What further evaluation is needed before initiating donepezil in a patient with suspected dementia?

Pre-Treatment Workup Before Initiating Donepezil

Before starting donepezil, you must exclude reversible causes of cognitive impairment—specifically delirium, major depression, and medication effects—but structural neuroimaging is recommended though not an absolute prerequisite for initiating therapy. 1

Essential Clinical Assessment

Exclude Acute Reversible Causes (Required Before Starting)

• Rule out delirium by assessing for acute infection, metabolic disturbances (electrolyte abnormalities, renal/hepatic dysfunction, hypoglycemia), and acute medical illness 1
• Screen for major depression as a primary cause of cognitive symptoms, since late-onset depressive disorder can mimic dementia 2, 1
• Review all medications to identify and discontinue anticholinergic agents that may worsen cognition 1

Confirm Appropriate Disease Stage

• Verify mild to moderate dementia (MMSE 10-26 or MoCA approximately 16/30), as donepezil is indicated for this population 2, 1, 3
• Do not prescribe for mild cognitive impairment alone, as evidence shows no significant benefit and higher rates of adverse events in this population 4, 5

Neuroimaging Recommendations

When to Order Brain Imaging

Structural brain imaging (CT or MRI) is recommended in most cases but should not delay initiation of donepezil once reversible causes are excluded. 1 The primary purpose is to detect treatable structural lesions and refine the differential diagnosis, not to confirm eligibility for treatment.

• Order imaging promptly (within days to weeks) while proceeding with treatment 1
• Expedite imaging urgently if any of the following are present: 1
  • New focal neurological deficits
  • Recent significant head trauma
  • New severe headache or seizures
  • Anticoagulation therapy or bleeding risk
  • Symptom onset ≤2 years
  • Unexpected or rapid cognitive decline
  • History of cancer

Baseline Assessments Before Starting Donepezil

Cognitive and Functional Baseline

• Document baseline cognitive function using validated tools (ADAS-Cog, MMSE, or MoCA) to allow assessment of treatment response at 6-12 months 2, 1
• Assess activities of daily living using standardized scales (IADL or ADCS-ADL) 2
• Obtain caregiver input on behavioral symptoms and functional changes 2, 1

Medical Contraindications and Precautions

• No routine laboratory monitoring is required for donepezil, as it is not hepatotoxic (unlike tacrine) 2
• Assess for cardiac conduction abnormalities, particularly sick sinus syndrome or significant bradycardia, as cholinesterase inhibitors can cause bradycardia 2
• Review for gastrointestinal conditions that may be exacerbated by cholinergic effects (active peptic ulcer disease, severe gastroesophageal reflux) 2

Setting Realistic Expectations

Communicate Expected Benefits Before Starting

• Inform patients and families that benefits are modest: approximately 20-35% of patients show clinically meaningful improvement equivalent to delaying decline by one year 2
• Explain the assessment timeline: full efficacy evaluation requires 6-12 months of continuous therapy 2, 1
• Clarify that donepezil does not cure or reverse dementia; it may temporarily stabilize cognition or slow the rate of decline 2, 3

Common Pitfalls to Avoid

• Do not wait for neuroimaging results to start donepezil if acute reversible causes have been clinically excluded 1
• Do not use brief mental status tests alone (like MMSE) to assess treatment response, as they are relatively insensitive to drug effects; incorporate caregiver reports and functional assessments 2, 1
• Do not prescribe for asymptomatic individuals or those with mild cognitive impairment without functional decline, as screening asymptomatic adults is not recommended 2, 4