In a patient two years status post cerebrovascular accident (stroke) with new cognitive decline, what laboratory tests and diagnostic studies should be ordered?

Workup for Post-Stroke Cognitive Impairment

For a patient 2 years post-stroke presenting with cognitive concerns, obtain thyroid-stimulating hormone (TSH), vitamin B12, comprehensive metabolic panel, complete blood count, and brain MRI, followed by formal neuropsychological testing if screening suggests impairment. 1

Laboratory Testing

Mandatory First-Line Tests

• TSH (with free T4 if abnormal): Hypothyroidism is a common reversible cause of cognitive impairment that must be excluded 1
• Vitamin B12: Deficiency can cause dementia that substantially improves with treatment 1
• Comprehensive metabolic panel: Evaluates electrolyte disturbances (particularly hyponatremia), renal function, glucose abnormalities, and hepatic function—all potentially reversible causes 1
• Complete blood count: Screens for anemia and infection as contributors to cognitive symptoms 1

Additional Laboratory Considerations

• Liver function tests (ALT, AST): Hepatic encephalopathy can present with attention deficits and forgetfulness 2
• Hemoglobin A1c: Diabetes control affects cognitive trajectory after stroke 1, 2
• Lipid panel: For vascular risk stratification, as ongoing vascular disease contributes to progressive cognitive decline 2

Neuroimaging

Brain MRI (Preferred Modality)

MRI is superior to CT for evaluating post-stroke cognitive impairment because it detects: 2, 3

• White matter disease and small vessel changes
• New silent infarcts (stroke recurrence occurs and accelerates cognitive decline)
• Hippocampal atrophy patterns
• Cerebral atrophy progression
• Lacunar infarcts

The American College of Radiology recommends MRI over CT due to superior sensitivity for vascular lesions and subtle structural abnormalities. 2 CT is acceptable only if MRI is contraindicated or unavailable. 2

Cognitive Assessment

Initial Screening

• Montreal Cognitive Assessment (MoCA): Generally recommended over Mini-Mental State Examination because it has less ceiling effect and is more sensitive to mild cognitive impairment in the subacute and chronic phases after stroke 1
• The MMSE has significant ceiling effects and may miss subtle yet impactful cognitive changes 1, 4

When to Proceed to Comprehensive Neuropsychological Testing

If screening suggests impairment or functional concerns exist, proceed to formal neuropsychological evaluation. 1, 4 Standard screening tools were not designed to identify the heterogeneous presentation of post-stroke cognitive deficits and often miss subtle changes. 1, 4

A tailored comprehensive neuropsychological evaluation should: 1, 4

• Use appropriate normative data considering age, sex, and educational attainment
• Account for stroke-related deficits (motor weakness, neglect, aphasia)
• Assess multiple domains: memory (immediate and delayed recall), attention, processing speed, executive function, language, and visuospatial abilities
• Identify mild cognitive changes over time

Differential Diagnosis Considerations

Rule Out Reversible Causes

The workup must differentiate post-stroke cognitive impairment from: 1

• Depression: Affects approximately one-third of stroke survivors and causes cognitive symptoms that may resolve with treatment 1

  • Use a depression screening tool validated in stroke patients
  • Risk factors include physical disability, prestroke depression/anxiety, and lack of social support

• Sleep disorders: Including obstructive sleep apnea, which affects 50-60% of stroke survivors 1

• Medication effects: Review for sedating and anticholinergic medications 1

• Sensory impairments: Hearing and vision problems can mimic or exacerbate cognitive deficits 1

Distinguish Pre-Stroke from Post-Stroke Decline

Question the patient and an informant about cognitive-related activities of daily living (finances, shopping, organizing medications) to determine if impairment predated the stroke. 1 Consider using validated questionnaires like the Informant Questionnaire on Cognitive Decline in the Elderly. 1

Advanced Testing (Selected Cases Only)

When to Consider Alzheimer's Disease Biomarkers

In elderly patients, mixed dementia (combination of vascular disease and Alzheimer's pathology) is common. 1 However, biomarkers of Alzheimer's disease (β-amyloid and tau in cerebrospinal fluid, blood, or by PET) are currently expensive, invasive, or not widely available for routine use. 1

Consider CSF Alzheimer's biomarkers or blood biomarkers for amyloid pathology only in selected cases where: 2

• Early-onset cognitive impairment exists
• Rapidly progressive dementia is present
• Autoimmune/infectious/paraneoplastic causes are suspected

Critical Timing Considerations

Most cognitive recovery occurs within the first 3 to 6 months after stroke. 4 At 2 years post-stroke, the patient is well beyond the acute recovery phase, making new cognitive concerns particularly significant as they may represent: 1

• Progressive vascular cognitive impairment (incidence of new dementia is 1.7% per year after stroke)
• Recurrent silent strokes
• Development of mixed dementia
• Treatable comorbid conditions

Common Pitfalls to Avoid

• Do not rely solely on brief screening tools: They miss subtle deficits that impact daily functioning 1, 4, 5
• Do not dismiss concerns as "normal aging": Stroke doubles the risk of dementia even after adjustment for age and other factors 1
• Do not skip informant interview: Anosognosia (lack of awareness of deficits) often results in underreporting by patients 1
• Do not order CT when MRI is available: CT has limited sensitivity for detecting the white matter disease and subtle changes critical to understanding post-stroke cognitive impairment 2, 3