At what point should dementia medications be initiated in a patient?

When to Initiate Dementia Medications

Start cholinesterase inhibitors (donepezil, rivastigmine, or galantamine) immediately upon diagnosis of mild to moderate Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease dementia, or vascular dementia. 1, 2, 3

Specific Indications for Starting Treatment

Alzheimer's Disease

• Initiate cholinesterase inhibitors at diagnosis of mild to moderate AD (MMSE scores typically 10-26), as these agents provide modest but clinically meaningful cognitive benefits equivalent to delaying decline by approximately one year 1, 4, 3
• Start memantine when patients reach moderate to severe AD (MMSE ≤14), either as monotherapy or in combination with a cholinesterase inhibitor already on board 1, 5, 3
• Combination therapy with memantine plus donepezil is recommended for severe AD in patients already tolerating a cholinesterase inhibitor 2, 5, 3

Other Dementia Types

• Begin cholinesterase inhibitors immediately upon diagnosis of dementia with Lewy bodies or Parkinson's disease dementia, as these conditions respond well to cholinergic enhancement 1, 2, 3
• Consider cholinesterase inhibitors for vascular dementia or mixed dementia at diagnosis, though evidence is stronger for mixed presentations 1, 2, 3

When NOT to Start Dementia Medications

Contraindicated Conditions

• Do not prescribe cholinesterase inhibitors or memantine for mild cognitive impairment (MCI), as they are ineffective and not indicated 1, 2, 3
• Avoid cholinesterase inhibitors in frontotemporal dementia, as they are ineffective and may worsen agitation 1, 2, 3
• Do not initiate in severe/end-stage dementia with complete dependence in basic ADLs, inability to respond to environment, or limited life expectancy 1

Relative Contraindications

• Severe cardiovascular disease or underlying cardiac abnormalities require careful risk-benefit assessment 6
• Patients with significant anticholinergic burden from other medications need medication reconciliation first 7

Practical Initiation Strategy

Cholinesterase Inhibitor Dosing

• Donepezil: Start 5 mg once daily, increase to 10 mg after 4 weeks; take with food to minimize GI side effects 1, 4
• Rivastigmine: Start 1.5 mg twice daily, titrate by 3 mg/day every 4 weeks to target 6-12 mg/day 1
• Galantamine: Start 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, consider 12 mg twice daily based on tolerability 1

Memantine Dosing

• Start 5 mg once daily, increase weekly by 5 mg/day in divided doses to target 20 mg/day (10 mg twice daily) 5
• Common side effects include confusion, dizziness, and falls—monitor closely during titration 1, 2

Setting Realistic Expectations

Communicate to patients and families that benefits are modest: expect 5-15% improvement over placebo, equivalent to stabilization or slowing decline by approximately 6-12 months, not dramatic reversal 1

Monitoring Response

• Assess treatment effectiveness at 6-12 months using caregiver reports, functional assessments (ADCS-ADL), cognitive testing, and global clinical impression 1, 2
• Do not rely solely on brief mental status tests like MMSE, as they are relatively insensitive to medication effects 1
• Continue medications if there is any evidence of stabilization, slowed decline, or improvement in cognition, function, or behavior 1

Critical Pitfalls to Avoid

• Never delay treatment waiting for "worse" dementia—benefits are greatest when started early in the disease course 1, 4, 3
• Do not discontinue medications simply because dementia progresses—continue as long as there is any clinical benefit 1, 2, 3
• Never stop cholinesterase inhibitors abruptly in patients with active psychosis, agitation, or aggression until these symptoms stabilize 1, 8, 2
• Avoid polypharmacy with anticholinergic medications, which can negate benefits and worsen cognition 7
• Do not expect dramatic improvements—the goal is slowing decline and maintaining function 1, 2