Frontotemporal Dementia

The frontotemporal dementias (FTD) are a group of degenerative brain disorders that share many clinical features. All result from progressive damage to cells in the anterior temporal and/or frontal lobes of the brain. The disorders are also known as frontotemporal lobar degeneration (FTLD). The hallmark of FTD is a gradual, progressive decline in behavior and/or language that has a relatively young age of onset. As the disease progresses, it becomes increasingly difficult for people to plan or organize activities, behave appropriately in social or work settings, interact with others, and care for oneself, resulting in increasing dependency.

Brain Image

The onset of FTD symptoms typically occurs in the 50’s to early 60’s, but has been seen as early as 21 and as late as 80 years. The average age of onset is about 60 years. FTD occurs equally in men and women. In a small percentage of cases it is inherited.

FTD represents an estimated 10%-20% of all dementia cases and is recognized as one of the most common dementias affecting a younger population. It is estimated that FTD affects approximately 250,000 Americans. While there are currently no treatments to slow or stop the progression of the disease, FTD research is yielding a greater understanding of the disorders. We anticipate that this knowledge will result in a growing number of potential therapeutics entering clinical testing within the next few years.

Difficulties with diagnosis – Is it FTD or Alzheimer’s disease?

Historically, physicians had a difficult time distinguishing FTD from Alzheimer’s disease, psychiatric problems or several other neurological disorders. Today, increased medical understanding and advanced brain imaging techniques help the physician to make an accurate diagnosis. Both FTD and Alzheimer disease (AD) are characterized by atrophy of the brain, and a gradual, progressive loss of brain function. Frontotemporal dementia however, is primarily a disease of behavior and language dysfunction, while the hallmark of AD is loss of memory. FTD often begins earlier than AD, and affects areas in the brain that are more anterior or ‘forward’ than those affected by Alzheimer’s .

See Diagnosis for more and common diagnostic tests.

Clinical Presentations

The frontal lobes of the brain are associated with decision making and control of behavior, and the temporal lobes with emotion and language. While FTD is marked by a range of behavioral, personality, and cognitive changes, several subtypes of the disorder have been identified based on distinct symptoms and clinical presentation.

Frontotemporal dementia characterized by loss of empathy and increasingly inappropriate social behavior is known clinically as behavioral variant FTD (bvFTD), Pick’s disease, or frontal variant FTD (fvFTD). Some of the disorders (semantic dementia and progressive aphasia) exhibit problems in language as a key feature. Others (FTD with motor neuron disease, corticobasal degeneration, and FTDP-17 which are related disorders) often include muscle weakness and/or parkinsonian symptoms as well as behavior and personality changes.

Behavioral presentation
Behavioral changes are typically seen as changes in personality, emotional blunting or loss of empathy that result in increasingly inappropriate social behavior. People gradually become less involved in routine daily activities and withdraw emotionally from others. Unusual behaviors may include swearing, overeating or drinking, impulsivity, shoplifting, hypersexual behavior, and deterioration in personal hygiene habits. Accompanying this is a decreasing self-awareness: the patient displays little insight into how inappropriate his or her behavior is, and little or no concern for its effect on other people, including family and friends. Patients may also display repetitive, stereotyped behaviors, such as hand clapping, humming the same song over and over, or walking to the same place day after day.

Language presentation
The language deficits experienced by FTD patients are distinguished by two presenting issues: problems with expression of language or severe naming difficulty, and problems with word meaning. People with progressive aphasia become hesitant in their speech and begin to talk less, but appear to retain the meaning of words longer. In semantic dementia, people experience a progressive deterioration of understanding words and recognizing objects, but retain the ability to produce fluent speech.

Cognitive and emotional symptoms
Damage to the brain’s frontal and temporal lobes affect complex thinking and reasoning abilities which can result in other symptoms commonly associated with FTD. Increasing impairment in “executive functions” affects a person’s ability to plan, organize and execute activities, while emotional changes impact relationships. Symptoms may include:

• Distractibility and impersistence, increasing difficulty staying on task mentally.
• Mental rigidity and inflexibility, insistence on having his or her own way, increasing difficulty adapting to new or changing circumstances.
• Planning and problem solving impairments, abstract reasoning decreases. Examples of this would include difficulty coordinating the cooking of a meal, or making a shopping list and performing necessary errands.
• Poor financial judgment, impulsive spending or financial risk taking
• Reduced initiative, lack of motivation, and an apparent loss of interest in previously enjoyed hobbies and social activities.
• Lack of insight into one’s behavior develops early; the patient does not recognize changes in his or her own behaviors and shows no concern for the effect of these behaviors on others, including loved ones.
• Mood changes that can be abrupt and frequent.

