Laboratory Evaluation for Sundowning Syndrome
In patients with sundowning syndrome, obtain a complete blood count with differential, comprehensive metabolic panel (including liver and renal function, glucose), thyroid function tests (TSH), vitamin B12, and urinalysis to exclude reversible medical causes of delirium and agitation.
Essential Laboratory Tests
The diagnostic workup for sundowning requires precise evaluation to identify treatable underlying causes, as the syndrome often reflects acute medical decompensation superimposed on dementia rather than a primary circadian phenomenon 1.
Core Laboratory Panel
Complete Blood Count (CBC) with differential: Screen for infection (leukocytosis), anemia (which can worsen confusion), and lymphocytopenia (suggesting immunosuppression or chronic illness) 2, 1
Comprehensive Metabolic Panel (CMP): Evaluate for electrolyte disturbances, renal dysfunction, hepatic impairment, and hyperglycemia or hypoglycemia—all of which can precipitate or worsen evening agitation 3, 1
Thyroid Function (TSH at minimum): Hypothyroidism or hyperthyroidism can manifest as cognitive changes and behavioral disturbances; TSH should be assessed at least once in patients with suspected dementia-related syndromes 4
Vitamin B12 level: Deficiency causes cognitive impairment and neuropsychiatric symptoms that may worsen in the evening 3
Urinalysis: Urinary tract infections are a common precipitant of acute confusion and agitation in elderly patients with dementia, often presenting without classic symptoms 1
Additional Considerations Based on Clinical Context
When Infection is Suspected
- Blood cultures if fever or systemic signs of infection are present 1
- Chest radiography if respiratory symptoms exist 1
When Metabolic Derangement is Likely
- Calcium and magnesium levels: Hypercalcemia and hypomagnesemia can cause confusion and agitation 4
- Liver function tests (AST, ALT, alkaline phosphatase, bilirubin): Hepatic encephalopathy can present with diurnal variation in mental status 4
When Nutritional Deficiency is Suspected
- Vitamin D and folate levels: Particularly if malabsorption or poor nutrition is evident 4
- Thiamine level: In patients with alcohol use history or malnutrition 4
What NOT to Routinely Order
Avoid shotgun laboratory testing without clinical indication, as this leads to false positives, unnecessary anxiety, cost, and delayed appropriate treatment 4. Specifically:
- Do not order extensive autoimmune panels (ANA, rheumatoid factor) without specific clinical suspicion of autoimmune disease 4
- Do not routinely check heavy metal levels, Lyme titers, or exotic infectious serologies without epidemiologic risk factors 4
- Serum cortisol, ACTH, and other endocrine tests should be reserved for patients with specific clinical features suggesting endocrinopathy 4
Critical Clinical Pitfalls
The most common mistake is attributing evening agitation solely to "sundowning" without investigating acute medical illness. Sundowning often represents delirium superimposed on dementia, with reversible causes including 1, 5:
- Urinary tract infection (most common)
- Medication effects or polypharmacy
- Pain (often unrecognized in non-verbal patients)
- Constipation or urinary retention
- Hypoxia or occult infection
A normal alkaline phosphatase does not exclude significant medical pathology, just as normal labs do not rule out delirium if clinical suspicion is high 4. The diagnosis remains clinical, supported by laboratory exclusion of reversible causes 1, 5.
Practical Algorithm
- First-line labs for ALL patients: CBC, CMP, TSH, B12, urinalysis 2, 3, 1
- If labs abnormal or infection suspected: Add targeted studies (cultures, imaging, additional chemistries) 1
- If all labs normal: Focus on non-pharmacologic interventions (bright light therapy, sleep hygiene, environmental modification) and consider acetylcholinesterase inhibitors if not already prescribed 5, 6
- Reserve advanced testing (MRI, EEG, lumbar puncture) for atypical presentations or when focal neurologic signs emerge 1
The goal is identifying and treating reversible medical causes while avoiding unnecessary testing that delays appropriate behavioral and environmental interventions 4, 1, 5.