What is the appropriate workup for a patient with onset of cognitive disorder?

Workup for New-Onset Cognitive Disorder

For any patient presenting with new cognitive symptoms, initiate a structured multi-tiered evaluation that includes detailed history with informant corroboration, standardized cognitive testing, comprehensive laboratory workup, and structural brain imaging. 1

Initial Clinical Assessment

History Taking

• Obtain detailed information about the onset, nature, and progression of cognitive symptoms, specifically asking about memory loss, language difficulties, visuospatial problems, executive dysfunction, and personality/behavioral changes 1
• Document functional impact on instrumental activities of daily living including financial management, medication management, driving, household tasks, cooking, and shopping 1, 2
• Assess for specific triggers such as recent infections, fever, head trauma, or new medications (particularly anticholinergics and sedative-hypnotics) 3, 4
• Review sleep patterns and screen for untreated sleep apnea, which can significantly impact cognition 2

Corroborative History (Essential)

• Always obtain informant history using structured tools like the AD8 or Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) 1, 3, 2
• This step has significant prognostic value and is critical for accurate diagnosis—failing to obtain this represents a major pitfall 3, 4

Cognitive Testing

Office-Based Assessment

• Administer the Montreal Cognitive Assessment (MoCA) as first-line screening tool for detecting mild cognitive impairment 1, 2
• Add Clock Drawing Test as a complementary screening measure 1, 3
• If MoCA is normal but symptoms persist with positive informant history, proceed to formal neuropsychological testing 1

Formal Neuropsychological Testing (When Indicated)

• Order when office-based testing is inconclusive or when patient reports concerning symptoms but performs within normal limits 1
• Must include normed testing of: learning and memory (delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language 1
• Key diagnostic pattern for functional cognitive disorder: relatively weak immediate recall but preserved delayed recall and retention, contrasting with neurodegenerative patterns 5

Laboratory Workup (Tier 1 - Obtain in All Patients)

Essential Blood Tests

• Complete blood count with differential to rule out anemia 3, 4
• Comprehensive metabolic panel including electrolytes, calcium, magnesium, kidney function, and liver function tests 3, 4
• Thyroid function tests (TSH, free T4) 3, 2
• Vitamin B12, folate, and homocysteine levels 3, 4
• Inflammatory markers (ESR, CRP) if autoimmune conditions suspected 3, 4

Critical context: Treatable causes account for 72% of rapid cognitive impairment cases (onset <12 months), with immune/inflammatory (37%), infectious (22%), and vascular (22%) etiologies being most common 6

Neuroimaging (Mandatory)

Structural Imaging

• Obtain brain MRI without contrast as the preferred initial study 1, 4
• If MRI contraindicated or unavailable, obtain head CT 1
• Imaging is particularly critical when: cognitive symptoms began within past 2 years, unexpected decline in cognition/function, recent significant head trauma, unexplained neurological signs, or significant vascular risk factors 3, 4

Psychiatric Assessment

Mood and Anxiety Screening

• Screen for depression using PHQ-9 and anxiety using GAD-7, as these commonly manifest as or exacerbate cognitive symptoms 1, 4, 2
• Use structured behavioral scales including the Neuropsychiatric Inventory Questionnaire (NPI-Q) for informant-reported behavioral symptoms 1

Specialty Referral Criteria

Refer Expeditiously to Dementia Specialist When:

• Atypical presentations: aphasia, apraxia, agnosia, cortical visual abnormalities, movement disorders, or gait disturbances 1
• Rapidly progressive course (decline over weeks to months) suggesting prion disease, atypical neurodegenerative disease, or infectious/inflammatory conditions 1
• Early-onset dementia (age <65 years) 1
• Severe neuropsychiatric symptoms: profound anxiety, depression, apathy, psychosis, or personality changes 1
• Diagnostic uncertainty after initial workup 1

Advanced Biomarkers (Specialty Setting Only)

Consider When Alzheimer's Disease Suspected

• Cerebrospinal fluid analysis for Aβ42, total tau, and phosphorylated tau 1, 3
• Amyloid PET or Tau PET imaging 3
• Blood-based biomarkers (plasma p-tau) may be used as adjunct but should be confirmed with CSF or PET 1

Important caveat: Blood biomarkers should only be used in symptomatic patients at specialist clinics with established thresholds, and results require confirmation whenever possible 1

Common Pitfalls to Avoid

• Never assume "normal aging" without proper evaluation—this constitutes suboptimal care 1
• Do not overlook medication effects, particularly anticholinergics, sedative-hypnotics, and polypharmacy 3, 4, 2
• Avoid missing functional cognitive disorder by failing to recognize the pattern of internal inconsistency (impaired immediate recall but preserved delayed recall) 5
• Do not neglect comorbid conditions like obesity, chronic kidney disease, or diabetes that can influence biomarker interpretation 4
• Never skip informant history—this is essential and its absence significantly compromises diagnostic accuracy 3, 4

Follow-Up Strategy

• For patients with subjective cognitive decline and normal testing but positive informant history: annual follow-up with reassessment 1, 2
• For patients with confirmed cognitive impairment: follow-up every 6-12 months using multi-dimensional assessment of cognition, function, behavior, and caregiver burden 1, 2
• Use MMSE or MoCA for longitudinal cognitive tracking 1