Do the crossword every day. Exercise 150 minutes per week. Follow the Mediterranean diet.
While for most people these commandments of healthy living lower the risk of developing dementia with advancing age, in some individuals cognitive decline is unrelated to what they do, or fail to do. It is coded in their DNA, tied to a specific genetic mutation — and may well emerge during the prime of life no matter what healthy habits they adopt.
In his new book, “The Vanishing Family: Love, Fate and the Quest to End Dementia,” Robert Kolker chronicles three generations of a family grappling with just such a cruel reality. The author tells their dramatic story while also interweaving a broader one — how the medical understanding of dementia has progressed in fits and starts over the past 150 years and how, in the last decade, scientists have come to recognize that families like the one Kolker profiles may be key to finding a cure for all types of age-related brain impairment.
The resulting book is an unlikely page-turner, a dual-track narrative by turns absorbing and wrenching, informative and inspiring. It’s a worthy follow-up to Kolker’s 2020 best-selling “Hidden Valley Road: Inside the Mind of an American Family,” about the descent into schizophrenia of six members of the Galvin family, and the genetic origins of that terrifying disease.
In both books studying the science “was in the service of understanding the people, of walking in their footsteps,” Kolker told The Post. Contacted four years ago by members of this family (their last name is not provided for privacy reasons) the author agreed to do a deep dive into their history just as he did with the Galvins’.
Barb, 50, is the anchoring figure in “The Vanishing Family.” She was born the youngest of nine children of a prosperous couple, Ollie and Jean, who lived in the suburbs of Pittsburgh. Still at home when her much-older siblings had left, Barb witnessed first-hand the breakdown of her parents’ marriage and the drastic changes in her mother.
Once energetic and attentive, Jean, while still in her 50s, withdrew from the world and spent her days sitting in front of the television, smoking and drinking. She hid from everyone the symptoms of breast cancer, and after she passed away from that disease at age 62, Barb and her siblings concluded that their mother’s unhealthy lifestyle brought about her death.
Six years later, when Barb was attending college, Christy, the second oldest in the family, and a successful executive with two children, underwent an eerily familiar transformation. Her marriage ended, and Christy, then age 44, stopped taking care of herself. She refused to make meals, acted strangely in social situations, could no longer handle her job. The situation reminded Barb of what had happened with her mother: Both women’s marriages had failed and they lost interest in life. Was there some strain of melancholia that ran in the family?
Barb’s next oldest sister, Jenny, pushed for a more definitive diagnosis. Eventually, Christy was told she suffered from Pick’s disease, a form of frontotemporal dementia that occurs in people under age 65. Most cases of Pick’s are “sporadic,” meaning not inherited.
Nonetheless, in 2001, Jenny contacted an expert at the University of San Francisco where scientists were beginning to link certain genes to dementia. She, Barb, Christy and another sister, Sue, who gave up her career to take care of Christy, submitted DNA samples. After hearing nothing back from the lab, they assumed they were in the clear.
As the author makes clear throughout the book, denial is a frequent response to mysterious medical events. “Of course, there is a difference between failing to find a hereditary link to a rare disease and proving without doubt that the disease isn’t hereditary,” Kolker writes.
Four years later, Barb and her husband were living near Denver when they received an unexpected visit from her one of her older sisters, Mary, then 47. Mary couldn’t explain why she had come, did not extend everyday courtesies to Barb’s friends and family and spoke about her complicated profession in juvenile language.
“That weekend Barb saw it all — the same movie, playing again,” Kolker writes. “The old Mary was disappearing, with nothing to replace her.”
For Barb that was the moment when she became convinced that Jean, Christy and Mary suffered from a genetic condition, and “we might all have it.”
In the suspenseful chapters that follow — which Kolker based on his lengthy interviews with numerous family members — Barb and her sisters piece together clues, including those offered by distant relatives, and consult experts. They eventually discover that a mutation on chromosome 17, V337M, which causes a rare form of early-onset FTD, runs in their family. Offspring of those carrying the mutation have a 50/50 chance of inheriting it themselves. Everyone in the family thus has a choice: Should they take the test and learn if they will succumb to dementia while still in midlife?
Thanks to Kolker’s intimate, empathetic writing, the fate of individual family members takes on great urgency. The family pulls together to support and care for each other as the bad news unspools.
“I think every reader will naturally ask themselves if they had a crystal ball would they really want to know?” the author told the Post.
The scientific chapters of “The Vanishing Family” contain their own drama and poignancy. For most of history, dementia was considered a natural, generalized condition, evidence of a brain inevitably slowing down. Then, in the early 20th century, Dr. Alois Alzheimer identified unique brain abnormalities — amyloid plaques and neurofibrillary tangles of a protein called tau — present in the brain tissue of those who died with dementia.
By the 1970s Alzheimer’s was widely accepted as the leading cause of cognitive decline in the elderly, and many researchers fixated on the “amyloid cascade hypothesis” — the theory that the accumulation of plaque brought on the disease. “It’s a story of group think, the kind that often happens in science,” Kolker explained to The Post. Even as drug after drug designed to clear plaque ended up having no positive benefit for patients, the way abnormal changes in tau might contribute to Alzheimer’s progression remained relatively unexplored.
Only recently have scientists grasped that rarer, simpler forms of dementia, including FTD, can, in Kolker’s words, “actually teach you something about how to treat Alzheimer’s.” Barb’s family’s mutation —which causes normally helpful tau proteins to malfunction, and negatively impact behavior, personality, and cognitive function — falls in this category.
Barb and other family members have, through the Association for Frontotemporal Degeneration, lobbied scientists to pay more attention to the disease. Kolker reports that “tau-targeting drugs are currently in the testing phase, and also gene therapy and gene editing may address specific mutations in future.”
But it’s vital that patients get tested and come forward. “Doctors don’t want to bother testing for incurable rare diseases because what’s the point,” Kolker told The Post. “But if there is to be a hope of a cure, they need patients on the rolls to convince researchers and drug companies that it’s worth trying to find a treatment.” The estimated number of FTD cases in the US — 60,000 — is likely a massive undercount.
“The Vanishing Family” provides a fascinating window on innovations the future could hold, but also what might happen to any of us as we — and our loved ones — change over time.
