Frontotemporal Dementia (FTD)

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The term "Frontotemporal Dementia" or FTD refers to a group of diseases that are commonly misdiagnosed as Alzheimer's Disease (AD). We use the term FTD as a general term to refer to disorders that are also referred to as:

• Pick's Disease
• Frontotemporal Lobar Degeneration
• Progressive Aphasia
• Semantic Dementia

It is important to identify these patients early in their course and to refer them to physicians in neurology and psychiatry who are experienced with their management. This referral is primarily important because the clinical course of FTD patients is different than patients with AD. Patients with FTD have markedly different behavioral manifestations early in the course of disease and appear to have a longer clinical course overall. In addition, when behavioral symptoms predominate, FTD patients who become ill in mid-life may initially be confused with patients with atypical late life depression, or when the onset is in younger persons, it may be confused with Schizophrenia or Bipolar Disorder.

There have been remarkable advances in the understanding of the underlying pathophysiology and genetic mechanisms of FTD that allow counseling of patients and families in ways that were not possible in the past. In addition, research groups interested in FTD are exploring new therapeutic approaches.

• Read a chapter on FTD (requires Adobe Reader).

Demographics
FTD affects an estimated 250,000 Americans or the prevalence of FTD among people ages 45 to 64 was estimated to be 6.7 per 100,000. The disease affects both sexes equally. About 40% of patients have a clear-cut family history. The mean duration of the illness is about eight years.

Symptoms
Patients with FTD present with two patterns:

• Gradual and progressive changes in behavior
  or
• Gradual and progressive language dysfunction

Behavioral Symptoms
The most common presentation is an early change in social and personal conduct, characterized by difficulty modulating behavior to the social demands of a situation. This is often associated with a lack of inhibition , resulting in impulsive or inappropriate behavior, such as swearing at inappropriate times, outbursts of frustration, or lack of social tact.

As the disease progresses, this may lead to frank criminal behavior (e.g. shoplifting), poor financial judgment or impulsive buying. At the extreme, the impulsivity can be self-destructive, as when patients try to get out of a moving car. In some individuals, inappropriate sexual behavior occurs.

There may also be repetitive or compulsive behaviors. This may include a preoccupation with repeating specific acts (e.g., reading the same book over and over) or repeating specific physical actions (e.g., walking to the same location repeatedly).

Dietary habits and personal hygiene may also change. Overeating is common as well as food fads in which only certain foods are eaten. There is a loss of concern for one's personal appearance and patients may be increasingly unkempt early in the course of disease.

All this occurs in the setting of the patient showing very little insight into or personal concern for their actions.

Even though there are complaints of memory disturbance, these patients do not have a true amnestic syndrome. They are able to keep track of day to day events and to be oriented.

At the UCSF Memory and Aging Center, doctors have found a small group of FTD patients who develop new creative skills in music and art. The artistic talents developed when brain cell loss occurred predominantly in the left frontal lobe, which controls functions such as language. It is believed that the right side of the brain regulates more abstract reasoning. For more information about this please see the Director’s Interest in Creativity and Dementia.

Language symptoms
Early and progressive change in language function is the alternate and less common presentation of FTD. This occurs in the setting of relative preservation of other cognitive domains, such as memory. The majority of such patients present with problems in the expression of language, marked by problems using the correct word, including naming objects or expressing oneself. Difficulties reading and writing then develop. Understanding of word meaning is, however, relatively well preserved in such individuals.

With progression of disease, less and less language is used, until the patient may be virtually mute. Less commonly, patients present with a severe problem with naming and with understanding word meaning. This becomes progressively worse, but patients continue to have otherwise normal speech output as the disease progresses.

To understand more about language, see our Speech and Language section.

Comparison with Alzheimer's Disease (AD)
Unlike AD, which increases markedly with age, it is rare to have the onset of FTD after 75.

The early appearance of behavioral symptoms, so common in FTD, is distinctly unusual in AD. Unlike patients with FTD, patients with early AD tend to be socially appropriate. Despite their memory deficits, they preserve their social graces and are usually adept at covering up their memory difficulties. As AD progresses, patients may act inappropriately in financial and other situations requiring judgment. This is primarily related to their cognitive problems, rather than impulsiveness or lack of concern for social norms.

Apathy in AD patients is likely to occur in situations that are confusing and overwhelming to the patient, whereas apathy in FTD patients is more pervasive and more often reflects a lack of concern for others, or is sometimes a generalized lack of initiative and passivity.

Unlike patients with FTD, AD patients have an early and profound difficulty learning and retaining new information. As the disease progresses, memory for new and old information is lost. In contrast, most mildly impaired FTD patients are oriented and able to keep track of recent events, but may be variable in performance on memory testing due to lack of concern or effort in the testing situation.

In FTD, language dysfunction occurs as an isolated cognitive deficit with or without associated behavioral disturbance. In contrast, when language dysfunction occurs in AD, it is almost always associated with some degree of memory abnormality.

In both FTD and AD, early in the course there is difficulty with cognitive flexibility and tasks that require set shifting. Thus, an assessment of these functions will not easily differentiate these patients.

When AD and FTD are in the advanced stages, they often appear very similar. What distinguishes them is the course they took to reach this advanced stage of brain dysfunction.

Genetics
Approximately 40% of patients with frontotemporal dementia have a positive family history of a similar dementia while 60% seem to occur sporadically with no apparent hereditary link.

