Frontotemporal dementia (FTD) is one of a group of conditions that cause progressive degeneration of the anterior temporal lobe (the decision-making and behavior control center) and frontal lobe (the language and emotion control center) of the brain. Dementia is not a disease in itself, but is a general term used to describe the loss of the ability to think, reason, and remember, all symptoms that may accompany a wide variety of conditions and diseases.
Description
Although less common than Alzheimer's disease, the most common of the dementias, FTD is a relatively new category and is the third most common dementia. The second more common is dementia with Lewy bodies, a condition in which brain cells abnormally accumulate a protein called alphasynuclein in structures called Lewy bodies, which are deposits in the brain containing damaged nerve cells.
Arnold Pick, a neuropsychiatrist, identified the first type of FTD in the early 1890s, when he noticed the dramatic shrinkage in frontal and temporal brain regions during the autopsies of some people with a dementia. This shrinkage seriously disrupted the ability of these individuals to use language.
In later examinations of Pick's tissue samples, the pioneer neuropathologist, Alois Alzheimer, the first to identify Alzheimer's disease, observed that the shrunken brain regions showed similar microscopic changes. Some nerve cells appeared swollen; others contained spherical abnormalities. Later, the swollen cells became known as Pick's cells; the tiny spheres were called Pick's bodies; and the disorder itself became known as Pick's disease.
As scientists acquired more knowledge of brain pathology, they observed that in some cases of FTD degeneration, Pick's cells or bodies were not present. And during the 1970s and 1980s, new diagnostic imaging techniques revealed that frontotemporal degeneration comprised a wide variety of symptoms aside from language difficulties. Imaging studies also suggested that frontotemporal disease is more common than was originally believed, representing up to 20% of dementia cases.
A combination of all of these factors, including reduced emphasis on Pick's abnormalities, varied symptoms, and newly recognized frequency, contributed to an expanding list of names for frontotemporal disorders. To help clarify the situation, researchers adopted the term frontotemporal dementia to encompass all the disorders resulting from gradual deterioration of the frontal and temporal regions of the brain. Sometimes, however, the terms Pick's disease, FTD, and frontotemporal lobar degeneration (FTLD) are used interchangeably.
A variety of pathologic findings has been identified in the brains of patients with FTD. Although some findings are specific to one or two of the FTD subtypes, there is a general profile of FTD brain pathology that emerges.
In general terms, damage to cells in the temporal lobe appears to produce language and emotional dys-function. Patients with the most severe damage to the frontal lobe experience more severe problems with decision-making function and behavior. Initially, the damage may occur on just one side of the brain. In most cases, however, as the disease progresses, both sides of the brain are affected.
Scientists have recently demonstrated that in some FTD subtypes, these damaged cells contain deposits of an abnormal form of a protein called tau. Tau is present in all neurons and plays an important role in the structure and function, that is, the metabolism, of normal neuron function. In the brain cells of patients with FTD, however, pathologists are finding a variety of combinations: excessive deposits of tau, abnormal versions of tau, or an absence of tau. This evidence is providing increasing support for the scientific theory that different forms of FTD are caused by abnormalities in the tau protein. In most cases, however, the cause of these tau abnormalities is unknown.
Frontotemporal dementia most commonly refers to a group of specific disorders. These include:
Pick's disease: A rare brain disease that is characterized by shrinkage of the tissues of the brain's frontal and temporal lobes and the presence of small deposits (Pick's bodies) in the nerve cells of the affected area. Pick's bodies are not always present in FTD. The disease resembles Alzheimer's disease in the personality changes and disorientation that may precede memory loss.
Corticobasal degeneration: A progressive neurologic disorder that is characterized by nerve cell loss and shrinkage of multiple areas of the brain, including the cerebral cortex and basal ganglia. Symptoms, such as rigidity and loss of muscle coordination, resemble those symptoms found in Parkinson's disease.
Progressive aphasia: A rare neurologic disorder that is characterized by progressively impaired language abilities, although other mental functions and activities of daily living are preserved.
Semantic dementia: Also known as fluent progressive aphasia, semantic dementia is a language disorder in which patients exhibit a progressive deterioration of the understanding and recognition of words, although impairment in other cognitive faculties is not present.
Frontotemporal dementia with Parkinsonism-17 (FTDP-17): A type of progressively worsening dementia that involves the frontal and temporal areas of the brain and is characterized by behavioral and cognitive changes, psychiatric symptoms, language difficulties, and Parkinsonian symptoms, such as tremor and muscle rigidity. This form of FTD is linked to chromosome 17.
Frontotemporal dementia with motor neuron disease (FTD-MND): A disorder in which FTD coexists with MND and primarily affects the temporal lobe of the brain; also known as amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) with dementia. ALS is a neuromuscular disease that progressively weakens and destroys motor neurons, the cells in the nervous system that send messages from the brain to the rest of the body.
