(NIA) Frontotemporal disorders are the result of damage to neurons (nerve cells) in parts of the brain called the frontal and temporal lobes. As neurons die in the frontal and temporal regions, these lobes atrophy, or shrink. Gradually, this damage causes difficulties in thinking and behaviors normally controlled by these parts of the brain. Many possible symptoms can result, including unusual behaviors, emotional problems, trouble communicating, difficulty with work, or difficulty with walking.
Frontotemporal disorders are forms of dementia caused by a family of brain diseases known as frontotemporal lobar degeneration (FTLD). Dementia is a severe loss of thinking abilities that interferes with a person’s ability to perform daily activities such as working, driving, and preparing meals. Other brain diseases that can cause dementia include Alzheimer’s disease and multiple strokes. Scientists estimate that FTLD may cause up to 10 percent of all cases of dementia and may be about as common as Alzheimer’s among people younger than age 65. Roughly 60 percent of people with FTLD are 45 to 64 years old.
People can live with frontotemporal disorders for up to 10 years, sometimes longer, but it is difficult to predict the time course for an individual patient. The disorders are progressive, meaning symptoms get worse over time. In the early stages, people may have just one type of symptom. As the disease progresses, other types of symptoms appear as more parts of the brain are affected.
No cure or treatments that slow or stop the progression of frontotemporal disorders are available today. However, research is improving awareness and understanding of these challenging conditions. This progress is opening doors to better diagnosis, improved care, and, eventually, new treatments.
Changes in the Brain
Frontotemporal disorders affect the frontal and temporal lobes of the brain. They can begin in the frontal lobe, the temporal lobe, or both. Initially, frontotemporal disorders leave other brain regions untouched, including those that control short-term memory.
The frontal lobes, situated above the eyes and behind the forehead both on the right and left sides of the brain, direct executive functioning. This includes planning and sequencing (thinking through which steps come first, second, third, and so on), prioritizing (doing more important activities first and less important activities last), multitasking (shifting from one activity to another as needed), and monitoring and correcting errors.
When functioning well, the frontal lobes also help manage emotional responses. They enable people to avoid inappropriate social behaviors, such as shouting loudly in a library or at a funeral. They help people make decisions that make sense for a given situation. When the frontal lobes are damaged, people may focus on insignificant details and ignore important aspects of a situation or engage in purposeless activities. The frontal lobes are also involved in language, particularly linking words to form sentences, and in motor functions, such as moving the arms, legs, and mouth.
The temporal lobes, located below and to the side of each frontal lobe on the right and left sides of the brain, contain essential areas for memory but also play a major role in language and emotions. They help people understand words, speak, read, write, and connect words with their meanings. They allow people to recognize objects and to relate appropriate emotions to objects and events. When the temporal lobes are dysfunctional, people may have difficulty recognizing emotions and responding appropriately to them.
Which lobe—and part of the lobe—is affected first determines which symptoms appear first. For example, if the disease starts in the part of the frontal lobe responsible for decision-making, then the first symptom might be trouble managing finances. If it begins in the part of the temporal lobe that connects emotions to objects, then the first symptom might be an inability to recognize potentially dangerous objects—a person might reach for a snake or plunge a hand into boiling water, for example.
Types of Frontotemporal Disorders
Frontotemporal disorders can be grouped into three types, defined by the earliest symptoms physicians identify when they examine patients.
- Progressive behavior/personality decline—characterized by changes in personality, behavior, emotions, and judgment (called behavioral variant frontotemporal dementia).
- Progressive language decline—marked by early changes in language ability, including speaking, understanding, reading, and writing (called primary progressive aphasia).
- Progressive motor decline—characterized by various difficulties with physical movement, including the use of one or more limbs, shaking, difficulty walking, frequent falls, and poor coordination (called corticobasal syndrome, supranuclear palsy, or amyotrophic lateral sclerosis).
In the early stages it can be hard to know which of these disorders a person has because symptoms and the order in which they appear can vary widely from one person to the next. Also, the same symptoms can appear in different disorders. For example, language problems are most typical of primary progressive aphasia but can also appear later in the course of behavioral variant frontotemporal dementia. The table below summarizes the three types of frontotemporal disorders and lists the various terms that could be used when clinicians diagnose these disorders.
