It is estimated that FTD affects approximately 60,000 people in the United States [3]. As noted, the age of onset for FTD is typically 45 to 64 years, with a mean of 58.5 years and a reported range between 21 and 80 years of age [2,3,4,5]. In the United States, the prevalence in people 45 to 64 years of age is estimated at 15 to 22 per 100,000 population; the incidence in this group is 2.7 to 4.1 per 100,000 [5]. It is estimated that 60% of those with FTD have onset between 45 and 64 years of age; 10% have onset before 45 years of age, and 30% have onset after 64 years of age [5]. FTD is now considered by some to be the most common form of pre-senile dementia in patients younger than age 60, even more common than AD in this group [6,7,8].

Patients with FTD experience a progressive loss of neurons in the frontal and anterior temporal lobes, resulting in atrophy in these areas of the brain. They may also develop gliosis in the frontal and temporal lobes where neurons have been lost or damaged.

FTD causes a gradual, progressive decline in behavior and/or language; movement disorders may also be involved. Behavior or language problems are typically the first and most prominent symptoms of FTD, whereas memory problems are the first symptoms of AD [5]. Subtypes of FTD have been identified based on clinical presentation (Table 1). Behavioral variant FTD (bvFTD) is the most common form and involves changes in behavior, personality, and emotions. Language presentations are referred to as primary progressive aphasia (PPA) and can take one of three forms: nonfluent/agrammatic variant PPA (nfvPPA), semantic variant PPA (svPPA), or logopenic variant PPA (lvPPA) [12]. Nonfluent/agrammatic PPA begins with problems in speech production, while svPPA involves impaired word comprehension and object recognition and lvPPA involves word-finding problems. A movement presentation may appear as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), or motor neuron disease (MND). Some patients may present with symptoms that overlap the different subtypes of FTD or may develop symptoms of other subtypes of FTD as the disease evolves. As more is learned about FTD, the terminology and classification of the subtypes may be revised.

As noted, bvFTD is the most common type of FTD, estimated to account for more than half of all cases [13]. The prominent features include disinhibition, apathy/inertia, loss of empathy, compulsive behaviors, hyper-orality, and impaired executive function (Table 2) [14]. People with FTD may become socially withdrawn, inflexible, and impulsive. They may have a shortened attention span and a tendency to be easily distracted. Behavior may become socially inappropriate. People with bvFTD are usually unaware of the changes in their personality and behavior and the impact these changes have on others. Memory and visual-spatial functioning are initially relatively spared in bvFTD. Some individuals with bvFTD may develop symptoms similar to Parkinson disease, such as bradykinesia, rigidity, postural instability, and masked face.

Nonfluent/agrammatic variant PPA, also referred to as progressive non-fluent aphasia (PNFA), accounts for about 25% of all FTD cases and involves problems with language expression [13]. People with nfvPPA have difficulty producing speech but retain the meaning of words and know what they want to say. As a result, speech may become hesitant, slow, and labored. Speech patterns may be "agrammatic" or "telegraphic," meaning that only the most important content words are used, without connecting words. For example, a patient might say "Tuesday…hospital…sister." Patients with nfvPPA have difficulty talking on the telephone and tend to talk progressively less. Eventually, some may become mute. While in the early stages, these patients continue to understand the speech of others, but this comprehension is eventually lost also. Reading and writing skills are better preserved than speech, although these abilities are also eventually lost. As the disease progresses, patients may develop behavioral symptoms. Some individuals with nfvPPA may develop extrapyramidal symptoms of rigidity and tremors, as seen in CBS and PSP.

Clinical genetic testing is available for the MAPT, GRN, and C9orf72 genetic mutations causing hereditary FTD, as well as some of the other very rare genetic mutations. Genetic testing may be ordered after informed consent and clear discussion of the implications with the patient and his/her family. For patients with FTD, identification of a genetic mutation confirms the diagnosis of FTD and provides information about risk to other family members. Each of the patient's siblings and each of the patient's children would be at 50/50 risk for having inherited the genetic mutation causing FTD. If a genetic mutation causing FTD is identified, other at-risk family members may be tested.

