Genetics of Frontotemporal Dementia: A Family Story

Almost 30 years ago, a middle-aged man traveled to an Alzheimer’s Association meeting with a copy of his mother’s autopsy in his bag. It read simply: dementia lacking distinct characteristics. He’d had his mother’s brain sent cross-country to try to figure out why she – and her two brothers and a cousin – died with a dementia that caused them to act impulsively and irrationally. It wasn’t just the bizarre behavior he was curious and concerned about. In illness, his mother’s brain was shrinking, and she’d lost so much of who she had been in her younger years. (She was 50 when people began noticing something very odd about her behavior.) But as her cognitive skills diminished she gained something rather remarkable: an exquisite talent for painting gazelles and churches and people.

The doctor talking to the small gathering was Bruce Miller, who was at the beginning of his own journey into unraveling the puzzle of people with these unusual dementias that start with behavioral and psychiatric changes. He looked at the autopsy results. His mother’s brain was not lacking distinct characteristics, at all, and this chance meeting between a worried son and a neurologist would turn into a lasting friendship.

One year ago, the man, now in his 80s, arrived at Bruce Miller’s door with a new puzzle. One of his daughters was losing her mind. It was serious – she was ignoring her teenage kids in favor of sleeping. She was forgetful, apathetic, depressed. She was nothing like the elegant young woman with a keen eye for houses who had made a better than good living buying, decorating, selling and renting them. She was confident and always loved what she did.

In the ensuing years, he had joined a research study at the Memory and Aging Center and was drawn into Dr. Miller’s pioneering work. At 50, when his mother’s brain was losing its power to think and act in socially predictable ways, he had gone back for a doctoral degree in psychology.

He’d spent decades counseling people and felt that the annual neuropsychological tests and exams would help in the grand effort to figure out genetic diseases like the one that had wiped out his mother’s generation.

He felt that he’d somehow escaped this fate, but now he worried that he had somehow passed a familial disease gene down to his daughter.

It is 2017. The month is January. The city is San Francisco. This is the second year that this man’s daughter is undergoing testing. This year she has no memory for the year or the month. When prompted, she does know she and her father have traveled to UCSF. She can no longer look at a picture of a screw or a hammer and tell you what it is. She spends her days eating and watching CNN with her aging mother. She has grown so disabled that she now lives with her parents.

For two days, father and daughter undergo blood draws and brain scans and carry out an intense battery of neuropsychological and neurological exams. It is exhausting for cognitively normal people, but his daughter goes through each question and delivers whatever she can. Much of the time she will shake her head, shrug her shoulders, offer a shy smile and say: I don’t know what you are talking about. Later, at a meeting with her team, it will become clear that much of her cognitive prowess that she once had is lost to the disease. Yet, unlike her ancestors, she shows no signs of irrational or odd behavior. When her mother walks into the house with groceries she knows to walk towards her and ask if she needs help. She still can get into her car and find her way to the store. Her father worries that she has gotten lost a few times and wonders whether he will be forced to take her keys away soon.

This father does have a gene that triggers frontotemporal dementia. His cognitive skills are sharp. Scientists do not understand how he escaped the symptoms, but for now, he has. By contrast, his daughter’s life before frontotemporal dementia is packed in a storage unit. He also wonders whether she will ever see her possessions again, or even cares.

“I have traveled all over the world,” she says. “And I have a bunch of rentals all over the place.”

Her brother is now managing her finances. Her father is now managing her life. For the first time in decades, he is not sure whether he can continue to hold this new world on his shoulders.


Jamie Talan is an Atlantic Fellow at the Global Brain Health Institute, a collaboration between University of California, San Francisco and Trinity College in 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.