Dementia medications explained

What dementia medications are

Dementia medications are the FDA-approved treatments for Alzheimer's disease and, for some medications, other dementias. There are three groups in current use.

The cholinesterase inhibitors (donepezil, rivastigmine, galantamine) block an enzyme that breaks down acetylcholine. That raises acetylcholine levels at nerve junctions, which supports memory and other cognitive functions. They were the first approved treatments for Alzheimer's, starting in the 1990s, and they remain first-line for mild to moderate Alzheimer's disease. Rivastigmine is also approved for Parkinson's disease dementia. Donepezil is approved across mild, moderate, and severe stages.

Memantine is an NMDA receptor antagonist. It works differently from the cholinesterase inhibitors, and it's used for moderate to severe Alzheimer's disease. It's often combined with a cholinesterase inhibitor.

Lecanemab and donanemab are monoclonal antibodies given by IV infusion that target beta-amyloid, one of the proteins that builds up in the Alzheimer's brain. They're approved for early Alzheimer's disease (mild cognitive impairment due to Alzheimer's, or mild Alzheimer's dementia) in people with confirmed amyloid pathology. They're the first medications shown to modestly slow the disease itself, though they come with significant risks and require careful monitoring.

The dementia medications covered here are donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), memantine (Namenda), lecanemab (Leqembi), and donanemab (Kisunla).

How they work

The cholinesterase inhibitors block acetylcholinesterase, the enzyme that breaks down acetylcholine in the synaptic gap. Alzheimer's disease is associated with a loss of cholinergic neurons, meaning cells that use acetylcholine. Blocking the breakdown enzyme lets the acetylcholine that's still being released stick around longer, which supports memory, attention, and other functions. Rivastigmine also inhibits butyrylcholinesterase, a related enzyme. The differences between donepezil, rivastigmine, and galantamine come down to dosing schedule, side-effect profile, and formulation (rivastigmine has a patch, which many people prefer).

Memantine blocks the NMDA glutamate receptor in a specific way. Glutamate is the main excitatory messenger in the brain, and in Alzheimer's disease glutamate signaling becomes chronically overactive, which is thought to damage neurons over time (excitotoxicity). Memantine blocks the NMDA receptor at low levels of activation while allowing normal signaling to get through. That balance is thought to protect neurons from ongoing excitotoxic injury.

Lecanemab and donanemab are anti-amyloid monoclonal antibodies. They bind to different forms of beta-amyloid (lecanemab preferentially targets soluble aggregates called protofibrils; donanemab targets pyroglutamate amyloid found in established plaques). Both promote clearance of amyloid plaques from the brain over months of infusions. That plaque clearance is associated with a modest slowing of cognitive and functional decline. Whether plaque removal is the mechanism of clinical benefit is still debated, but that's the pharmacology.

The important limit to name honestly. None of these medications cure Alzheimer's disease. The older medications are symptomatic. The new anti-amyloid antibodies do slow disease progression, but the effect is measurable at the trial level (around 25% to 35% slowing of decline over 18 months) rather than a dramatic clinical turnaround. That's important context.

How the class developed

Tacrine was the first cholinesterase inhibitor, approved in 1993. It was hard to use because of liver toxicity and four-times-daily dosing, and it fell out of use. Donepezil arrived in 1996 with once-daily dosing and no liver monitoring requirement, and it became the standard cholinesterase inhibitor. Rivastigmine and galantamine followed in the early 2000s.

Memantine was approved in the U.S. in 2003 for moderate to severe Alzheimer's disease. It offered a different mechanism, and combining memantine with a cholinesterase inhibitor became a common approach.

For roughly twenty years after memantine, no new medications for Alzheimer's disease were approved. Many drug trials failed, particularly ones targeting amyloid. That started to change in 2021 with aducanumab, which received accelerated approval but was later withdrawn from the market because of limited evidence of clinical benefit and controversy over the approval decision. Lecanemab received accelerated approval in early 2023 and traditional approval in mid-2023, based on the CLARITY AD trial, which showed a 27% slowing of decline on a functional scale over 18 months. Donanemab received traditional approval in mid-2024 based on the TRAILBLAZER-ALZ 2 trial with similar findings.

The anti-amyloid antibodies are the first approvals for disease-modifying treatment of Alzheimer's, and they've changed how mild Alzheimer's disease is worked up. Getting the diagnosis right, using amyloid PET or CSF biomarkers, and considering treatment early are now on the table for people with mild cognitive impairment where they weren't in the previous era.

