Alzheimer’s disease is the most common cause of dementia, characterized by progressive memory loss and cognitive decline1 . It is marked by the buildup of amyloid-β plaques and tau tangles in the brain, which damage neurons and impair brain function2 . With over 6.5 million Americans affected, new treatment options that improve quality of life and ease of use are urgently needed1 . Recently, the FDA approved a once-weekly transdermal patch delivering donepezil, offering a novel approach to managing symptoms of Alzheimer's dementia3 .
Mechanism of Action
Alzheimer’s disease involves the loss of cholinergic neurons and reduced levels of acetylcholine, a neurotransmitter essential for memory and cognition1 4. Cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, are first-line treatments that work by blocking the enzyme acetylcholinesterase, which breaks down acetylcholine. This inhibition increases acetylcholine availability in the brain, temporarily enhancing communication between brain cells and improving memory and attention1 5.
The newly approved weekly patch delivers donepezil transdermally, providing a steady release of the medication through the skin into the bloodstream3 . This method maintains consistent drug levels, similar to oral administration, but with potentially improved tolerability6 . Donepezil’s action helps reduce symptoms of confusion and cognitive decline in mild to severe stages of Alzheimer's dementia3 .
While cholinesterase inhibitors provide symptomatic relief, they do not cure or halt the progression of the disease4 . They mainly improve short-term memory and daily functioning but do not address the underlying pathology such as amyloid plaques or tau tangles4 . Newer monoclonal antibody therapies target these pathological features but are limited to early disease stages and require biomarker confirmation7 8.
Common side effects of cholinesterase inhibitors, including donepezil, may involve gastrointestinal symptoms like nausea and diarrhea, as well as dizziness and vivid dreams9 3. The patch formulation may cause skin reactions such as redness and itching at the application site3 .
“This FDA action demonstrates continued progress in the field of Alzheimer's treatment. We are seeing the evolution of amyloid targeting antibody treatments, including improvements in drug delivery and acknowledgment that this class of treatments continues to demonstrate clinical benefit beyond the 18-month clinical trial data.”
— Maria C. Carrillo, Alzheimer's Association10
Availability and Access
The weekly donepezil patch, marketed as ADLARITY, is FDA-approved for treating mild, moderate, and severe dementia of the Alzheimer’s type3 . The patch is applied to the skin on the upper back, chest, or upper arm, providing a convenient alternative to daily oral pills9 3. This transdermal system ensures continuous drug delivery over a week, which may improve medication adherence by reducing the burden of daily dosing6 .
“The expectation with subcutaneous delivery of Alzheimer's treatment is that patients and care partners find it easier, simpler and more convenient to use, and that it reduces the need to travel for hospital or infusion center visits, compared to intravenous infusion. The result is that more people will continue taking their medicine and experiencing treatment benefits.”
— Maria C. Carrillo, Alzheimer's Association10
Insurance coverage for transdermal patches can vary, and prior authorization may be required, potentially limiting access for some patients . Patients should consult healthcare providers and insurers to understand coverage options.
The patch is contraindicated in individuals allergic to donepezil, piperidine derivatives, or any component of the patch, and those with a history of allergic contact dermatitis to ADLARITY3 . Patients should monitor for side effects such as skin irritation, headache, muscle spasms, and gastrointestinal symptoms3 .
Common side effects reported with ADLARITY include:
- Headache (15%) 3
- Application site itching (9%) 3
- Muscle spasms (9%) 3
- Sleeplessness (7%) 3
- Abdominal pain (5%) 3
- Skin irritation or redness at the patch site (6%) 3
- Dizziness and abnormal dreams (4%) 3
💡 Did You Know? ADLARITY is the first and only FDA-approved once-weekly transdermal system that consistently delivers donepezil while worn, offering a new option for Alzheimer's dementia management3 .
Alternative Alzheimer's Treatments
Besides cholinesterase inhibitors, several other FDA-approved medications are available for Alzheimer's disease, each with distinct mechanisms and indications4 . Memantine, for example, is an NMDA receptor antagonist used in moderate to severe stages to regulate glutamate and protect neurons from excitotoxic damage1 .
More recently, disease-modifying therapies targeting amyloid-beta plaques have been approved, including aducanumab, lecanemab, and donanemab11 1012. These monoclonal antibodies aim to slow disease progression by clearing toxic amyloid deposits in the brain7 8.
- Lecanemab (Leqembi) is approved for early Alzheimer's disease with confirmed amyloid pathology. It is administered via intravenous infusion every two weeks, with a new option for weekly subcutaneous maintenance dosing using an autoinjector, allowing at-home administration10 13.
- Donanemab (Kisunla) is given as a monthly intravenous infusion for patients with mild cognitive impairment or mild dementia due to Alzheimer's, requiring biomarker confirmation12 14.
- These therapies require careful patient selection, including amyloid PET scans or cerebrospinal fluid tests to confirm amyloid presence, and genetic testing for ApoE ε4 status to assess risk of side effects like amyloid-related imaging abnormalities (ARIA) 157.
| Treatment | Delivery Method | Indication | Biomarker Requirement | Dosing Frequency |
|---|---|---|---|---|
| Donepezil Patch | Transdermal patch3 | Mild to severe Alzheimer's dementia | No | Once weekly3 |
| Lecanemab | IV infusion or subcutaneous autoinjector10 13 | Early Alzheimer's disease | Amyloid confirmation required10 | Biweekly IV or weekly SC10 |
| Donanemab | IV infusion12 | Early symptomatic Alzheimer's | Amyloid confirmation required12 | Monthly12 |
| Memantine | Oral | Moderate to severe Alzheimer's | No | Daily |
Transdermal patches like the donepezil patch provide an alternative to oral medications, potentially improving compliance and reducing gastrointestinal side effects common with oral cholinesterase inhibitors6 . Rivastigmine is another cholinesterase inhibitor available as a transdermal patch, offering continuous medication delivery9 .
“Marketers prey on this population, pitching products that make unproven claims that they can prevent, treat, delay, or even cure Alzheimer's disease. These purported miracle cures are sold primarily on the Internet. At best, the products offered by these scam artists will have no effect on the patient; at worst they may pose a danger to a patient who takes them.”17
Limitations of Current Therapies
Despite advances, no current treatment stops or reverses Alzheimer's disease. Most medications provide symptom relief for a limited time, and disease-modifying therapies are limited to early stages and require careful monitoring. 174
Current FDA-approved Alzheimer's medications, including cholinesterase inhibitors and memantine, provide only modest symptomatic relief and do not cure or stop disease progression4 . The clinical benefits of cholinesterase inhibitors are often difficult to measure and vary among patients, with only a minority experiencing noticeable improvement4 .
Common side effects of cholinesterase inhibitors include gastrointestinal symptoms, bradycardia (slow heartbeat), dizziness, and vivid dreams, which may limit their use in some patients9 4. The decision to start or stop these medications is typically individualized, based on patient tolerance and clinical judgment .
Disease-modifying therapies targeting amyloid plaques, such as aducanumab, lecanemab, and donanemab, have shown promise in slowing cognitive decline but come with challenges:
- They are approved only for early stages of Alzheimer's disease with confirmed amyloid pathology11 7.
- These treatments carry risks of amyloid-related imaging abnormalities (ARIA), including brain swelling and microbleeds, especially in ApoE ε4 carriers7 12.
- Monitoring with MRI scans is required during treatment to detect ARIA15 7.
- The efficacy of these therapies is modest and has been met with some controversy due to mixed clinical trial results16 11.
