What is the most appropriate pharmacotherapy for a 72-year-old male with gradually progressive memory loss, disorientation, and normal laboratory results, consistent with mild to moderate Alzheimer's disease?

Pharmacotherapy for Mild to Moderate Alzheimer's Disease

Donepezil is the most appropriate pharmacotherapy for this 72-year-old male patient with mild to moderate Alzheimer's disease, starting at 5 mg once daily for 4-6 weeks and then increasing to 10 mg daily if tolerated. 1

Clinical Assessment and Diagnosis

The patient presents with classic symptoms of Alzheimer's disease:

• Gradually progressive memory loss over two years
• Difficulty with financial management (bank account)
• Spatial disorientation (getting lost in familiar neighborhood)
• Impaired recall (0/3 objects after five minutes)
• Disorientation to time and space
• Normal laboratory results (TSH, B12) ruling out reversible causes

These findings are consistent with mild to moderate Alzheimer's disease, requiring appropriate pharmacological intervention.

First-Line Treatment Selection

Cholinesterase inhibitors are the first-line treatment for mild to moderate Alzheimer's disease 1. Among the available options (donepezil, rivastigmine, and galantamine), donepezil offers several advantages:

• Approved for mild, moderate, and severe Alzheimer's disease 1
• Once-daily dosing, improving adherence 1
• Fewer gastrointestinal side effects compared to other cholinesterase inhibitors 1
• Straightforward titration schedule 2

Dosing and Administration

The recommended dosing protocol for donepezil is:

• Start at 5 mg once daily for 4-6 weeks 1
• If well-tolerated, increase to 10 mg once daily (optimal therapeutic dose) 1
• The 10 mg dose provides additional clinical benefit over the 5 mg dose for many patients 3

Expected Benefits

Treatment with donepezil can provide:

• Improvement in cognitive function as measured by standardized scales 4
• Stabilization of functional abilities 5
• Potential improvement in global clinical state 4
• Slowing of disease progression, though not reversal 1

Clinical trials demonstrate that donepezil produces improvements in cognitive function with an average reduction of 2.67 points on the ADAS-Cog scale compared to placebo 4. While these treatment effects are modest, they represent meaningful stabilization or slowing of decline in a progressive disease.

Monitoring and Follow-up

The patient should be monitored for:

• Response to treatment (typically assessed after 3-6 months) 1
• Adverse effects, particularly during dose escalation
• Realistic expectations should be set—donepezil slows progression but does not reverse the disease 1

Potential Adverse Effects

Common adverse effects to monitor include:

• Gastrointestinal symptoms (nausea, vomiting, diarrhea) 1
• Neurological symptoms (dizziness, headache, insomnia) 1
• Cardiovascular symptoms (bradycardia, syncope) 1

If adverse events occur, consider temporary dose reduction rather than discontinuation 1.

Pitfalls to Avoid

1. Rapid titration: This increases risk of adverse events without improving outcomes 1
2. Discontinuing treatment too early: Benefits may take 3-6 months to become apparent 1
3. Setting unrealistic expectations: Explain that treatment slows progression but doesn't reverse disease 1
4. Neglecting non-pharmacological approaches: These should complement medication
5. Overlooking comorbid conditions: The patient's smoking history (2 packs daily for 40 years) should be addressed as it may impact vascular health and cognitive function

Future Considerations

As the disease progresses to moderate-severe stages, adding memantine to donepezil may be beneficial, with evidence suggesting superior outcomes compared to donepezil monotherapy in terms of cognition, activities of daily living, and behavior 1.