Laboratory Workup for Dementia
All patients with suspected dementia should receive a standardized Tier 1 laboratory panel including complete blood count with differential, complete metabolic panel (electrolytes, glucose, calcium, magnesium, phosphate, renal and hepatic function), thyroid-stimulating hormone (TSH), vitamin B12, homocysteine, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), along with structural brain imaging (MRI preferred, CT if contraindicated). 1, 2
Tier 1: Routine Laboratory Tests (Required for All Patients)
The following tests should be obtained in all or almost all patients presenting with cognitive or behavioral symptoms:
Hematologic and Metabolic Panel
- Complete blood count (CBC) with differential to evaluate for anemia, infection, or hematologic disorders 1, 2, 1
- Complete metabolic panel (Chem-20) including:
Endocrine and Vitamin Assessment
- Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1, 2, 3
- Vitamin B12 level to identify deficiency 1, 2, 3
- Homocysteine level as an additional marker 1, 2
Inflammatory Markers
This Tier 1 panel is nearly universally recommended by specialty society practice parameters and represents the standard of care for dementia evaluation. 1 These tests help identify common comorbid conditions that rarely cause but often contribute to cognitive symptoms. 1
Tier 1: Structural Neuroimaging (Required for All Patients)
Brain MRI without contrast is the preferred imaging modality for dementia workup, providing superior detection of vascular lesions, regional atrophy patterns, and subtle pathology. 1, 2
MRI Protocol (When Available)
- 3T MRI preferred over 1.5T if available and no contraindications exist 1
- Required sequences include:
CT Protocol (If MRI Contraindicated or Unavailable)
Imaging Interpretation
Use semi-quantitative scales for standardized assessment: 1
- Medial temporal lobe atrophy (MTA) scale for hippocampal involvement
- Fazekas scale for white matter changes
- Global cortical atrophy (GCA) scale for overall atrophy
Neuroimaging is essential to exclude non-degenerative conditions (hydrocephalus, tumors, subdural hematomas), assess vascular contributions (infarcts, leucoaraiosis), and identify patterns of regional atrophy consistent with specific neurodegenerative diseases. 1, 2
Tier 2: Selective Testing Based on Clinical Suspicion
These tests should be ordered when specific clinical features, risk factors, or atypical presentations suggest particular etiologies:
Infectious Disease Screening
- Syphilis serology (RPR, FTA-ABS) in patients with atypical presentations or risk factors 2
- HIV testing when risk factors are present 2, 3
Additional Metabolic and Inflammatory Markers
- Lipid profile in patients with vascular risk factors 2
- HbA1c for diabetes assessment 2
- Antithyroid antibodies (anti-TPO, anti-thyroglobulin) to rule out Hashimoto's encephalopathy 2
Special Population Considerations
- Enhanced thyroid screening in patients with Down syndrome due to higher prevalence of hypothyroidism 2
Tier 3-4: Advanced Testing for Complex Cases
Reserve these specialized investigations for atypical presentations, including early-onset dementia (age <65 years), rapidly progressive dementia, or when initial workup is inconclusive:
Cerebrospinal Fluid Analysis
Lumbar puncture with CSF biomarkers (Aβ42, total tau, phosphorylated tau, amyloid-tau index) for patients with: 1, 2
- Early-onset dementia
- Rapidly progressive cognitive decline
- Atypical presentations
- Diagnostic uncertainty after standard workup
Advanced Neuroimaging
- Amyloid PET imaging to detect amyloid plaques (currently limited reimbursement in clinical practice) 1, 2
- Tau PET imaging for research or specialized clinical settings 1
- FDG-PET to assess cellular glucose metabolism patterns, particularly useful for distinguishing Alzheimer's disease from frontotemporal lobar degeneration 1, 2
Emerging Biomarkers
Blood-based biomarkers are rapidly evolving and may become part of routine clinical practice as disease-modifying therapies become available, particularly since DMT clinical trials require confirmed AD pathology. 1, 2
Critical Implementation Considerations
Common Pitfalls to Avoid
- Never rely solely on laboratory results without integrating clinical history from both patient and reliable informant 1, 4
- Do not overlook medication review, particularly anticholinergics and sedative-hypnotics that contribute to cognitive symptoms 1, 4
- Avoid missing medical conditions (obesity, chronic kidney disease) that can influence biomarker interpretation 2, 4
- Do not order advanced biomarkers routinely in straightforward cases, as they add cost without changing management 1
When to Refer for Specialty Evaluation
Consider referral to neurology, geriatrics, or neuropsychology when: 1, 4
- Screening tests are normal but high clinical suspicion persists
- Patients have extremes of age, education, or intelligence affecting test interpretation
- Complex medical, demographic, language, or cultural considerations exist
- Rapid progression or early onset (<65 years) suggests atypical dementia
Timing of Follow-up Testing
Serial cognitive assessment should occur at 6-12 month intervals using the same validated instrument to track progression and determine whether the patient is declining, improving, or remaining stable. 1, 5 This longitudinal approach has prognostic implications and guides treatment decisions.
The multi-tiered approach balances comprehensive evaluation with cost-effectiveness, recognizing that most dementia diagnoses can be established through careful history, physical examination, Tier 1 laboratory testing, and structural neuroimaging. 1, 3 More extensive testing should be reserved for cases where clinical features suggest specific treatable conditions or when diagnostic uncertainty persists after initial evaluation.