Frontotemporal Dementia

Frontotemporal dementia (FTD) is a progressive, degenerative brain disease that gradually destroys the ability to behave appropriately, empathize with others, learn, reason, make judgments, communicate and carry out daily activities. In people under age 60, FTD is the most common cause of dementia and affects as many people as Alzheimer’s disease in the 45-64 age group. Men are affected more commonly than women. There are several forms of the disease that lead to slightly different behavioral, language and/or motor symptoms. Due to the symptoms, FTD can be mistaken for Alzheimer’s disease, Parkinson’s disease or a primarily psychiatric disorder like depression, manic-depression, obsessive-compulsive disease or schizophrenia. There is no treatment or cure yet that can reverse the damage, but medications and lifestyle changes can help relieve the symptoms. FTD is not contagious.

Forms of Frontotemporal Dementia

Based on the distinct patterns of signs and symptoms, three different clinical syndromes have been grouped together under the category of “frontotemporal dementia” (FTD):

  1. Behavioral-variant frontotemporal dementia (bvFTD)
  2. Semantic dementia (SD) and
  3. Progressive non-fluent aphasia (PNFA).

Previously, researchers sometimes used “FTD” to refer only to bvFTD, which has also been called “frontal variant FTD” (fvFTD) or Pick’s Disease. The language variants (SD and PNFA) are sometimes grouped together under the term “primary progressive aphasia” (PPA). PPA has since been split into three subgroups: progressive non-fluent aphasia, semantic dementia and logopenic progressive aphasia (LPA). At autopsy, patients with LPA are often found to have Alzheimer’s disease, not FTLD. SD was previously referred to at times as “temporal variant FTD” (tvFTD).

A small number of people affected by FTD also develop motor neuron disease (FTD/MND), (sometimes called FTD with amyotrophic lateral sclerosis or FTD/ALS).

Corticobasal degeneration (CBD), also called corticobasal syndrome or corticobasal ganglionic degeneration, and progressive supranuclear palsy (PSP) are two related diseases that are not classified as FTD but often share some symptoms with FTD.

Image Brain MRI scans from a patient with behavioral variant frontotemporal dementia.
a | MRI scan of the case patient taken on initial presentation
b | MRI scan taken 2 years after initial presentation showing more-severe frontal atrophy. © 2010 Nature Publishing Group.

Behavioral Variant Frontotemporal Dementia (bvFTD)

Behavioral variant frontotemporal dementia (bvFTD) has also been referred to as “frontal variant FTD” (fvFTD) or “Pick’s disease.” Approximately 60% of people with any form of FTD have bvFTD. By definition, this form of FTD affects social skills, emotions, personal conduct, and self-awareness. Deficits in these functions most often reflect damage to specific regions within the frontal and temporal lobes. With damage to these areas, people may show mood and behavior changes including stubbornness, emotional coldness or distance, apathy and selfishness. Unlike Alzheimer’s disease, which affects a different area of the brain, many people with bvFTD don’t show any confusion or forgetfulness about where they are or what day it is, at least at first.

Semantic Dementia (SD)

Semantic dementia, which has also been called “temporal variant FTD,” accounts for 20% of FTD cases. Language difficulty, the predominant complaint of people with SD, is due to the disease damaging the left temporal lobe, an area critical for assigning meaning to words. The language deficit is not in producing speech but is a loss of the meaning, or semantics, of words. At first, you might notice someone substituting a word like “thingy” for more unusual words, but eventually a person with SD will lose the meaning of more common words as well. For example, early in the illness a patient might lose the word for a falcon, later-on forget the word for a chicken, then call all winged creatures “bird” and eventually call all animals “things.” Not only do they lose the ability to recall the word, but the concept of these words is also lost. “What is a bird?” might be a typical response for a patient with advanced SD. Reading and spelling usually decline as well, but the person may still be able to do arithmetic and use numbers, shapes or colors well. Names of people, even good friends, can become quite difficult for people with SD. Like the behavioral variant, memory, an understanding of where they are, and sense of day and time tend to function as before. Muscle control for daily life and activities tends to remain good until late in the disease. Some of these skills may seem worse than they actually are because of the language difficulty people with SD have when they try to express themselves.

When SD starts in the right temporal lobe, people in the early stages have more trouble remembering the faces of friends and familiar people. Additionally, these people show profound deficits in understanding the emotions of others. The loss of empathy is an early, and often initial, symptom of patients with this right-sided form of SD. Eventually people with right-sided onset progress to the left side and then develop the classical language features of SD. Similarly, left-sided cases progress to involve the right temporal lobe and then the person experiences difficulty recognizing faces, foods, animals and emotion. SD patients eventually develop classical bvFTD behaviors including disinhibition, apathy, loss of empathy and diminished insight. The time from diagnosis to the end is longer than for those with bvFTD, typically taking about six years.

