The Challenge of Dementia: A Personal Journey

Engaging in a daily crossword puzzle, committing to 150 minutes of exercise a week, and adopting the Mediterranean diet—these are, well, the usual recommendations for maintaining cognitive health. For many, these strategies indeed help reduce the risk of developing dementia as they age. Yet, it seems, for some individuals, the decline in cognitive function isn’t necessarily tied to lifestyle choices but is rooted deep within their DNA, due to specific genetic mutations. This realization, somewhat sobering, suggests that even the healthiest habits might not shield some people from this reality.

In his latest book, “The Vanishing Family: Love, Fate and the Quest to End Dementia,” Robert Kolker tells the story of a family that is facing this harsh truth. He captures their experiences while also tracing the medical field’s sometimes erratic journey in understanding dementia over the last century and a half. Interestingly, Kolker posits that families like the one he chronicles might play a pivotal role in unlocking potential cures for various age-related brain disorders.

This book, as it turns out, is quite a captivating read. It’s a dual narrative that combines heartbreak and hope, weaving together the personal stories with enlightening insights. It’s reminiscent of Kolker’s previous work, “Hidden Valley Road,” which examined the genetic roots of schizophrenia through the lens of the Galvin family.

In both volumes, Kolker emphasizes that delving into the science served to better understand the individuals involved, allowing readers to walk metaphorically in their shoes. About four years ago, Kolker was approached by this unnamed family, and he agreed to explore their complex history much like he had with the Galvins.

At the center of “The Vanishing Family” is Barb, who at 50, serves as a cornerstone for this narrative. As the youngest of nine from a well-to-do family in Pittsburgh, she witnessed the decline of her parents’ marriage and the troubling changes in her mother’s demeanor.

Her mom, Jean, once vibrant and engaged, became increasingly withdrawn, spending her days glued to the TV, smoking, and drinking. She concealed her battle with breast cancer from her family, and after passing away at 62, Barb and her siblings believed her lifestyle choices had led to her demise.

Years later, while in college, Barb observed a similarly unsettling shift in her older sister Christy, a successful executive. Christy’s marriage faltered, and she neglected herself, abandoning her usual routines and struggling both socially and professionally. It all seemed distressingly familiar to Barb, echoing the pattern they had seen with their mother. Was this sadness something inherited?

Jenny, another sister, demanded a clearer diagnosis, and after consultations, Christy was diagnosed with Pick’s disease, a rare form of frontotemporal dementia typically affecting younger individuals. Typically, such instances are sporadic rather than inherited.

Still, Jenny initiated contact with experts at the University of San Francisco, where researchers were beginning to identify connections between certain genes and dementia. Barb, along with her sisters Christy and Sue, submitted their DNA for testing, but when they received no feedback, they were relieved, thinking they were in the clear.

Kolker identifies denial as a common reaction to ambiguous health issues. There’s a fine line between not finding a hereditary link to a rare condition and ensuring that such a link doesn’t exist at all.

A few years later, Barb and her husband were settling in Colorado when her sister Mary arrived unexpectedly. Mary’s behavior was concerning—she was vague, unable to communicate normally, and seemed to speak about her work in childish terms.

Kolker describes Barb’s realization in that moment: “It was the same story, repeating itself.” The loss of what she knew as Mary struck Barb hard. It was then she became convinced that not only Jean, Christy, but now Mary might all have a genetic issue—and perhaps they were all at risk.

In the gripping sections that follow, based on Kolker’s in-depth interviews, Barb and her siblings piece together information, consult experts, and even connect with distant relatives. Their journey leads to the discovery of a mutation on chromosome 17, known as V337M, predisposing them to early-onset FTD. Individuals with this mutation face a 50/50 chance of passing it to their children. The family is now confronted with a difficult choice: to be tested and face the reality of possible dementia in midlife.

Kolker’s empathetic storytelling adds tension and urgency to the family’s saga as they navigate this tumultuous path of knowledge and support. “I think it’s a natural question for readers: If they had a crystal ball, would they really want to know?” Kolker reflects.

The scientific discussions within “The Vanishing Family” are equally compelling. Historically, dementia was viewed as a natural outcome of aging. However, in the early 20th century, Dr. Alois Alzheimer made significant strides, identifying distinct brain changes—amyloid plaques and neurofibrillary tangles associated with dementia.

By the 1970s, Alzheimer’s disease had gained traction as the leading cause of cognitive decline in older adults. Many researchers honed in on the “amyloid cascade hypothesis,” suggesting that plaque accumulation was the main culprit. Kolker describes how this line of thinking, while prevalent, led to numerous failed drug trials, with little exploration into how tau protein abnormalities might contribute to the disease’s progression.

Recently, however, a new understanding has emerged: rarer forms of dementia, like FTD, could actually inform treatments for Alzheimer’s. The mutation in Barb’s family, which causes tau proteins to malfunction, impacting cognition and personality, is part of this new narrative.

Motivated by their circumstances, Barb and her family have advocated for greater focus on frontotemporal degeneration, working with organizations dedicated to the cause. Kolker mentions that potential treatments, including tau-targeting drugs and gene therapies, are being explored, but advocates urge patients to step forward for testing. “Doctors may hesitate to check for rare diseases since they seem untreatable,” he explains, “but documenting cases is crucial for convincing researchers and industry to pursue answers.” It’s estimated that the actual number of FTD cases in the U.S. could be significantly higher than the recorded 60,000.

In sum, “The Vanishing Family” offers a thought-provoking glimpse into future innovations and the profound changes we might all face as time marches on, both for ourselves and the people we care about.