What laboratory tests should be ordered to evaluate acute cognitive decline in an older adult?

Laboratory Testing for Acute Cognitive Decline in Older Adults

Order a focused laboratory panel including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone (TSH), vitamin B12, and urinalysis to identify reversible causes of acute cognitive decline. 1, 2, 3

Essential Laboratory Tests

The following tests should be ordered for every older adult presenting with acute cognitive decline:

• Complete blood count (CBC) with differential to detect infection, anemia, or hematologic abnormalities 2, 3
• Comprehensive metabolic panel (CMP) to identify electrolyte disturbances (particularly hyponatremia), renal dysfunction, hepatic dysfunction, and glucose abnormalities 2, 4, 3
• Thyroid-stimulating hormone (TSH) to screen for hypothyroidism, which accounts for 1.7-2.6% of reversible cognitive impairment 1, 2, 5
• Vitamin B12 level to detect deficiency, which represents 1.7% of reversible causes 1, 2, 5
• Urinalysis to identify urinary tract infections, the most common infectious cause of delirium in older adults 1, 2, 3

Additional Testing Based on Clinical Context

Consider these tests when clinical suspicion warrants:

• Hemoglobin A1C for patients with diabetes or suspected hyperglycemia, as poor glycemic control is associated with cognitive decline 1, 2
• Urine toxicology screen if substance use is suspected 2, 3
• Blood cultures if systemic infection is suspected 3
• Medication levels for drugs with narrow therapeutic windows (e.g., digoxin, anticonvulsants) 3

Critical Distinction: Delirium vs. Dementia

Before ordering extensive testing, use validated screening tools to differentiate acute delirium from chronic dementia:

• Delirium characteristics: acute onset, fluctuating course, disordered attention and consciousness, hallucinations often present 1, 3
• Dementia characteristics: insidious onset, constant course, attention generally preserved (until advanced stages) 1, 3
• Use the Brief Confusion Assessment Method (bCAM) for delirium screening in the emergency or acute care setting 1, 3

Medication Review as Priority

Immediately review all medications for anticholinergic burden and sedating effects before extensive laboratory workup, as medications are among the most common and immediately reversible causes of acute cognitive decline 1, 2:

• High-risk medications include anticholinergics, benzodiazepines, opioids, first-generation antihistamines, muscle relaxants, and tricyclic antidepressants 2, 4
• Polypharmacy and drug-drug interactions are particularly problematic in older adults 1

Neuroimaging Considerations

While not strictly "laboratory" testing, MRI brain (with and without contrast when possible) is superior to CT for identifying structural lesions including normal pressure hydrocephalus, subdural hematoma, and vascular changes 2, 4, 5:

• Normal pressure hydrocephalus accounts for 0.9% of reversible dementias 5
• Chronic subdural hematoma accounts for 0.4% 5
• Neuroimaging should be performed when clinically indicated rather than routinely 5, 6

Depression Screening

Screen systematically for depression using validated instruments (PHQ-9, GDS), as depression is the most common potentially reversible cause of cognitive symptoms in older adults 1, 4, 6:

• Depression can present with prominent cognitive complaints ("pseudodementia") 3, 6
• Treatment of depression resulted in partial cognitive improvement in 0.9% of dementia cases 5

Common Pitfalls to Avoid

• Do not rely on routine laboratory panels alone without clinical context, as abnormal results do not always correlate with cognitive outcomes 7
• Do not assume all metabolic abnormalities will reverse cognitive symptoms, even when treated—true full reversibility is rare (1.7% in one study) 5, 8
• Do not miss neuroinfections, which accounted for 11/24 (46%) of reversible cases in one prospective study and showed substantial improvement with treatment 8
• Avoid hypoglycemia in diabetic patients, as it increases dementia risk; check glucose immediately if diabetes is present 1, 3

Expected Yield of Testing

The evidence suggests realistic expectations for reversibility:

• Potentially reversible conditions are identified in 7.3-18% of dementia cases 5, 8
• However, actual clinical improvement occurs in only 1.7-20% of cases, and is usually partial rather than complete 5, 8
• The most commonly identified reversible causes are hypothyroidism, B12 deficiency, depression, normal pressure hydrocephalus, and infections 5, 8, 6