What is the appropriate workup for a patient presenting with short term memory loss?

Workup for Short-Term Memory Loss

For a patient presenting with short-term memory loss, obtain corroborative history from a reliable informant using validated tools (AD8 or Alzheimer's Questionnaire), perform objective cognitive testing with the Montreal Cognitive Assessment (MoCA), order comprehensive laboratory testing including thyroid function, vitamin B12, and metabolic panel, and obtain brain MRI to exclude structural lesions. 1, 2

Step 1: Obtain Structured Informant-Based History

• Interview a reliable informant separately from the patient using validated questionnaires such as the AD8, Alzheimer's Questionnaire (AQ), ECog, or IQCODE to assess changes in cognition, function, and behavior. 3, 1

• Ask the informant to provide specific examples of memory difficulties, as patients and families often use terms like "memory loss" to describe word-finding difficulty, inattention, or disorientation rather than true episodic memory impairment. 3

• Document the temporal course: determine whether symptoms appeared abruptly or gradually, their frequency and intensity, and whether they are episodic or persistent. 3

• Assess impact on instrumental activities of daily living including balancing checkbook, cooking, driving, and manipulation of electronics. 3

Step 2: Perform Direct Cognitive Assessment

• Administer the Montreal Cognitive Assessment (MoCA) as the preferred screening instrument, as it has superior sensitivity for mild cognitive impairment compared to the Mini-Mental State Examination (MMSE). 3, 4, 5

• Alternative rapid screening options include the Mini-Cog, Memory Impairment Screen (MIS) plus Clock Drawing Test, or the four-item MoCA if time is limited. 3, 4

• The MMSE lacks sensitivity for early cognitive impairment and should not be the primary screening tool. 4

Step 3: Complete Laboratory Workup for Reversible Causes

Order the following mandatory first-line tests: 3, 1, 2

• Complete blood count with differential to rule out anemia 3, 2
• Comprehensive metabolic panel including electrolytes, glucose, calcium, magnesium, renal function, and liver function tests 3, 1, 2
• Thyroid function tests (TSH, free T4) as hypothyroidism commonly mimics dementia 1, 2
• Vitamin B12, folate, and homocysteine levels to identify nutritional deficiencies 3, 1, 2
• Hemoglobin A1c and lipid panel 4
• Erythrocyte sedimentation rate and C-reactive protein as inflammatory markers 3, 2

Step 4: Obtain Structural Brain Imaging

• Order brain MRI (preferred) or head CT if MRI is contraindicated to evaluate for stroke, white matter disease, atrophy patterns, hydrocephalus, subdural hematoma, tumors, and space-occupying lesions. 3, 2, 4

• MRI is superior to CT for detecting vascular lesions and subtle structural abnormalities in patients with cognitive impairment. 4

• Neuroimaging is particularly indicated when there is onset of cognitive symptoms within the past 2 years, unexpected decline in cognition/function, or significant vascular risk factors. 2

Step 5: Conduct Focused Neurologic and Medical Evaluation

• Perform a neurologic physical examination to identify focal deficits or signs of neurodegenerative disease. 3

• Screen for depression and anxiety using PHQ-9 and GAD-7, as psychiatric conditions commonly manifest as cognitive complaints and can exacerbate true cognitive impairment. 1, 2

• Review all medications, particularly anticholinergics and sedative-hypnotics, which can contribute to cognitive symptoms. 3, 2

• Assess for cerebrovascular risk factors including hypertension, diabetes, hyperlipidemia, and history of stroke or TIA. 2, 4

• Evaluate sleep quality and screen for sleep apnea, which significantly impacts cognition. 1

Step 6: Determine Cognitive Domain Pattern

• Determine whether episodic memory (learning and recalling newly acquired information and recent life events) is the primary impaired domain, as this pattern is most commonly seen in patients who progress to Alzheimer's disease dementia. 3, 4

• Assess whether impairments in other cognitive domains predominate, such as executive function, attention, language, or visuospatial abilities, which may suggest alternative diagnoses. 2, 4

Step 7: Consider Advanced Biomarker Testing in Selected Cases

Consider the following advanced testing when diagnosis remains uncertain or results will change management: 3, 1, 2

• Lumbar puncture for CSF analysis of Aβ42, total tau, and phosphorylated tau when diagnosis is unclear 3, 1, 2

• Amyloid PET imaging when patient is under 65 years with suspected Alzheimer's disease, atypical features are present, or prognostic information is needed 1

• Tau PET imaging or blood-based biomarkers as they become available 3, 2

• Autoimmune encephalitis and paraneoplastic antibody panels in cases with early-onset presentation or rapidly progressive course 4

Step 8: Establish Clinical Classification and Monitoring Plan

• Diagnose as Mild Cognitive Impairment (MCI) if objective cognitive impairment is present without significant functional impact on activities of daily living. 3, 1

• Schedule follow-up visits every 6-12 months to track disease progression using serial cognitive assessments with the same instrument. 3, 1, 2

• Conduct serial assessments at intervals of at least 6 months to reduce practice effects and determine whether the patient is declining, improving, or remaining stable. 3

• Monitor all domains annually: cognition, functional autonomy, behavioral symptoms, and caregiver burden. 1, 2

Common Pitfalls to Avoid

• Do not rely solely on patient self-report, as diminished insight is common in cognitive impairment and patients may have divergent opinions from informants about symptom severity. 3, 1

• Do not attribute cognitive changes solely to "normal aging" without thorough evaluation, as changes that may be common in advancing age are not always normal and could benefit from diagnostic evaluation. 3

• Do not overlook medical conditions that can influence biomarker interpretation, such as obesity or chronic kidney disease. 2

• Do not fail to consider subspecialty referral to neurology, geriatrics, geriatric psychiatry, or neuropsychology when diagnosis remains uncertain after initial workup. 3, 2