Family's Genetic Dementia Struggle Illuminates Path to Potential Cure

While healthy habits are often promoted to ward off dementia, some individuals face a form of the disease driven by genetic mutations that emerge in midlife, irrespective of lifestyle choices. Robert Kolker's new book, "The Vanishing Family: Love, Fate and the Quest to End Dementia," delves into the story of one family experiencing such a cruel reality, weaving it with the broader scientific progress in understanding dementia over the past 150 years.

Kolker, also the author of "Hidden Valley Road," which explored a family's struggle with schizophrenia, stated that in both his books, the study of science served to deepen the understanding of the people involved. For "The Vanishing Family," he agreed to document the history of a family after being contacted by its members, whose last name is withheld for privacy.

The narrative centers on Barb, who, as the youngest of nine children, witnessed firsthand the decline of her mother, Jean. Jean, in her 50s, withdrew from life, showing symptoms that were later recognized as a form of frontotemporal dementia (FTD). After Jean's death from breast cancer at age 62, Barb and her siblings attributed her decline to an unhealthy lifestyle.

Years later, Barb's older sister, Christy, then 44 and a successful executive, began exhibiting similar changes. Her marriage ended, she neglected her health, acted strangely, and struggled with her job. This pattern of marital failure and loss of interest in life echoed her mother's experience, leading to speculation about a possible inherited melancholic strain.

Jenny, another sister, advocated for a definitive diagnosis. Christy was eventually diagnosed with Pick's disease, a form of FTD that affects individuals under 65. While most cases of Pick's disease are sporadic, Jenny contacted experts at the University of San Francisco in 2001, where scientists were beginning to connect specific genes to dementia. Barb, Christy, Jenny, and another sister, Sue, who cared for Christy, submitted DNA samples.

Four years later, Barb's sister Mary, then 47, visited and displayed similar cognitive and behavioral changes, convincing Barb that Jean, Christy, and Mary suffered from a genetic condition. Through research and consultation with experts, the family discovered a mutation on chromosome 17, V337M, linked to a rare form of early-onset FTD. Offspring of carriers have a 50% chance of inheriting the mutation, presenting a difficult choice about genetic testing.

Historically, dementia was considered a natural consequence of aging. However, early 20th-century work by Dr. Alois Alzheimer identified specific brain abnormalities like amyloid plaques and tau tangles. By the 1970s, Alzheimer's disease was widely accepted as the primary cause of cognitive decline in the elderly, with much research focusing on the "amyloid cascade hypothesis."

Kolker notes that despite numerous drugs targeting amyloid plaques failing to benefit patients, the role of tau protein in Alzheimer's progression remained less explored. Recent scientific understanding suggests that rarer, simpler forms of dementia, such as FTD, can provide crucial insights into treating Alzheimer's. The mutation found in Barb's family involves malfunctioning tau proteins, impacting behavior, personality, and cognitive function.

Through organizations like the Association for Frontotemporal Degeneration, Barb and other family members have urged scientists to focus more attention on FTD. Kolker reports that tau-targeting drugs, gene therapy, and gene editing are in development. However, he emphasizes the critical need for patients to undergo testing and participate in research to encourage pharmaceutical companies to invest in treatments.

The book "The Vanishing Family" offers a detailed look at potential future medical innovations and serves as a poignant reminder of the profound impact of neurological diseases on individuals and their families. It highlights how studying these less common, genetically driven forms of dementia could be key to unlocking cures for broader cognitive impairments.