Frontotemporal Dementia 

Frontotemporal dementia (FTD) is a group of neurodegenerative disorders characterized by progressive degeneration of the frontal and/or temporal lobes, leading to:

  • Early behavioral changes
  • Language dysfunction
  • Relative preservation of memory in early stages

 Typically presents earlier than Alzheimer’s disease (age 45–65 years)

 

 Epidemiology 

  • Second most common cause of early-onset dementia (<65 yrs) after Alzheimer’s disease
  • Peak onset: 50–60 years
  • Strong genetic association (~30–40%)

 Classification 

1. Behavioral Variant FTD (bvFTD) — Most common

  • Personality and behavioral changes dominate

2. Primary Progressive Aphasia (PPA)

Subtypes:

  • Semantic variant (svPPA)
  • Nonfluent/agrammatic variant (nfvPPA)
  • Logopenic variant (usually Alzheimer pathology, not classic FTD)

 Pathology 

Proteinopathies:

  1. Tau-positive (FTLD-tau)
    • Pick bodies (rounded inclusions)
    • Associated with:
      • MAPT mutations
  1. TDP-43 proteinopathy (FTLD-TDP)
    • Most common
  2. FUS proteinopathy (rare)

 Genetics 

  • Autosomal dominant inheritance (~10–20%)

Key genes:

  • MAPT (tau gene)
  • GRN (progranulin)
  • C9orf72 repeat expansion
    → Also associated with Amyotrophic lateral sclerosis

 Pathophysiology

  • Selective degeneration of:
    • Frontal lobes → behavior/executive dysfunction
    • Temporal lobes → language and semantic memory
  • Neurochemical:
    • Relative cholinergic preservation (contrast with Alzheimer’s)

 Clinical Features 

 Behavioral Variant FTD (bvFTD)

Feature

Description

Disinhibition

Socially inappropriate behavior

Apathy

Loss of motivation

Loss of empathy

Emotional blunting

Compulsive behavior

Repetitive rituals

Hyperorality

Increased eating, sweet preference

Executive dysfunction

Poor planning, judgment

 Memory relatively preserved early

 Primary Progressive Aphasia

1. Semantic variant (svPPA)

  • Loss of word meaning
  • Fluent but empty speech
  • Anomia
  • Temporal lobe atrophy

2. Nonfluent/agrammatic variant (nfvPPA)

  • Effortful, halting speech
  • Agrammatism
  • Speech apraxia

 Red Flags Suggesting FTD 

  • Early personality change
  • Loss of social decorum
  • Compulsive behaviors
  • Early language impairment
  • Family history
  • Onset <65 years

 Diagnosis 

1. Clinical Criteria (Rascovsky criteria for bvFTD)

  • Progressive deterioration
  • ≥3 of:
    • Disinhibition
    • Apathy
    • Loss of empathy
    • Perseverative behavior
    • Hyperorality
    • Executive dysfunction

2. Neuroimaging

4

  • MRI brain:
    • Frontal and/or anterior temporal atrophy
    • “Knife-edge” gyri
  • FDG-PET:
    • Hypometabolism in frontal/temporal lobes

3. Neuropsychological Testing

  • Executive dysfunction >> memory impairment

4. CSF Biomarkers

  • Helps differentiate from Alzheimer’s disease
  • FTD: normal or mildly altered Aβ/tau

 Differentiation from Alzheimer’s 

Feature

FTD

Alzheimer’s

Age

Younger

Older

Early symptom

Behavior/language

Memory

Personality change

Prominent

Late

MRI

Frontal/temporal

Hippocampal

Cholinesterase inhibitors

Poor response

Good response

 

 Management (Guideline-Based, No Disease-Modifying Therapy)

1. Non-Pharmacological (First-line)

  • Behavioral strategies
  • Caregiver education
  • Structured routine

2. Pharmacological

For behavioral symptoms:

  • SSRIs → first-line (disinhibition, compulsions)
  • Trazodone → agitation

Antipsychotics (cautious use)

  • Severe behavioral disturbance only

 Not recommended:

  • Cholinesterase inhibitors (e.g., Donepezil)
  • Memantine
     May worsen behavior

FTD–ALS Spectrum 

  • Overlap with Amyotrophic lateral sclerosis
  • Especially C9orf72 mutation
  • Features:
    • Dementia + motor neuron signs

 Prognosis

  • Progressive and fatal
  • Survival: 6–8 years (average)
  • Faster progression than Alzheimer’s