What is the most appropriate next step in evaluating a 65‑year‑old woman with new short‑term memory loss?

Evaluation of Short-Term Memory Loss in a 65-Year-Old Female

Begin with a comprehensive clinical assessment that includes obtaining corroborative history from a reliable informant using structured tools (AD-8, IQCODE, or ECog), performing objective cognitive testing with the Montreal Cognitive Assessment (MoCA), conducting targeted laboratory workup to exclude reversible causes, and obtaining brain MRI to rule out structural lesions. 1, 2

Step 1: Establish Whether Objective Cognitive Impairment Exists

Obtain informant-based history using validated structured questionnaires to document changes in cognition, function, and behavior—this is the single most important diagnostic step with critical prognostic significance. 1, 3 If no informant is available or the informant reports no observable changes despite patient concerns, the likelihood of true dementia is very low. 3

Perform objective cognitive testing:

• Use the Montreal Cognitive Assessment (MoCA) as the primary screening tool, as it is more sensitive than MMSE for detecting mild cognitive impairment in this age group. 4, 2
• Add the Clock Drawing Test as a supplementary assessment. 4, 3
• If time is limited, rapid screening combinations such as Mini-Cog, MIS + Clock Drawing, or GPCOG are acceptable alternatives. 2

Assess functional status using structured scales (Pfeffer Functional Activities Questionnaire or Disability Assessment for Dementia) to determine whether cognitive changes interfere with instrumental activities of daily living such as medication management, financial handling, transportation, household tasks, and shopping. 4, 3 The key distinction between mild cognitive impairment and dementia rests on whether there is significant interference with daily functioning. 3

Step 2: Conduct Laboratory Testing for Reversible Causes

Order targeted laboratory workup to identify treatable conditions that may cause or contribute to cognitive symptoms: 2

• Complete blood count with differential
• Comprehensive metabolic panel (including glucose and electrolytes)
• Thyroid function tests (TSH, free T4)
• Vitamin B12, folate, and homocysteine levels
• Consider HIV testing if risk factors are present 3

Common pitfall: Depression and anxiety are the most frequent reversible causes of subjective cognitive complaints and must be systematically screened using PHQ-2/PHQ-9 for depression and GAD-7 for anxiety. 3

Step 3: Comprehensive Medication Review

Compile a complete medication list by having the patient or caregiver bring in all medication bottles, including prescription drugs, over-the-counter medications, and supplements. 1, 2 Specifically identify:

• Anticholinergic medications (major contributor to cognitive impairment)
• Potentially inappropriate medications per Beers Criteria
• Drug interactions that may contribute to cognitive symptoms 2

Step 4: Obtain Structural Neuroimaging

Order brain MRI (preferred over CT) to exclude vascular lesions, tumors, normal-pressure hydrocephalus, subdural hematomas, and other structural abnormalities. 4, 3 MRI is particularly indicated when: 3

• Onset of cognitive symptoms within the past 2 years
• Unexpected decline in cognition or function
• Recent significant head trauma
• Unexplained neurological manifestations
• Significant vascular risk factors present

MRI may also reveal medial temporal lobe atrophy, a marker of neurodegeneration in Alzheimer's disease. 4

Step 5: Assess for Additional Contributors

Evaluate specific conditions that commonly contribute to cognitive symptoms in this age group: 3

• Sleep disorders: Screen for sleep deprivation and obstructive sleep apnea
• Sensory deficits: Assess for hearing loss and vision impairment
• Pain: Undiagnosed pain is disproportionately common in patients with cognitive impairment 1
• Vascular risk factors: Document history of stroke/TIA, hypertension, diabetes, and hyperlipidemia 4
• Recent delirium: Any recent episode of acute confusion 2

Step 6: Diagnostic Classification and Next Steps

Based on the integration of informant history, cognitive testing, functional assessment, and workup results, classify the patient into one of the following categories:

If Cognitive Testing is Normal (Subjective Cognitive Decline)

• Provide reassurance if informant confirms no observable changes 3
• Treat identified reversible causes (depression, anxiety, sleep disorders, medication effects) 3
• Schedule follow-up in 6-12 months if concerns persist 4
• Do not order amyloid PET or CSF biomarkers, as they cannot reliably predict short- or medium-term cognitive decline in cognitively normal individuals and may cause psychological harm through inappropriate labeling 3

If Mild Cognitive Impairment is Identified

• Document the specific impaired cognitive domain(s); episodic memory impairment is the strongest predictor of progression to Alzheimer's dementia 4
• Consider referral to neurology, geriatrics, or neuropsychology for comprehensive neuropsychological testing to establish baseline 4, 2
• Schedule follow-up every 6-12 months with serial cognitive assessments using the same instrument to monitor for progression 4, 3
• Aggressively manage vascular risk factors (hypertension, diabetes, hyperlipidemia) 4
• Consider blood-based biomarkers for Alzheimer's disease only in specialist settings after discussion with the patient, particularly in clinically uncertain cases or atypical presentations 1

If Dementia is Suspected

• Refer to dementia specialist (neurologist, geriatrician, or geriatric psychiatrist) for confirmatory evaluation and consideration of disease-modifying therapies if Alzheimer's disease is suspected 1, 2
• The specialist will determine eligibility for disease-modifying therapies through confirmatory testing (CSF or amyloid PET) and APOE genotyping 1

Critical Considerations

Actual reversibility of dementia is rare: Only 3.6% of memory clinic patients with potentially reversible conditions show improvement or resolution with treatment, and these patients typically have milder cognitive deficits (MMSE ≥24). 5 However, thorough evaluation remains warranted because early detection allows for treatment of contributing factors and appropriate planning. 5, 6

Avoid premature closure: Rapidly progressive cognitive decline (over weeks to months rather than years) should prompt evaluation for atypical causes including autoimmune encephalitis, prion disease, CNS infections, or paraneoplastic syndromes. 7

Never rely solely on patient self-report without informant corroboration, as lack of insight (anosognosia) is common in dementia and leads to missed diagnoses. 1, 3