What labs are recommended to screen for the risk of Alzheimer's disease?

Laboratory Tests for Alzheimer's Disease Risk Screening

For patients with suspected cognitive impairment, a multi-tiered laboratory approach is recommended, with a basic set of Tier 1 laboratory tests including complete blood count, comprehensive metabolic panel, thyroid function, vitamin B12, homocysteine, and inflammatory markers. 1

Tier 1 Laboratory Tests (Recommended for All Patients)

• Complete blood count (CBC) with differential 1
• Comprehensive metabolic panel including:
  • Renal function tests 1, 2
  • Hepatic function tests 1, 2
  • Electrolytes (sodium, potassium) 1, 2
  • Glucose 1, 2
  • Calcium, magnesium, and phosphate 1, 2
• Thyroid-stimulating hormone (TSH) 1, 2
• Vitamin B12 level 1, 2
• Homocysteine level 1, 2
• Inflammatory markers:
  • C-reactive protein (CRP) 1, 2
  • Erythrocyte sedimentation rate (ESR) 1, 2

Structural Brain Imaging (Tier 1)

• Magnetic resonance imaging (MRI) without contrast is preferred 1, 2
• Computed tomography (CT) if MRI is contraindicated 1, 2

Additional Tests Based on Clinical Suspicion (Tier 2)

• Lipid profile 2
• HbA1c (in patients with suspected diabetes) 2
• Antithyroid antibodies (anti-TPO, anti-thyroglobulin) to rule out Hashimoto's encephalopathy 2
• Serology for syphilis (RPR, FTA-ABS) in cases with atypical presentations 2
• HIV serology in certain risk groups 2

Specialized Biomarker Tests (Tier 3-4)

• Blood-based biomarkers (BBMs) for triage in patients typically aged ≥55 years in primary care settings 1
• Cerebrospinal fluid (CSF) analysis for:
  • Amyloid beta (Aβ) 1
  • Total tau and phosphorylated tau (p-tau) 1
• Advanced neuroimaging:
  • Amyloid PET imaging 1
  • Tau PET imaging 1
  • FDG-PET in special circumstances 1

Clinical Pearls and Pitfalls

• Laboratory tests should not be interpreted in isolation but integrated with the patient's overall risk profile, history, and other diagnostic findings 1
• Blood-based biomarker results must be interpreted considering medical conditions (e.g., obesity, chronic kidney disease) and medications that may influence biomarker concentrations 1
• Normal laboratory values do not exclude Alzheimer's disease, as the definitive diagnosis requires biomarker evidence of amyloid and tau pathology 1
• In cases with conflicting biomarker results (e.g., reduced CSF Aβ but normal tau), additional biomarkers or imaging may be needed to clarify the diagnosis 1
• For early-onset (<65 years) or rapidly progressive dementia, a broader panel including tests for autoimmune, paraneoplastic, or infectious diseases should be considered 2

Algorithm for Laboratory Screening

1. Begin with Tier 1 laboratory tests and structural brain imaging for all patients with cognitive concerns
2. If Tier 1 tests are normal but cognitive concerns persist, proceed to cognitive testing with validated instruments
3. For patients with objective cognitive impairment and normal Tier 1 tests, consider Tier 2 tests based on clinical presentation
4. For patients with persistent cognitive decline despite normal Tier 1-2 tests, consider referral to a specialist for advanced biomarker testing (Tier 3-4)

This structured approach to laboratory screening helps identify potentially treatable causes of cognitive impairment while establishing a foundation for more specialized testing when Alzheimer's disease is strongly suspected 1, 2.