From the Guidelines
For patients presenting with memory changes, a comprehensive laboratory workup should include thyroid function tests, vitamin B12, homocysteine, complete blood count with differential, complete metabolic panel, erythrocyte sedimentation rate, and C-reactive protein, as recommended by the most recent guidelines 1. When evaluating patients with memory changes, it is essential to consider a broad range of potential causes, including reversible conditions such as thyroid disorders, vitamin deficiencies, and metabolic disturbances.
- Initial laboratory tests should include:
- Thyroid function tests to evaluate for hypothyroidism or hyperthyroidism
- Vitamin B12 level to assess for deficiency
- Homocysteine level to evaluate for hyperhomocysteinemia
- Complete blood count with differential to assess for anemia, infection, or other hematologic abnormalities
- Complete metabolic panel to evaluate liver and kidney function, as well as electrolyte levels
- Erythrocyte sedimentation rate and C-reactive protein to assess for inflammation
- Additional tests may be considered based on individual patient risk factors and clinical suspicion, such as syphilis serology, HIV testing, or heavy metal screening 1.
- It is crucial to note that laboratory testing should be part of a comprehensive evaluation that includes thorough history-taking, physical examination, cognitive assessment, and often neuroimaging to properly diagnose and manage memory changes.
- A multi-tiered and individualized approach to laboratory testing is recommended, with routine Tier 1 laboratory studies obtained in all patients, as suggested by the Alzheimer's Association clinical practice guideline 1.
From the Research
Laboratory Tests for Memory Changes
When patients present with memory changes, several laboratory tests can be recommended to identify potential underlying causes. The following tests may be considered:
- Complete blood count (CBC) to rule out anemia or other blood-related disorders 2
- Serum vitamin B12 level to assess for deficiency or insufficiency 2, 3, 4, 5
- Serum methylmalonic acid to confirm vitamin B12 deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12 2
- Thyroid function tests (TSH, free T3, free T4) to evaluate for thyroid dysfunction 6
- Folate level to assess for deficiency or insufficiency 6, 5
- Homocysteine level to evaluate for elevated levels, which may be associated with dementia or cognitive decline 3, 5
Rationale for Laboratory Tests
The rationale for these laboratory tests is based on the potential associations between vitamin B12 deficiency, thyroid dysfunction, and cognitive impairment. Studies have shown that:
- Vitamin B12 deficiency is associated with cognitive impairment and dementia 3, 4, 5
- Low-normal vitamin B12 levels may be associated with poorer memory performance and reduced microstructural integrity of the hippocampus 4
- Thyroid dysfunction may be associated with cognitive impairment, although the evidence is mixed 6
- Elevated homocysteine levels may be associated with dementia or cognitive decline 3, 5
Considerations for Laboratory Testing
When ordering laboratory tests for patients with memory changes, consider the following:
- Screening average-risk adults for vitamin B12 deficiency is not recommended, but screening may be warranted in patients with one or more risk factors (e.g., gastric or small intestine resections, inflammatory bowel disease, use of metformin or proton pump inhibitors) 2
- The effectiveness of vitamin B12 supplementation in improving cognitive function is uncertain, and more research is needed to determine its potential benefits 3, 5