____________________________________________________________________ Frontotemporal Dementia
The disease duration for FTD can range from 2 to 20 years from symptom onset to death, with a mean duration of 8 to 10 years [3; 5; 10]. Pneumonia is the most common cause of death [3].
INTRODUCTION Frontotemporal dementia (FTD) is a group of degenera- tive brain disorders characterized by behavior and language problems and also overlapping with some motor/movement diseases. FTD causes progressive deterioration in a person’s ability to function as the result of damage to the frontal and temporal lobes of the brain. FTD is also referred to as fronto- temporal degeneration, frontotemporal lobar degeneration, and Pick disease. Dr. Arnold Pick, a Czech neurologist, psychiatrist, and neuropathologist, first described frontal and temporal lobe atrophy causing dementia and progressive aphasia in 1892 [1]. The clinical syndrome subsequently became known as “Pick disease.” FTD is the third leading cause of dementia across all age groups, after Alzheimer disease (AD) and Lewy body dementia [2]. It is one of the most common causes of early-onset dementia, with onset typically between 45 and 64 years of age [2; 3]. The clinical presentation of FTD can be complex, and obtain- ing an accurate diagnosis can be challenging. The unique clinical symptoms of FTD, neuropsychologic assessment, and brain imaging can help distinguish it from AD and other dementias. There is presently no effective treatment for FTD, and symptom management can be challenging for healthcare providers and family caregivers. Research is in progress to bet- ter understand FTD, hopefully leading to effective treatment, cure, and prevention of this devastating disease. EPIDEMIOLOGY OF FTD 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 inci- dence 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]. FTD affects both men and women. However, it is unclear if men and women are affected equally, or if some subtypes of FTD may be more common in one gender or the other [9]. Significant time (average: 3.6 years) often passes between symptom onset and actual clinical diagnosis [5].
PATHOGENESIS AND PATHOPHYSIOLOGY OF FTD 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. In FTD, affected neurons have an abnormal accumulation of protein within the cell, called inclusions. Three types of intra-neuronal inclusions have been identified, based on the protein involved. In some cases, the inclusions are composed of an abnormal form of the protein tau. In other patients, the inclusions are composed of the transactive response DNA- binding protein 43 (TDP-43). In a smaller number of FTD cases, the inclusions are composed of fused in sarcoma (FUS) protein [11]. The frontal and anterior temporal lobes of the brain control executive functions (e.g., planning, organizing, abstract think- ing, judgment, decision making), personality, social behavior, and language. The changes associated with FTD causes impair- ments in executive function, personality, behavior, and/or language. The location of the neurodegeneration correlates fairly well with the clinical presentation [11]. Changes in other areas of the brain may cause overlapping movement problems. While the cause of most cases of FTD is not known, some cases are now known to be caused by genetic mutations. CLINICAL PRESENTATION 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 com- mon 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
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MDRI2026
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