Frontotemporal Degeneration

Frontotemporal degeneration (FTD) is a disease process that results in progressive damage to the anterior temporal and/or frontal lobes of the brain. It causes a group of brain disorders that share many clinical features. The hallmark of FTD is a gradual, progressive decline in behavior and/or language that often has a relatively young age at onset (mid-50s to 60s), but has been seen as early as 21 and as late as 80 years. 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.

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 50,000-60,000 Americans. FTD occurs equally in men and women. In a minority of cases, it is inherited.

While there are currently no treatments to slow or stop the progression of the disease, FTD research is expanding, producing 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.

Brain Image

Brain Image

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

Historically, physicians had a difficult time distinguishing FTD from Alzheimer’s disease (AD), and several other neurological disorders or psychiatric problems. Today, increased understanding of the clinical features and sophisticated brain imaging techniques help the physician to make an accurate diagnosis. Both FTD and AD are characterized by atrophy of the brain, and a gradual, progressive loss of brain function. Frontotemporal degeneration, however, is primarily a disease of behavior and language dysfunction, while the hallmark of AD is loss of memory. FTD often begins at an earlier age than AD; roughly 60% of cases occur in people 45-64 years old (Knopman, 2011).

See Diagnosis for more information on the distinction between FTD and Alzheimer’s, and tests used to diagnose FTD.

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 degeneration 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). When problems in language are prominent, the clinical syndrome is known as primary progressive aphasia (PPA). FTD with motor neuron disease, corticobasal syndrome, and progressive supranuclear palsy are subtypes of FTD characterized by muscle weakness, rigidity and/or parkinsonian symptoms.

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. Despite acting this way at home, they may also become disinhibited when in public or with strangers. Unusual behaviors may include swearing, overeating (especially carbohydrates) 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
Language deficits experienced by FTD patients are distinguished by principally two presenting issues: problems with expression of language and problems with word meaning. People with nonfluent/agrammatic PPA become hesitant in their speech and begin to talk less, but appear to retain the meaning of words longer. In semantic variant PPA, people experience a progressive deterioration of understanding words and recognizing objects, but retain the ability to produce fluent speech. A third variant, logopenic PPA, is characterized by deterioration in a person’s ability to retrieve words.

Movement presentation
Problems in motor skills and movement characterize two frontotemporal disorders. Corticobasal syndrome (CBS) begins with a decrease in movement on one side of the body and muscle rigidity with a tremor. Progressive supranuclear palsy (PSP) causes problems with control of gait and balance. The inability to coordinate eye movements is a characteristic symptom of PSP. Problems similar to those seen in Parkinson’s disease or ALS may also be seen.

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.
  • Emotional blunting or abnormal emotional reactions to others. Examples would include being inappropriately calm when a significant other has been hurt or is threatened, or being unfeeling or self-centered when empathy would usually be called for (such as a funeral). Some show emotions that may be exaggerated or inappropriate for the circumstance.
  • Apathy, 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 these behaviors on others, including loved ones.
  • Mood changes that can be abrupt and frequent.

The Frontotemporal Disorders
The specific subtypes of frontotemporal degeneration are described in individual articles under the links to the right:

Behavioral variant FTD
Nonfluent/agrammatic variant primary progressive aphasia
Semantic variant primary progressive aphasia
Logopenic variant primary progressive aphasia
Corticobasal syndrome or degeneration
FTD/Motor neuron disease
Progressive supranuclear palsy

Pathology of FTD

The pathology underlying the severe loss of brain cells in FTD is complex. 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. Upon autopsy, almost all cases of FTD are found to have abnormal accumulation of protein within brain cells; however, the specific protein can vary.

In approximately 40% of FTD cases, the pathology is characterized by intracellular accumulations of an abnormal form of the protein tau. In a slightly higher percentage of cases (approximately 50%), including most of the patients who develop FTD in combination with amyotrophic lateral sclerosis (ALS), the protein that accumulates is TDP-43. In 2009 investigators identified that the final subset of patients (~10%) have accumulation of the protein FUS.

 

Although some of the clinical subtypes of FTD are reliably a certain pathology (For example, PSP and CBS patients almost always have tau pathology, and FTD-ALS patients predictably have TDP-43 pathology), other clinical subtypes may involve any one of these pathologies. A major initiative is currently underway to identify biomarkers, which would permit the physician to know which pathology is causing a patient’s disease during his or her lifetime. The ability to identify a patient’s pathology accurately will be critical in the effort to develop and test appropriate therapies.

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 often an isolated (sporadic) case, which appears to pose no significant elevated risk to family members. In a significant minority 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.

More information is provided in AFTD’s detailed Genetics article on this website.

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 depression) and/or acetylcholinesterase inhibitors (used in Alzheimer’s disease), which prolong the activity of neurotransitters 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. Other medications under consideration include agents that impact the phosphorylation (biochemistry) of tau.

Continuing research advances in the field are making early clinical trials of drugs for FTD more of a reality.  See the Research section of this website for information on opportunities to participate in research.

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 2 to over 20 years with a mean course of 8 years from the onset of symptoms. FTD itself is not life-threatening. It does, however, predispose patients 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, and 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.NewlyDxcover

AFTD has created a publication that helps individuals and families take a strategic approach to a diagnosis of FTD and prepare for the changes it brings – A Guide for Managing a New Diagnosis – The Doctor Thinks It’s FTD. Now What?.  If you are requesting more than 4 copies, please click here for our order form, which includes a $1/book charge to cover shipping costs.

See Support and Resources for additional information on caregiving.
For additional information and support:

The Association for Frontotemporal Degeneration
Radnor Station #2, Suite 320
290 King of Prussia Rd.
Radnor, PA 19087
Toll free: 866-507-7222
E-mail: info@theaftd.org
www.theaftd.org