What is the diagnostic approach for frontotemporal dementia?

Diagnosing Frontotemporal Dementia

The diagnosis of frontotemporal dementia (FTD) requires a comprehensive clinical assessment including detailed history from caregivers, neuropsychiatric evaluation, neuropsychological testing, social cognition assessment, and neuroimaging to identify characteristic patterns of frontal and/or anterior temporal lobe atrophy. 1

Clinical History and Presentation

Essential History Elements

• Obtain caregiver-based history (essential due to patient's impaired insight)
• Collect history from multiple informants when possible
• Document clear timeline of symptoms:
  • Age at onset (typically 40-70 years)
  • Predominant early symptoms
  • Progression pattern (insidious onset with gradual progression)
  • Relationship to life events

Behavioral Variant FTD (bvFTD) Features

• Personality and behavioral changes:
  • Disinhibition and social inappropriateness
  • Apathy and emotional blunting
  • Loss of empathy
  • Stereotyped or compulsive behaviors
  • Hyperorality and dietary changes
  • Executive dysfunction with relatively preserved memory 2, 3

Language Variant FTD Features

• Progressive nonfluent aphasia:
  • Effortful speech
  • Grammatical errors
  • Hesitant speech
• Semantic dementia:
  • Loss of word meaning
  • Impaired object knowledge
  • Difficulty with comprehension 2, 3

Neurological Examination

• Perform comprehensive neurological examination to identify associated motor signs:
  • Parkinsonism (present in 25-80% of FTD cases)
  • Oculomotor abnormalities
  • Signs of motor neuron disease/ALS
  • Asymmetric rigidity (suggesting corticobasal syndrome)
  • Vertical gaze palsy (suggesting progressive supranuclear palsy) 1, 4

Psychiatric Assessment

• Apply DSM-5 criteria to identify specific psychiatric disorders that may mimic FTD
• Evaluate for:
  • Depressive symptoms
  • Anxiety
  • Apathy
  • Manic symptoms
  • Delusions and hallucinations
  • Obsessive-compulsive symptoms
• Note: Lack of insight is more common in bvFTD than in psychiatric disorders 1

Cognitive Assessment

Bedside Screening

• Montreal Cognitive Assessment (MoCA) is superior to MMSE for FTD detection
  • Classification accuracy of 88% (78% sensitivity, 98% specificity)
• Note: Normal MMSE scores are common in early bvFTD 1

Comprehensive Neuropsychological Testing

• Evaluate multiple cognitive domains:
  • Attention (e.g., Digits Forward, Trail Making Test-A)
  • Language (expressive and receptive)
  • Memory (episodic verbal and non-verbal)
  • Working memory (e.g., Digits Backward)
  • Visuoperceptual tasks
  • Executive function (e.g., Stroop Test, Trail Making Test-B)
  • Action word naming (more affected in FTD than object naming)

Social Cognition Assessment

• Perform at least one structured test of social cognition:
  • Ekman 60 Faces Test
  • Social Cognition and Emotional Assessment (SEA or Mini-SEA)
• Note: Social cognition deficits are often prominent in bvFTD 1

Neuroimaging

Structural Imaging

• Brain MRI with T1 and FLAIR sequences including coronal cuts
  • Look for frontal and/or anterior temporal lobe atrophy
  • 3D T1 sequence (e.g., MPRAGE) recommended
• Brain CT with coronal views only if MRI contraindicated

Functional Imaging

• FDG-PET in ambiguous cases without clear structural abnormalities
  • Hypometabolism in frontal and/or temporal regions
• Note: Non-specific FDG-PET findings should prompt reconsideration of psychiatric etiology 1

Laboratory Testing

CSF Biomarkers

• Consider CSF analysis of amyloid-β42, tau, and p-tau to rule out Alzheimer's disease
• CSF neurofilament light chain (NfL) can help differentiate FTD from psychiatric disorders
  • High diagnostic accuracy (AUC 0.93) 1
• Plasma NfL is elevated in bvFTD compared to schizophrenia, depression, and bipolar disorder

Genetic Testing

• Consider genetic testing, especially with:
  • Family history of FTD or related disorders
  • Early onset (<65 years)
  • Atypical presentations
• Common genetic mutations in FTD:
  • C9orf72 repeat expansion
  • MAPT (tau)
  • GRN (progranulin) 1, 5

Diagnostic Challenges

• FTD is commonly misdiagnosed as a psychiatric disorder
• Key distinguishing features from psychiatric disorders:
  • Insidious onset with progressive course
  • Middle to late adulthood onset
  • Lack of insight
  • Neuroimaging abnormalities
  • Elevated CSF/plasma NfL
  • Presence of neurological signs

Diagnostic Algorithm

1. Obtain detailed history from caregivers focusing on behavioral/personality changes or language deficits
2. Perform neurological examination looking for associated motor signs
3. Conduct bedside cognitive screening (MoCA preferred over MMSE)
4. Assess social cognition with structured tests
5. Order brain MRI with focus on frontal and temporal lobes
6. If diagnosis remains unclear:
   • Perform comprehensive neuropsychological testing
   • Consider FDG-PET
   • Consider CSF biomarkers including NfL
   • Consider genetic testing in appropriate cases

Pitfalls to Avoid

• Relying solely on patient self-report (due to impaired insight)
• Misattributing symptoms to late-onset psychiatric disorders
• Overemphasizing memory deficits (relatively preserved in early FTD)
• Relying on normal MMSE scores to exclude FTD
• Failing to obtain corroborating history from caregivers
• Missing associated neurological signs that suggest specific FTD variants

By following this systematic approach, clinicians can improve diagnostic accuracy for frontotemporal dementia and distinguish it from psychiatric disorders that may present with similar behavioral features.