Frontotemporal dementia

Frontotemporal dementia (FTD), also known as frontotemporal lobar degeneration (FTLD), Pick disease, or frontotemporal neurocognitive disorder, is a group of progressive neurodegenerative disorders primarily affecting the frontal and temporal lobes of the brain. It is one of the most common causes of early-onset dementia, typically presenting before age 65. The disease leads to progressive deterioration of behavior, personality, language, and executive function due to selective atrophy of the frontal and temporal cortical regions. FTD encompasses several clinical subtypes. The behavioral variant (bvFTD) is characterized by progressive changes in personality, social conduct, and behavior, including disinhibition, apathy, loss of empathy, compulsive or ritualistic behaviors, hyperorality, and impaired executive function. The language variants include progressive nonfluent aphasia (characterized by effortful, halting speech and grammatical errors) and semantic dementia (characterized by loss of word meaning and object knowledge). As the disease progresses, patients may develop motor symptoms overlapping with amyotrophic lateral sclerosis (ALS) or parkinsonism. Memory is often relatively preserved in early stages, distinguishing FTD from Alzheimer disease. Approximately 30-50% of FTD cases are familial, with autosomal dominant inheritance identified in a significant proportion. Major causative genes include MAPT (microtubule-associated protein tau), GRN (progranulin), and C9orf72 (chromosome 9 open reading frame 72 hexanucleotide repeat expansion), the latter also being the most common genetic cause of ALS. Other rarer genes include VCP, CHMP2B, TBK1, and TARDBP. Currently, there is no disease-modifying treatment for FTD. Management is symptomatic and supportive, involving behavioral interventions, speech and language therapy, and pharmacological management of specific symptoms such as agitation or depression with selective serotonin reuptake inhibitors (SSRIs). Antipsychotics may be used cautiously for severe behavioral disturbances. Multidisciplinary care and caregiver support are essential components of management.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Frontotemporal dementia