What laboratory tests are indicated for a patient presenting with decreased cognition?

Laboratory Testing for Decreased Cognition

All patients presenting with decreased cognition should undergo routine Tier 1 laboratory testing including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone (TSH), and vitamin B12 levels, with additional testing individualized based on clinical presentation and risk factors. 1, 2

Mandatory Tier 1 Laboratory Tests

These tests should be obtained in all patients presenting with cognitive impairment to identify potentially reversible causes:

• Complete blood count (CBC) - screens for anemia and infection 1, 2
• Comprehensive metabolic panel - evaluates electrolyte disturbances, renal function, glucose abnormalities, and hepatic function 1, 2
• Thyroid-stimulating hormone (TSH) with free T4 if abnormal - hypothyroidism is a common reversible cause 1, 2, 3
• Vitamin B12 and folate levels - deficiency can cause dementia that substantially improves with treatment 1, 2, 4
• Liver function tests (ALT, AST) - hepatic encephalopathy presents with attention deficits and forgetfulness 2

Tier 2 Laboratory Tests (Based on Clinical Context)

Add these tests when specific risk factors or clinical features are present:

• Hemoglobin A1c - for patients with diabetes or metabolic syndrome 2
• Lipid panel - for vascular risk stratification 2
• HIV testing - if risk factors present 5
• Syphilis serology (RPR/VDRL) - particularly in younger patients or those with risk factors 3

Tier 3-4 Specialized Testing (Selected Cases Only)

These are reserved for specific clinical scenarios and should not be routine:

• Lumbar puncture with CSF analysis - indicated for early-onset dementia (<65 years), rapidly progressive dementia, or suspected autoimmune/infectious/paraneoplastic causes 2
• CSF Alzheimer's biomarkers (Aβ42/Aβ40 ratio, p-tau181, t-tau) - strong recommendation for patients with mild dementia to identify or exclude AD as the underlying cause 1
• Blood biomarkers for amyloid pathology - emerging tools that may reduce need for CSF or PET imaging in appropriate clinical contexts (patients with objective cognitive impairment where AD is suspected after comprehensive workup) 1, 2

Critical Accompanying Assessments

Laboratory testing must be paired with these evaluations:

• Validated cognitive testing (MoCA, Mini-Cog, or MMSE) to establish objective cognitive impairment - laboratory results alone are insufficient 1, 2
• Structural brain imaging (MRI preferred over CT) to evaluate for stroke, white matter disease, atrophy patterns, hydrocephalus, and space-occupying lesions 1, 2, 5
• Corroborative informant history about changes in cognition, function, and behavior using structured tools 1, 6, 5

Evidence on Reversibility

The potential for reversibility justifies comprehensive laboratory screening:

• 18% of dementia cases in one prospective study had reversible causes (neuroinfections, normal pressure hydrocephalus, vitamin B12 deficiency), with substantial improvement following treatment 4
• However, true complete reversibility is rare (1.4-3.6% in clinical practice), though partial improvement occurs more frequently 7
• Depression is the most common potentially reversible condition affecting cognition 3

Common Pitfalls to Avoid

• Do not order extensive laboratory panels indiscriminately - abnormal results often do not correlate with diagnosis or cognitive outcome when clinical indicators are absent 8
• Do not rely on laboratory tests alone - careful clinical history and examination are most useful for identifying potentially reversible causes 7
• Do not assume "reversible dementia" means full recovery - even when etiology is treatable, cognitive symptoms may only partially improve 3, 7
• Do not skip structural neuroimaging - CT scan detected reversible causes only in patients with neurological signs, but MRI is superior for vascular and structural lesions 2, 7