Understanding frontotemporal dementia, the leading cause of dementia under age 60

Bruce Willis’ family recently announced that the 67-year-old actor has been diagnosed with a progressive neurodegenerative disease called frontotemporal dementia (FTD). It helped explain how things changed after retired Aphasia is a disorder involving problems understanding speaking and hearing that can occur when certain brain areas are damaged by disease or injury.

“Unfortunately, communication problems are just one symptom of the illness Bruce faces,” his family said. official statement in February. “It’s heartbreaking, but I’m relieved to finally have a definite diagnosis.”

Last week, Willis’ wife, Emma Heming Willis, shared how the family is Learn to navigate dementia careSince there is no cure for FTD, a definitive diagnosis and learning how to deal with the inevitable progression of the disorder is essentially a task for loved ones and caregivers of people with FTD. It’s your main lifeline. Scientists are now studying people with FTD or at risk of developing the disease to better understand what’s going on in the brain. is in clinical trials.

Although less common than certain other neurodegenerative diseases such as Alzheimer’s and Parkinson’s, FTD is the most common form of dementia in people under the age of 60. It tends to develop earlier than other dementias. However, FTD usually appears between the ages of 40 and 60. Estimate 60,000 in the US alone.

The term FTD refers to a range of disorders that affect the frontal and temporal lobes of the brain (regions associated with personality, behavior, language, and other high-level brain functions). The disease can be devastating for FTD patients and their spouses, children, or grandchildren, he said. Elizabeth Finger, a neurologist and professor at Western University, Ontario. One of the most insidious aspects of FTD is that it seems to suddenly change someone’s personality.

“Physically, you may be fine for a while, so it’s like having strangers living with you in your family,” says Finger. “It helps if the family gets a diagnosis because they have been living in isolation for a while.At least now they can understand that this is a brain disease that the patient has no control over.”

What are the symptoms of FTD?

FTD has several variant.Each is characterized by a set of symptoms related to where in the brain the disease begins. frontal and temporal lobes, the most common. It includes symptoms such as apathy, blunted emotions, impulsiveness, and decision-making and judgment problems.

Variants associated with changes in language ability are known as primary progressive aphasia and usually involve the dominant frontal and temporal lobes (for most people, these are on the left side of the brain). These variants include her three main subtypes: semantic, non-fluent, and logpenic. Semantic subtypes mainly lead to loss of word comprehension. An affected person’s vocabulary diminishes over time, making it increasingly difficult to read, write, and understand dialogue. People with the non-fluent subtype have difficulty speaking but retain the meaning of words. In the early stages of this subtype, words may be difficult to pronounce and slurred. In advanced stages, they may stop speaking altogether. People with the log-decreasing variant have trouble finding the right words during conversation.As the disease progresses, these people may have trouble understanding complex sentences.

Movement disorders are the most prominent symptom of other variants. This can happen when an FTD appears. Amyotrophic Lateral Sclerosis (ALS)a neurodegenerative disease that leads to progressive loss of neurons involved in locomotion.

All of these variants overlap to some extent. Yolanda Peinenburg, neurologist, professor at the University Medical Center of Amsterdam. “The syndromes are most distinct when they are in their initial state,” she says.

find out the cause

FTD is commonly associated with loss of neurons in the frontal and temporal lobes of the brain. But what caused that loss? Postmortem examination of the FTD patient’s brain revealed that the condition was primarily associated with abnormal accumulation of two proteins in her, tau and her TDP-43. thought to be involved in Alzheimer’s diseaseScientists have found other proteins that may be responsible for FTD, but changes in tau and TDP-43 explain more than that. 90% of all casessay Shiadi Onikea neuropsychiatrist at Johns Hopkins University.

Studies suggest that genetic mutations cause FTD. one-third of those affected. dozens of mutations The most common appear to be in specific genes that cause abnormal accumulation of tau and TDP-43.