What they treat

• Alzheimer's disease. Cholinesterase inhibitors are approved across mild to severe stages (donepezil for all stages; rivastigmine and galantamine for mild to moderate). Memantine is approved for moderate to severe. Lecanemab and donanemab are approved for early Alzheimer's disease (MCI due to AD or mild AD dementia) with confirmed amyloid pathology.
• Parkinson's disease dementia. Rivastigmine (patch or capsules) is FDA-approved for this.
• Dementia with Lewy bodies. Cholinesterase inhibitors, particularly rivastigmine, are used off-label and often work well.
• Vascular dementia and mixed dementia. Cholinesterase inhibitors are used off-label with modest evidence.

Dementia medications aren't a substitute for the non-medication parts of dementia care, which are substantial: management of cardiovascular risk factors, treatment of hearing loss, physical activity, cognitive and social engagement, careful medication review to remove drugs with anticholinergic burden, and support for caregivers.

Individual medications in this class

• Donepezil (Aricept). Cholinesterase inhibitor. Once-daily oral dosing at 5 mg, 10 mg, or 23 mg. Approved for mild, moderate, and severe Alzheimer's disease. The most commonly prescribed dementia medication.
• Rivastigmine (Exelon). Cholinesterase inhibitor that also inhibits butyrylcholinesterase. Available as capsules (twice daily) and a transdermal patch (once daily). Approved for Alzheimer's disease (mild to moderate) and Parkinson's disease dementia.
• Galantamine (Razadyne). Cholinesterase inhibitor with additional nicotinic receptor modulation. Available as immediate-release (twice daily) and extended-release (once daily). Approved for mild to moderate Alzheimer's disease.
• Memantine (Namenda). NMDA receptor antagonist. Available as immediate-release (twice daily) and extended-release (once daily). Approved for moderate to severe Alzheimer's disease.
• Lecanemab (Leqembi). Anti-amyloid monoclonal antibody. IV infusion every two weeks. Approved for early Alzheimer's disease with confirmed amyloid pathology.
• Donanemab (Kisunla). Anti-amyloid monoclonal antibody. IV infusion every four weeks. Approved for early Alzheimer's disease with confirmed amyloid pathology. Trial protocol allowed treatment discontinuation once amyloid plaques were substantially cleared.

Common side effects across the class

Cholinesterase inhibitors: nausea, diarrhea, decreased appetite, weight loss, muscle cramps, vivid dreams or sleep disturbance. The GI effects come from increased acetylcholine in the gut. Starting at a low dose and titrating up slowly helps. The rivastigmine patch has less GI effect than oral rivastigmine because the peak drug level is lower and steadier. Slower heart rate can occur, and syncope has been reported.

Memantine: dizziness, headache, confusion, constipation. Generally well tolerated.

Lecanemab and donanemab: infusion reactions (flushing, chills, muscle aches) are common, especially with the first few infusions. Headache is common. The most important adverse effects specific to these medications are ARIA (amyloid-related imaging abnormalities), described below.

Serious warnings across the class

Cholinesterase inhibitors. Slower heart rate and rare syncope, particularly in people with heart block or sick sinus syndrome. GI bleeding risk goes up slightly. Care with anticholinergic medications, which work against cholinesterase inhibitors and worsen cognition.

Memantine. Generally low-warning. Care in significant renal impairment because dose adjustment is needed.

Anti-amyloid antibodies (lecanemab, donanemab). These carry the most weight.

ARIA-E and ARIA-H. ARIA stands for amyloid-related imaging abnormalities. ARIA-E is edema, meaning fluid in the brain, and ARIA-H is hemorrhage, meaning small bleeds. Both are seen on MRI, and both are more common in people who are ApoE4 homozygotes (two copies of the ApoE4 gene). Most ARIA is asymptomatic and found on routine monitoring MRIs. A meaningful minority is symptomatic (headache, confusion, visual changes, seizures) and can be serious or rarely fatal. Deaths from severe ARIA and intracerebral hemorrhage have been reported in clinical trials and post-marketing, including in people on blood thinners.

ApoE4 genotyping is now recommended before starting lecanemab or donanemab, so the risk can be discussed with the patient and family. ApoE4 homozygotes have the highest ARIA risk (approximately 15% to 30% ARIA-E). ApoE4 heterozygotes have intermediate risk. Non-carriers have the lowest risk.

Boxed warning for both lecanemab and donanemab regarding ARIA and, particularly, the risk of intracerebral hemorrhage in people on anticoagulants (blood thinners like warfarin, apixaban, rivaroxaban). Concurrent anticoagulation is generally a contraindication or cautionary condition.

Infusion reactions can be significant, especially with the first two infusions of lecanemab. Pretreatment with an antihistamine or acetaminophen is sometimes used.

Monitoring MRIs are required at specific timepoints (typically before the 5th, 7th, and 14th infusions of lecanemab, and around 1, 2, 3, 4, 6, and 12 months for donanemab, or as specified in the current prescribing information). Any suspicious symptoms trigger an off-schedule MRI.

