What are the recommended treatments for Alzheimer's disease?

Treatment of Alzheimer's Disease

Start donepezil 5 mg once daily as first-line pharmacotherapy for Alzheimer's disease, increase to 10 mg daily after 4-6 weeks if tolerated, and add memantine 20 mg/day when patients progress to moderate or severe disease. 1

First-Line Pharmacologic Treatment

Donepezil is the preferred initial agent due to its once-daily dosing, favorable side effect profile, lack of hepatotoxicity, and established efficacy across all disease stages. 1, 2, 3

Dosing Strategy for Donepezil

• Start at 5 mg once daily for at least 4-6 weeks 1, 2, 3
• Increase to 10 mg once daily after the initial period if well-tolerated 1, 2, 3
• Take with food to minimize gastrointestinal side effects 2
• The 10 mg dose provides marginally larger benefits than 5 mg, with acceptable tolerability 4

Alternative Cholinesterase Inhibitors

If donepezil is not tolerated or appropriate, consider these alternatives:

Rivastigmine: 2, 3

• Start at 1.5 mg twice daily with food
• Increase by 1.5 mg twice daily every 4 weeks as tolerated
• Maximum dose: 6 mg twice daily (12 mg per day)

Galantamine: 2, 3

• Start at 4 mg twice daily with morning and evening meals
• Increase to 8 mg twice daily after 4 weeks
• May increase to 12 mg twice daily based on individual tolerability

Treatment for Moderate to Severe Disease

Add memantine 20 mg/day when patients progress to moderate or severe Alzheimer's disease. 1, 2, 3 Memantine shows statistically significant improvement in cognition and can be used alone or in combination with cholinesterase inhibitors. 1, 5

The combination of memantine with donepezil provides additional cognitive and functional benefits in moderate to severe disease compared to donepezil alone. 5

Monitoring Treatment Response

Allow 6-12 months to properly assess treatment benefit before considering discontinuation. 1, 2, 3 Use comprehensive assessments including:

• Physician global assessment 1, 2
• Caregiver report of functional and behavioral changes 1, 2
• Neuropsychological testing (ADAS-Cog, MMSE, or SIB depending on disease severity) 1, 2

Common Pitfall: Discontinuing treatment prematurely before adequate time to assess benefit. Treatment effects associated with donepezil abate within 6 weeks of discontinuation. 6

Managing Side Effects

Common adverse effects of cholinesterase inhibitors are cholinergic in nature, occurring in 7-30% of patients, and are generally mild and transient. 1, 2, 7 These include:

• Nausea, vomiting, diarrhea 1, 2, 7
• Dizziness and abdominal pain 1, 2
• Headaches and fatigue 2

Strategies to Minimize Side Effects:

• Take medication with food 2, 7
• Use slower dose titration 1, 7
• Consider switching to a different cholinesterase inhibitor if side effects persist 1

Important Caveat: Donepezil lacks the hepatotoxicity seen with tacrine, making it safer for long-term use. 2, 7

Nonpharmacologic Interventions

Implement nonpharmacologic strategies alongside medication throughout the disease course. 1, 2, 3 These include:

• Providing predictable routines and simplifying tasks 1
• Creating a safe environment 1
• Using calendars and labels for orientation 1
• Caregiver education and support groups 3
• Day care programs 1
• Register in the Alzheimer's Association Safe Return Program 1

Exhaust nonpharmacologic interventions before adding medications for behavioral symptoms. 1 When behavioral disturbances persist despite cholinesterase inhibitor therapy and nonpharmacologic interventions, use of a psychotropic agent may be necessary, starting with low doses and increasing slowly while monitoring for side effects. 2

Comprehensive Management Plan

Develop a comprehensive management plan immediately upon diagnosis that addresses: 1, 2, 3

• Patient and family values, preferences, and comorbid conditions 1, 3
• Realistic expectations for drug therapy (5-15% benefit over placebo, equivalent to delaying decline by approximately one year) 3
• Future care choices and advance planning, including driving safety, financial planning, and healthcare directives 3
• Optimization of comorbid conditions, as this can reduce disability and maximize function 1

Additional Considerations

Vitamin E (2,000 IU daily) may slow the progression of functional symptoms, based on one well-constructed study and current expert consensus. 2

Rapid cognitive decline (RCD) occurs in up to one-third of patients, more commonly in moderate dementia, and patients with RCD may achieve greater benefits from rivastigmine and galantamine. 2