But scientists know very little about what causes the disease in the other two-thirds of affected people without the genetic disorder, the so-called sporadic FTD. The only risk factor that has yet been identified is a history of concussion or traumatic brain injury, says Finger. But that alone explains only a small part of the risk, she adds. This is because the majority of FTD patients have not experienced such brain damage, and most who have had them have not developed her FTD.

know the signs

According to Pijnenburg, diagnosing FTD presents several challenges.currently takes Average 3.6 years For people to receive an accurate diagnosis of the condition. Most people with FTDs, especially behavioral variants, are unaware that changes are occurring and rarely seek medical help on their own. Another possible explanation is the disease or another mental health condition. Importantly, Pijnenburg says there is a relative lack of public awareness of the disease.

A definitive FTD diagnosis is only possible if researchers perform postmortem brain examinations, Finger notes, or if a person carries a so-called autosomal dominant mutation.

However, there are other tools for evaluating FTD, including neurological and psychiatric evaluation, neuroimaging, genetic screening, and analysis of personal medical history. Neuroimaging techniques such as magnetic resonance imaging and positron emission tomography can reveal signs indicating her FTD of brain damage or dysfunction.genetic screening Can identify FTD-associated mutations In a subset of people with FTD who have them. According to Pijnenburg, these techniques can pinpoint somewhere in between. 74 percent To 93 percent For FTD cases.

Researchers around the world are now studying asymptomatic people with genetic mutations associated with FTD. This is an attempt to understand how the disease develops and potentially help develop treatments, including treatments that slow, stop or prevent the disease.

In Canada and some European countries, Hereditary Frontotemporal Dementia Initiative (GENFI) is conducting a study that tracks over 1,000 people with FTD-related genetic mutations. The group is trying to determine how to detect early changes in asymptomatic individuals deemed at risk, said the GENFI coordinator. Jonathan Lawler, a neurologist at University College London. Now, ten years after his research, Rohrer says behavioral and brain pathological observations to date show: subtle change Changes in cognition and brain structure can occur many years before the onset of symptoms.

Geneva joined forces Rohrer said he founded the Frontotemporal Dementia Prevention Initiative (FPI) in 2019, working with researchers based in the United States, Australia, and several countries in Asia, South America, and Africa. I’m here. The team involved is pooling data to create an international registry of his FTD study participants who can be enrolled in clinical trials. Ultimately, a global research effort plans to set up clinical trials for treatments that might prevent people from developing FTD symptoms.

testing new treatments

Studying people with a genetic form of FTD is already A variety of potential disease-modifying treatments, and some have been tested in clinical trials. These include Phase 3 trials of treatments targeting Progranulin. Progranulin is a multifunctional protein whose decreased levels in the FTD lead to accumulation of her TDP-43. Trials of therapeutics aimed at restoring or attenuating the activity of known FTD-associated mutated genes are also underway.

Scientists hope that if these treatments work, they may be used to help people with sporadic FTD. “There is a growing belief in the field that genetic forms of therapy may be translatable into sporadic forms,” says Finger.

But before that happens, Rohrer points out, scientists need to overcome another major obstacle to treating sporadic FTD. It is to identify biomarkers such as biomarkers that can reveal tau or TDP-43 protein in blood or spinal fluid to determine which pathological processes. playing.

There are now ways to manage and treat certain FTD symptoms. One important aspect of care today is family and caregiver education. Other approaches include: psychotherapy and pharmaceutical interventions It targets specific behavioral or cognitive symptoms and speech disorders. Physical therapy or occupational therapy can address language and movement problems. Lifestyle again environment (such as limiting driving and using credit cards, maintaining a quiet environment, and providing a structured routine) can help with behavioral symptoms. I’m starting to look into how to do that. For example, combining brain stimulation with speech therapy for people with aphasia.

Although disease-modifying treatments are not yet available, researchers see some promise in recent treatment advances. “We are optimistic and moving forward,” he says Onyike. “Ten years ago clinical trials were about drugs to reduce symptoms or boost cognition. Today they stop neurodegeneration and rehabilitate the brain.”