Frontotemporal Dementias -- An Overview

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Frontotemporal Dementia (FTD) is a group of related conditions that share many clinical features and all result from progressive degeneration of the anterior temporal and frontal lobes of the brain. These areas of the brain are associated with decision-making and control of behavior (frontal lobe) and emotion and language (temporal lobe).

The hallmark of FTD is a gradual, progressive decline in behavior and/or language. Patients may suffer from a decline in one or both of these areas, but they are always characterized by a gradual onset at a relatively young age, and a continuing decline after onset. As the disease progresses, these deficits cause significant impairment in social and/or occupational functioning and result in an increasing dependency on caregivers.

The behavioral changes are typically witnessed as a change in personality, characterized by increasingly inappropriate social behavior. Examples of this include swearing, overeating or drinking, impulsivity, shoplifting, hypersexual behavior, and a deterioration in personal hygiene habits.

Accompanying this inappropriate behavior 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.

The language deficits experienced by patients range from problems with expression of language (generating meaningful, grammatical sentences), to problems with word meaning or a severe difficulty in finding the correct name for common, familiar objects.

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. FTD occurs equally in men and women.

Although there has been little research done to determine the overall incidence of FTD in the population, it is estimated that between 4% and 20% of patients at dementia and memory disorder clinics have FTD, and that 12% of patients with onset of dementia before the age of 65 suffer from FTD.


Is it FTD or Alzheimer Disease?

Historically, medical science has had a difficult time distinguishing between these two types of dementia. Today, a number of clues exist to help the physician make an accurate clinical diagnosis. Definition: Both FTD and Alzheimer Disease (AD) are dementias, characterized by atrophy of the brain, which results in a gradual but progressive loss of brain function. FTD, however, is primarily a disease of behavior and language dysfunction, while the hallmark of AD is loss of memory. Age of onset: FTD usually begins when the patient is in his or her mid-50's. This is approximately 10 years earlier than the average age of diagnosis for AD. Moreover, the risk of Alzheimer continues to increase with age, while the incidence of FTD peaks at age 62 and then decreases with age. Symptoms: FTD patients exhibit behavioral symptoms and personality changes (lack of concern for social norms or other people; lack of insight into their own behaviors), but retain cardinal features of memory, keeping track of day-to-day events and orientation to space and time. AD patients display increasing memory deficits, but typically retain socially appropriate behavior. Some FTD patients may have only language dysfunction (this is seen in the two types of progressive aphasia: semantic dementia and progressive non-fluent aphasia). The pattern of language loss may be extremely specific, such as an inability to name a familiar, everyday object. This is in contrast to the language decline seen in Alzheimer patients, which is less specific and results from the general memory loss. Physical Manifestations: FTD patients are more likely to display an increase in motor abnormalities , such as difficulty walking, rigidity, or tremor (similar to Parkinson Disease), or muscle atrophy and weakness .


Diagnosis

It is important to note that medical science today still does not have a completely clear picture of FTD. Current technology is providing us with the first evidence of the pathological changes that occur in the brain to cause FTD; specifically, the types of changes in different areas of the brain that produce the variety of symptoms. For example, loss of function in the temporal lobe produces language disorder, while loss of function in the frontal lobe appears to lead to behavioral symptoms.

Because of its symptoms, FTD is often initially misdiagnosed as a psychiatric problem, Alzheimer disease, or Parkinson disease. However, a trained and experienced health care professional can look for features that rule out other diagnoses and identify features that pinpoint FTD. Diagnosis generally involves:

* Medical history and detailed neurological examination;
* Neuropsychological examination to assess language, behavior, memory, executive, and visual-spatial functions;
* Neuroimaging to determine where and how extensively brain regions have atrophied, or may be experiencing decreased blood flow. Some of these neuroimaging studies are: MRI (magnetic resonance imaging), PET (positron emission tomography), and SPECT (single photon emission computed tomography.
(For more information, see Tests Used in Diagnosis)

One specific source of confusion for families may be the distinction between clinical diagnosis of FTD and pathological diagnosis of FTD. A clinical diagnosis is carried out by the physician meeting with the patient and family, and consists of the elements listed above: detailed examinations of changes in cognition, behavior and personality, and neuroimaging studies.

A pathological diagnosis is determined through autopsy, and requires looking at the brain tissue under a microscope. It is during this examination that physicians can determine the specific type of abnormality present in the brain, and thus the definitive cause of the progressive symptoms experienced during life.


Subtypes of FTD

The term “FTD” currently comprises the following list of specific disorders.

* Pick's Disease
* Corticobasal Degeneration
* Progressive Aphasia
* Semantic Dementia
* FTDP-17
* Related Disorders
* FTD/MND (FTD with Motor Neuron Disease). This is also known as ALS [amyotrophic lateral sclerosis or Lou Gehrig's disease] with Dementia.


