Frontotemporal Disorders

Clinically, frontotemporal disorders (FTDs) are classified into two main types of syndromes:

1. Behavioral variant frontotemporal dementia (bvFTD) involves changes in behavior, judgment and personality. People with this disorder may have problems with cognition, but their memory may stay relatively intact. They may do impulsive things that are out of character or may engage in repetitive, unusual behaviors. People with bvFTD may say or do inappropriate things or become uncaring. Over time, language and/or movement problems may occur.
2. Primary progressive aphasia (PPA) involves changes in the ability to speak, understand and express thoughts and/or words, and to write and read. Many people with PPA, though not all, develop symptoms of dementia. Problems with memory, reasoning and judgment are not apparent at first but can develop and progress over time. Sometimes a person with PPA cannot recognize the faces of familiar people and common objects (semantic PPA). Other individuals have increasing trouble producing speech and may eventually be unable to speak at all (agrammatic PPA). PPA is a language disorder that is not the same as the problems with speech and ability to read and write (aphasia) that can result from a stroke.

Other types of frontotemporal disorders include:

• Corticobasal degeneration (CBD) involves progressive nerve-cell loss and atrophy of specific areas of the brain, which can affect memory, behavior, thinking, language and movement. The disease is named after parts of the brain that are affected—the cerebral cortex (the outer part of the brain) and the basal ganglia (structures deep in the brain involved with movement). Not everyone who has CBD has problems with memory, cognition, language or behavior. The disease tends to progress gradually, with early symptoms beginning around age 60. Some of the movement symptoms of CBD are similar to those seen in Parkinson’s disease.
• Frontotemporal dementia with motor neuron disease (FTD/MND, also known as FTD-ALS) is a combination of behavioral variant frontotemporal dementia and the progressive neuromuscular weakness typically seen in amyotrophic lateral sclerosis (ALS). ALS is a neurodegenerative disease that attacks nerve cells responsible for controlling voluntary muscles (muscle action that can be controlled, such as in the arms, legs and face). Symptoms of either disease may appear first, with other symptoms developing over time.
• Pick’s disease is characterized by Pick bodies—masses composed of the tau protein that accumulates inside nerve cells, causing them to appear enlarged or balloon-like. It is usually seen with bvFTD but sometimes with PPA. Some symptoms are similar to those of Alzheimer’s disease, including loss of speech, changes in behavior and trouble with thinking. However, while inappropriate behavior characterizes the early stages of Pick’s disease, memory loss is often the first symptom of AD. Antidepressants and antipsychotics can control some of the behavioral symptoms of Pick’s disease, but no treatment is available to stop the disease from progressing.
• Progressive supranuclear palsy (PSP) is a brain disease that can cause problems with thinking, memory, behavior, problem solving and judgment. It also affects the control of eye movements, mood, speech, swallowing, vision, concentration and language. Because certain parts of the brain that control movement are damaged, this disease shares some of the problems with movement seen in people with corticobasal degeneration and Parkinson’s disease.

Scientists are beginning to understand the biological and genetic basis for the changes observed in brain cells that lead to frontotemporal disorders (FTD).

Scientists describe FTD using the patterns of change in the brain seen in an autopsy after death. These changes include loss of neurons and abnormal amounts, or forms of proteins called tau and TDP-43. These proteins occur naturally in the body and help cells function properly. When the proteins don’t work properly, for reasons not yet fully understood, neurons in specific brain regions are damaged.

In most cases, the cause of a FTD is unknown. Individuals with a family history of FTD are more likely to develop such a disorder. About 10% to 30% of bvFTD is due to specific genetic causes. FTD that runs in a family is often related to variants (permanent changes) in certain genes. Genes are basic units of heredity that tell cells how to make the proteins the body needs to function. Even small changes in a gene may produce an abnormal protein, which can lead to changes in the brain and, eventually, disease.

Scientists have discovered several different genes that, when mutated, can lead to FTD:

• Tau gene (also called the MAPT gene): A change in this gene causes abnormalities in a protein called tau, which then forms tangles inside neurons and ultimately leads to the destruction of brain cells. Inheriting a variant in this gene means a person will almost surely develop a frontotemporal disorder, usually bvFTD, but the exact age of onset and symptoms cannot be predicted.
• GRN gene: A change in this gene can lead to lower production of the protein progranulin, which in turn causes another protein, TDP-43, to go awry in brain cells. Many frontotemporal disorders can result, though bvFTD is the most common. The GRN gene can cause different symptoms in different family members and cause the disease to begin at different ages.
• C9ORF72 gene: An unusual change in this gene appears to be the most common genetic abnormality in familial frontotemporal disorders and familial ALS. This variant can cause a frontotemporal disorder, ALS, or both conditions.

