Do the crossword every day. Exercise 150 minutes per week. Follow the Mediterranean diet.
While for most people, these commandments of a healthy lifestyle reduce the risk of developing dementia as they age, for some people, cognitive decline is not related to what they do or don’t do. It’s coded in their DNA, linked to a specific genetic mutation – and may well appear in the prime of life, regardless of the 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 such a cruel reality. The author tells their dramatic story while interweaving a larger story: how the medical understanding of dementia has advanced in fits and starts over the past 150 years, and how, over the past decade, scientists have come to recognize that families like the one Kolker introduces may be key to finding a cure for all types of age-related brain deficiencies.
The resulting book is an unlikely page-turner, a two-track tale by turns gripping and heartbreaking, informative and inspiring. It’s a worthy sequel to Kolker’s 2020 bestseller, “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 this terrifying illness.
In both books, studying science “was about understanding people, following in their footsteps,” Kolker told the Post. Contacted four years ago by members of this family (their last names are not given for confidentiality reasons), the author agreed to delve into their story in depth, just as he did with that of the Galvins.
Barb, 50, is the leading figure in “The Vanishing Family.” She is the youngest of nine children of a prosperous couple, Ollie and Jean, who lived in suburban Pittsburgh. Still at home when her much older siblings left, Barb witnessed the breakdown of her parents’ marriage and the drastic changes in her mother.
Once energetic and attentive, Jean, while still in her fifties, withdrew from the world and spent her days sitting in front of the television, smoking and drinking. She hid the symptoms of breast cancer from everyone, and after her death at the age of 62, Barb and her siblings concluded that their mother’s unhealthy lifestyle had caused her death.
Six years later, while Barb was attending college, Christy, the second oldest in the family and a successful executive with two children, underwent an oddly familiar transformation. Her marriage ended and Christy, then 44, stopped taking care of herself. She refused to prepare meals, behaved strangely in social situations and could no longer cope with her job. The situation reminded Barb of what happened to her mother: both women’s marriages had failed and they had lost interest in life. Was there a kind of melancholy that reigned in the family?
Barb’s next oldest sister, Jenny, insisted on a more definitive diagnosis. Eventually, Christy learned she had Pick’s disease, a form of frontotemporal dementia that occurs in people younger than 65 years old. Most cases of Pick are “sporadic,” meaning not hereditary.
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 care for Christy, submitted DNA samples. Having received no response from the lab, they assumed they were in the clear.
As the author points out throughout the book, denial is a common response to mysterious medical events. “Of course, there is a difference between not finding a hereditary link to a rare disease and proving beyond doubt that the disease is not hereditary,” Kolker writes.
Four years later, Barb and her husband were living near Denver when they received an unexpected visit from one of her older sisters, Mary, then 47. Mary couldn’t explain why she had come, failed to show everyday courtesy to Barb’s friends and family, and spoke about her complicated profession in juvenile language.
“That weekend, Barb saw everything – the same movie, in replay,” Kolker writes. “Old Mary was disappearing, with nothing to replace her. »
For Barb, it was at this point that she became convinced that Jean, Christy and Mary suffered from a genetic disease and that “we could all have it.”
In the suspenseful chapters that follow — which Kolker draws on his extensive interviews with many members of his family — Barb and her sisters piece together clues, including those offered by distant relatives, and consult experts. They eventually discovered that a mutation on chromosome 17, V337M, which causes a rare form of early-onset FTD, ran in their family. Descendants of people carrying the mutation have a 50/50 chance of inheriting it themselves. So everyone in the family has a choice: should they take the test and find out if they will succumb to dementia while they are still in their 40s?
Through Kolker’s intimate and empathetic writings, the plight of each family member takes on great urgency. The family comes together to support and care for each other as the bad news unfolds.
“I think every reader will naturally wonder 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, widespread disease, evidence of an inevitable slowing of the brain. 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 people who died of dementia.
By the 1970s, Alzheimer’s disease was widely accepted as the leading cause of cognitive decline in older adults, and many researchers focused on the “amyloid cascade hypothesis” – the theory that plaque buildup caused the disease. “It’s a story of groupthink, as often happens in science,” Kolker told the Post. Although drugs designed to remove plaque did not provide any positive benefit for patients, how abnormal changes in tau might contribute to the progression of Alzheimer’s disease remained relatively unexplored.
Only recently have scientists realized that rarer, simpler forms of dementia, including FTD, can, in Kolker’s words, “actually teach you something about how to treat Alzheimer’s disease.” Barb’s family mutation, which causes dysfunction of normally helpful tau proteins and negatively impacts behavior, personality and cognitive function, falls into this category.
Barb and other members of her family have, through the Frontotemporal Degeneration Association, lobbied scientists to pay more attention to the disease. Kolker reports that “drugs targeting the Tau protein are currently in testing, and gene therapy and gene editing may also treat specific mutations in the future.”
But it is essential that patients get tested and come forward. “Doctors don’t want to go to the trouble of testing for incurable rare diseases, because what’s the point,” Kolker told the Post. “But if there is to be any hope of a cure, they need patients on the list to convince researchers and pharmaceutical companies that it’s worth trying to find a treatment.” The estimated number of FTD cases in the United States – 60,000 – is likely greatly underestimated.
“The Vanishing Family” offers a fascinating window into the innovations the future might hold, but also into what might happen to each of us as we – and those close to us – evolve over time.
Gn Health
