Frontotemporal Dementia

What Causes Frontotemporal Dementia?

FTD occurs when abnormal proteins accumulate in brain tissue. Over time, these proteins interfere with brain cells’ function, and eventually, the cells die. As more cells die, the affected part of the brain shrinks, and the functions controlled by that part of the brain are impaired.

FTD affects the frontal and/or temporal lobes of the brain. The frontal lobes are behind the forehead, directly above the eyes on both sides of the brain. They help control thought processes such as planning, judgment, and emotional responses. The frontal lobes also play a role in some language skills (such as sentence-building) and some movement functions. The temporal lobes are below and to each side of the frontal lobes. They play a vital role in processing language, as well as being responsible for some memory functions.

The symptoms experienced by an individual FTD sufferer vary depending on which parts of the brain are affected. The progression of the symptoms varies according to the pattern of degeneration in the brain.

Scientists are not sure what causes FTD disorders. More than one abnormal protein seems to be involved in the development of the diseases, and it’s not clear what causes the proteins to accumulate in the brain.

Is Frontotemporal Dementia Hereditary?

The majority of FTD cases are not inherited. In about 60% of cases, the disorders occur spontaneously in patients who don’t have a family history of related conditions. In about 40% of FTD cases, the patient does have a strong family history of FTD or other degenerative neurological disorders. In almost half of those inherited cases, genetic testing can detect a specific genetic cause.

FTD is associated with variations in several different genes, each of which plays a role in producing the proteins that are thought to cause the disorders. Scientists don’t know precisely how these genetic variations trigger the disease, but different genetic factors might contribute to different types of FTD disorders or different symptom patterns.

If you have a family history of FTD or other degenerative neurological disorders, a genetic counselor can help you assess the risks you face.

How Is Frontotemporal Dementia Detected?

There is no cure for FTD, and there is no treatment that will stop the progression of its symptoms. Early detection of the disorders, however, can help sufferers seek interventions that will keep them safe.

Early signs of FTD often include:

• Loss of interest in daily activities
• Withdrawal from social interaction
• Shifts in mood or depressive behavior
• Changes in personality
• Loss of social inhibition
• Sudden onset of inappropriate behavior
• Obsessive or repetitive behaviors
• Binge eating or rapid weight gain

How Is Frontotemporal Dementia Diagnosed?

There is currently no test or exam that will definitively detect FTD. The disorders are often misdiagnosed because their early symptoms look similar to the symptoms of other conditions. Common misdiagnoses include depression, schizophrenia, and Alzheimer’s disease.

As part of the diagnostic process, doctors will typically administer physical exams, neurological exams, and laboratory tests to rule out conditions other than FTD that could be causing the symptoms. The process will include interviews with the patient and with loved ones or caregivers to get a complete picture of the pattern of symptoms.

Brain imaging scans such as magnetic resonance imaging (MRI) and positron emission tracer (PET) scans may also be employed to look for evidence of other brain disorders. The physical effects of FTD itself are not always detectable on scans, especially in the early stages.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Frontotemporal Dementia Treated?

No treatment will slow, stop, or reverse the effects of FTD. Medications that show promise in treating other forms of dementia appear to be ineffective at treating FTD, and some may even make symptoms worse. The course of treatment for FTD is focused on directly treating symptoms and attempting to manage their effects.

Medications

• Antidepressants such as citalopram, paroxetine, or sertraline may be used to treat symptoms such as depression or mood changes.
• Antipsychotics such as olanzapine or quetiapine may be used to treat behavioral symptoms. These medications carry the risk of severe and potentially life-threatening side effects, so they must be administered cautiously.

Therapy

Speech therapy may help sufferers cope during the early stages of language-related FTD disorders.

How Does Frontotemporal Dementia Progress?

FTD symptoms become progressively worse over time, and in some cases, symptoms become so severe that sufferers require full-time care. The signs themselves are not life-threatening, but they can become so debilitating that the sufferer is at risk of severe medical and behavioral complications. The time from the initial appearance of symptoms until the disorder reaches its peak impact can be as short as two years or as long as 20 years.

Potential long-term complications of FTD include:

• Infections or illnesses such as pneumonia
• Accidents or falls
• Risky behavior that can endanger the sufferer or others
• Total loss of the ability to communicate

How Is Frontotemporal Dementia Prevented?