In recent years researchers have discovered several other genetic changes in genes that lead to rare familial types of frontotemporal disorders. These other variants account for less than 5% of all cases of FTD.

The only known risk factor for frontotemporal disorders (FTDs) is family history of dementia. In some cases, risk is reduced with weight management and cessation of smoking. In most cases, the cause of a FTD is unknown. About 10% to 30% of FTD is due to specific genetic causes.

The National Alzheimer’s Project Act (NAPA), a coordinated national plan to address Alzheimer’s disease and improve care and services. The project calls for increased collaboration among scientists, the federal government and public organizations while improving patient care. NAPA’s National Plan to Address Alzheimer’s Disease (AD) is designed to expand research in prevention and treatment of Alzheimer’s disease and related dementias, and to move the most promising drugs from discovery into clinical trials.

The plan also calls for increased federal funding for AD research, as well as support for those affected by AD and their families, increased public awareness about AD, and improved data collection and analysis. These goals also apply to dementia with frontotemporal disorders (FTD).

The Tau Center Without Walls program, designed to increase collaboration and sharing of data and resources among researchers to better understand the protein tau and its involvement in such disorders as frontotemporal degeneration (FTD). These efforts may lead to advances in prevention, diagnosis or treatment of tau toxicity associated with FTD, and contribute to tool development that can be applied in FTD clinical trials and other tau-related disorders.

Studying groups of people over time may lead to ways to identify those at risk of developing dementia or cognitive impairment. Three NIH-funded research teams are conducting longitudinal studies of individuals in which frontotemporal disorders run in families and appear on their own (sporadic) to understand the progression of FTD both before and after symptom onset; identify genes; discover biomarkers for diagnosis, progression and prognosis; and establish a clinical research consortium to support FTD therapy development. A number of studies are targeting the buildup of amyloid, which forms plaques that are characteristic in Alzheimer’s disease. Other research hopes to better understand how proteins become harmful in frontotemporal disorders.

In the early stages, it can be hard to know which type of frontotemporal disorders (FTD) a person has because symptoms and the order in which they appear can vary from one person to another. Also, the same symptoms can appear across different disorders and vary from one stage of the disease to the next as different parts of the brain are affected.

Symptoms of FTD are often misunderstood. Family members and friends may think that a person is misbehaving, leading to anger and conflict. It is important to understand that people with these disorders cannot control their behaviors and other symptoms and lack any awareness of their illness.

Overall, symptoms of dementia are different depending on the cause. If you are experiencing or witnessing any combination of the following cognitive, psychological and behavioral changes, it may be time to see a doctor:

• Depression, anxiety and agitation
• Paranoia
• Personality changes or unusual/inappropriate behavior
• Hallucinations
• Disorientation and confusion in normal situations
• Notable memory loss
• Struggling to find the right words/communication problems
• Complex tasks have become more difficult
• Struggling with basic gross- and fine-motor function
• Coordination issues
• Disorientated while planning, organizing or navigating (e.g., driving a well-known route)

The most common FTD, bvFTD, involves changes in personality, behavior, and judgment. People with this disorder may have problems with cognition, but their memory may stay relatively intact. Symptoms can include:

• Problems planning and sequencing (thinking through which steps come first, second and so on)
• Difficulty prioritizing tasks or activities
• Repeating the same activity or saying the same word over and over
• Acting impulsively or saying or doing inappropriate things without considering how others perceive the behavior
• Becoming disinterested in family or activities they used to care about

Over time, language and/or movement problems may occur, and the person living with bvFTD will need more care and supervision.

Primary progressive aphasia (PPA) involves changes in the ability to communicate—to use language to speak, read, write and understand what others are saying. This includes difficulty using or understanding words (aphasia) and difficulty speaking properly (e.g., slurred speech). People with PPA may have one or both of these symptoms. They may become mute or unable to speak.

Many people with PPA develop symptoms of dementia. Problems with memory, reasoning and judgment are not apparent at first but can develop over time. In addition, some people with PPA may experience significant behavioral changes, similar to those seen in bvFTD, as the disease progresses.

There are three types of PPA, categorized by the kind of language problems that appear first.

