Frontotemporal dementia

Based on Wikipedia: Frontotemporal dementia

The Dementia That Steals Your Personality First

Imagine watching someone you love become a completely different person. Not forgetful, like in Alzheimer's disease. Not confused about where they are or what year it is. Instead, they simply stop being themselves. They might start making crude jokes at funerals. They might lose all interest in their grandchildren. They might begin shoplifting despite having plenty of money—not because they want the items, but because the part of their brain that says "don't do that" has quietly died.

This is frontotemporal dementia.

Unlike the memory-robbing progression of Alzheimer's disease that most people picture when they hear the word "dementia," frontotemporal dementia—often called FTD—attacks the regions of the brain responsible for personality, behavior, and language. It typically strikes people in the prime of their lives, between ages 45 and 65, though it can appear earlier or later. It affects men and women equally, and as of now, there is no cure.

A Tale of Two Brain Regions

To understand frontotemporal dementia, you need to understand a bit about brain geography. Your frontal lobes sit right behind your forehead. They're the executive suite of your brain—they handle planning, judgment, impulse control, and social behavior. They help you decide not to say exactly what you're thinking at a dinner party. They keep you from eating an entire cake in one sitting. They allow you to feel embarrassed when you should feel embarrassed.

Your temporal lobes, meanwhile, sit on either side of your head, roughly behind your ears. They're crucial for language—understanding words, finding the right word when you want to say something, and connecting words to their meanings.

When these regions begin to degenerate—when the neurons there start dying at an accelerated rate—the result depends on which area goes first and how the damage spreads. This is why frontotemporal dementia isn't really one disease. It's a family of related conditions, each with its own signature pattern of destruction.

The Behavioral Variant: When Personality Dissolves

The most common form is called behavioral variant frontotemporal dementia, sometimes still referred to as Pick's disease after the physician Arnold Pick, who first described its features between 1892 and 1906. This form accounts for roughly four times as many cases as the language variants.

People with the behavioral variant change in one of two directions. Some become impulsive and disinhibited—they lose the internal editor that keeps most of us from acting on every passing thought. They might make inappropriate sexual comments, spend money recklessly, or engage in petty theft. Social conventions become meaningless to them, not because they're rebelling against society, but because the brain regions that encoded those conventions are literally dying.

Others go the opposite direction, becoming apathetic and emotionally flat. They lose interest in hobbies they once loved. They stop caring about family members. They can sit for hours doing nothing, not because they're depressed exactly, but because the motivation circuits in their brain have gone dark.

What makes this particularly cruel is how gradual it is. The changes creep in slowly, over months or years. Family members often spend a long time wondering if their loved one is just stressed, or going through a phase, or perhaps dealing with depression. By the time anyone thinks to see a neurologist, the disease has often been progressing silently for quite some time.

When Words Slip Away

The language variants of frontotemporal dementia attack communication itself, but in fascinatingly different ways.

In semantic dementia, people gradually lose the meaning of words. They can still speak fluently, with perfect grammar, but the words become disconnected from their meanings. Someone might point to a cat and ask, genuinely puzzled, "What is that thing?" They might describe a hammer as "that thing you hit with" because the word "hammer" has floated free from the concept it once anchored to. Eventually, even common objects become mysterious—not because of vision problems, but because the brain's dictionary has been systematically erased.

Progressive nonfluent aphasia works differently. Here, people know what they want to say, but producing speech becomes increasingly difficult. They struggle to form words, their sentences become shorter and more halting, and grammar starts to fall apart. It's as if the machinery of speech production is grinding down, one gear at a time.

The Strange Overlap with Motor Neuron Disease

There's a disturbing connection between frontotemporal dementia and amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease. ALS attacks the motor neurons that control voluntary movement, eventually leading to paralysis. You might not expect a disease of movement and a disease of personality to have anything in common.

But they share more than anyone would like. Up to half of people with ALS develop some degree of cognitive or behavioral symptoms, and about ten to fifteen percent meet the full criteria for frontotemporal dementia. The relationship goes both ways—some people who start with frontotemporal dementia eventually develop motor symptoms similar to ALS.

Researchers now believe these aren't really two separate diseases that sometimes occur together. Instead, they represent different points on a spectrum—a single underlying process that can manifest primarily as cognitive changes, primarily as motor changes, or both. When they occur together, the prognosis worsens significantly, shortening survival by about a year compared to ALS alone.

The Genetics of Neural Destruction

Frontotemporal dementia has a stronger genetic component than many other neurodegenerative diseases, including Alzheimer's. In many families, the condition follows a clear inheritance pattern, passed from parent to child with devastating regularity.

Scientists have identified several genetic culprits. Mutations in a gene called MAPT, which encodes a protein called tau, can cause a form linked to chromosome 17. The tau protein normally helps stabilize the internal scaffolding of neurons, but when mutated, it forms abnormal clumps that poison the cells.

Another gene, called GRN, encodes a protein called progranulin. Mutations here lead to a different pattern of cellular destruction involving a protein called TDP-43, which normally helps regulate how genes are expressed. When things go wrong, TDP-43 accumulates in toxic aggregates.

Perhaps the most dramatic genetic finding came from a gene with the mundane name C9ORF72—pronounced "C nine orf seventy-two" and standing for "chromosome 9 open reading frame 72." In some families, a short sequence of genetic letters repeats itself over and over—not a handful of times, as in healthy individuals, but hundreds or even thousands of times. This expanded repeat disrupts normal cellular function and is now recognized as a major genetic contributor to both frontotemporal dementia and ALS, providing molecular evidence for the clinical observation that these diseases are related.

