What is the most appropriate pharmacotherapy for an 87-year-old woman with progressive memory loss, diagnosed with mild cognitive impairment, and having a Mini-Mental State Examination (MMSE) score of 23/30, with normal laboratory studies, including serum vitamin B12 (cyanocobalamin), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels, and a computed tomography (CT) scan of the head showing mild volume loss?

Pharmacotherapy for Progressive Memory Loss in an 87-Year-Old Woman

A cholinesterase inhibitor is the most appropriate pharmacotherapy for this 87-year-old woman with progressive memory loss, likely mild to moderate Alzheimer's disease, as evidenced by her MMSE score of 23/30 and CT scan showing mild volume loss.

Clinical Assessment and Diagnosis

The patient presents with:

• Progressive memory loss over 2 years
• Repetitive speech patterns
• Medication adherence issues
• MMSE score of 23/30 (indicating mild cognitive impairment)
• Normal laboratory studies (vitamin B12, T4, TSH)
• CT scan showing mild volume loss
• No other apparent causes for cognitive decline

These findings are consistent with mild to moderate Alzheimer's disease, which requires appropriate pharmacological management.

Recommended Pharmacotherapy

First-line Treatment: Cholinesterase Inhibitor

Cholinesterase inhibitors are the standard of care for mild to moderate Alzheimer's disease 1. Three main options are available:

1. Donepezil:

   • Most commonly prescribed
   • Acts specifically on acetylcholinesterase
   • Statistically significant improvement in cognition and global function 1
   • Once-daily dosing (5-10mg)

2. Rivastigmine:

   • Dual mechanism (inhibits both acetylcholinesterase and butyrylcholinesterase)
   • May offer additional benefit in rapid cognitive decliners 1
   • Available in oral and transdermal formulations
   • Higher incidence of gastrointestinal side effects compared to donepezil

3. Galantamine:

   • Dual mechanism (cholinesterase inhibition and nicotinic receptor modulation)
   • Similar efficacy to donepezil in cognitive improvement 1

Treatment Selection Considerations

For this 87-year-old patient:

• Donepezil may be preferred initially due to once-daily dosing and potentially better tolerability profile
• Start with 5mg daily for 4-6 weeks, then consider increasing to 10mg if well-tolerated
• Monitor for common adverse effects: nausea, diarrhea, vomiting, and bradycardia

Evidence for Efficacy

Cholinesterase inhibitors have demonstrated:

• Statistically significant improvement in cognition as measured by ADAS-cog scores 1
• Positive effects on global function assessment 1
• Modest but meaningful clinical benefits in a subset of patients 1

While the average improvement may be modest (not always reaching the clinically significant threshold of 4 points on ADAS-cog), individual responses vary, and a significant proportion of patients achieve clinically meaningful improvement 1.

Important Clinical Considerations

Monitoring

• Reassess cognitive function, behavior, and activities of daily living after 3-6 months
• Continue medication if stabilization or improvement occurs
• Consider dose adjustment based on response and tolerability

Potential Pitfalls

• Unrealistic expectations: Explain to the patient and family that these medications do not reverse the disease but may slow progression and improve symptoms
• Medication adherence: Given the patient's history of forgetting medications, implement a system for medication management (pill organizers, caregiver supervision)
• Side effect management: Monitor for gastrointestinal symptoms, which are the most common adverse effects

Contraindications and Cautions

• Cardiac conduction abnormalities (monitor for bradycardia)
• History of GI bleeding or ulcers
• Severe hepatic impairment

Alternative Considerations

If cholinesterase inhibitors are not tolerated or contraindicated:

• Memantine may be considered, though it's typically reserved for moderate to severe Alzheimer's disease 1
• Combination therapy with a cholinesterase inhibitor and memantine has equivocal evidence 1

Non-pharmacological Approaches

In addition to pharmacotherapy:

• Cognitive stimulation activities
• Regular physical exercise
• Caregiver education and support
• Safety assessment and modifications at home
• Regular follow-up appointments

Conclusion

Based on the clinical presentation and current evidence, a cholinesterase inhibitor (option B from the question) is the most appropriate pharmacotherapy for this patient with mild to moderate cognitive impairment consistent with Alzheimer's disease.