• Semantic PPA: A person slowly loses the ability to understand single words and sometimes to recognize the faces of familiar people and common objects.
• Agrammatic PPA: A person has more and more trouble speaking and may omit words that link nouns and verbs (such as to, from, the). Eventually, the person may no longer be able to speak at all. The person may eventually develop movement symptoms similar to those seen in corticobasal syndrome.
• Logopenic PPA: A person has trouble finding the right words during a conversation but can understand words and sentences. The person does not have problems with grammar.

Researchers do not fully understand the biological basis of the different types of PPA. But they hope one day to link specific language problems with the changes in the brain that cause them.

Two rare neurological movement disorders associated with FTD, corticobasal syndrome and progressive supranuclear palsy, occur when the parts of the brain that control movement are affected. The disorders may affect thinking and language abilities, too.

• Corticobasal syndrome can be caused by corticobasal degeneration, a gradual atrophy (shrinkage) and loss of nerve cells in specific parts of the brain. This degeneration causes progressive loss of the ability to control movement, typically beginning around age 60. The most prominent symptom may be apraxia, the inability to use the hands or arms to perform a movement despite normal strength, such as difficulty closing buttons or operating small appliances. Other symptoms can include muscle rigidity and difficulty swallowing. Symptoms may appear first on one side of the body, but eventually both sides are affected. Occasionally, a person with corticobasal syndrome first has language problems or trouble orienting objects in space and later develops movement symptoms. Not everyone who has corticobasal syndrome has problems with memory, cognition, language or behavior.
• Progressive supranuclear palsy causes problems with balance and walking. People with the disorder typically move slowly, experience unexplained falls, lose facial expression and have body stiffness, especially in the neck and upper body—symptoms similar to those of Parkinson’s disease. A hallmark sign of this disorder is trouble with eye movements, particularly looking down. These symptoms may give the face a fixed stare. Problems with behavior, memory, problem solving and judgment can also develop.

Other movement-related types of FTD include frontotemporal dementia with parkinsonism and frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS).

• Frontotemporal dementia with parkinsonism can be an inherited disease caused by a genetic tau genetic variant. Symptoms include movement problems similar to those of Parkinson’s disease, such as slowed movement, stiffness, and balance problems, and changes in behavior or language.
• FTD-ALS, also called FTD with motor neuron disease, is a combination of bvFTD and ALS, the latter commonly known as Lou Gehrig’s disease. In addition to the behavioral and/or language changes seen in bvFTD, people with FTD-ALS experience the progressive muscle weakness seen in ALS, fine jerks, and wiggling in muscles. Symptoms of either disease may appear first, with other symptoms developing over time. Changes in certain genes have been found in some people with FTD-ALS, though most cases are not hereditary.

FTD can be hard to diagnose because the symptoms are similar to those of other conditions. For example, bvFTD is sometimes misdiagnosed as a mood disorder, such as depression. To make matters more confusing, a person can have both FTD and another type of dementia, such as Alzheimer’s disease. Also, because these disorders are rare, physicians may be unfamiliar with the signs and symptoms.

To help diagnose frontotemporal dementia, a doctor may:

• Perform an exam and ask about symptoms
• Look at personal and family medical history
• Use laboratory tests to help rule out other conditions
• Order genetic testing
• Conduct tests to assess memory, thinking, language skills and physical functioning
• Order imaging of the brain

A psychiatric evaluation can help determine if depression or another mental health condition is causing or contributing to the condition. Only genetic tests in familial cases or a brain autopsy after a person dies can confirm a diagnosis of FTD.

Researchers are studying ways to diagnose FTD earlier and more accurately and to distinguish them from other types of dementia. One area of research involves biomarkers, such as proteins or other substances in the blood or cerebrospinal fluid which can be used to measure disease progression or the effects of treatment. Researchers are also exploring ways to improve brain imaging and neuropsychological testing.

So far, there is no cure for FTD and no way to slow down or prevent these diseases. However, there are ways to manage symptoms. A team of specialists—doctors, nurses and speech, physical and occupational therapists — familiar with these disorders can help guide treatment.

Behavior changes associated with bvFTD can upset and frustrate family members and other caregivers. Understanding changes in personality and behavior and knowing how to respond can reduce frustration and help provide the best care for a person with FTD.

