What are the recommended treatments for dementia?

Pharmacological Treatment of Dementia

Primary Treatment Recommendations

For mild to moderate Alzheimer's disease, initiate treatment with a cholinesterase inhibitor (donepezil, rivastigmine, or galantamine); for moderate to severe disease, use memantine alone or in combination with a cholinesterase inhibitor. 1, 2

Treatment Selection by Disease Severity

Mild to Moderate Dementia

• Start with a cholinesterase inhibitor as first-line therapy for Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, or vascular dementia 1
• Donepezil: Begin at 5 mg once daily, increase to 10 mg daily after 4-6 weeks 3
• Rivastigmine: Start at 1.5 mg twice daily, increase by 1.5 mg twice daily every 4 weeks as tolerated, maximum 6 mg twice daily 3, 4
• Galantamine: Initiate at 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, may increase to 12 mg twice daily based on tolerability 3

Moderate to Severe Dementia

• Memantine (target dose 20 mg/day) is FDA-approved and recommended 2
• Combination therapy with memantine plus donepezil provides superior benefit compared to monotherapy and is recommended in many countries 1, 5
• When adding memantine to existing donepezil therapy, continue donepezil at the established dose (typically 10 mg/day) while titrating memantine 5

Severe Dementia

• Combination therapy with memantine and donepezil is specifically recommended 1
• Cholinesterase inhibitors have demonstrated efficacy even in severe disease stages 6

Choosing Between Agents

Base medication selection on tolerability, adverse effect profile, ease of use, and cost—there is insufficient evidence to demonstrate superiority of one cholinesterase inhibitor over another. 7, 8

• All three cholinesterase inhibitors (donepezil, galantamine, rivastigmine) show equivalent efficacy for cognitive function, activities of daily living, and behavioral outcomes 8
• Donepezil may have fewer adverse events compared to rivastigmine, and offers simpler once-daily dosing with straightforward titration 8
• If no benefit is achieved with one cholinesterase inhibitor after adequate trial, switching to another agent in this class may be beneficial 9

Expected Treatment Benefits

Patients treated with cholinesterase inhibitors for 6-12 months show:

• Cognitive improvement of approximately 2.7 points on the 70-point ADAS-Cog scale (a modest but clinically meaningful benefit) 6, 8
• 1.05 point improvement on MMSE 6
• Better global clinical state as rated by clinicians 6, 8
• Improved activities of daily living 6, 8
• Benefits maintained for approximately 21-81 weeks with continued treatment 10

Critical caveat: These medications provide symptomatic benefit only and do not alter the underlying disease progression—patients will continue to decline over time despite treatment. 3

Monitoring and Assessment

• Assess medication effectiveness by monitoring cognition, function, and neuropsychiatric symptoms 1
• Before attributing clinical worsening to medication failure, rule out delirium from infections, review all medications for anticholinergic effects, ensure comorbid conditions are optimally treated, and verify medication adherence 5
• Patients with MMSE <20 at treatment onset, vascular risk factors, or rapid decline require more frequent monitoring 5

When to Discontinue Treatment

Consider discontinuing cholinesterase inhibitors after 12 months if: 1

• Clinically meaningful worsening despite treatment
• No observed benefit after adequate trial
• Progression to severe/end-stage dementia
• Intolerable side effects
• Poor medication adherence

Do NOT discontinue cholinesterase inhibitors in patients with clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized. 1

Deprescribing Protocol

• Reduce dose by 50% every 4 weeks until reaching the initial starting dose 1
• After 4 weeks at starting dose, discontinue the medication 1
• Never abruptly discontinue—gradual tapering is essential 1

Adverse Effects

Cholinesterase Inhibitors

• Approximately 29% of patients discontinue due to adverse events versus 18% on placebo 8
• Most common: nausea, vomiting, diarrhea (cholinergic effects) 6, 8
• Generally mild and transient, particularly if titration is gradual over more than 3 months 8
• No evidence of hepatotoxicity 10

Memantine

• Common side effects include confusion, dizziness, and falls 1
• Generally well-tolerated with careful titration 5

Contraindications and Inappropriate Use

Do NOT use cholinesterase inhibitors for: 1

• Frontotemporal dementia
• Other non-indicated dementia conditions
• Any indication other than Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, or vascular dementia

Avoid medications with anticholinergic properties as they worsen cognitive symptoms and counteract cholinesterase inhibitor effects 3

Non-Pharmacological Interventions

While pharmacological treatment is the focus, integrate these evidence-based approaches: 1

• Cognitive training
• Physical exercise programs
• Brain-healthy diet
• Reminiscence therapy

Common Pitfalls to Avoid

• Expecting dramatic improvements—benefits are typically modest; stabilization (no decline) represents a positive outcome 1, 11
• Discontinuing donepezil when adding memantine—evidence supports combination therapy, not substitution; discontinuation leads to significant worsening 5
• Using rapid titration schedules—gradual dose escalation over 6+ weeks minimizes adverse events 8, 10
• Continuing medications indefinitely without reassessment—periodically evaluate for continued benefit 1
• Abrupt discontinuation—always taper gradually 1
• Overlooking treatable causes of decline—assess for delirium, medication interactions, and undertreated comorbidities before attributing worsening to disease progression 5