FTD Disorders

The specific subtypes of frontotemporal dementia are described in individual articles available through the navigation outline in the upper right.

Pathology of FTD

The pathology underlying the severe loss of brain cells in FTD is complex.  The pathological and clinical diagnoses of FTD often do not match.  The same clinical pattern can have different varieties of underlying pathology and vice versa. Pathologists may use different terminology depending on the current technology.

In general, when viewed under the microscope, the frontal and temporal lobes show loss of neurons and gliosis (scar tissue in the brain), and many of the remaining neurons are shrunken or abnormally shaped and contain abnormal protein aggregates.

At least two different disease proteins are implicated in FTD pathology. These include tau and TDP-43. A tauopathy (FTLD-TAU) is the term used when the protein tau is found to be responsible in the disease process, such as when it accumulates as aggregates in Pick’s disease, corticobasal degeneration and progressive supranuclear palsy. A TDP-43 proteinopathy (FTLD-TDP) is the term used when abnormal TDP-43 accumulates in nerve cells.

A subset of patients with FTLD-TAU and FTLD-TDP have a family history and genetic mutations have been identified. These inherited cases of FTLD-TAU are associated with mutations in the tau gene where as FTLD-TDP cases may be associated with abnormalities of the progranulin gene or the TDP-43 gene.

Scientists are hopeful that continuing research will provide more information on these and other potential targets for treatment.

See Understanding the Science for more.

Genetics

In the majority of cases FTD is sporadic, meaning it is a disorder that develops in that person by chance rather than being inherited. When FTD is diagnosed in a patient with no family history of FTD or dementia, it is an isolated (sporadic) case, which appears to pose no significant elevated risk to family members. In 5-10% percent of FTD patients, a family history suggests a hereditary condition with an autosomal dominant pattern of inheritance. This means there is a clear pattern of FTD-type diagnoses being passed from parent to child, with virtually every patient having an affected parent and each child of an affected person having a 50% chance to inherit the disorder.

See Genetics for more.

Treatment

There is no cure for FTD, and in most cases its progression cannot be slowed. Although no medications have been proven effective specifically for FTD, many clinicians look to the medications and treatment approaches used in other, similar disorders to develop a therapeutic approach. For instance, some FTD patients benefit from selective serotonin reuptake inhibitors (SSRIs used in treating obsessive-compulsive disorder). 

In one controlled randomized study the cholinesterase inhibitor Reminyl (galantamine), significantly slowed deterioration and in some cases improved language function for people with progressive aphasia.

Clinicians may also employ antioxidants, such as coenzyme Q10, which are known to slow the progression of damage to brain cells in general.

Continuing research advances in the field are making early clinical trials of drugs for FTD more of a reality.
See Research for more and how to participate.

Management and Prognosis

Although specific symptoms may vary from patient to patient, FTD is marked by an inevitable, progressive deterioration in functioning. The length of progression varies, from 3 to as long as 17 years with a mean course of 8 years from the time of diagnosis. FTD itself is not life-threatening. In the advanced stage patients are predisposed to serious complications such as pneumonia, infection, or injury from a fall. The most common cause of death is pneumonia.

It is important for caregivers and families to think about long-term management issues and identify a team of experts who can help with difficult medical, financial and emotional challenges. It is imperative to have a physician who is knowledgeable about FTD and approaches to treatment. Other medical specialists who may be helpful include: speech and language pathologists, occupational and physical therapists, neuropsychologists, nurses (especially home-care nursing), social workers and genetic counselors.

Lawyers and financial advisors can be helpful in obtaining financial aid, arranging power of attorney, preparing a living will and helping to secure the patient’s estate or finances so that they are available at later stages of the disease. Social workers can also help families identify resources (medical supplies, equipment, housing, nursing care), financial assistance and support groups for caregivers.

It is also important to consider care options for later stages of the disease. In-home nursing care, assisted living, or nursing home care are three such options. When plans are made ahead of time they can afford the family a smoother transition and allow the patient to be involved in the decision-making process if he/she is capable.

Managing the wide-ranging challenges associated with frontotemporal dementia can be extremely stressful for individuals and families. It is essential that people reach out to health care providers, AFTD, and community organizations for the information and support they need. Caregivers who feel informed, empowered, and supported will be better able to ensure the dignity of the patient and their own well-being.

See Support and Resources for more on caregiving.