What is the initial step in a full workup for dementia to exclude secondary causes?

Initial Workup for Dementia to Exclude Secondary Causes

The initial step in a full workup for dementia should include comprehensive laboratory testing to rule out reversible causes, followed by brain imaging with MRI (or CT if MRI is contraindicated). 1, 2

Laboratory Testing (First-tier)

• Complete blood count (CBC) - to evaluate for anemia, infection
• Comprehensive metabolic panel - to assess electrolytes, kidney and liver function
• Thyroid function tests (TSH, free T4) - hypothyroidism can mimic dementia
• Vitamin B12 and folate levels - deficiencies can cause cognitive impairment
• Glucose level - to evaluate for diabetes or hypoglycemia
• Syphilis testing (RPR or VDRL) - especially in high-risk populations
• HIV testing - when risk factors are present
• Urinalysis - to rule out infection 2, 1

Brain Imaging

• MRI brain without contrast - preferred modality to evaluate for:
  • Structural abnormalities (tumors, subdural hematomas)
  • Vascular changes (infarcts, white matter disease)
  • Patterns of atrophy suggestive of specific dementia types
  • Normal pressure hydrocephalus
• CT head without contrast - if MRI is contraindicated 2, 1

Additional Considerations Based on Clinical Presentation

When to Consider Second-tier Testing:

• Atypical presentation (age <65, rapid progression, focal neurological signs)
• First-tier tests normal but high clinical suspicion
• Family history suggesting genetic cause

Second-tier Testing May Include:

• Lumbar puncture with CSF analysis - for suspected inflammatory, infectious causes or Alzheimer's biomarkers (Aβ, tau, phospho-tau)
• EEG - particularly for suspected seizure disorders or rapidly progressive dementias
• Advanced neuroimaging - FDG-PET, amyloid PET, or SPECT in selected cases
• Specialized blood tests - depending on clinical suspicion:
  • Copper and ceruloplasmin (Wilson's disease)
  • Paraneoplastic antibodies
  • Inflammatory markers (ESR, CRP)
  • Heavy metal screening 2

Common Pitfalls to Avoid

1. Missing treatable causes - Always complete first-tier laboratory testing before concluding a primary neurodegenerative process
2. Inadequate medication review - Many medications can cause cognitive impairment, especially anticholinergics and sedatives
3. Overlooking depression - Can mimic or coexist with dementia; consider PHQ-9 screening
4. Failing to assess for sleep disorders - Sleep apnea can significantly impact cognition
5. Neglecting to evaluate for delirium - Use Confusion Assessment Method to distinguish from dementia 2, 1

Special Considerations

• Age-specific approach - Younger patients (<65) require more extensive workup including genetic testing consideration
• Rapidly progressive symptoms - Warrant urgent and more extensive evaluation including prion disease markers
• Intellectual disability patients - Assessment should be based on decline from personal baseline, not population norms 2

Following this systematic approach ensures that potentially reversible causes of cognitive impairment are identified before attributing symptoms to irreversible neurodegenerative conditions.