Progressive Nonfluent Aphasia (PNFA)

PNFA accounts for only about 20% of all people with FTD. Unlike semantic dementia where the person maintains the ability to speak but loses the meaning of the word, people with PNFA have difficulty producing language fluently even though they still know the meaning of the words they are trying to say. The person may talk slowly, having trouble saying the words, and have great trouble with the telephone, talking within groups of people or understanding complex sentences. In recent years it has become apparent that many patients with PNFA go on to develop severe Parkinsonian symptoms that overlap with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) such as an inability to move the eyes side-to-side, muscle rigidity in the arms and legs, falls, and weakness in the muscles around the throat.

FTD with Motor Neuron Disease

Approximately 15% of patients with FTD also develop motor neuron disease (FTD-MND). Most often, this combination occurs in patients with bvFTD, and only rarely does MND arise in patients with SD or PNFA. MND affects motor nerve cells in the spinal cord, the brain stem (which sits on top of the spinal cord), and the cerebral cortex. Because the brainstem was once referred to as the “bulb”, you may hear some MND symptoms described as “bulbar symptoms”. The most common type of MND is amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease, which can occur as a purely motor disorder.  More often, however, patients with ALS also have behavioral or cognitive problems similar to those seen in FTD. MND symptoms include slurring of speech, difficulty swallowing, choking, limb weakness or muscle wasting. In patients with FTD-MND, there is often (but not always) a family history of the disease, and scientists are getting closer to identifying gene mutations that cause the illness.

Behavioral Symptoms

Apathy is often the first symptom reported by caregivers and may be mistaken for depression. People experiencing these changes may become self-centered, emotionally distant, withdrawn, unaware of the emotions of others, avoid social contact or neglect previous hobbies and interests. They may develop a lack of concern for their personal appearance and become increasingly unkempt early in the course of disease.

Impulsive behavior is another common complaint from caregivers who may find the changes in social and personal conduct embarrassing or frustrating. These behaviors are often associated with a lack of inhibition, resulting in impulsive or inappropriate behavior, such as overeating, outbursts of frustration, touching strangers, urinating in public or diminished social tact. Overeating is common and “food fads” can occur where the person with bvFTD will only eat certain foods. Caregivers often notice an overactive “sweet tooth.” Restlessness, irritability, aggressiveness, violent outbursts or excessive sentimentality are not unusual either.

There is usually difficulty in reasoning, judgment, organization and planning, and consequently, these patients can be quite gullible and fall prey to scams on the computer or in person. As the disease progresses, this lack of judgment may lead to criminal behavior (such as shoplifting, indecent exposure, running stop lights, 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 people, inappropriate sexual behavior occurs.

There may also be repetitive or compulsive behaviors that may include hoarding, doing the same thing over and over (for instance, reading the same book several times or walking to the same location again and again), pacing, or repeating particular “catch phrases” over and over in their speech.

The person with bvFTD may experience false thoughts (delusions) that are jealous, religious or bizarre in nature. Or they can develop a euphoria – excessive or inappropriate elation or exaggerated self-esteem.

Even though they might complain of memory disturbance, patients with the behavioral variant of frontotemporal dementia can usually keep track of day-to-day events and understand what is going on around them. Also, for people with bvFTD, their language skills and memory usually remain intact until late in the disease.

These behaviors have a physical cause and are not something that the person can usually control or contain. Indeed, often the person has little or no awareness of the problem behaviors

Language Symptoms

The majority of patients with the language variants have problems expressing themselves with language while their memory stays relatively intact. Difficulties reading and writing then develop. To understand more about language, see our Speech and Language section.

At the UCSF Memory and Aging Center, we have found a small group of FTD patients who develop new creative skills in music and art as their language skills decline. For more information about this topic, please see this article on Personality and Creativity.

Semantic Dementia (SD)

The most common complaint of people with semantic dementia (SD) is increasing trouble naming people, objects, facts and words. As the disease progresses, they lose not only the ability to name something, but also the meaning of what it is they are trying to name – like how to use it or to what context it belongs. People with SD usually know they are having trouble finding their words and understanding what is being said to them. Their speech tends to keep the usual speed and rhythm, but they may substitute similar but incorrect words or replace a word with “thing” or “stuff.” Patients continue to speak the same amount, even as the disease progresses. Some people may develop an inability to recognize familiar faces. Later in the disease course, similar behavioral changes to those seen in bvFTD may appear.