There is no known way to prevent FTD. The cause of sporadic cases of FTD (those that occur without a family history) remains unknown, so there are no avoidable risk factors associated with the FTD disorders.

If you have a family history of FTD or degenerative neurological disorders, a genetic counselor can help you decide if you should undergo genetic testing. Genetic tests can identify whether or not you’ve inherited one of the genetic variants that have been associated with FTD disorders.

Frontotemporal Dementia Caregiver Tips

Taking care of a loved one with frontotemporal dementia is extremely taxing, both physically and emotionally. To help yourself and your loved one cope with the effects of the disease, keep these tips in mind:

• Learn all you can about FTD. Some FTD symptoms can be shocking, and you’ll be better equipped to deal with them if you understand their cause. Your loved one may exhibit agitation, aggression, or socially unacceptable behavior. It’s crucial that you not take this behavior personally and understand that it is part of the disease.
• Create soothing surroundings. The symptoms of both behavior- and language-related FTD can be easier to manage if your loved has a calm, distraction-free environment. Work to identify situations that seem to trigger problematic behavior and limit those situations as much as possible.
• Take care of yourself. Caregivers for people with FTD are at particular risk of physical and mental health issues themselves. Don’t hesitate to take time for yourself away from your loved one when you can, and seek help from a support group, either locally or online.

Many people with FTD also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with FTD:

• People with FTD are at increased risk for depression or an anxiety disorder.
• Some studies have associated FTD with borderline personality disorder and other personality disorders.
• FTD can occur at the same time as Alzheimer’s disease and other types of dementia.

FTD presents symptoms sometimes similar to those of Lewy Body Dementia and Corticobasal Degeneration.

Frontotemporal Dementia Brain Science

FTD is caused by the buildup of abnormal proteins in the brain. As these proteins accumulate in the brain’s nerve cells, they impede the cells’ function and eventually cause them to die. Scientists have identified several genes and more than one protein associated with various FTD disorders. Usually, the genes control the production of proteins that play an essential role in proper brain function. However, specific abnormal changes (mutations) in the genes seem to trigger abnormal protein formation.

Some of the genes associated with FTD include:

• C9orf72. This gene was discovered relatively recently, but its mutations seem to be the most common FTD cause. C9orf72 mutations have been associated with about a quarter of all inherited FTD cases and about 6% of non-inherited cases. Scientists are currently studying the role this gene plays in protein production.
• Microtubule-associated protein tau (MAPT). Mutations in this gene are associated with 5-10% of FTD cases. The gene is related to the production of a protein called tau, which is vital for proper nerve-cell function and health.
• Progranulin (GRN or PGRN). This gene plays a role in the production of a protein called progranulin. The protein helps nerve cells resist and recover from inflammation and injury. The GRN gene is associated with 5-10% of FTD cases.

These gene mutations may be passed from parents to their children, and inherited mutations are responsible for about 40% of FTD cases. The remainder of cases result from spontaneous gene mutations that occur sometime later in life. Scientists are still unsure what causes these spontaneous mutations.

Frontotemporal Dementia Research

Title: Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia (Lithium)

Stage: Recruiting

Contact: Edward Huey, MD

Columbia University Medical Center

New York, NY 

Behavioral symptoms of Frontotemporal dementia (FTD), including agitation, aggression, and inappropriate repetitive behaviors, are common. This can be distressing to patients and caregivers, often leading to institutionalization, and can be very difficult and expensive to treat. There is a scarcity of medication for treating these symptoms in FTD. Typically, antidepressants and antipsychotic medications are prescribed – with low efficacy and with the latter class, carry serious adverse effects such as parkinsonism and increased cardiovascular-related mortality. The investigators propose a study on the effectiveness of lithium carbonate compared to placebo in the treatment of agitation, aggression, and inappropriate repetitive behaviors in 60 patients with FTD in a randomized, double-blind, two-arm parallel 12-week trial. Lithium is a highly effective treatment for mania and symptoms of agitation or aggression in bipolar disorder. It also inhibits tau aggregation and phosphorylation, leading to considerable interest in its use as a disease-modifying treatment for tauopathies such as FTD and Alzheimer’s disease. Unfortunately, earlier trials using typical doses (i.e., doses prescribed for treatment of bipolar disorder) showed a high incidence of serious adverse effects (including confusion and delirium). For the proposed study, the investigators will: 1) use lower doses and lower target serum concentrations than have preceding trials (shown in preliminary data from a Columbia study and data from other labs to be well-tolerated) and 2) target behavioral symptoms rather than cognitive outcomes.

