What medications are used to treat memory loss, particularly in patients with Alzheimer's disease?

Medications for Memory Loss in Alzheimer's Disease

For patients with mild to moderate Alzheimer's disease, initiate treatment with a cholinesterase inhibitor—donepezil is the preferred first-line agent due to its once-daily dosing, favorable tolerability profile, and lack of hepatotoxicity. 1

First-Line Treatment: Cholinesterase Inhibitors

Donepezil (Preferred Agent)

• Start at 5 mg once daily, increase to 10 mg after 4 weeks 1
• Most commonly prescribed due to convenience and tolerability 2
• No hepatotoxicity or laboratory monitoring required 1
• Can be taken with food to minimize gastrointestinal side effects (nausea, vomiting, diarrhea) 1
• Available as oral tablet or transdermal patch (weekly application) 2
• Caution: Monitor for cardiac conduction abnormalities 2

Alternative Cholinesterase Inhibitors

Rivastigmine:

• Start 1.5 mg twice daily, titrate by 3 mg/day every 4 weeks to maximum 6-12 mg/day 1
• Fewer cardiac side effects than donepezil but causes local application-site reactions with transdermal patch 2
• Higher rates of nausea and adverse events compared to donepezil 1, 3
• Consider if donepezil is not tolerated 1, 3

Galantamine:

• Start 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, consider 12 mg twice daily based on response 1, 4
• Improves cognitive symptoms rapidly and delays behavioral symptoms 2
• Minimal drug-drug interactions due to multiple metabolic pathways 2
• Caution: Monitor cardiac conduction; dose adjustment needed for hepatic (moderate) or renal impairment (CrCl 9-59 mL/min) 4

Tacrine:

• Not recommended as first-line due to hepatotoxicity (40% develop elevated liver enzymes) and four-times-daily dosing 1, 5

Expected Outcomes with Cholinesterase Inhibitors

• Modest improvements: 1-3 point improvement on ADAS-cog scale (clinically significant change is ≥4 points) 1, 6
• Stabilization or delayed deterioration rather than dramatic improvement 1, 3
• Effects apparent over 6-12 months of observation 1
• Benefits are symptomatic only—these drugs do not stop or reverse neurodegeneration 6

Moderate to Severe Disease: Add Memantine

For patients with moderate to severe Alzheimer's disease already on a cholinesterase inhibitor, add memantine 3

• Memantine improves global assessment, quality of life, and reduces caregiver burden when combined with donepezil 3
• Once-daily dosing (immediate or sustained-release formulation) 2
• Acts as glutamate regulator with neuroprotective, anti-Parkinsonian, and antidepressant effects 2
• Well-tolerated with withdrawal rates similar to placebo (8-12% vs 7-13%) 3
• Produces 1-3 point improvements on ADAS-cog, though clinical significance remains uncertain 1

Assessment and Monitoring

Evaluate response at 6-12 months using: 1

• Physician's global assessment
• Primary caregiver report
• Mental status testing (though brief tests are relatively insensitive)
• Behavioral and functional changes

Discontinue treatment if: 1

• Intolerable side effects develop
• Poor adherence
• Deterioration continues at pre-treatment rate after 6-12 months

Switching Between Agents

If a patient fails to respond or cannot tolerate one cholinesterase inhibitor, trial a different one 1, 7

• Prior discontinuation does not predict poor response to a different effective treatment 7
• No head-to-head studies demonstrate superiority of one agent over another 1

Adjunctive Therapy

Vitamin E (2,000 IU daily) may be considered to slow functional decline, though evidence is limited 1

Do not use: 3

• Antidepressants for cognitive decline (no evidence of benefit unless comorbid depression exists)
• NSAIDs or estrogen (insufficient evidence)

Critical Counseling Points

Set realistic expectations with patients and families: 1, 3

• Benefits are modest and represent slowing of decline, not cure
• Improvement of 1-3 points on cognitive scales is typical
• Stabilization of symptoms is a successful outcome
• Treatment is symptomatic, not disease-modifying (except newer agents like lecanemab/aducanumab) 2

Common Pitfalls to Avoid

• Cardiac monitoring is essential with donepezil and galantamine due to conduction disturbances 2
• Dose adjustments required for galantamine in hepatic/renal impairment 4
• Gradual titration minimizes cholinergic side effects (nausea, vomiting, diarrhea) 1, 5
• Taking medication with food reduces adverse effects for most agents 1, 5
• Do not expect rapid improvement—observe for 6-12 months before declaring treatment failure 1