Treatments for Alzheimer's Disease
Although there is no cure for Alzheimer’s disease, certain treatments can help control or delay its symptoms, particularly in the early stages of the disease.
The newest treatments approved to fight Alzheimer’s disease are immune-based anti-amyloid therapies. They work by clearing different forms of amyloid-beta in the brain. Also known as disease-modifying medications, they target the potential cause of the disease, not just the symptoms.
Other commonly prescribed medications include cholinesterase and glutamate inhibitors, which can help treat symptoms of Alzheimer’s. Non-drug interventions include repetitive transcranial magnetic stimulation, or rTMS, the noninvasive application of magnetic fields to stimulate specific brain regions.
In addition, therapies and techniques are available to help manage agitation, depression, and psychiatric symptoms (hallucinations, delusions, or paranoia) that may arise as the disease progresses.
Sometimes, a person may need treatment for multiple symptoms related to Alzheimer’s disease, and a physician should be consulted in such cases about safety, dosing, and potential drug interactions.
Below is a listing of some of the available treatments for the management of Alzheimer’s disease. Consult a physician before taking any medications.
Anti-Amyloid Treatments
These newest treatments to fight Alzheimer’s disease are immunotherapies targeting toxic amyloid-beta proteins that form plaques in the brain, a defining feature of the disease. Removing amyloid-beta from the brain reduces cognitive and functional decline in people living with early Alzheimer’s. Talk with your clinician about the risks and side effects associated with drugs in this class.
Leqembi®
FDA status: Approved in 2023
Effective for: Early cognitive impairment or mild dementia caused by Alzheimer’s disease
How it works: By clearing toxic amyloid from the brain, Leqembi can slow the cognitive decline associated with Alzheimer’s disease by 25%. It is the first drug in the class of amyloid-targeting immunotherapies shown to slow cognitive decline and receive full FDA approval. This drug specifically targets a small, especially toxic, soluble form of amyloid-beta.
Delivery method: Administered through a vein every two weeks at specialized centers, with each treatment lasting about an hour. How long patients should undergo the treatments is not clear; treatment lasted 18 months in clinical trials. Other medications, such as antihistamines or anti-inflammatories, may be given beforehand to reduce risks for reactions to the treatment.
Side effects: Headache, infusion-related reactions, and amyloid-related imaging abnormalities (also known as ARIA); imaging scans every few months may be needed to screen for these abnormalities.
Note: In granting full approval for this drug, the FDA included a boxed warning in the prescribing information regarding the potential risks associated with ARIA. Having two copies of an Alzheimer’s disease–related genetic variant called ApoE ε4 allele is linked to an increased risk for ARIA and for more severe and symptomatic ARIA. The FDA information includes guidance to test for ApoE ε4 status before starting Leqembi to obtain information about this risk factor. The FDA also cautions that in clinical trials, use of blood thinners (anticoagulant medications) linked to more cases of brain bleeds (called intracerebral hemorrhages) in the Leqembi compared with the placebo group and that care should be taken in considering Leqembi for patients who take these drugs or have other risk factors related to brain bleeds.
Aduhelm®
FDA status: Approved in 2021
Effective for: Early Alzheimer’s disease
How it works: Aduhelm slows cognitive decline by removing aggregated amyloid protein from the brain. This form of amyloid immunotherapy results in shrinkage of amyloid-beta plaques.
Delivery method: Administered through a vein once every month at specialized centers
Side effects: Amyloid-related imaging abnormalities (ARIA), headache, diarrhea, confusion, and disorientation; 41% of participants in clinical trials experienced brain swelling or bleeding that was mild in most cases and resolved with dose reduction.
Note: The approval of this medication was highly controversial, even drawing congressional scrutiny. Critics have cited the limited evidence that it slows cognitive decline, the risks for brain bleeding or swelling, and its high costs. The drug was linked to reductions in amyloid plaques, but critics point out that reducing plaques, as assessed using indirect measures, has not correlated with cognitive function benefits in clinical trials. The U.S. agency overseeing Medicare coverage took the unusual step of limiting coverage for this drug only to people participating in approved clinical trials.
Not Yet FDA-Approved
Donanemab
FDA status: The drug manufacturer expects FDA approval by the end of 2023.
