What is the treatment for Alzheimer's disease in geriatric patients?

Treatment of Alzheimer's Disease

Initiate treatment with a cholinesterase inhibitor (donepezil, rivastigmine, or galantamine) immediately upon diagnosis of mild to moderate Alzheimer's disease, combined with structured non-pharmacological interventions including daily exercise routines, environmental modifications, and aggressive management of cardiovascular comorbidities. 1

First-Line Pharmacological Treatment for Mild to Moderate Disease

The three cholinesterase inhibitors are equivalent first-line options, with selection based on dosing convenience, side effect profile, and patient-specific contraindications 1:

Donepezil (Preferred for Simplicity)

• Start at 5 mg once daily, increase to 10 mg after 4-6 weeks 2, 1, 3
• Can be taken at any time of day; taking with food reduces gastrointestinal side effects 1, 3
• Requires cardiac monitoring due to potential conduction disturbances and QTc prolongation 3, 4
• Most commonly prescribed due to once-daily dosing and lower cost 4
• Available as transdermal patch for once-weekly application 4

Rivastigmine (Best for Cardiac Concerns)

• Start at 1.5 mg twice daily with food, increase by 1.5 mg twice daily every 4 weeks to maximum 6 mg twice daily 2, 1
• Fewer cardiac side effects than donepezil, but watch for weight loss 2, 4
• Transdermal patch option reduces gastrointestinal side effects but may cause application-site reactions 4

Galantamine (Contraindicated in Hepatic/Renal Disease)

• Start at 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, consider 12 mg twice daily based on tolerance 2, 1, 5
• Absolutely contraindicated in hepatic or renal impairment 2, 1, 5
• Delays development of behavioral symptoms and has minimal drug-drug interactions 4
• Requires dose adjustment if creatinine clearance 9-59 mL/min; avoid if <9 mL/min 5

Tacrine (No Longer Recommended)

• Second-line agent due to hepatotoxicity requiring biweekly liver monitoring and four-times-daily dosing 2, 1

Treatment for Moderate to Severe Disease

Add memantine to ongoing cholinesterase inhibitor therapy when disease progresses to moderate-to-severe stage, or use memantine monotherapy if cholinesterase inhibitors are not tolerated 1:

• Memantine provides cumulative benefits when combined with cholinesterase inhibitors 1
• Acts as anti-Parkinsonian agent and antidepressant in addition to cognitive benefits 4
• Available as once-daily immediate-release or sustained-release formulation 4
• Donepezil 10 mg and rivastigmine transdermal patch 13.3 mg/24h are also indicated for moderate-to-severe disease 6

Non-Pharmacological Interventions (Mandatory Foundation)

Implement these structured interventions before and alongside all pharmacological treatment 1:

Daily Routine Structure

• Establish predictable schedules for exercise, meals, and sleep 1, 7
• Structured exercise program including walking, aerobic exercise, resistance training, and balance exercises 1
• Cognitive training activities: reading, games, music therapy 1

Environmental Modifications

• Eliminate hazards: remove sharp-edged furniture, throw rugs, reduce clutter 1, 7
• Install safety locks, GPS pendants, in-home cameras, electronic pill dispensers 1
• Use calendars and labels for orientation 1
• Optimize lighting to reduce confusion, especially at night 7

Dietary Interventions

• Mediterranean diet with nuts, berries, leafy greens, and fish 1

Aggressive Management of Comorbidities (Critical for Slowing Progression)

Optimize treatment of all comorbid conditions, as these significantly accelerate cognitive decline 1:

• Hypertension and diabetes require aggressive treatment - these conditions substantially increase AD risk and progression 1
• Correct vision and hearing deficits - sensory impairments worsen cognitive function 1
• Treat depression aggressively with SSRIs (citalopram or sertraline preferred due to minimal anticholinergic effects) 1, 7
• Optimize cardiovascular disease, infections, pulmonary disease, renal insufficiency, arthritis 1
• Avoid anticholinergic medications, benzodiazepines, sedative-hypnotics, and narcotics - these worsen cognitive impairment 1

Assessment of Treatment Response

Monitor for 6-12 months before determining treatment failure 2:

• Only 20-35% of patients show meaningful response to cholinesterase inhibitors 1
• Benefits are dose-dependent and symptomatic, not disease-modifying 1, 8
• Assess response through physician global assessment, caregiver report, neuropsychologic testing, or functional/behavioral changes 2
• Brief mental status tests are relatively insensitive for detecting cholinesterase inhibitor effects 2

When to Discontinue or Switch

• Discontinue if side effects persist, adherence is poor, or deterioration continues at pretreatment rate after 6-12 months 2
• Patients who fail one cholinesterase inhibitor may respond to another - switching is appropriate 2, 6

Management of Behavioral Symptoms

Exhaust non-pharmacological strategies before using psychotropic medications, except in emergencies involving imminent danger 1, 7:

The "Three R's" Approach (First-Line)

• Repeat instructions, Reassure the patient, Redirect to alternative activities 1, 7
• Simplify environment, reduce overstimulation, avoid crowded places 7
• Ensure pain, infection, constipation are treated - these precipitate behavioral disturbances 7

Pharmacological Management (When Non-Pharmacological Fails)

• Atypical antipsychotics (risperidone preferred): start 0.25 mg at bedtime, maximum 2-3 mg/day in divided doses 7
• Lower risk of extrapyramidal symptoms than typical antipsychotics 7
• Avoid benzodiazepines - risk of tolerance, addiction, cognitive impairment, and paradoxical agitation in 10% of patients 7
• Trazodone alternative: start 25 mg/day, maximum 200-400 mg/day for agitation 7
• For depression with agitation: SSRIs (citalopram or sertraline) as first-line 7

Caregiver Support (Impacts Patient Outcomes)

Link families to community resources immediately upon diagnosis 1:

• Alzheimer's Association and "Safe Return" program 1
• Caregiver burden significantly impacts patient outcomes 1

Early Planning

Discuss advance directives, future care preferences, and legal/financial planning during early disease stage 1:

• Reassess every 6 months as symptoms progress 1
• Consider end-of-life care planning early 1

Common Pitfalls to Avoid

• Do not delay treatment initiation - start cholinesterase inhibitors immediately upon diagnosis 1, 6
• Do not use galantamine in hepatic or renal impairment - this is an absolute contraindication 2, 1, 5
• Do not prescribe benzodiazepines for behavioral symptoms - high risk of worsening cognition and paradoxical agitation 7
• Do not use antipsychotics as first-line for agitation - increased risk of cerebrovascular events 1
• Monitor cardiac function with donepezil - risk of QTc prolongation and conduction disturbances 3, 4
• Watch for weight loss with rivastigmine - particularly in patients <55 kg 2, 3

Emerging Disease-Modifying Therapies

Disease-modifying therapies targeting amyloid (aducanumab, lecanemab) are available but require careful patient selection 1, 4:

• Administered intravenously every 2-4 weeks 4
• Risk of amyloid-related imaging abnormalities, especially in ApoE4 carriers 4
• May be most beneficial in early confirmed AD 1