What lab work-up is recommended for patients presenting with memory loss?

Laboratory Work-up for Memory Loss

The initial laboratory work-up for patients presenting with memory loss should include complete blood count (CBC), comprehensive metabolic panel, thyroid function tests (TSH, free T4), vitamin B12 level, folate level, glucose level, ESR, and CRP to rule out underlying medical conditions that could contribute to cognitive impairment. 1

Basic Laboratory Testing

The following laboratory tests are essential components of the initial evaluation:

• Complete blood count (CBC)
• Comprehensive metabolic panel - to evaluate electrolyte and metabolic status
• Thyroid function tests - TSH and free T4
• Vitamin B12 level - to evaluate vitamin B12 deficiency
• Folate level - to evaluate folate deficiency
• Glucose level - to evaluate glucose metabolism
• Inflammatory markers - ESR and CRP

Additional Laboratory Tests to Consider

In certain clinical scenarios, additional laboratory tests may be warranted:

• Serology for syphilis
• HIV testing
• Heavy metal screening
• Ammonia levels
• Antithyroid peroxidase and thyroglobulin antibodies - to assess for Hashimoto's Encephalopathy 1

Imaging and Advanced Diagnostic Testing

Beyond laboratory testing, a comprehensive evaluation should include:

• Structural brain imaging - MRI is preferred (or head CT if MRI is contraindicated) to assess for:

  • Regional brain atrophy patterns
  • Vascular injury
  • Infarcts and microhemorrhages
  • Non-degenerative conditions 1

• Cerebrospinal fluid (CSF) biomarkers - In specialized settings, CSF analysis for Aβ1-42, tau, and phosphorylated tau (p-tau) may help identify Alzheimer's disease pathology 2

Diagnostic Algorithm

1. Initial cognitive screening using validated tools (MoCA, Mini-Cog, or informant-based questionnaires like AQ or AD8)

2. Basic laboratory panel as outlined above to identify potentially reversible causes

3. Structural brain imaging with MRI (or CT if MRI contraindicated)

4. If initial evaluation is inconclusive or suggests neurodegenerative disease:

   • Consider referral to a memory clinic for specialized assessment
   • Consider advanced biomarker testing (CSF analysis or amyloid-PET) in appropriate settings 2, 1

Important Clinical Considerations

• Mixed etiology is common - Many older adults with cognitive impairment have multiple contributing conditions 1

• Blood-based biomarkers - While promising, blood-based biomarkers for Alzheimer's disease are still being validated and should currently only be used in symptomatic patients at specialist clinics, with results confirmed by CSF or PET when possible 2

• Reversible causes to consider:

  • Depression and other mood disorders
  • Sleep disorders
  • Undetected or worsening seizure disorders
  • Undiagnosed or undertreated pain
  • Medication effects (particularly anticholinergics or sedatives) 1, 3

• Follow-up - Regular assessment at 6-month intervals using the same cognitive instruments can help track progression 1

Pitfalls to Avoid

• Relying solely on cognitive screening - A positive cognitive screening test is not a diagnosis and requires comprehensive evaluation 1

• Overlooking psychiatric causes - Depression is a common cause of memory complaints in older adults and should be thoroughly assessed 3

• Misinterpreting performance validity testing - Tests like the Test of Memory Malingering (TOMM) may yield false positives in patients with certain types of dementia, potentially leading to misdiagnosis 4

• Failing to consider educational and occupational background - Higher educational and occupational attainment may mask cognitive decline due to cognitive reserve 5