How it works: Donanemab is another type of amyloid immunotherapy drug which targets a plaque-specific form of amyloid that is highly toxic and increases amyloid aggregation. In a phase 3 clinical trial, it slowed the progression of cognitive and functional decline by 35% in participants with early signs of Alzheimer’s disease, with 76.4% of participants showing amyloid clearing with PET imaging.
Delivery method: Administered intravenously (through a vein); in clinical trials, treatment was administered every four weeks for up to 72 weeks.
Side effects: In the phase 3 trial, common side effects included amyloid-related imaging abnormalities (ARIA), headache, and infusion-related reactions.
Remternetug
FDA Status: This drug is currently in phase 3 clinical trials, with results expected in 2025.
How it works: This immunotherapy drug targets the same plaque specific form of amyloid as donanemab, but due to better efficiency, may require lower doses and less invasive administration. Both delivery methods are being tested and compared in a phase 3 trial.
Delivery method: Administered intravenously (through a vein) or subcutaneously (injection under the skin)
Side effects: Early reports describe amyloid-related imaging abnormalities (ARIA) that track with dosage levels, but complete safety results are pending.
Related: Watch a recording of a July 2023 episode of Zoom in on Dementia & Alzheimer’s: Dementia Drugs Town Hall, where Harvard’s Dr. Cynthia Lemere explains the latest Alzheimer’s drugs in the pipeline.
Cholinesterase Inhibitors
Three cholinesterase inhibitors have been approved by the FDA to manage Alzheimer’s disease symptoms. These medications work by regulating levels of acetylcholine, an important brain chemical involved in nerve cell communication. Acetylcholine levels are reduced in the brains of people with Alzheimer’s disease compared with unaffected brains. Cholinesterase inhibitors slow the breakdown of acetylcholine so that more of this chemical is available for nerve cell communication. The effects are slowed progression of cognitive impairment in some patients in the early to middle stages of Alzheimer’s disease.
Razadyne®
Generic name: galantamine
FDA Status: Approved in 2001
Effective for: Early to moderate Alzheimer’s disease
How it works: Razadyne, formerly known as Reminyl®, prevents the breakdown of acetylcholine and stimulates recognition proteins to respond more strongly to signals from acetylcholine and release more of it in the brain. Users may experience improvements in thinking and memory.
Delivery method: Oral medication available as tablets, in a liquid form, or in extended-release capsules
Side effects: Nausea, vomiting, diarrhea, weight loss, dizziness, headache, and tiredness
Exelon®
Generic name: rivastigmine
FDA status: Approved in 2000
Effective for: Early to moderate Alzheimer’s disease
How it works: Exelon prevents the breakdown of acetylcholine and butyrylcholine (a chemical similar to acetylcholine) in the brain. Users may experience improvements in memory and cognition.
Delivery method: Oral medication or skin patch, applied once daily and worn for 24 hours, with two dosage options
Side effects: Nausea, diarrhea, increased frequency of bowel movements, vomiting, muscle weakness, loss of appetite, weight loss, dizziness, drowsiness, and upset stomach
Aricept®
Generic name: donepezil
FDA status: Approved in 1996
Effective for: Early, moderate, and severe Alzheimer’s disease
How it works: Aricept prevents the breakdown of acetylcholine in the brain, preserving its activity, which has been linked to slower progression of cognitive impairment. Users may experience improvements in awareness, memory, and daily functions.
Delivery method: Oral medication in the form of tablets to swallow or that can dissolve in the mouth
Side effects: Diarrhea, dizziness, loss of appetite, muscle cramps, nausea, tiredness, trouble sleeping, vomiting, and weight loss
Other: Aricept also may have a limited slowing effect on the progression from mild cognitive impairment to Alzheimer’s disease. In 2006, Aricept was also approved by the FDA for the management of severe Alzheimer’s symptoms.
Glutamate Inhibitors
These medications protect brain cells by regulating an excitatory nerve communication chemical called glutamate, which Alzheimer’s-damaged cells release in abnormally high amounts. Among its many roles, it promotes efficient learning and memory. Hyperactive or dying cells can release too much glutamate which leads to toxicity, additional cell damage, and ultimately cell death. Glutamate inhibitors interfere with this binding. One FDA-approved glutamate inhibitor is currently available.
Namenda®
Generic Name: memantine
FDA status: Approved in 2003
Effective for: Moderate to severe Alzheimer’s disease
How it works: Namenda appears to protect the brain’s nerve cells against excess glutamate by binding with glutamate’s recognition proteins and inhibiting glutamate’s access to them. Users may experience less forgetfulness or confusion.