What tips the choice within the class

Stage of disease. For very early Alzheimer's disease with confirmed amyloid, the anti-amyloid antibodies are an option to slow decline, if the patient wants them, understands the risks, isn't on anticoagulants, and can access biweekly or monthly IV infusions and MRI monitoring. For mild to moderate Alzheimer's disease, a cholinesterase inhibitor is standard. For moderate to severe Alzheimer's disease, memantine is added or used alone, and donepezil is often continued.

Combination. Donepezil plus memantine is a common combination in moderate to severe Alzheimer's disease. A single-pill combination is available.

Formulation. If GI side effects are the barrier with oral rivastigmine, the patch is a reasonable alternative. If pill swallowing is difficult, memantine oral solution and donepezil orally disintegrating tablets exist.

Genotype. Before starting an anti-amyloid antibody, ApoE4 genotyping is standard. ApoE4 homozygotes have the highest ARIA risk, and the risk-benefit conversation is different than for non-carriers.

Anticoagulation. If someone is on a blood thinner and it can't be safely stopped, anti-amyloid antibodies generally aren't an option. Cardiovascular history and stroke risk factor them into the discussion.

Access and support. The anti-amyloid antibodies require infusion capacity, MRI monitoring, and coordinated care. That's not available everywhere, and cost is meaningful even with Medicare coverage.

Non-Alzheimer's dementia. Rivastigmine has particular evidence in Parkinson's disease dementia and dementia with Lewy bodies. The anti-amyloid antibodies aren't indicated in those conditions.

Common questions

Do these medications reverse dementia? No. None of these medications reverse Alzheimer's disease or restore lost function to what it was before. Cholinesterase inhibitors and memantine are symptomatic treatments. They can support function and modestly slow decline for a period, but the disease continues to progress. Lecanemab and donanemab are the first disease-modifying treatments approved, meaning they act on the underlying pathology. They slow decline (roughly 25% to 35% slowing in trials) but don't stop or reverse it. The realistic goal is more function preserved for longer, not a cure.

What are ARIA-E and ARIA-H? ARIA (amyloid-related imaging abnormalities) are findings on MRI seen with anti-amyloid antibodies. ARIA-E is fluid buildup (edema) in an area of the brain. ARIA-H is small bleeds (hemorrhages), including microbleeds and superficial siderosis. Most ARIA is silent and found on routine monitoring MRI. Some ARIA causes symptoms like headache, confusion, seizures, or visual changes. Severe ARIA is uncommon but can be dangerous. That's why ApoE4 genotyping is done in advance, why anticoagulation is a concern, and why MRI monitoring is required.

Should I get ApoE4 testing before an anti-amyloid antibody? Yes. ApoE4 status changes the ARIA risk substantially, and current guidance recommends genotyping before starting lecanemab or donanemab. ApoE4 homozygotes (two copies of ApoE4) have the highest ARIA risk. ApoE4 heterozygotes have intermediate risk. Non-carriers have the lowest risk. The result is used to inform the risk-benefit discussion. Some ApoE4 homozygotes still choose treatment; some choose not to; the point is to make that choice with the actual information.

How long can someone stay on a cholinesterase inhibitor? There's no fixed stopping point. In practice, they're often continued as long as they seem to be helping, which can mean years. If the disease has progressed to a point where the medication no longer appears to add benefit, a taper can be considered. Stopping abruptly can cause a temporary drop in function, so a taper is preferred. In severe dementia, the balance shifts, and continuing indefinitely isn't always the right choice. That decision is worth revisiting with a prescriber every so often.

What about the non-medication parts of dementia care? They matter as much as the medication, sometimes more. Treating cardiovascular risk factors (blood pressure, cholesterol, diabetes, atrial fibrillation), addressing hearing loss (hearing aids), maintaining physical activity, staying socially and cognitively engaged, sleeping well, and removing medications with anticholinergic burden all support function. Caregiver support, home safety, and planning for future care are equally important. Medications are one part of dementia care, not the whole of it.

Sources

This guide draws on current prescribing information and public health references. It's reviewed for clinical accuracy and updated as guidance changes. This is educational content and isn't medical advice.

1. U.S. Food and Drug Administration. Prescribing information.
2. MedlinePlus, U.S. National Library of Medicine.
3. National Institute on Aging.
4. Alzheimer's Association. 2024 Alzheimer's Disease Facts and Figures.
5. American Academy of Neurology. Practice guidelines related to dementia diagnosis and management.
6. van Dyck CH, et al. Lecanemab in early Alzheimer's disease. NEJM 2023.
7. Sims JR, et al. Donanemab in early symptomatic Alzheimer disease. JAMA 2023.