What is the most appropriate medication to initiate for an 81-year-old male with Alzheimer's dementia and a declining Mini-Mental State Exam (MMSE) score?

Donepezil is the Most Appropriate Treatment for WW's Alzheimer's Dementia

Donepezil 5 mg orally daily is the most appropriate treatment to initiate for WW's Alzheimer's dementia at this time. 1

Rationale for Donepezil Selection

Disease Severity Assessment

• WW has Alzheimer's dementia with declining cognitive function (MMSE score decreased from 25/30 to 18/30 over 18 months)
• Current MMSE score of 18/30 indicates moderate Alzheimer's disease
• No behavioral symptoms reported by family members

Evidence Supporting Donepezil

• Donepezil is recommended as first-line therapy for mild to moderate Alzheimer's disease by the American Academy of Neurology and American College of Physicians 1
• Provides statistically significant improvement in cognition with high-quality evidence 1
• Cochrane reviews confirm that donepezil improves cognitive function, with an average improvement of 2.7 points on the ADAS-Cog scale 2
• Benefits extend to activities of daily living and global clinical function 2, 3

Dosing Considerations

• Starting dose should be 5 mg once daily 1
• Can be titrated to 10 mg once daily after 4-6 weeks if well tolerated 1
• The 5 mg dose has fewer adverse events while still providing clinical benefit 2

Why Not the Other Options?

Memantine

• Memantine is primarily recommended for moderate to severe Alzheimer's disease 1, 4
• While WW's MMSE score of 18 indicates moderate disease, the standard approach is to start with a cholinesterase inhibitor first 5
• Memantine can be added later if disease progresses or as an adjunct to donepezil 5
• FDA studies show memantine is most beneficial in patients with more advanced disease (MMSE scores ≤ 14) 4

Lecanemab-irmb

• Not appropriate as first-line therapy for established Alzheimer's dementia
• More suited for earlier stages of disease
• Requires extensive screening and monitoring
• Significant risk profile not justified for an 81-year-old with recent CVA

Quetiapine

• Antipsychotics should be avoided in patients with dementia unless absolutely necessary
• WW has no behavioral symptoms that would warrant antipsychotic treatment
• Antipsychotics carry significant risks including increased mortality in elderly patients with dementia 1

Implementation Plan

1. Initiation Phase:

   • Start donepezil at 5 mg once daily
   • Take in the evening to minimize gastrointestinal side effects
   • Can be taken with or without food

2. Monitoring:

   • Assess for common side effects: nausea, diarrhea, vomiting, and sleep disturbances
   • Monitor for potential bradycardia given patient's cardiovascular history (recent CVA)
   • Schedule follow-up in 4-6 weeks to assess tolerability

3. Dose Titration:

   • If well tolerated after 4-6 weeks, consider increasing to 10 mg daily
   • The 10 mg dose may provide marginally larger benefits than the 5 mg dose 2
   • However, higher doses have higher rates of adverse events 2

4. Efficacy Assessment:

   • Evaluate response after 6-12 months of treatment 1
   • Look for stabilization or slowing of cognitive decline
   • Assess functional abilities and caregiver reports

Special Considerations for WW

• Recent CVA History: Monitor for cardiovascular side effects of donepezil
• Age (81 years): Start at lower dose and titrate cautiously
• Polypharmacy: Currently on aspirin, clopidogrel, atorvastatin - watch for potential drug interactions
• Living Situation: Family's goal is to keep WW at home - emphasize the importance of treatment adherence to potentially delay functional decline

Potential Pitfalls and Caveats

• Expectations Management: Explain to family that donepezil may slow cognitive decline but will not reverse the disease process
• Gastrointestinal Side Effects: Most common adverse events are nausea, vomiting, and diarrhea; taking medication with food may help
• Monitoring for Rapid Decline: If WW experiences rapid cognitive decline (loss of ≥3 MMSE points in 6 months), consider adding memantine 5
• Treatment Duration: Evidence supports continued benefit for at least one year of treatment 3
• Advance Care Planning: Initiate discussions about goals of care and advance directives while WW still has decision-making capacity 1

Donepezil represents the most appropriate choice for WW given his moderate Alzheimer's disease, absence of behavioral symptoms, and the established efficacy and safety profile of cholinesterase inhibitors in this patient population.