Title: Rehabilitating and Decelerating Language Loss in Primary Progressive Aphasia With tDCS Plus Language Therapy

Stage: Recruiting

Principal investigator: Argye E Hillis, MD, MS

Johns Hopkins School of Medicine

Baltimore, MD 

Primary Progressive Aphasia (PPA) is a debilitating disorder characterized by the gradual loss of language functioning, even though cognitive functioning is relatively well preserved until the disease’s advanced stages. There are three main PPA variants classified based on the pattern of language impairments and areas of atrophy, but anomia is present across all variants in the earliest stages. While there is a significant amount of Research investigating multiple treatment approaches for individuals with aphasia resulting from stroke, individuals with PPA have far fewer treatment options from which to choose. Recently, a growing body of literature on treatment in stroke-based aphasia has found promising results for pairing traditional language therapy with non-invasive neurostimulation via transcranial direct current stimulation (tDCS). The limited number of studies of the effects of tDCS applied to the left inferior frontal gyrus (IFG) in PPA also yield promising results that show tDCS can enhance generalization to untreated structures. Research in stroke-based aphasia has demonstrated that language outcomes significantly improve when participants are treated with more complex language stimuli because this treatment approach results in enhanced generalization. For example, therapy that has participants build sentences around verbs has improved word-level verb and noun naming. The current proposal aims to investigate whether combining the benefits of tDCS while providing verb retrieval therapy that uses sentence building to improve word-level retrieval deficits will enhance word retrieval deficits in PPA and slow the loss of language functioning. It is hypothesized that the proposed study will investigate the atrophy patterns at baseline to determine which atrophy patterns are predictive of improved word retrieval. Specifically, this proposal aims: 1) to determine whether tDCS to left IFG coupled with therapy promoting verb retrieval within sentences improve noun and verb retrieval in treated and untreated items in individuals with PPA, and 2) To investigate which patterns of atrophy are predictive of maintenance and generalization of word-retrieval in individuals with PPA following tDCS+therapy vs. sham+therapy. This proposed Research will allow the investigators to evaluate the potential benefits and sustainability of tDCS in PPA, the generalization of trained items to untrained items, as well as the deceleration of language loss.

Title: TMS for the Treatment of Primary Progressive Aphasia

Stage: Recruiting

Principal investigator:  Alexandra Touroutoglou, PhD  

Massachusetts General Hospital

Boston, MA

Primary Progressive Aphasia (PPA) is a progressive syndrome in the family of Alzheimer’s disease and related disorders involving devastating language impairments caused by selective neurodegeneration of the brain’s language network. Unfortunately, there is no treatment for PPA. An exciting possibility for treatment is non-invasive repetitive transcranial brain stimulation (rTMS), which induces electric currents in degenerating brain networks, making them, in some cases, more efficient.

Therapeutic benefits from rTMS have been demonstrated when it is applied in many sequential sessions. For example, repeated sessions of rTMS to the left dorsolateral prefrontal cortex (dlPFC) are approved by the US Food and Drug Administration as a treatment for major depressive disorder. With respect to language, high-frequency rTMS increases the response rate for picture naming in healthy individuals and patients with Alzheimer’s disease. Further, in a sham-controlled study, Cotelli and colleagues demonstrated that in a group of 10 non-fluent PPA patients, high-frequency rTMS over the left and right dlPFC improved the percent of correct responses for action naming. When rTMS was applied for five consecutive days in a sham-controlled single case study, Finocchiaro and colleagues showed lasting improvements in language (up to 1 week) in a patient with non-fluent PPA. Trebbastoni and colleagues further showed the same lasting improvements in language (up to 1 week) in a patient with logopenic PPA. Recently, in a sham-controlled single case study, Bereau and colleagues applied a more intense rTMS protocol for ten consecutive days and demonstrated significant linguistic improvements in a logopenic PPA patient that lasted for 1 month. These studies have contributed valuable insights into the potential use of rTMS in treating the language symptoms of PPA patients.