Memory Digest

Cholinesterase Inhibitors and Memantine

Donepezil, rivastigmine, galantamine and memantine—how these long-used dementia medicines work, who they help, and side effects.

Last reviewed: October 2026

For more than 25 years, the main medicines for Alzheimer's symptoms have been the cholinesterase inhibitors—donepezil, rivastigmine and galantamine—and memantine. They don't stop the disease, but for some people they help memory, thinking and daily function for a period of time. They are inexpensive generics and are widely used.

Cholinesterase inhibitors

How they work

Acetylcholine is a chemical messenger important for memory, attention and learning. In Alzheimer's, the cells that make it are damaged. Cholinesterase inhibitors block an enzyme that breaks acetylcholine down, so more of it remains available.

The three medicines

They are also commonly used—and often particularly helpful—in Lewy Body Dementia. They're sometimes used in Vascular Dementia and mixed dementia. They generally don't help frontotemporal dementia and may worsen behavior there, and they are not proven to help Mild Cognitive Impairment (MCI).

What to expect

Benefits are modest and vary. A Cochrane review of donepezil found small improvements in thinking, daily function and overall impression of change compared with placebo over 6 to 12 months. Some people and families notice clearer thinking, better attention or engagement; others notice no change. Often the goal is slowing decline for a time rather than improvement. It can take several weeks to tell, and doctors usually start with a low dose and increase gradually.

Side effects

• Nausea, vomiting, diarrhea and loss of appetite or weight (usually lessen over time; taking with food helps)
• Vivid dreams or trouble sleeping (donepezil may be taken in the morning)
• Muscle cramps
• Slow heart rate, dizziness or fainting—tell the doctor about any heart rhythm problems or falls
• The rivastigmine patch causes fewer stomach side effects but can irritate the skin

Memantine

How it works

Memantine (brand Namenda) works differently: it regulates glutamate, a chemical involved in learning and memory that can damage nerve cells in excess.

Who it's for

Memantine is approved for moderate to severe Alzheimer's disease. It is often combined with donepezil (a combination capsule exists). Reviews show small benefits in thinking, daily activities and behavior in moderate to severe Alzheimer's, but not clear benefit in mild Alzheimer's.

Side effects

Generally well tolerated. Possible side effects include dizziness, headache, confusion, constipation and sleepiness. Doses are lower for people with kidney problems.

Practical tips

• Use a pill organizer or have a caregiver manage doses.
• Report side effects instead of stopping suddenly—the dose or form can often be adjusted.
• Keep a simple diary of thinking, mood and daily function to help judge whether it's working.
• Stopping abruptly after long use can sometimes lead to a noticeable decline; discuss any stop with the doctor.
• Ask the pharmacist to check for interactions, especially with anticholinergic medicines that work in the opposite direction (see Reversible Causes of Memory Problems).

When to reconsider

There's no fixed rule about how long to take these medicines. Reasonable times to review include troublesome side effects, unclear benefit, swallowing problems, or the late stage when goals of care shift toward comfort.

Where they fit

These medicines can be used alongside anti-amyloid treatments like Lecanemab (Leqembi) and Donanemab (Kisunla), and alongside non-drug approaches, which remain the foundation of good care. See Dementia Treatments: An Overview and Non-Drug Treatments for Dementia.

Sources

1. National Institute on Aging: How Is Alzheimer's Disease Treated?
2. Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev, 2018
3. McShane R et al. Memantine for dementia. Cochrane Database Syst Rev, 2019
4. Alzheimer's Association: Medications for Memory

Not medical advice. This article is general information, not a diagnosis or treatment plan for any individual. Talk with a doctor about your situation.

Related articles

• Dementia Treatments: An Overview
• Alzheimer's Disease
• Lewy Body Dementia
• Donanemab (Kisunla)
• Lecanemab (Leqembi)