What is the recommended treatment approach for Alzheimer's disease?

Alzheimer's Disease Treatment Approach

Start donepezil 5 mg once daily immediately upon diagnosis, 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

Dosing Strategy for Donepezil:

• Start at 5 mg once daily for at least 4-6 weeks 1
• Increase to 10 mg once daily after the initial period if well-tolerated 1
• Allow 6-12 months to properly assess treatment benefit before considering discontinuation, using comprehensive assessments including physician global assessment, caregiver report of functional and behavioral changes, and neuropsychological testing 1

Alternative Cholinesterase Inhibitors:

• Galantamine and rivastigmine are also indicated for mild-to-moderate AD and can be used if donepezil is poorly tolerated or ineffective 2
• Rivastigmine transdermal patch (13.3 mg/24 h) is indicated for moderate-to-severe AD 2
• Treatment choice should be based on patient or caregiver preference, ease of use, tolerability, and cost 2

Treatment for Moderate to Severe Disease

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

• Combination therapy with memantine and donepezil is recommended for severe AD, showing additional benefit over monotherapy 3, 4
• Memantine acts as an N-methyl-d-aspartate (NMDA) receptor antagonist and provides complementary mechanisms to cholinesterase inhibitors 2

Managing Side Effects

Common adverse effects of cholinesterase inhibitors include nausea, vomiting, diarrhea, dizziness, and abdominal pain, occurring in 7-30% of patients but are generally mild and transient. 1

Strategies to minimize side effects:

• Take medication with food 1
• Use slower dose titration 1
• Consider switching to a different cholinesterase inhibitor if side effects persist 1
• Start psychotropic agents at low dosages and increase slowly if needed for behavioral symptoms, monitoring for side effects and drug interactions 3

Nonpharmacologic Interventions

Exhaust nonpharmacologic interventions before adding medications for behavioral symptoms. 1 These measures should be implemented alongside medication throughout the disease course:

Environmental and Routine Modifications:

• Provide predictable routines for exercise, meals, and bedtime 3
• Allow patients to dress in their own clothing and keep possessions 3
• Explain all procedures and activities in simple language before performing them 3
• Simplify all tasks by breaking complex tasks into steps with instructions for each step 3
• Use distraction and redirection to divert patients from problematic situations 3

Safety Measures:

• Create a safe environment with no sharp-edged furniture, slippery floors, throw rugs, or obtrusive electric cords 3
• Equip doors and gates with safety locks 3
• Install grab bars by the toilet and in the shower 3
• Register patients at risk for wandering in the Alzheimer's Association Safe Return Program 3, 1

Orientation Aids:

• Use calendars, clocks, labels, and newspapers for orientation to time 3
• Use color-coded or graphic labels on closets, table service, and drawers as cues for orientation 3
• Use lighting to reduce confusion and restlessness at night 3
• Avoid glare from windows and mirrors, noise from television, and household clutter 3

Behavioral Management:

• Teach caregivers the three R's approach: repeat, reassure, and redirect 3
• Implement scheduled toileting or prompted voiding to reduce urinary incontinence 3
• Reduce excess stimulation and outings to crowded places 3
• Consider day care programs for patients with Alzheimer's disease 3, 1

Managing Behavioral Problems and Mood Disorders

Behavioral symptoms such as agitation and wandering become common as Alzheimer's disease progresses. 3

Treatment Algorithm for Behavioral Symptoms:

1. First, optimize nonpharmacologic interventions as described above 3
2. If behavioral disturbances persist, cholinesterase inhibitors may improve these symptoms 3
3. If symptoms continue despite cholinesterase inhibitor therapy, add a psychotropic agent 3

Depression Management:

• Selective serotonin reuptake inhibitors (SSRIs) such as citalopram and sertraline are the agents of choice for depression in patients with dementia due to minimal anticholinergic side effects 3
• Depression is common in older adults with Alzheimer's disease and is often untreated 3

Comprehensive Management Plan

Develop a comprehensive management plan immediately upon diagnosis that addresses patient and family values, preferences, and comorbid conditions. 1

Key Components:

• Optimize management of comorbid conditions, as this can reduce disability and maximize function 3, 1
• Discuss realistic expectations for drug therapy and solicit patient and family preferences on future care choices 3
• Assist with advance planning for future care challenges 3
• Identify the primary caregiver and assess the adequacy of family and other support systems 3
• Refer to social service agencies and support organizations, including the Alzheimer's Association 3

Monitoring and Reassessment:

• Reassess patients every 6 months or more frequently if indicated 3
• Conduct assessments of daily function, cognitive status, other medical conditions, and behavioral problems 3
• Monitor for evidence of abuse and report as required by local law 3
• Report the diagnosis to appropriate motor vehicle departments in accordance with local law 3

Emerging Disease-Modifying Therapies

Two amyloid-targeting therapies are currently approved: donanemab (Kisunla™) and lecanemab (Leqembi®), which can slow disease progression and cognitive and functional decline in patients with mild cognitive impairment/mild dementia due to AD. 5

Important Considerations:

• These treatments are associated with amyloid-related imaging abnormalities (ARIA) as a class-based safety concern 5
• They are indicated for mild cognitive impairment/mild dementia due to AD 5
• Monitoring and management protocols are required for patients receiving these treatments 5