Frontotemporal dementia (FTD) encompasses a spectrum of
neurodegenerative diseases with heterogeneous clinical presentations and two predominant types of underlying neuropathology. FTD typically comprises three distinct clinical syndromes: behavioral variant
frontotemporal dementia (bvFTD), semantic variant
primary progressive aphasia (svPPA), and nonfluent variant
primary progressive aphasia (nfvPPA). FTD also frequently overlaps both clinically and neuropathologically with three other neurodegenerative syndromes:
corticobasal syndrome (CBS),
progressive supranuclear palsy (PSP), and
amyotrophic lateral sclerosis (ALS). Each syndrome can be associated with one or more underlying neuropathological diagnoses and are referred to as
frontotemporal lobar degeneration (
FTLD). Although the various FTD syndromes can substantially differ in terms of clinical symptoms and underlying pathology, the symptoms can be broadly categorized into behavioral, cognitive and motor domains. Currently there are no Food and Drug Administration (FDA) approved
therapies for the above syndromes except
riluzole for ALS. FTD treatment strategies generally rely on
off-label use of medications for symptomatic management, and most
therapies lack quality evidence from randomized, placebo-controlled clinical trials. For behavioral symptoms,
selective serotonin reuptake inhibitors may be effective, while case reports hint at possible efficacy with
antipsychotics or anti-epileptics, but use of these latter agents is limited due to concerns regarding side effects. There are no effective
therapies for cognitive complaints in FTD, which frequently involve executive function, memory, and language. Motor difficulties associated with FTD may present with parkinsonian symptoms or
motor neuron disease, for which
riluzole is indicated as
therapy. Compared to
idiopathic Parkinson's disease, FTD-related atypical
parkinsonism is generally not responsive to
dopamine replacement
therapies, but a small percentage of patients may experience improvement with a trial of
carbidopa-levodopa. Physical and
occupational therapy remain an important corner stone of motor symptom management in FTD.
Speech therapy may also help patients manage symptoms associated with
aphasia,
apraxia, and
dysarthria. Recent advances in the understanding of
FTLD pathophysiology and genetics have led to development of potentially disease-modifying
therapies as well as symptomatic
therapies aimed at ameliorating social and behavioral deficits.