What is the workup and management of frontotemporal dementia (FTD)?

Workup and Management of Frontotemporal Dementia (FTD)

The comprehensive workup and management of frontotemporal dementia requires a systematic diagnostic approach including detailed history taking, neurological examination, cognitive testing with emphasis on social cognition, neuroimaging, and consideration of genetic testing, followed by symptom-targeted treatment. 1

Diagnostic Workup

History Taking

• Obtain detailed history from caregivers (essential due to impaired insight in FTD patients) 1
• Establish clear timeline of symptoms including age at onset (typically 40-70 years), progression pattern, and relationship to life events 1
• Document insidious onset with progressive course (rather than abrupt onset or fluctuating course) 1
• Review medication use, substance use, and vascular risk factors 1
• Assess for key behavioral changes including disinhibition, apathy, loss of empathy 2
• Obtain family history focusing on neurodegenerative disorders (FTD, ALS) and psychiatric conditions 1

Physical and Neurological Examination

• Perform comprehensive neurological examination including: 1
  • Testing for parkinsonism (bradykinesia, rigidity, parkinsonian gait)
  • Assessment for motor neuron signs and primitive reflexes (e.g., grasp reflex)
  • Evaluation of smooth pursuit and saccadic eye movements
  • Testing for vertical gaze palsy (may suggest progressive supranuclear palsy)
  • Assessment for unilateral dystonia, apraxia, or alien limb phenomenon (may suggest corticobasal syndrome)

Cognitive Assessment

• Perform bedside cognitive screening with Montreal Cognitive Assessment (MoCA) or Addenbrooke's Cognitive Examination (ACE-III) 1
• Conduct comprehensive neuropsychological testing of all cognitive domains 2
• Include at least one structured test of social cognition (e.g., Ekman 60 Faces Test, Social Cognition and Emotional Assessment) 1, 2
• Assess for executive dysfunction using specific tests (e.g., Frontal Executive Screen) 1

Neuroimaging

• Brain MRI with 3D-T1 and FLAIR sequences is essential 1, 2
  • Look for pathological atrophy in frontal or anterior temporal areas
  • Use standardized review protocol with validated visual atrophy rating scales
  • Consider volumetric analyses if available
• FDG-PET should be considered in cases with normal or equivocal MRI findings 1, 2
  • Note that normal FDG-PET helps exclude FTD
  • Be cautious of non-specific abnormal findings which have lower specificity (68%)

Laboratory Testing

• Perform standard laboratory tests to exclude reversible causes: 1
  • Thyroid function tests
  • Vitamin B12 and homocysteine levels
  • Complete blood count
  • Comprehensive metabolic panel
  • Inflammatory markers (ESR, CRP)
• Consider CSF analysis for: 2
  • Amyloid-β42, tau, and p-tau (helps rule out Alzheimer's disease)
  • Neurofilament light chain (NfL) to differentiate FTD from psychiatric disorders

Genetic Testing

• Consider genetic testing for C9orf72, MAPT, and GRN mutations, especially with family history 1, 2
• C9orf72 testing should be strongly considered in all possible/probable FTD cases and suspected cases with strong psychiatric features 1
• Provide genetic counseling before testing 1

Management Approach

Non-pharmacological Interventions

• Caregiver education and support are essential components of treatment 2, 3
• Implement environmental modifications to manage behavioral symptoms 3
• Address safety concerns (driving, financial management, etc.) 2
• Provide family counseling 2
• Assemble an interdisciplinary care team 3

Pharmacological Management

• No FDA-approved medications specifically for FTD 4, 5
• Behavioral symptoms may respond to selective serotonin reuptake inhibitors 4, 6
• Use antipsychotics with caution for severe behavioral disturbances due to risks (cardiovascular, mortality) 4, 6
• Avoid cholinesterase inhibitors and memantine as they lack consistent positive effects in FTD 4

Follow-up and Monitoring

• Regular follow-up to assess disease progression and treatment response 1
• Monitor for development of motor neuron disease symptoms (ALS) 1
• Reassess safety concerns as disease progresses 3
• Adjust management plan based on evolving symptoms 6

Special Considerations

• FTD variants include behavioral variant FTD, semantic dementia, and progressive nonfluent aphasia, each with distinct clinical presentations 3, 7
• Genetic forms of FTD (40-50% of cases) may have different progression patterns 5
• Diagnostic accuracy improves with systematic application of clinical scales, neuropsychiatric consultation, and advanced neuroimaging 2