Progressive Non-fluent Aphasia (PNFA)

People with PNFA tend to come to the doctor’s office with complaints about changes in their fluency or rhythm of speech, pronunciation or word finding difficulty. These patients tend not to show the behavioral characteristics of FTD until quite late in the disease, and they are keenly aware of their difficulties. Depression and social withdrawal are common features of PNFA. As the disease progresses, less and less language is used, until the patient may be virtually mute.

Motor Symptoms

People with FTD often describe a general weakening of their muscles or slowing of their movements. They might feel uncoordinated or like they are walking through water – harder to move and slower going. They may also experience muscle spasms. In a neurological exam, the doctor may also finds some slowing of particular eye movements, changes in the typical reflexes and muscle stiffness or slowness.

Diagnosis

The first step in the treatment of FTD is an accurate diagnosis. Although not uncommon, FTD is the second most common dementia in those under 65, these patients often go undiagnosed and instead get treated as psychiatric patients. bvFTD, the behavioral variant of FTD, presents with changes in personality, behavioral problems, executive impairment or any combination of these signs and symptoms. The behavioral and social inappropriateness of FTD are a source of grief and frustration for caregivers and in some instances patients and can endanger the patient and those with whom the patient interacts. Improving these symptoms can improve quality of life for both patients and their caregivers. Treatment begins with discussing the diagnosis and educating the family about the disease. The caregivers need to be informed about safety concerns for both the patient’s safety (e.g., leaving pots on the stove, wandering outside while inappropriately clothed or becoming lost) but also the risk to the caregiver needs to be assessed because the patient’s lack of insight and disinhibition may lead to potentially dangerous behaviors whereby aggressive outbursts by the patient could lead to harm. There may be a need to remove dangerous items from the home and eliminate driving if the patient is unsafe.

SD, often presents with marked language impairment, usually in the form of a loss of memory for words or a loss of word meaning. SD patients are usually aware of their expressive difficulties which is a source of frustration but they often lack insight into their comprehension deficits. There are also behavioral signs and symptoms. Many of the treatments for bvFTD can also be used for SD. PNFA, on the other hand, involves changes in fluency or word finding difficulty without associated cognitive and behavioral abnormalities so that depression and social withdrawal are more common problems in this subtype of FTD.

Alzheimer’s disease (AD) is the most common dementia in older people. Therefore, it should be one of the first diseases your doctor considers. Alzheimer’s disease usually begins with memory loss while FTD is usually a behavior or language disorder.

People with either disease will show cognitive difficulties and multitask poorly. And at the end stages, AD and FTD look very similar. Doctors use the early symptoms and the brain image, usually done on a MRI (magnetic resonance imaging) scanner, to reach the most appropriate diagnosis.

  • The probability of AD is strongly affected by the age of the person showing the symptoms. The odds of having Alzheimer’s disease increase markedly the older you get while the odds for FTD may decrease with age.
  • FTD often begins with distinct behavioral changes (socially inappropriate, apathetic, impulsive, etc.) while people with Alzheimer’s in the early stages tend to remain socially graceful despite their memory problems (they may even become skilled at covering up their difficulties). In advanced AD, people generally have trouble managing their finances, show poor judgment and irritability, and may become equally difficult to manage as FTD.
  • Apathy in AD patients is milder, whereas apathy in FTD patients is more pervasive and more often reflects a lack of concern for others or lack of initiative.

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. These memory problems may lead to language problems as well, but the root is a problem remembering. In contrast, most mildly impaired FTD patients generally know the day or time and their location, and they are able to keep track of recent events. They may not test well, but that may be due to lack of concern or effort in the testing situation.

Confirming an FTD diagnosis

Once other likely diseases have been ruled out, an FTD diagnosis is made by looking at the data from a neurological exam and personal history (which may come from the patient, family or other caregiver); neuropsychological tests that help quantify memory, language and other cognitive skills; and a brain image – usually a MRI (magnetic resonance imaging) scan but perhaps a functional scan like PET (positron emission tomography) which can show increased or lowered brain activity in the frontal and anterior temporal areas.

An accurate diagnosis made after ruling out other possible explanations is essential for successful treatment or management of any disease. As new medical treatments become available, early intervention will be more and more important. Regardless of medical treatments, the sooner patients and caregivers have an accurate diagnosis, they sooner they can plan for upcoming care. As FTD tends to affect younger people than Alzheimer’s or other dementias and lasts for eight years on average, creating a care plan is particularly important for everyone touched by this disease.