“Unspecified Type” of FTD--A Special Note About Diagnosis

Given the lack of clarity in the current state of knowledge on FTD, it is not unusual for diagnosis to be an evolving process. For example, a patient who has FTD symptoms that do not neatly fit the profile of any one FTD subtype may at first receive a diagnosis of “FTD—Unspecified Type”. Or, a patient's initial subtype diagnosis may later be changed, to encompass new symptoms as they develop. Such a change in diagnosis may also occur after the patient has died, when the clinician has additional information from a pathological exam (autopsy).

While a change in specific diagnosis can be disconcerting to a family, it need not be upsetting, and does not reflect a “mistake” on the part of the doctors. On the contrary, a good clinician is sufficiently familiar with the patient to identify and respond to a change in symptoms. Moreover, a change in diagnosis may suggest new therapeutic approaches not yet tried with the patient. It also offers more accurate information for future generations in the family.


Defining FTD: A Work in Progress

As our knowledge advances, some of the FTD subtypes may be found to actually be the same disease, and entirely new subtypes may be defined. Research on FTD is a work in progress, one which is advancing our understanding each year. This understanding, in turn, is leading to more effective approaches to treatment and management of symptoms. It is also giving us a clearer picture of prognosis (the course the disease will likely take) and whether or not there is a hereditary risk in a family, making genetic counseling possible for many families.


Range of Clinical Features Associated with FTD

A diagnosis of FTD encompasses a wide spectrum of symptoms: behavioral, language, cognitive, emotional, neurological, and psychiatric (listed below). It is important to remember that no one patient will exhibit all of the symptoms, neither is there a set order in which they appear. Each patient experiences a unique course of disease, and while no physician can predict which symptoms will develop in a person, it is known that some symptoms are more closely associated with one subtype than another. (See the subtype descriptions for a list of those symptoms most commonly associated with each specific type of FTD). What follows is a description of the range of symptoms associated with FTD in general.

Behavioral Symptoms
A progressive deterioration in the patients' ability to control or adjust his/her behavior appropriately in different social contexts is the hallmark of all of these behavior changes, and results in the embarrassing, inappropriate social situations that can be one of the most disturbing facets of FTD.
* Hyperoral behaviors include overeating, dietary compulsions, in which the person restricts himself to eating only specific foods (such as a certain flavor of Lifesaver, or eating food only from one fast food restaurant), or attempts to consume inedible objects. Patients may consume excessive amounts of liquids, alcohol and cigarettes.
* Stereotyped and/or Repetitive behaviors can include re-reading the same book multiple times, hand rubbing and clapping, humming one tune repeatedly, or walking to the same location day after day.
* Personal hygiene habits deteriorate early in the disease progression, as the person fails to perform everyday tasks of bathing, grooming, and appropriate dressing.
* Hyperactive behavior is exhibited by some patients, and can include agitation, pacing, wandering, outbursts of frustration, and aggression.
* Hypersexual behavior can range from a preoccupation with sexual jokes to compulsive masturbation.
* Impulsive acts can include shoplifting, impulsive buying, and grabbing food off of another person's plate.

Language Symptoms
There are some FTD subtypes (semantic dementia and progressive non-fluent aphasia) which have specific language deficits as their cardinal feature. Listed below are the general symptoms of language deterioration that can accompany any FTD diagnosis.
* Aphasia (reduced output of speech)
* Dysarthria (increased difficulty producing speech due to weakness or incoordination – speech sounds are weak, imprecise and uncoordinated)
* Agrammatica refers to an increasing difficulty in remembering or understanding the rules of grammar that help us get meaning from a sentence.
* Decrease in Reading and Writing Comprehension occurs as the patient experiences problems with word meaning and recognition.
* Echolalia refers to a repetition of a word or phrase said by another person.
* Perseveration is the repetition of a word or phrase said by the patient himself.
* Mutism eventually develops in many FTD patients during advanced stages of the disease. Though at this stage the person has lost all ability to speak, he or she may still be able to retain some understanding of what is spoken to them.

Cognitive Symptoms
FTD patients typically suffer increasing impairment in “executive functions”, listed below.
* Distractibility and impersistence mean the person has increasing difficulty staying on task mentally.
* Mental rigidity and inflexibility develop as the person may insist on having his or her own way, or have increasing difficulty adapting to new or changing circumstances.
* Planning and problem solving impairments develop as the ability for abstract reasoning decreases. Examples of this would include difficulty planning and coordinating the cooking of a meal, or making a shopping list and performing necessary errands.
* Poor financial judgment can produce additional, troubling situations for families.