Behavioral Variant Frontotemporal Dementia
The most common frontotemporal disorder, behavioral variant frontotemporal dementia (bvFTD), involves changes in personality, behavior, and judgment. People with this dementia can act strangely around other people, resulting in embarrassing social situations. Often, they don’t know or care that their behavior is unusual and don’t show any consideration for the feelings of others. Over time, language and/or movement problems may occur, and the person needs more care and supervision.
In the past, bvFTD was called Pick’s disease, named after Arnold Pick, the German scientist who first described it in 1892. The term Pick’s disease is now used to describe abnormal collections in the brain of the protein tau, called “Pick bodies.” Some patients with bvFTD have Pick bodies in the brain, and some do not.
Primary Progressive Aphasia
Primary progressive aphasia (PPA) involves changes in the ability to communicate—to use language to speak, read, write, and understand what others are saying. 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 seen at first. 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 abnormalities in the brain that cause them.
In semantic PPA, also called semantic dementia, a person slowly loses the ability to understand single words and sometimes to recognize the faces of familiar people and common objects.
In agrammatic PPA, also called progressive nonfluent aphasia, a person has more and more trouble producing speech. Eventually, the person may no longer be able to speak at all. He or she may eventually develop movement symptoms similar to those seen in corticobasal syndrome.
In logopenic PPA, a person has trouble finding the right words during conversation but can understand words and sentences. The person does not have problems with grammar.
Two rare neurological disorders associated with FTLD, corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), occur when the parts of the brain that control movement are affected. The disorders may affect thinking and language abilities, too.
CBS can be caused by corticobasal degeneration—gradual atrophy 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 the inability to use the hands or arms to perform a movement despite normal strength (called apraxia). Symptoms may appear first on one side of the body, but eventually both sides are affected. Occasionally, a person with CBS first has language problems or trouble orienting objects in space and later develops movement symptoms.
PSP 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 PSP is trouble with eye movements, particularly looking down. These symptoms may give the face a fixed stare. Behavior problems can also develop.
Other movement-related frontotemporal disorders 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 mutation. 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 is a combination of bvFTD and ALS, commonly called Lou Gehrig’s disease. Symptoms include the behavioral and/or language changes seen in bvFTD as well as the progressive muscle weakness seen in ALS. Symptoms of either disease may appear first, with other symptoms developing over time. Mutations in certain genes have been found in some patients with FTD-ALS.
Frontotemporal lobar degeneration (FTLD) is not a single brain disease but rather a family of brain diseases that share some common molecular features. Scientists are beginning to understand the biological and genetic basis for the changes observed in brain cells that lead to FTLD.
Scientists describe FTLD in terms of 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 frontotemporal disorder is unknown. In about 15 to 40 percent of people, a genetic (hereditary) cause can be identified. Individuals with a family history of frontotemporal disorders are more likely to have a genetic form of the disease than those without such a history.
Familial and inherited forms of frontotemporal disorders are often related to mutations (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 frontotemporal disorders:
- Tau gene (also called the MAPT gene)—A mutation in this gene causes abnormalities in a protein called tau, which forms tangles inside neurons and ultimately leads to the destruction of brain cells. Inheriting a mutation 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.
- PGRN gene—A mutation in this gene can lead to lower production of the protein progranulin, which in turn causes TDP-43, a cellular protein, to go awry in brain cells. Many frontotemporal disorders can result, though bvFTD is the most common. The PGRN gene can cause different symptoms in different family members and cause the disease to begin at different ages.
- VCP, CHMP2B, TARDBP, and FUS genes—Mutations in these genes lead to very rare familial types of frontotemporal disorders.
- C9ORF72 gene—An unusual mutation in this gene appears to be the most common genetic abnormality in familial frontotemporal disorders and familial ALS. This mutation can cause a frontotemporal disorder, ALS, or both conditions in a person.
Families affected by inherited and familial forms of frontotemporal disorders can help scientists further research by participating in clinical studies and trials. For more information, talk with a healthcare professional, contact any of the research centers listed at the end of this booklet, or search www.clinicaltrials.gov.
For More Information
- Frontotemporal Disorders: Information for Patients, Families, and Caregivers
- Frontotemporal Disorders: A Resource List (National Institute on Aging)
- Frontotemporal Dementia information (University of California, San Francisco, Memory and Aging Center)
- What Is Frontotemporal Degeneration (bvFTD)? (PDF, 78K) (Northwestern University)
- What Is PPA? (PDF, 394K) (Northwestern University)
- Primary Progressive Aphasia (University of California, San Francisco, Memory and Aging Center)
National Institute on Aging