Genetic profile
Frontotemporal dementia may be sporadic (occurring in one family member), familial (involving two or more family members), or hereditary. In most cases (about 60%), FTD is sporadic. When FTD is diagnosed in a person with no family history of FTD or dementia, the isolated, or sporadic, case appears to pose no increased risk to family members.
About 40% of FTD cases are believed to have a genetic component, such as a positive family history for FTD or a related neurodegenerative condition or dementia. Of those, about 10% have mutations in the microtubule-associated protein tau (MAPT) gene, which is located on chromosome 17. The children of a person with a mutation in this gene have a 50% chance of inheriting that same disease-causing mutation. Researchers have found some linkage to chromosome 9 and some to chromosome 3, and other FTD genes are likely to be found in the future.
About 5–10% of patients have a family history that suggests a hereditary condition with an autosomal dominant patter of inheritance, meaning that 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 of inheriting the disorder. Only one of the subtypes, FTDP-17, is exclusively hereditary.
Demographics
It is estimated that as many as seven million Americans may be affected with some form of dementia, and FTD may account for about 25% of those dementias. Frontotemporal dementia occurs most frequently between the ages of 35 and 75, and was believed to affect men and women equally. Recent studies, however, have indicated that FTD appears to be more common in men and is a more common cause of early-onset dementia than previously recognized.
Signs and symptoms
Frontotemporal dementia comprises a wide variety of symptoms that vary widely from person to person, depending on the degree of involvement of the frontal and temporal lobes and the side of the brain affected.
Although two major symptom patterns emerge in all forms of FTS, namely gradual and progressive changes in behavior and language, some symptoms are more closely associated with one subtype of FTD than another. In general, the range of symptoms associated with FTD includes behavioral, linguistic, cognitive, emotional, neurologic, and psychiatric.
A progressive deterioration in the ability to control or adjust behavior appropriately in different social contexts is the characteristic feature of all the behavioral changes. This results in embarrassing, inappropriate social situations that can be one of the most disturbing aspects of FTD. Patients with FTD often present two seemingly opposite behavioral profiles in the early and middle stages of the disease. Some people are hyperactive, restless, distracted, and uninhibited. Others are apathetic, lack spontaneity, and are emotionally blunted.
impulsive or inappropriate behaviors involving, for example, sexuality
changes in sleep patterns, including prolonged sleepiness, especially in those with more apathetic behaviors
Linguistic symptoms include:
decreasing speech to the point of total silence in some patients, and conversation is not spontaneous but, rather, mechanical
weak-sounding, imprecise, or incoherent speech
difficulties remembering grammar rules
repetition of a word or phrase uttered by another
repetition of a word or phrase uttered by the person themselves
loss of the ability to speak
Cognitive symptoms include:
distractibility and impatience
rigid and inflexible thinking and impaired judgment
abstract reasoning difficulty
poor financial judgment
As opposed to those affected by Alzheimer's disease, patients with FTD tend to have normal results on intelligence tests until that point in the disease process at which apathy results in lower scores.
Emotional symptoms include:
apathy or indifference to people and events
lack of understanding of self and others
lack of empathy toward and understanding of others, including family members and close friends
Although medical knowledge of FTD is still evolving and a broad range of subtypes is involved, current technology is providing the first evidence of the pathologic changes that occur in specific areas of the brain that cause FTD's varied symptoms. For example, loss of function in an individual's temporal lobe produces language changes, and loss of function in the frontal lobe appears to lead to behavioral symptoms, including aggressive, antisocial, and other socially unacceptable behaviors.
Because of its symptoms, FTD is often initially misdiagnosed as a psychiatric problem, Alzheimer's disease, or Parkinson's disease. However, there are features that rule out other diagnoses and identify features that pinpoint FTD.
Medical history
The presentation of the disorder within families can vary. Some people may have FTD alone, and others may develop parkinsonism or psychiatric symptoms. Because of this variability, a careful analysis of family medical and social history can help clarify whether an affected person has a sporadic or a hereditary form of the disorder.
It is important to interview another source, such as a spouse, partner, or adult child, regarding changes in the patient's cognitive performance or behavior that are having a negative impact on the patient's activities of daily living. This source is important in establishing information about past performance and behavior, as well as the progression of symptoms that the patient may not be able to provide reliably. The additional source may also provide information that can be used to test the patient's recent and long-term memory. Significant functional changes in memory and other cognitive domains that interfere with everyday activities (such as driving, functioning at work, and/or interactions with family and friends) signal a disease state and are not part of the typical aging process.
It is essential to determine the potential for medication-induced confusion or dementia by studying the patient's drug inventory and looking for compounds that may cause or exacerbate any loss of mental capacity.
Physical examination
A targeted physical examination should be performed in all patients with dementia. Signs of systemic disorders, such as vasculitis, systemic lupus erythematosus (SLE, a chronic inflammatory condition), tuberculosis, and hypothyroidism, suggest that further evaluation is necessary. Physical problems, such as profound hearing or visual loss, may exacerbate FTD.