Emotional Symptoms
* Apathy or an indifference toward events and the surrounding environment can be marked by reduced initiative, and lack of motivation.
* Lack of insight into the person's own behavior develops early. The patient typically does not recognize the changes in his or her own behaviors, nor do they exhibit awareness or concern for the effect these behaviors have on the people around them, including loved ones.
* Emotional blunting develops early in the course of the disorder, and is manifested as a loss of emotional warmth, empathy, and sympathy, and development of what appears to be indifference toward other people, including loved ones.
* Mood changes can be abrupt and frequent.

Neurological Symptoms
* Movement Dysfunction symptoms may be some of the first to develop, and are similar to those seen in Parkinson disease (in these patients the term “parkinsonism” is used to distinguish the fact that they do not have Parkinson disease, though they do exhibit some of these symptoms). These include: decreased facial expression, bradykinesia (slowness of movements), rigidity (resistance to imposed movement), and postural instability. Less commonly, patients may develop symptoms seen in Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), including difficulty with eye movements, dystonia (abnormal muscle postures), or alien hand syndrome (in which the person does not recognize his hand as being part of his own body).
* Muscle Dysfunction is seen in patients diagnosed with FTD/MND. These patients experience many of the muscular problems seen in ALS: weakness, muscle atrophy, and myoclonus (muscle jerks).

Psychiatric Symptoms
Some FTD patients may experience psychiatric manifestations, including depression, mania, persecutory delusions (thinking people are “out to get you”) and visual or auditory hallucinations. It is not uncommon for an individual to first be diagnosed with mental illness (for example bipolar disorder, schizophrenia, or depression) before learning about their FTD diagnosis. This is especially common in patients who develop the behavioral symptoms first.


Range of Pathological Features Associated with FTD

A variety of pathological findings have been identified in the brains of FTD patients. Although some findings are specific to one or two of the FTD subtypes (see subtype descriptions for specifics), there is a general profile of FTD brain pathology.

This includes: atrophy or shrinkage of the frontal and temporal lobes; neuron loss; gliosis (overgrowth, or development of tumors); cellular inclusions (called Pick bodies); and spongiosis (swelling with excess fluid).

In general, damage to cells in the temporal lobe appears to produce language and emotional dysfunction; patients in whom this damage is most severe in the frontal lobe experience more severe problems with decision-making and behavior. Damage may initially occur on just one side of the brain (unilateral); in most cases, however, as the disease progresses, it affects both sides of the brain.

Scientists have recently determined that in many FTD subtypes these affected cells contain deposits of an abnormal form of the protein tau. Tau is present in all neurons, and it plays important roles in the structure and function (metabolism) of normal neuron function. In brain cells of FTD patients, however, pathologists are finding excessive deposits of tau, abnormal versions of tau, or a lack of tau. This evidence is providing increasing support for the scientific theory that many different forms of FTD are “tauopathies”, meaning they are caused by abnormalities in the protein tau. In most cases, however, the cause of these tau abnormalities is unknown.


Genetics

FTD can be sporadic, familial, or hereditary.

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 elevated risk to family members.

Approximately 20% to 50% of patients have a positive family history for FTD or a related neurodegenerative condition or dementia (e.g. Alzheimer Disease, Parkinson Disease, or ALS). This may indicate that there is a predisposition for this type of neurological disease in the family, and that members of the family may be at increased risk to develop one of these disorders. The term “familial” is used to describe this unspecified risk in relatives. In such a family, a meeting with a genetic counselor, who will take a detailed family history and discuss the possibility of such a risk, may be informative.

5% - 10% of FTD patients have a family history that 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. Only one of the subtypes, FTDP-17, is exclusively hereditary. For a more detailed discussion of genetics, see below.


Treatment

There is no cure for FTD, and in most cases its progression cannot be slowed. Although no medications have been proven effective specifically in 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 depression) and/or acetylcholinesterase inhibitors (used in Alzheimer disease), which prolong the activity of neurotransmitters in the brain. Clinicians may also employ antioxidants, such as vitamin E or coenzyme Q10, which are known to slow the progression of damage to brain cells in general.


Management and Prognosis

FTD is progressive and over time (usually a few years) the patient's ability to live and function independently are diminished, leaving them dependent on others for activities of daily living. 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 therapists, occupational and physical therapists, neuropsychologists, nurses (especially home-care nursing), 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 the type of care situations that may be necessary during later stages of the disease. In-home nursing care, transition to life-care community, or a nursing home 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.


References

References

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National Institute of Neurological Disorders and Stroke. www.ninds.nih.gov.

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Van Swieten J, Heutink P. Frontotemporal Dementia with Parkinsonism-17. Geneclinics. www.geneclinics.org/profiles/ftdp-17.

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Material prepared by Jennifer M. Farmer, MS, CGC, Website Clinical Consultant and Susan L-J Dickinson, MS, CGC, Website Medical and Science Writer.