Managing behavioral symptoms can involve several approaches. Here are some strategies to consider:

• Try to accept rather than challenge someone with behavioral symptoms. Arguing or reasoning will not help, because they cannot control their behaviors or see that they are unusual or upsetting to others. Instead, be as sensitive as possible and understand that it’s the illness “talking.”
• Take a “timeout” when frustrated—take deep breaths, count to 10, or leave the room for a few minutes.
• To deal with apathy, limit choices and offer specific choices. Open-ended questions, such as “What do you want to do today?” are more difficult to answer than specific ones, such as “Do you want to go to the park or for a walk?”
• Maintain a regular schedule, reduce distractions and modify the environment to reduce confusion and improve the person’s sleep.
• If compulsive eating is an issue, consider supervising eating, limiting food choices, locking cabinets and the refrigerator, and distracting the person with other activities.

To ensure the safety of a person and their family, caregivers may have to take on new responsibilities or arrange care that was not needed before.

Medications are available to treat certain behavioral symptoms. Antidepressants called selective serotonin reuptake inhibitors are commonly prescribed to treat social disinhibition and impulsive behavior. People with aggression or delusions sometimes take low doses of antipsychotic medications. If a particular medication is not working, a doctor may try another. Always consult a doctor before changing, adding or stopping a drug or supplement.

Treatment of PPA has two goals—maintaining language skills and using new tools and other ways to communicate. Treatment tailored to a person’s specific language problem and stage of PPA generally works best. Since language ability declines over time, different strategies may be needed as the illness progresses. The following strategies may help:

• Use a communication notebook (an album of photos labeled with names of people and objects), gestures and drawings to communicate without talking.
• Store lists of words or phrases in a computer or phone to point to.
• Speak slowly and clearly, use simple sentences, wait for responses and ask for clarification if needed.
• Work with a speech-language pathologist familiar with PPA to determine the best tools and strategies to use. Note that many speech-language pathologists are trained to treat aphasia caused by stroke, which requires different strategies from those used with PPA.

Medications and physical and occupational therapy may provide modest relief for the movement symptoms of FTD. A doctor who specializes in these disorders can guide treatment.

For people with corticobasal syndrome, Parkinson’s disease medicines may offer some temporary improvement. Physical and occupational therapy may help the person move more easily. Speech therapy can help them manage language symptoms.

For people with progressive supranuclear palsy, sometimes Parkinson’s disease drugs provide temporary relief for slowness, stiffness, and balance problems. Exercises can keep the joints limber, and weighted walking aids—such as a walker with sandbags over the lower front rung—can help maintain balance. Speech, vision and swallowing difficulties usually do not respond to any drug treatment. Antidepressants have shown modest success. For people with abnormal eye movements, bifocals or special glasses called prisms are sometimes prescribed.

People with FTD-ALS typically decline quickly over two to three years. During this time, physical therapy can help treat muscle symptoms, and a walker or wheelchair may be useful. Speech therapy may help a person speak more clearly at first. Later on, other ways of communicating, such as a speech synthesizer, can be used. The ALS symptoms of the disorder ultimately make it impossible to stand, walk, eat and breathe on one’s own.

Physicians, nurses, social workers and physical, occupational and speech therapists who are familiar with these conditions can ensure that people with movement disorders get appropriate medical treatment and that their caregivers can help them live as well as possible.

Some dementia patients may benefit from reality orientation training, which involves actions like hanging signs around the home to identify objects and memories or repeating the person’s name, today’s date and the time of day. Additionally, removing clutter from the home and limiting peripheral noises and sensory stimulating appliances like TVs and radios can help those with dementia stay focused. It’s also important to remove or relocate anything dangerous from the home, such as firearms or knives, and to hide car keys.

Lifestyle changes, daily routines and structure also help patients with their morale, as well as overall physical health. Fitness classes or walks for cardiovascular health are always beneficial, as are light activities and pastimes like gardening, dancing or household chores. A diet rich in foods that are good for the brain and healthy sleep habits also contribute to overall wellness.

Working with specialists and occupational and physical therapists can help with maintaining physical movement, address speech and swallowing issues, and help people learn new ways to handle loss of skills with everyday tasks such as feeding oneself. It is important to educate family, friends and caregivers about a loved one’s medical issues. Also, in-person and online support groups available through many disease awareness and caregiver advocacy organizations can give families and other caregivers additional resources, as well as opportunities to share experiences and express concerns.

Researchers are continuing to explore the biological changes in the body, including genetic variants and proteins, that lead to FTD and identify and test possible new drugs and other treatments. They are also developing better ways to track disease progression, so that treatments, when they become available, can be directed to the right people. Clinical trials and studies are underway to advance these efforts. People with FTD and healthy people may be able to participate. To find out more, talk to your healthcare provider or visit the Alzheimers.gov Clinical Trials Finder.