Medications for Behavioral Symptoms

Medications for behavioral symptoms should be started at a low dose and then increased slowly based on the patient’s response and the presence of side effects. It is only fair to note that very few clinical studies exist examining the benefits of the following medications, and the following information is base primarily on clinical experience.

Antidepressants

While originally created to treat depression, certain antidepressants are effective in treating anxiety disorders, preventing panic attacks and obsessive compulsive behavior. One group of antidepressants called selective serotonin reuptake inhibitors (SSRIs) may be useful in reducing the aggressive impulses, poor impulse control and carbohydrate craving associated with early Pick’s/FTD. People with FTD usually do not experience many side effects with SSRIs, and they are generally considered the best available medications for controlling problematic behaviors.

Examples of SSRIs include:

  • fluoxetine (Prozac®)
  • sertraline (Zoloft®)
  • paroxetine (Paxil®)
  • fluvoxamine (Luvox®)
  • citalopram (Celexa®)
  • escitalopram (Lexapro®)

Other antidepressants (not SSRIs) that may be useful:

  • trazodone (Desyrel®)
  • venlafaxine (Effexor®)
  • duloxetine (Cymbalta®)
  • bupropion (Wellbutrin®)
  • mirtazepine (Remeron®)

Antipsychotics

Antipsychotic medications block the effects of dopamine, a chemical messenger that can increase hallucinations, delusions (false beliefs) and can alter rational thought. Low doses of these medications can help manage aggressive, irrational and compulsive behaviors that may develop with frontotemporal dementia. The potential benefit of antipsychotics must be weighed against potential risks including weight gain, slowing of movement and thinking, accelerating heart disease and, in rare instances, death. Typical antipsychotics are associated with muscle problems and should be avoided, since patients with FTD are likely to show muscle stiffness and trembling.

Examples of atypical antipsychotic medications include:

  • olanzepine (Zyprexa®)
  • quetiapine (Seroquel® or Ketipinor®)
  • risperidone (Risperdal®)
  • ziprasidone (Geodon®)
  • aripiprazole (Abilify®)
  • paliperidone (INVEGA®)

Other classes of drugs that might be useful, but have not been studied in Pick’s/FTD are anti-anxiety drugs and anti-seizure medications used as “mood stabilizers.”

  • valproic acid and divalproex sodium (Depacon™, Depakene®, Depakote®, Depakote® ER)
  • carbamazepine (Tegretol®)
  • gabapentin (Neurontin®)

Medications for Memory

Memantine (Namenda®), a NMDA-receptor antagonist, is approved for treating Alzheimer’s. Preliminary evidence suggests it may provide some benefit for people with Pick’s/FTD as well. The Memory and Aging Center will soon complete a research trial on memantine.

Lifestyle and Environmental Changes

Once you have a diagnosis, as a patient or caregiver you should ask your doctor for resources where you can learn more about the disease and find others who are going through a similar experience. Frontotemporal dementia, particularly the behavioral type, can create safety issues in the home and around driving. Patients might leave pots on the stove, wander outside while inappropriately dressed, get lost, have aggressive outbursts or exhibit other potentially risky behaviors. You may need to remove dangerous items from the home and take away driving privileges.

Often times, adjusting expectations and making changes to the environment can help improve the patient’s behaviors. Learning to roll with disruptive but non-dangerous behavior takes patience, but sometimes saving your energy for more serious matters is the best strategy. Support groups are another great way to learn non-medical ways to manage the disease – other caregivers often have great ideas.

An exercise program that combines both strength training and aerobics is important for maintaining cognitive health. Cardiovascular exercise 2-4 days/week for approximately 30 minutes each time is beneficial. A regular walk is one form of cardiovascular exercise and does not require membership to a gym. A common saying at the Memory Aging Center is, “What is good for the heart is good for the brain.” Individuals should consult with their physician before beginning any exercise program. Regular exercise can help you and your loved one maintain your ability to function for a longer time. Don’t only think about the patient getting exercise, consider a formal regimen for yourself. Getting enough sleep also helps maintain optimal cognitive performance.

More Information

(NINDS) The following publication was prepared by the Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, National Institutes of Health at Bethesda, Maryland. It is available as a free download.

Frontotemporal Disorders: Information for Patients, Families, and CaregiversFrontotemporal Disorders: Information for Patients, Families, and Caregivers

For more information, please visit The Association for Frontotemporal Degeneration at http://www.theaftd.org.

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