What Happens Inside the Brain

If you could look inside the brain of someone with frontotemporal dementia, you would see striking changes. The frontal and temporal lobes shrink, sometimes dramatically—the brain tissue wastes away in a process called atrophy, leaving widened grooves on the brain's surface and enlarged fluid-filled spaces within.

Under a microscope, the picture becomes more specific depending on the subtype. In the behavioral variant, you might see spherical structures called Pick bodies inside affected neurons—dense balls of abnormal tau protein that accumulate in the cells' cytoplasm. These were first described by Alois Alzheimer himself in 1911, the same physician who gave his name to the more common dementia.

A particularly striking finding involves a specialized type of neuron called spindle neurons, or von Economo neurons. These unusually shaped cells are found only in the brains of humans, great apes, elephants, whales, and dolphins. They're concentrated in brain regions involved in social and emotional processing—the same regions hit hard by frontotemporal dementia. In people with this disease, more than seventy percent of spindle neurons may be lost, while other neuron types remain relatively intact. No one fully understands why these particular cells are so vulnerable, but their loss likely contributes to the profound social and emotional changes that characterize the disease.

The Diagnostic Challenge

Frontotemporal dementia is notoriously difficult to diagnose, partly because its symptoms overlap with so many other conditions. Early behavioral changes might look like depression, or a midlife crisis, or even a personality disorder. When a previously responsible adult suddenly starts making impulsive decisions and showing poor judgment, psychiatric explanations often come to mind before neurological ones.

The language variants can be mistaken for other conditions affecting speech, and in early stages, brain scans may look normal. It's only as the disease progresses that the characteristic patterns of atrophy become visible on magnetic resonance imaging, or MRI, scans.

Specialized brain scans using positron emission tomography, or PET scanning, can show reduced metabolic activity in the frontal and temporal regions. This pattern differs from Alzheimer's disease, where the metabolic changes are typically seen in the parietal lobes toward the back of the brain.

Clinicians now look for six core features when diagnosing the behavioral variant: disinhibition, apathy or inertia, loss of sympathy or empathy, perseverative or compulsive behaviors, hyperorality (an increased focus on eating, often with changed food preferences), and problems with executive function. A patient needs to show at least three of these features for a possible diagnosis, with more certainty coming from brain imaging and, ultimately, examination of brain tissue.

The Mystery of Cravings and Compulsions

One of the stranger aspects of frontotemporal dementia is how it affects eating behavior. People with this disease often develop powerful cravings, particularly for sweets and carbohydrates. They may begin binge eating, consuming far more than they would have before the disease began.

But it goes beyond mere overeating. Some people start putting inedible objects in their mouths. Others might snatch food from strangers' plates in restaurants, seemingly oblivious to social convention. Brain imaging studies have linked these changes to damage in specific regions—the right ventral insula, parts of the striatum, and the orbitofrontal cortex—all areas involved in processing reward, regulating impulses, and making judgments about appropriate behavior.

Other compulsive behaviors can emerge too. Some people develop ritualistic behaviors, repeating the same actions over and over. Others might become fixated on collecting certain objects or following rigid daily routines. These compulsions appear related to the loss of frontal lobe function that normally keeps such impulses in check.

A Reversible Mimic

There's a twist in this story that offers a glimmer of hope, at least for some patients. Occasionally, what looks exactly like frontotemporal dementia turns out to be something else entirely: a leak of cerebrospinal fluid.

The cerebrospinal fluid is the clear liquid that surrounds and cushions the brain and spinal cord. Sometimes, this fluid can leak through small tears in the membranes surrounding the brain. When this happens, it can create a condition called spontaneous intracranial hypotension—essentially, the pressure inside the skull drops too low.

Remarkably, this pressure change can cause neuropsychiatric symptoms that perfectly mimic behavioral variant frontotemporal dementia. A person might show the same disinhibition, apathy, and personality changes that characterize the degenerative disease. But unlike true frontotemporal dementia, this version can be treated. Repairing the leak often leads to partial or complete resolution of symptoms.

This possibility makes thorough diagnostic workups essential. Among all the patients who present with symptoms suggesting frontotemporal dementia, a small fraction may have this treatable condition masquerading as an untreatable one.

The Road Ahead

As of now, there is no approved treatment that can slow or stop the progression of frontotemporal dementia. The research community has identified the genes involved, mapped the proteins that accumulate, traced the patterns of brain degeneration—but translating this knowledge into effective therapies has proven enormously difficult.

Some physicians prescribe medications off-label—drugs approved for other conditions that might help manage specific symptoms. Antidepressants can sometimes help with compulsive behaviors or with the emotional changes of the early stages. Behavioral interventions, working with caregivers to manage difficult symptoms and maintain safety, form the backbone of current care.

The disease remains, in many ways, a thief—stealing personality, stealing language, stealing the essence of what makes each person uniquely themselves. Its typical onset in middle age means it often strikes when people are at the height of their careers, in the midst of raising families, nowhere near ready to confront the loss of self that lies ahead.

Understanding this disease—its mechanisms, its genetics, its clinical signs—represents the first step toward eventual treatments. For now, recognition remains crucial: the earlier physicians and families understand what they're dealing with, the better they can prepare for what comes next, arrange appropriate care, and, for those with genetic forms, consider what this might mean for other family members.

Frontotemporal dementia reminds us that who we are—our personalities, our social selves, our capacity to communicate—depends on the integrity of specific brain regions. When those regions fail, the self they supported fails with them. It's a humbling and haunting reality, one that drives researchers forward in the search for answers that remain, for now, just out of reach.