Delivery method: Oral medication, available as tablets or an oral solution
Side effects: Back pain, constipation, diarrhea, dizziness, drowsiness, headache, pain, and weight gain
Combination Drugs
One FDA-approved drug combines cholinesterase inhibitors and glutamate inhibitors. This combination prevents both the breakdown of acetylcholine in the brain and protects the brain’s nerve cells against the effects of excess glutamate.
Namzaric®
Generic name: Combination drug containing both donepezil and memantine
FDA status: Approved in 2014
Effective for: Moderate to severe Alzheimer’s disease
How it works: Namzaric is a combination of two drugs that have already been on the market: memantine (Namenda) and donepezil (Aricept). Aricept prevents the breakdown of the signaling molecule acetylcholine in the brain. Namenda appears to protect the brain’s nerve cells against the effects of excess glutamate, a signaling molecule that is overproduced by damaged nerve cells in the brain in some neurological conditions, including Alzheimer’s disease. Users may experience improvements in cognition and overall daily functions, along with slowing of symptom progression.
Delivery method: Oral medication, available as capsules that are taken once daily. The contents of the capsules can be sprinkled on food such as applesauce for ingestion, but the capsules should not be divided, chewed, or crushed.
Side effects: Diarrhea, nausea, vomiting, loss of appetite, increased weight, loss of bladder control, back pain, headache, bruising, drowsiness, and dizziness
Treatment for Neuropsychiatric and Behavioral Symptoms
Often, as Alzheimer’s disease progresses, people experience depression, agitation, and psychiatric symptoms, such as paranoid thoughts, delusions, or hallucinations. These conditions may manifest in different ways, including screaming, asking repetitive questions, hoarding, or pacing. They are also sometimes associated with aggression, hyperactivity, or combativeness. The symptoms may have an underlying medical origin such as a drug interaction or physical pain. If these causes are suspected, a physician should be consulted.
Changes in the environment, caregivers, or surroundings can also cause fear, anxiety, or fatigue and lead to agitation. In these cases, non-medical intervention is recommended to determine the source of the problem, modify the environment, and mitigate the behavior. If non-medical intervention does not work or there are concerns about self-endangerment or danger to others, a physician should be consulted to evaluate the need for medical treatments for depression, psychosis, or anxiety.
Rexulti®
Generic name: brexpiprazole
FDA status: Approved in 2015
Effective for: Moderate to severe Alzheimer’s disease
How it works: Rexulti was approved in 2015 for the treatment of schizophrenia and as an add-on treatment for major depressive disorder in adults. In 2023, the FDA approved its use for agitation associated with dementia resulting from Alzheimer’s disease.
Delivery method: Tablets taken by mouth daily
Side effects: Weight gain, sleepiness, dizziness, common cold symptoms, and restlessness or feeling the urgent need to move (akathisia)
Belsomra®
Generic name: suvorexant
FDA status: Approved in 2014 for insomnia; 2020 for sleep disorders in Alzheimer’s disease
Effective for: Moderate to severe Alzheimer’s disease
How it works: This drug blocks key proteins called orexin receptors, which are active in the sleep–wake cycle and associated with brain regions involved in cognition and Alzheimer's disease.
Delivery method: Tablets taken by mouth
Side effects: Drowsiness, dizziness, diarrhea, dry mouth, headache, and respiratory issues
Potential Future Treatments
Many potential treatments for Alzheimer’s disease are being investigated in laboratories and tested in human clinical trials. Below is a list of services where you can identify clinical trials and sign up to volunteer:
- Antidote. Antidote helps you discover new treatment options under development by medical researchers. Using answers to a few health questions, its search engine quickly and easily finds a trial that’s right for you. (1-888-509-1308).
- National Institutes of Health (NIH). This umbrella government research agency provides information on government-sponsored human trials and recruitment, with locations, purpose, eligibility requirements, and phone contacts. One relevant institute under the NIH is the National Institute on Aging (1-800-438-4380).
- Clinicaltrials.gov. This online registry and results database hosted by the NIH lists all publicly and privately supported clinical studies being conducted with human participants around the world. Follow prompts to look for active clinical trials located near you for a specific medical condition.
- ResearchMatch. This free and secure registry connects individuals with researchers who are looking for people to participate in their studies.
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