After 20 years of marriage, after raising two kids, after building a farm and tending horses and dogs, Caroline knew this much about the man she loves: he is tender-hearted, fun-loving and never lets stress land too long on his shoulders. Four years ago, the old Nick somehow morphed into a new guy, one who is not so patient. A guy who lost his social edge and seems unable to read faces. He is tired and withdrawn. “He’s just not the same guy,” she says. “I want him back.”
At 56, the old Nick, the sensitive husband who cried during sad movies, is gone. In his place is a man whose emotions and behavior are blunted by a brain disease. When one peers at a scan of new Nick’s brain you can see that discrete regions of the right temporal lobe that regulate emotion are getting smaller, the tissue is shrinking. Nick can still do many of the things he has done for decades: he is a manager at a construction company where he has worked for 37 years. Lately, he’ll see someone he is supposed to know but forgets who they are. He fixes things around the farm, although lately his son is called in to help with complex tasks that in his day were easy to do. He sleeps a lot. The dogs and horses are stressing him. “Too much to take care of,” he says.
Nick’s disease is called behavioral variant frontotemporal dementia, or bvFTD. It targets areas of the brain that are important for learning and remembering social information. In time, the new Nick may forget the manners important to maneuvering in any environment. Some people with bvFTD can drink out of old cans from a garbage pail or undress in the street or even forget how to carry out a normal conversation. The social rules that are governed by the right temporal lobe are lost to this disease.
Nick and Caroline are at the UCSF Memory and Aging Center for their second annual visit to the research institute. They flew in from Kentucky, and Nick spent two long days in testing. He met with neuropsychologists who administered tests that gauge his ability to understand emotions. He met with a neurologist. He had a brain scan and a lumbar puncture to collect cerebrospinal fluid. His wife also met separately with a nurse who wanted to know everything about his behavior at home, and of course how she is faring with the changes. A speech and language pathologist administered tests to better understand his language deficits.
“There are no absolute models to this disease,” said his wife. “People progress at different levels. We know it will get worse over time.”
People with bvFTD lose social pragmatics. At first, they might needle people and say or do things that they think are funny. But they can no longer understand social cues so they don’t understand when someone is not having fun. Nick jokes with waitresses, and he believes that they like it. “No one pays much mind to them, and they enjoy when I say things,” he says. His wife and children are embarrassed by the behavior. They eat home a lot more often these days.
The new Nick has some new obsessions, too. He inherited some coins from relatives and spends time cleaning and organizing them. He also bought a metal detector and goes around the farm searching for hidden treasures. There is also some loss of object knowledge. Caroline recently made some pasta and he asked what he was supposed to do with the sauce. Once a consummate dog lover, he now frequently complains that they are too much trouble.
A speech language pathologist tested every aspect of Nick’s linguistic abilities. More and more often he speaks in general words that lack specific content. His descriptions and stories have become vague. He is having trouble identifying low frequency words and the concepts and meanings behind words. He’ll read and pronounce a word like borough incorrectly, as if it is an entirely new word.
Experts in speech and language look for the nuance in these tests. People can have problems producing words for many different reasons. They might have difficulty with the meanings and content behind the words (semantics); selecting and organizing the right sounds in the word (phonology); or coordinating the movements of the larynx, tongue and lips to make the correct sounds (articulation). Nick has difficulty with semantics: the meanings, concepts and associations that lie behind the words we use. So he uses overly general terms like “stuff” or slightly wrong terms like “cooler” for “picnic basket.” Some people with neurological diseases that affect language can also have problems with grammar but not Nick. His sentence structures are fine.
Nick’s family noticed that he was having trouble recognizing the faces of people familiar to him too. Even with face recognition, there is a distinction between recognizing the face, producing or recognizing the name, and retaining biographical details about the person. Show him a photo of Martin Luther King and he doesn’t recognize the face. He thinks he’s an activist for black people who died in old age. Give him three names to choose from and he guesses it’s James Earl Jones. He correctly identified only two of 16 famous faces: John F. Kennedy and Hillary Clinton.
“His sparkle has faded away,” said his wife. “He’s fighting his disease every day.”
Caroline and Nick both say that they want to try anything that will stop this disease or slow its course.
There are no treatments for bvFTD. A number of experimental drugs targeting the toxic tau protein are now being tested. Normally, tau is a protein that stabilizes the structure of cells called microtubules. A build-up of tau in the nerve cells is at the center of the pathology in Alzheimer’s, about half of frontotemporal dementia and is strongly implicated in other neurodegenerative conditions, such as chronic traumatic encephalopathy.
Adam Boxer, MD, PhD, a neurologist who runs the clinical trials program at the Memory and Aging Center, is hopeful that they will find a medicine that reduces this abnormal buildup of tau. Dr. Boxer and his colleagues are conducting a number of studies testing anti-tau drugs drug in patients with progressive supranuclear palsy (PSP). What is so intriguing about PSP is that it is a so-called pure tauopathy. Tau is the singular protein that mucks up brain cells in PSP. Identifying treatments for this disease, marked by walking and balance problems, a locked gaze and speech and swallowing difficulties, will open the door to other tau-related neurodegenerative diseases.
Every day, patients come in to be part of the ongoing research studies on these neurodegenerative diseases “and we want to be able to offer them access to an experimental treatment study,” says Dr. Boxer. There are now several anti-tau drugs in various stages of clinical testing, including a drug that stabilizes microtubules, TPI-287; a synthetic derivative of the cancer drug taxol; and an aspirin-related drug called salsalate that has been around since, well, before aspirin. (This drug is being tested in patients with PSP and will soon be tested in Alzheimer’s. It’s been shown to reduce a chemical modification of tau called acetylation that makes it more toxic, and they will use biomarkers to see if the drug gets into the cerebrospinal fluid and affects acetylation.) An anti-tau antibody, Abb-8E12, has begun the second phase of testing for PSP and a second antibody, BMS-986168, will be tested in a similar study soon.
Jamie Talan is an Atlantic Fellow at the Global Brain Health Institute, a collaborative program between University of California, San Francisco and Trinity College Dublin. She will be spending several months at UCSF’s Memory and Aging Center writing about the inner workings of the brain and giving voice to patients and the doctors, nurses, psychologists, geneticists and researchers involved in building the foundation for a whole body of non-Alzheimer dementias that are often missed, lost or ignored.