Neurologic examination may reveal signs that vary according to which part of the brain is affected, either the temporal or the frontal lobe, with associated behavioral and language changes. Careful neurologic examination should include observation of gait and posture, cranial nerves, motor strength, sensation, and reflexes. In more advanced stages of FTD, neurologic examination often reveals motor dysfunction and reflex abnormalities.
Neuropsychological examination
This examination assesses, for example, language, behavior, abstraction, memory, executive, motor skills, and visual-spatial functioning. There are many tools available for cognitive testing. The goal of testing is to demonstrate a decline in intellectual function, to assess whether depression is a contributing factor, to make predictions about future functioning, and to plan care. The Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale may be administered by primary caregivers and should be performed on all patients with dementia. More detailed evaluation, such as the Wechsler Adult Intelligence Scale (WAIS), the Blessed Information-Memory-Concentration Test, visuospatial testing, and the Boston Diagnostic Aphasia Evaluation, also may be helpful in making a diagnosis.
Neuroimaging studies
These studies include magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon computed tomography (SPECT). They help to determine the exact location and extent of atrophy in the brain as well as areas of decreased blood flow. Electroencephalogram (EEG), or brain scan, results are usually normal, however, even in advanced stages of the disease.
Although differentiating FTD from dementias, such as Alzheimer's disease, has been difficult, with more sophisticated brain imaging, such as SPECT, some researchers have claimed that they can diagnose Alzheimer's disease with an accuracy rate of nearly 100%. Differentiating among the various subtypes of FTD, however, still remains a challenge. Sometimes definitive diagnosis of these conditions can be made only by brain autopsy.
Treatment and management
There is no cure for FTD, and in most cases, disease progression cannot be slowed. Although no medications have been proven effective specifically for FTD, many physicians look to the medications and treatment approaches used in other, similar disorders to develop a therapeutic approach. For example, some patients with FTD benefit from selective serotonin reuptake inhibitors (SSRIs), which are used in treating depression, and acetyl-cholinesterase inhibitors, which are used in treating Alzheimer's disease, to help prolong the activity of neurotransmitters in the brain. Physicians may also use antioxidants, such as vitamin E or coenzyme Q10, which are known to slow the progression of damage to brain cells in general.
Over time, FTD is progressive, and after a few years, a patient's ability to live and function independently are decreased, leaving them dependent on others for activities of daily living.
Care of patients with FTD focuses on maximizing quality of life, treating neuropsychiatric complications, ensuring patient safety, and supporting and educating care-givers. It is important for caregivers and families to consider long-term management issues and identify a team of experts who can help with difficult medical, financial, and emotional challenges. Also, it is important to have a physician who is knowledgeable about FTD and comprehensive approaches to treatment. In addition, speech therapists, occupational and physical therapists, neuropsychologists, nurses, and genetic counselors may be helpful.
Prognosis
Prognosis varies, but studies have shown that a person with FTD may live with the disease an average of eight years, with a range of 3–17 years. A more slowly progressive form of FTD occurs in the small percentage of people with familial tau-positive disease. People with FTD-MND have the shortest life expectancy, both before and after diagnosis.
BOOKS
Radin, Lisa, and Gary Radin, eds. What If It's Not Alzheimer's? A Caregiver's Guide to Dementia. Amherst, NY: Prometheus Books, 2003.
Weiner, Myron F., and Anne M. Lipton, eds. The Dementias: Diagnosis, Treatment, Research, 3rd Edition. Arlington, VA: American Psychiatric Publishing, 2003.
PERIODICALS
Wilhelmsen, Kirk C., et al. "17q-Linked Frontotemporal Dementia–Amyotrophic Lateral Sclerosis without Tau Mutations with Tau and alfa-Synuclein Inclusions." Archives of Neurology Vol. 61 (3) March 2004: 398–406.
Rabheru, Kiran. "Depression in Dementia: Diagnosis and Treatment." Psychiatric Times (November 2004 [April 20, 2005].) Available online: <http://www.psychiatrictimes.com/p041139.html>.
ORGANIZATIONS
Alzheimer's Association. 919 North Michigan Avenue, Suite 1100, Chicago, IL. 60611-1676. (800) 272-3900. (April 20, 2005.) <http://www.alz.org>.
Alzheimer's Disease Education and Research (ADEAR), National Institute on Aging. P.O. Box 8250, Silver Spring, MD. 20907-8250 (800) 4388-4380). (April 20, 2005.) <http://www.alzheimers.org/>.
Association for Frontotemporal Dementias (AFTD). P.O. Box 7191, St. David's, PA 19087-7191. (April 20, 2005.) <http://www.ftd-picks.org>.
The Genetic Alliance. 4301 Connecticut Ave., NW, Suite 404, Washington, DC 20008-2369. (202) 966-5557). (April 20, 2005.) <http://www.geneticalliance.org>.
National Organization for Rare Disorders (NORD), Inc. P.O. Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518. (April 20, 2005.) <http://www.rarediseases.org>.
