Initial Bloodwork for Dementia Evaluation
All patients presenting with cognitive or behavioral symptoms concerning for dementia should receive a comprehensive Tier 1 laboratory panel including: CBC with differential, complete metabolic panel (Chem-20 with renal and hepatic function, electrolytes, glucose, calcium, magnesium, phosphate), TSH, vitamin B12, homocysteine, CRP, and ESR. 1
Core Laboratory Tests (Tier 1 - Obtain in All Patients)
The 2025 Alzheimer's Association guidelines provide the most current and comprehensive recommendations for initial dementia workup, designating these as Strength of Recommendation A:
Complete Blood Count and Metabolic Panel
- CBC with differential to identify anemia, infection, or hematologic abnormalities that may contribute to cognitive symptoms 1
- Complete metabolic panel (Chem-20) including:
- Electrolytes (sodium, potassium, chloride, bicarbonate) - hyponatremia is a treatable cause of cognitive impairment 1, 2
- Renal function (BUN, creatinine) to assess for uremia 1
- Hepatic function (AST, ALT, alkaline phosphatase, bilirubin) 1
- Glucose - both hypoglycemia and hyperglycemia can cause cognitive dysfunction 1, 2
- Calcium - hypercalcemia from hyperparathyroidism is a reversible cause 1, 2
- Magnesium and phosphate 1
Endocrine and Vitamin Testing
- Thyroid-stimulating hormone (TSH) - hypothyroidism is one of the most common reversible causes of dementia 1, 3
- Vitamin B12 level - deficiency can mimic or exacerbate dementia symptoms 1, 3
- Folate level - though less commonly causative, should be checked alongside B12 1
Inflammatory Markers
- C-reactive protein (CRP) to assess for systemic inflammation 1
- Erythrocyte sedimentation rate (ESR) as an additional inflammatory marker 1
Additional Metabolic Markers
- Homocysteine level - elevated levels may contribute to vascular cognitive impairment 1
Rationale for This Comprehensive Approach
The multi-tiered laboratory approach serves to identify common comorbid conditions that rarely cause but often contribute to cognitive symptoms, allowing for treatment of reversible or exacerbating factors 1. This panel has high yield for uncovering conditions that influence cognition while ruling out metabolic encephalopathies, endocrine disorders, and nutritional deficiencies 1.
Key Clinical Considerations
The laboratory results should never be interpreted in isolation - they must be integrated with the patient's clinical history, cognitive testing results, and physical examination findings 1. While truly reversible dementias are less common than previously believed (occurring in approximately 9.5-11% of cases), identifying treatable contributing factors remains essential 2.
Selective Testing (Tier 2 - Based on Clinical Suspicion)
Beyond the core panel, additional tests should be ordered when specific clinical features suggest particular etiologies:
- Syphilis serology (RPR/VDRL) - only when clinical suspicion exists for neurosyphilis, not as routine screening 1, 3
- HIV testing - in patients with risk factors or atypical presentations 1
- Heavy metal screening - only with specific exposure history 1
- Urinalysis - when urinary tract infection is suspected as a delirium trigger 1
Common Pitfalls to Avoid
Do not order syphilis testing routinely - the 2001 American Academy of Neurology guidelines specifically state screening for syphilis is not justified unless clinical suspicion is present 3. This represents a shift from older practices that included universal syphilis screening.
Do not rely solely on laboratory values below reference ranges - the goal is to identify conditions that may be contributing to cognitive decline, even if values are technically "normal" but suboptimal (e.g., low-normal B12 levels) 1.
Do not delay structural neuroimaging - brain MRI (or CT if MRI contraindicated) should be obtained concurrently with laboratory testing, not sequentially, as it is equally essential for excluding structural lesions and identifying vascular contributions 1.
Cost-Effectiveness Considerations
While the comprehensive 2025 Alzheimer's Association panel is more extensive than older guidelines, it reflects current understanding that inflammatory markers and homocysteine provide additional diagnostic value 1. Earlier guidelines from 2000 showed significant cost variation ($198-$1,988) depending on comprehensiveness, but the clinical yield of identifying treatable conditions justifies the more thorough modern approach 1.