What are the diagnostic criteria and treatment options for frontotemporal dementia?

Diagnosis of Frontotemporal Dementia

Accurate diagnosis of frontotemporal dementia (FTD) requires a comprehensive clinical assessment including detailed history from caregivers, neuropsychiatric evaluation, neuropsychological testing with social cognition assessment, and specific neuroimaging protocols. 1

Clinical Assessment

History Taking

• Essential components:
  • Detailed timeline of symptom onset (typically age 40-70)
  • Predominant early symptoms (behavior, language, memory)
  • Relationship to life events
  • Progression pattern (insidious onset with gradual progression)
  • Caregiver-based history is essential due to impaired insight in FTD patients 2
  • Additional history from an independent relative/friend is recommended

Psychiatric Assessment

• Apply DSM-5 criteria to identify specific psychiatric disorders that may mimic FTD 2
• Evaluate for:
  • Depressive symptoms
  • Anxiety
  • Apathy
  • Manic symptoms
  • Delusions and hallucinations
  • Obsessive-compulsive symptoms
• Note: Lack of insight is more common in behavioral variant FTD (bvFTD) than in psychiatric disorders

Neurological Examination

• Identify motor signs associated with FTD (present in 25-80% of cases):
  • Parkinsonism (bradykinesia, rigidity, gait abnormalities)
  • Oculomotor abnormalities
  • Signs of motor neuron disease/ALS
  • Asymmetric rigidity (suggests corticobasal syndrome)
  • Vertical gaze palsy

Cognitive Assessment

Screening Tests

• Montreal Cognitive Assessment (MoCA) is superior to MMSE for FTD detection (88% accuracy) 1
• Normal MMSE scores are common in early bvFTD
• Addenbrooke's Cognitive Examination (ACE-III) is also recommended

Comprehensive Cognitive Testing

• Evaluate multiple domains:
  • Executive function (use tests like Frontal Assessment Battery)
  • Attention
  • Language (including action word naming)
  • Memory
  • Working memory
  • Visuoperceptual tasks

Social Cognition Assessment

• At least one structured test of social cognition should be performed 2
  • Ekman 60 Faces Test
  • Social Cognition and Emotional Assessment (SEA or Mini-SEA)
  • Theory of mind tasks

Neuroimaging

Structural Imaging

• Brain MRI with 3D T1 sequence and FLAIR is the first-line imaging test 2
  • Look for frontal and/or anterior temporal lobe atrophy
  • Use standardized visual atrophy rating scales
  • Consider volumetric analyses if available
• CT head (without contrast) can be used if MRI is contraindicated 2

Functional Imaging

• FDG-PET is recommended in ambiguous cases without clear structural abnormalities 2
  • Sensitivity of 60% and positive predictive value of 78.5% for differentiating FTD subtypes
  • Pattern of hypometabolism in frontal and/or temporal regions
  • Normal FDG-PET helps exclude bvFTD
  • Non-specific findings should prompt reconsideration of psychiatric etiology

Biomarkers

CSF Analysis

• Consider CSF analysis of:
  • Amyloid-β42, tau, and p-tau (to rule out Alzheimer's disease)
  • Neurofilament light chain (NfL) to differentiate FTD from psychiatric disorders (AUC 0.93) 1

Genetic Testing

• Genetic testing should be strongly considered in all possible/probable bvFTD cases 2
• Especially important with:
  • Family history of FTD or related disorders
  • Early onset (<65 years)
  • Atypical presentations
• Common genetic mutations:
  • C9orf72 repeat expansion
  • MAPT (tau)
  • GRN (progranulin)

Diagnostic Criteria for bvFTD

Possible bvFTD (≥3 of the following):

1. Early behavioral disinhibition
2. Early apathy or inertia
3. Early loss of sympathy/empathy
4. Early perseverative, stereotyped or compulsive behaviors
5. Hyperorality and dietary changes
6. Executive deficits with relative sparing of memory and visuospatial functions

Probable bvFTD:

• All criteria for possible bvFTD
• Significant functional decline
• Imaging results consistent with bvFTD (frontal and/or anterior temporal atrophy on MRI/CT, or frontal and/or anterior temporal hypoperfusion/hypometabolism on PET/SPECT)

Differential Diagnosis

• Alzheimer's disease
• Primary psychiatric disorders (depression, bipolar disorder, schizophrenia)
• Vascular dementia
• Dementia with Lewy bodies
• Substance-induced conditions
• Non-progressive "phenocopies" of bvFTD

Treatment Approaches

Non-pharmacological Management

• Behavioral management techniques that leverage preserved functions
• Caregiver education and support
• Environmental modifications
• Communication strategies

Pharmacological Management

• No disease-specific treatments are currently available
• Selective serotonergic antidepressants may help behavioral symptoms
• Antipsychotics should be used with caution due to motor, cardiovascular, and mortality risks
• Current antidementia drugs (cholinesterase inhibitors, memantine) have no consistent positive effects in FTD

Diagnostic Pitfalls

• FTD is often misdiagnosed as a psychiatric disorder due to behavioral symptoms
• C9orf72 mutation carriers can present with psychiatric symptoms years before typical FTD features
• Non-progressive "phenocopies" of bvFTD can be challenging to diagnose
• Lack of insight in patients may lead to underreporting of symptoms