SUPERStudy: Frontotemporal dementia (FTD)

By usmlevideoss

Introduction

Frontotemporal dementia (FTD) is a group of neurodegenerative disorders characterized by progressive degeneration of the frontal and temporal lobes of the brain, leading to significant changes in personality, behavior, and language. Unlike other dementias, FTD often presents at a younger age, typically between 45 and 65 years. 

Etiology

The exact cause of FTD is not fully understood, but it is associated with abnormal accumulations of proteins such as tau and TDP-43 within brain cells, leading to neuronal death. Approximately 10-30% of cases are familial, linked to mutations in genes like MAPT, GRN, and C9orf72. 

Epidemiology

FTD accounts for about 10-20% of all dementia cases and is the most common form of dementia in individuals under 60. Both men and women are affected equally. The prevalence is estimated at 15-22 cases per 100,000 people aged 45 to 64. 

Pathophysiology

FTD involves progressive atrophy of the frontal and temporal lobes. The accumulation of misfolded proteins disrupts normal neuronal function, leading to cell death. This degeneration impairs networks responsible for behavior, executive function, and language, correlating with the clinical manifestations observed. 

Clinical Manifestations

FTD presents in various forms, primarily:

  • Behavioral Variant (bvFTD): Characterized by significant changes in personality and behavior, including apathy, disinhibition, loss of empathy, compulsive behaviors, and dietary changes. Memory is often relatively preserved in the early stages. 
  • Primary Progressive Aphasia (PPA): Focuses on language impairments and is further subdivided into:

Semantic Variant: Loss of word meaning, leading to difficulties in naming and understanding words.

  • Nonfluent/Agrammatic Variant: Impaired speech production, resulting in halting, effortful speech with grammatical errors.

Diagnosis

Diagnosis is based on clinical evaluation, neuroimaging, and sometimes genetic testing. MRI and PET scans typically reveal atrophy or hypometabolism in the frontal and/or temporal lobes. Neuropsychological assessments help delineate specific cognitive deficits. Definitive diagnosis may require post-mortem examination. 

Treatment

There is currently no cure for FTD. Management focuses on symptom alleviation and supportive care. Selective serotonin reuptake inhibitors (SSRIs) may help manage behavioral symptoms. Speech therapy can assist those with language impairments. Caregiver support and education are essential components of care. 

Prognosis

FTD is a progressive disorder with a variable course. The average disease duration is approximately 8-10 years from symptom onset. As the disease advances, individuals may require comprehensive care due to significant cognitive and functional decline. 

Memory Aid or Mnemonic: FTD-BRAIN

F – Frontal and Temporal: Atrophy primarily in these lobes.

T – Types: Includes behavioral variant (bvFTD) and language variants (PPA).

D – Dementia: Leads to cognitive decline, but not always memory first.

B – Behavior changes in personality, social conduct, empathy loss.

R- Reflexes (in some cases): Motor neuron disease signs in FTD-ALS variant.

A – Aphasia: Language difficulties in PPA variants.

I – Inhibition: Loss of, leading to disinhibition or compulsive behaviors.

N – Neuroimaging: Key for diagnosis, showing specific patterns of atrophy.

Use “FTD-BRAIN” to remember that frontotemporal dementia involves frontal and temporal lobe dysfunction, varied clinical presentations, and distinct neuroimaging findings, all centered around behavioral changes or language impairment rather than memory loss.

SUPERPoint: Frontotemporal dementia is a neurodegenerative disorder affecting the frontal and temporal lobes, leading to early-onset changes in behavior, personality, and language, with memory often preserved in initial stages.

SUPERFormula

Middle aged patient presents with early-onset dementia + behavioral changes + language impairments + frontal/temporal atrophy = Frontotemporal Dementia

Reference

Degenerative Diseases of the Nervous System. In: Ropper AH, Samuels MA, Klein JP, Prasad S. eds. Adams and Victor’s Principles of Neurology, 12e. McGraw-Hill Education; 2023