What labs are recommended for a patient with suspected dementia or Alzheimer's disease?

Recommended Laboratory Tests for Suspected Dementia or Alzheimer's Disease

For patients with suspected dementia or Alzheimer's disease, a tiered approach to laboratory testing is recommended, starting with broad first-tier tests to rule out common reversible causes, followed by more specialized testing based on clinical presentation.

First-Tier Laboratory Tests (Recommended for All Patients)

• Complete Blood Count (CBC) with differential 1, 2
• Comprehensive Metabolic Panel including:
  • Electrolytes (sodium, potassium, chloride)
  • Calcium and magnesium
  • Glucose
  • Liver function tests 1, 2
• Thyroid Function Tests (TSH) 1, 2, 3
• Vitamin B12 level 1, 2, 3
• Homocysteine level 1, 2, 4
• Erythrocyte Sedimentation Rate (ESR) 1
• C-Reactive Protein (CRP) 1

Brain Imaging (First-Tier)

• Brain MRI without gadolinium (or non-contrast CT if MRI is unavailable or contraindicated) 1, 2
  • Assess for: atrophy patterns, vascular disease, non-degenerative conditions (hydrocephalus, mass lesions)

Second-Tier Laboratory Tests (Based on Clinical Suspicion)

Consider these tests when initial workup is inconclusive or when specific conditions are suspected:

• Syphilis serology (RPR, FTA-ABS) 1, 2
• HIV testing 1, 2
• Lyme disease antibodies 1, 2
• Thyroid peroxidase (TPO) antibodies 1
• Antithyroglobulin antibodies (TGA) 1
• Folate level 1, 2
• Ammonia level 1, 4
• Lead level 1, 4
• Antinuclear antibodies (ANA) 1, 2
• HbA1c 1
• Lipid profile 1

Third-Tier Tests (Specialist Setting)

These tests should be performed by or in consultation with specialists:

• Cerebrospinal Fluid (CSF) Analysis 1, 2

  • AD biomarker panel (Amyloid-β, tau, phospho-tau)
  • Cell count, glucose, total protein

• Advanced Neuroimaging 1, 2

  • Brain FDG PET (or SPECT) scan
  • Amyloid PET scan
  • Tau PET scan

Special Considerations

• Heavy Metal Testing: Consider testing for mercury, copper, and arsenic in patients with atypical presentations or environmental exposures 4

• Sleep Study: Consider for patients with symptoms suggestive of obstructive sleep apnea or REM sleep disorder (particularly if Lewy Body Dementia is suspected) 1

• Metabolic Assessments: Methylmalonic acid (MMA) may be useful when B12 deficiency is suspected despite normal B12 levels 1, 4

Clinical Pearls

• Homocysteinemia is one of the most common abnormalities found in patients with cognitive impairment (present in 67-71% of cases) 4

• Laboratory abnormalities are often found in combination - 92% of patients with cognitive impairment have at least one abnormal biomarker and 60% have two or more 4

• While the standard workup can identify most reversible causes of dementia, the prevalence of fully reversible dementias is lower than previously believed (approximately 9-10%) 3, 5

• The diagnostic accuracy of clinical criteria alone for Alzheimer's disease is approximately 77%, even among experts, highlighting the importance of laboratory and imaging studies 6

• Consider medication review, particularly for patients taking proton pump inhibitors, which may affect vitamin B12 absorption 4

By following this tiered approach to laboratory testing, clinicians can efficiently identify potentially reversible causes of cognitive impairment while appropriately utilizing more specialized testing for complex cases.