

By Dr. Ananya Mandal, MDMay 8 2012

Michael French suffered from a rare form of dementia. It made him do unwise things like throwing away tax documents, getting a ticket for trying to pass an ambulance and buying stock in companies that were obviously in trouble. He seemed withdrawn and no longer spoke to his wife over dinner. He also lost his job at the consulting firm. This happened in 2006. His wife found he had changed suddenly from the smart, good-natured, hardworking man and was considering divorce when his ailment came into the picture.

French, now 71, has frontotemporal dementia — a little-known and frequently misdiagnosed group of brain diseases that erode personality and language. Researchers have been making important discoveries about the biochemical and genetic defects that cause some forms of the disease, a dementia more devastating than Alzheimer’s. Frontotemporal dementia was first recognized more than 100 years ago. There is still no cure or treatment, and patients survive an average of only eight years after the diagnosis.

Now researchers have identified drugs that may be able to treat one of those defects, the build up of abnormal proteins in the brain. Tests in people, the first ever such drug trials in this disease, could begin as early next year at the University of California, San Francisco.

“I think,” said Dr. Bruce Miller, a professor of neurology and psychiatry there, “at least some subtypes of frontotemporal dementia will be the first neurodegenerative diseases we find a cure for.” Alzheimer’s is the most common form of dementia. But frontotemporal dementia strikes younger people, progresses faster and does not attack memory at first but begins with silence, apathy or bizarre personality changes. The disease is thought to afflict at least 50,000 to 60,000 people in the United States. “I think the way dementia is going in general now is to realize there are many different subtypes,” Miller said, adding that what is now labelled Alzheimer’s disease may actually turn out to include hundreds of different illnesses.

Frontotemporal dementia, also called frontotemporal degeneration or Pick’s disease, refers to a group of diseases that destroy nerve centers in the frontal and temporal lobes. These areas of the brain are seats for decision-making, emotion, judgment, behavior and language. Some forms of the disease also cause movement disorders.

Patients generally receive from one to four misdiagnoses, and it may take years to finally get the right answer. Mistaken diagnoses can include Alzheimer’s disease, stroke, midlife crisis or psychiatric illnesses like depression, bipolar disorder or post-traumatic stress. Many relatives of patients say doctors dismiss their reports of personality change.

There are eight subtypes of frontotemporal degeneration, sorted by the symptoms they cause. Some affect behavior. Others affect language. Still others affect movement, leading to disorders that resemble Parkinson’s or Lou Gehrig’s disease (ALS). But patients may match more than one category, and the subtype may change as the disease progresses. “I see a lot who don’t present like the textbook,” said Dr. Edward Huey, an assistant professor of psychiatry and neurology at Columbia University Medical Center.

In most patients, MRI and other scans reveal shrinkage in the frontal and temporal lobes, sometimes to a shocking degree. “If I showed you more extreme cases, you could read it from across the room,” Dr. Huey said. He said researchers were using imaging to find out if specific symptoms could be mapped to atrophy in certain spots.

“The frontal lobes are sort of the last frontier in the brain,” Dr. Huey said, adding that the losses these patients suffer are helping researchers understand more about what the frontal lobes do. As the brain atrophy progresses, Dr. Huey said, patients “have pieces of psychiatric syndromes, but not the whole syndrome.” For instance, they have compulsions, but not the usual accompaniment, obsessions. So they may wash their hands over and over again, but not in a worried or anxious way. Some lose their inhibitions and moral judgment. Shoplifting is not uncommon. Many have the apathy and social disconnection that usually go with depression, but they do not feel depressed.

“They’re not down, but they just don’t enjoy things as much as they used to,” Dr. Huey said. “There appears to be a dysfunction in the reward circuit, where activities that were rewarding and pleasurable no longer seem to be. These patients lose themselves.”

The Frenches managed on their own until 2009, when he fell down a flight of stairs in their apartment building while she was at work. He fractured his skull and came home in a wheelchair, so weak and frail that she hired an aide to help take care of him. In April of last year, Ruth French placed her husband in a nursing home. “At times, I ache for him to be back in the apartment,” she said. “But I ache for him to be back as him.”