There is presently no treatment to slow the progression of or cure FTD. No medication has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of FTD; however, medications used to treat other disorders may be prescribed off-label for the management of FTD symptoms. Their use may be limited by the potential adverse effects. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), may be prescribed for behavioral symptoms of FTD, and low-dose trazodone has been used for agitation and aggression [9]. While the anticholinesterase inhibitors donepezil, galantamine, and rivastigmine are beneficial for some patients with AD, they generally have not been helpful for patients with FTD [9]. The glutamate NMDA receptor antagonist memantine, used for moderate-to-severe AD, has been used for patients with FTD as well, but a 2013 study showed that it provided no benefit to patients with FTD and that it may be harmful to cognition [25]. Antipsychotics are occasionally used to treat significant agitation and behavioral symptoms, but only with caution, as antipsychotics can have serious adverse effects such as extrapyramidal adverse effects (parkinsonism), depression, sedation, falls, incontinence, and disinhibition, and patients with FTD may have an increased susceptibility to these effects [9]. Elderly patients with dementia who take antipsychotics have a 1.6- to 1.7-fold increase in mortality secondary to cardiac problems or infection, prompting the FDA to issue a warning about their use in older patients with behavioral disturbances [9]. L-DOPA has shown a minimal response for parkinsonism in patients with PSP and CBD [30]. Research is being done to further evaluate the use of available medications for the management of FTD and to find new, more effective treatments.

Apathy is a common symptom in patients with bvFTD, often resulting in neglect of their personal hygiene and grooming. Supervision, encouragement, and help with bathing, dressing, and grooming may be needed. For behavioral problems, simple interventions like distraction (e.g., introducing a new activity) may help interrupt the troublesome behavior. For some patients, modification of the environment or behavior may help minimize the potential for harm. For example, if the patient is pacing, creating a safe route for him or her to walk can be helpful. Physical therapists may be able to help develop an exercise program to maintain mobility. Exercise has also been shown to improve mood and cognition and may improve behavior management in patients with dementia [26]. If behaviors such as agitation or aggression become severe, a medication may be prescribed off-label to control difficult or dangerous behaviors. Supervision may be necessary to ensure patients take medications as prescribed.

Some individuals with FTD have eating problems, such as overeating, eating just one type of food, or craving sweets. For these patients, it may be necessary to monitor weight and provide help with meal preparation to provide a balanced, nutritious diet. Access to additional foods, drinks, or sweets should be limited.

Speech pathologists or therapists may be helpful in diagnosing the specific language problems exhibited by patients with FTD, including nonfluent/agrammatic, semantic, or logopenic variant PPA. Speech therapy may also help patients to find new communication strategies, such as sign language, carrying cards with specific messages, or using a computer with pre-programmed words or phrases [27]. Such techniques may help those with language problems communicate with family and friends. Speech therapists may also be able to evaluate and address swallowing problems, if these arise.

The goals for research on FTD include gaining a better understanding of the pathology; identifying causes and risk factors (genetic and environmental); improving the diagnosis of FTD through enhanced neuroimaging, biomarkers, and characterization of clinical features; developing therapies to treat, cure, or prevent FTD; and exploring new ways to support family caregivers. However, research on FTD is challenging. It is an uncommon disease, so awareness is low, there are fewer potential subjects available for research studies, and there is a relatively small market for medications. FTD is a complicated disease with a wide variety of presentations (behavior, language, and movement problems) and underlying causes (sporadic and genetic). Pathologically, microscopic brain inclusions may consist of different abnormal proteins (e.g., tau, TDP-43, FUS), and up until recently, there were no good biomarkers to diagnose FTD or to monitor the progression of the disease. However, ongoing studies have begun to show promise in this area. Biomarkers such as the neurofilament light-chain protein have been shown to rise before the onset of FTD symptoms, which may help in early identification and diagnosis of asymptomatic carriers of FTD [10]. Drug development still faces the challenge of creating a medication to treat FTD that can cross the blood/brain barrier.