What is the first line treatment for dementia?

First-Line Treatment for Dementia

Cholinesterase inhibitors (ChEIs) are the first-line pharmacological treatment for mild to moderate dementia of the Alzheimer's type, with donepezil being the preferred agent due to its once-daily dosing, favorable side effect profile, and demonstrated efficacy. 1

Types of Dementia and Appropriate First-Line Treatments

Alzheimer's Disease (Most Common Type)

• Mild to Moderate Alzheimer's Disease:

  • First choice: Donepezil 5 mg daily, increasing to 10 mg daily after 4-6 weeks if tolerated 2, 1
  • Alternatives: Rivastigmine or galantamine if donepezil is not tolerated 1

• Moderate to Severe Alzheimer's Disease:

  • First choice: Donepezil 10 mg daily 2
  • Add-on therapy: Memantine 20 mg daily can be added for moderate to severe disease 3, 1

Other Types of Dementia

• Parkinson's Disease Dementia:

  • First choice: Rivastigmine (starting at 1.5 mg twice daily, target dose 6-12 mg/day) 1, 4

• Vascular Dementia:

  • ChEIs may provide benefit similar to Alzheimer's disease 2

• Lewy Body Dementia:

  • ChEIs (particularly rivastigmine) may be beneficial 2, 1

Dosing and Administration

Donepezil

• Starting dose: 5 mg once daily
• After 4-6 weeks: Increase to 10 mg once daily if tolerated
• Advantage: Once-daily administration 1

Rivastigmine

• Starting dose: 1.5 mg twice daily
• Target dose: 3-6 mg twice daily (6-12 mg/day)
• Note: Higher rates of gastrointestinal side effects during titration 1, 4

Galantamine

• Starting dose: 4 mg twice daily
• Target dose: 8-12 mg twice daily
• Requires twice-daily dosing 1

Efficacy Considerations

ChEIs provide modest but statistically significant benefits in:

• Cognitive function (2.7 points improvement on the 70-point ADAS-Cog scale) 5
• Global clinical function 2
• Activities of daily living 6

However, these benefits are modest in magnitude. The average improvement in cognition does not typically reach what would be considered clinically significant (≥4 points on ADAS-Cog), though individual patient responses vary 2.

Monitoring Response to Treatment

• Assess response after 6-12 months of treatment 1
• Look for:
  • Stabilization or slowing of cognitive decline
  • Improvement or stabilization in functional abilities
  • Changes in behavior or neuropsychiatric symptoms
  • Caregiver reports of changes 1

When to Discontinue Treatment

Consider discontinuation if:

1. Clinically meaningful worsening despite treatment for >6 months
2. No observable benefit at any point during treatment
3. Development of severe or end-stage dementia
4. Intolerable side effects
5. Poor medication adherence 2

Common Side Effects and Management

• Most common adverse effects: Nausea, vomiting, diarrhea, anorexia 2, 6
• Management:
  • Start with lower doses
  • Gradual titration (particularly important for rivastigmine)
  • Take with food
  • Consider switching to another ChEI if side effects are intolerable 1

Special Considerations

• Frontotemporal dementia: ChEIs should be discontinued as they are not beneficial 2
• Mild cognitive impairment: ChEIs should be deprescribed as they are not indicated 2
• Neuropsychiatric symptoms: Continue ChEIs if they have reduced psychotic symptoms, agitation, or aggression, even if cognitive decline continues 2

Practical Pitfalls to Avoid

1. Premature discontinuation: Allow at least 6 months before determining lack of efficacy 1
2. Inadequate dose titration: Particularly with rivastigmine, slow titration reduces side effects 1
3. Overlooking add-on therapy: For moderate to severe Alzheimer's disease, consider adding memantine to donepezil 3
4. Failing to reassess: Regular monitoring is essential to determine ongoing benefit 2
5. Continuing treatment when contraindicated: ChEIs should be discontinued in frontotemporal dementia and mild cognitive impairment 2

While the benefits of ChEIs are modest, they represent the best available pharmacological approach for managing dementia symptoms, with donepezil typically being the preferred first-line agent due to its favorable dosing schedule and side effect profile.