The majority of cases where a genetic link is thought to be involved follow an autosomal dominant inheritance pattern. Thus, 50% of the children of an affected individual are at risk for developing FTD. The clinical presentation of the disease within families can be variable. Some people may have FTD alone while others may develop ALS (Lou Gehrig’s disease), parkinsonism, or psychiatric symptoms. Because of this variability, a careful analysis of family's medical and social history can help clarify whether an affected person has a sporadic or hereditary form of FTD. Even when a family exhibits an autosomal dominant inheritance of FTD, the exact genetic cause may not be known.

Four genes have been discovered as genetic causes of FTD. Two genes on Chromosome 17q21, microtubule-associated protein tau (MAPT) and progranulin (PGRN) account for about 20% of familial cases, two other genes representing a much smaller number of cases, valosin-containing protein (VCP) and charged multivesicular body protein 2B (CHMP2B), have also been discovered as a genetic cause of FTD.

Evaluation
Imaging and neuropsychological tests can both be used to evaluate FTD. One of the most useful tests in the evaluation of FTD is magnetic resonance imaging (MRI). The MRIs below illustrate the areas of the brain affected in patients who have Frontotemporal Dementia, Semantic Dementia, and Progressive Non-Fluent Aphasia.

FTD leads to loss of brain tissue that is visible on MRI scans of patients while patients are still alive. Different areas of the brain are affected (early on) by different types of FTD:

1. FTD (frontal lobes): responsible for personality, judgment and planning/organization
2. SD (anterior temporal lobes): store general information about the world; very important for language and face recognition
3. PNFA (left perisylvian cortex): produces spoken language

The diagram below shows most commonly affected brain regions (circled in red) in a representative patient with each type of disease.

(click on picture to see larger)

Structural imaging studies, either with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), may show atrophy of anterior temporal and frontal lobes. Perfusion studies, by Single Photon Emission Computed Tomography (SPECT) or perfusion MRI, typically demonstrate decreased perfusion of frontal and temporal lobes. More widespread atrophy or perfusion deficits, for example involving parietal lobes, are is more compatible with AD.

The electroencephalogram (EEG) is usually normal. Thus, a normal EEG does not mean that the behavioral manifestations are primarily the result of a psychiatric illness.

Neuropsychological testing is useful to obtain a clinical assessment of the disease. These tests evaluate conduct, language, visuospatial abilities, memory, abstraction, planning and mental control, motor skills and intelligence. Tests of the FTD patient may show visual and memory abilities in tact, however, many times the abstract types of tasks that are a component of the frontal lobes, also known as “executive functions”, are found to be disrupted on neuropsychological tests. Thought processes show impaired powers of abstraction, verbal response and design fluency. For example, in card and block sorting or picture arrangement, the FTD patient may abandon tasks, produce items eccentrically, not follow instructions, violate “rules,” etc.

At the UCSF Memory and Aging Center, patients undergo an extensive neurological, neuropsychological and nursing assessment, usually taking about three hours. Information from the caregiver is sought in every case.

Because memory loss and other related symptoms are often complex, a comprehensive evaluation is necessary. The evaluation may require two to three visits to determine the cause of the symptoms and recommend treatment.

After the evaluation, the medical team involved with each patient meets to discuss the diagnosis and potential treatments. After this meeting, the team discusses its findings with the patient and the family. In some cases, a diagnosis will be deferred until more information from blood tests or brain imaging is collected.

Caregivers
Being a caregiver of a person with dementia, regardless of whether it's Alzheimer's disease, FTD or another type, can be physically and emotionally exhausting.

However, Frontotemporal dementia can often be even harder on families because:

• The personality changes and behaviors are very distressing
• The diagnosis is often delayed
• There is not as much public awareness about the disease
• Patients affected with FTD are usually younger
• Language problems develop earlier

If you live in the San Francisco Bay Area, we hold a free monthly FTD Support Group for family members or caregivers.

For a more extensive discussion on the topic of caregiving for FTD patients please visit our Caregivers section.

Treatment
Therapy is designed to relieve the symptoms or behaviors caused by frontotemporal dementia, but there is no treatment to stop or reverse the underlying brain deterioration. If FTD is diagnosed early in the course of the disease, doctors can prescribe the appropriate medications and help families prepare and cope with symptoms. The condition may last from three to 17 years before death, with an average duration of eight years after diagnosis.

Antidepressants called selective serotonin reuptake inhibitors (SSRIs) may offer some relief from apathy and depression and help reduce food cravings, loss of impulse control and compulsive activity.

Doctors may prescribe anti-psychotics, medications that can alleviate extremely unrealistic or disorganized thinking such as hallucinations, delusions and aggression. Older anti-psychotic medications that block dopamine may be dangerous for FTD patients because some of them have Parkinson's disease effects, which cause a loss of dopamine, a chemical messenger that transmits signals within the brain.

Cholinesterase inhibitors -- the class of drugs currently used to treat memory symptoms in Alzheimer's do not help FTD patients. These drugs temporarily increase supplies of the messenger chemical acetylcholine to failing nerves, but FTD does not affect nerves in the acetylcholine communication system.

Some patients with FTD develop Lou Gehrig's disease, also known as amyotrophic lateral sclerosis (ALS). Doctors don't yet fully understand the connection between the two diseases but are studying the trend.

See our Medications section for more information about possible medications for Frontotemporal Dementia.

Non-pharmacological interventions may also be beneficial. For more information, see the Non-Medical Intervention section.

Resources
Please see our Resources for FTD where we list some other helpful websites on the topic.

• Click here to download and view the slides from a talk given recently by Dr. Joel Kramer.

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