A new era for dementia treatment
Recent FDA approvals have introduced new prescription options for dementia patients, particularly those in the early stages of Alzheimer's disease. Unlike previous treatments that focused solely on symptoms, these newer medications target the underlying biological changes in the brain. This represents a significant advancement in the approach to managing Alzheimer's.
Targeting amyloid plaques: Lecanemab and Donanemab
Two key medications, lecanemab (Leqembi) and donanemab (Kisunla), are monoclonal antibodies that aim to clear amyloid-beta plaques from the brain, which are a hallmark of Alzheimer's disease. Lecanemab, approved in 2023, is administered bi-weekly and has shown a 27% slowing of cognitive decline over 18 months in early-stage patients. Donanemab, approved in 2024, is given monthly for up to 18 months or until plaque clearance is achieved and has demonstrated approximately a 35% slowing of clinical progression in those with low-to-medium tau protein levels. Both are indicated for patients with mild cognitive impairment or mild dementia due to Alzheimer's with confirmed amyloid plaques.
Addressing agitation: Brexpiprazole
Managing behavioral symptoms is also a critical part of dementia care. Brexpiprazole (Rexulti), approved in 2023, is the first medication specifically indicated to treat agitation associated with dementia due to Alzheimer's. This oral tablet helps manage symptoms like restlessness and aggression, which can be challenging for both patients and caregivers. It works by affecting neurotransmitters in the brain. It's important to be aware of a Black Box warning regarding an increased risk of death in older adults with dementia-related psychosis when using this medication.
Considerations and risks of new treatments
While these new therapies offer hope, they also come with potential risks and require careful management. A notable concern with lecanemab and donanemab is Amyloid-Related Imaging Abnormalities (ARIA), which can involve brain swelling or microhemorrhages. Regular MRI scans are necessary to monitor for ARIA. Genetic testing for the APOE4 allele is also recommended, as carriers have a higher risk of ARIA. These treatments are not suitable for all patients and require careful evaluation by a healthcare provider.
| Feature | Donanemab (Kisunla) | Lecanemab (Leqembi) | Brexpiprazole (Rexulti) |
|---|---|---|---|
| Mechanism | Monoclonal antibody targeting mature amyloid plaques. | Monoclonal antibody targeting soluble amyloid protofibrils. | Atypical antipsychotic regulating neurotransmitters. |
| Indication | Early symptomatic Alzheimer's (MCI or mild dementia) with amyloid plaques. | Early symptomatic Alzheimer's (MCI or mild dementia) with amyloid plaques. | Agitation associated with dementia due to Alzheimer's. |
| Administration | Monthly IV infusion until plaque clearance, for up to 18 months. | Bi-weekly IV infusion. | Daily oral tablet. |
| Efficacy | Slowed cognitive decline by up to 35% in low/medium tau patients. | Slowed cognitive decline by 27%. | Showed dose-dependent improvement in agitation. |
| Key Risks | ARIA (swelling, bleeding in brain), infusion reactions. | ARIA (swelling, bleeding in brain), infusion reactions. | Black Box warning: increased risk of death in older dementia patients with psychosis. |
| Monitoring | Regular MRI scans required, especially in early treatment. | Regular MRI scans required to monitor for ARIA. | Requires careful medical supervision. |
The importance of comprehensive care
Medication is a part of a broader care strategy for dementia. Non-pharmacological approaches are vital for improving quality of life and managing symptoms.
- Cognitive Stimulation Therapy (CST): Engaging in activities to keep the mind active.
- Reminiscence Therapy: Using personal history to evoke positive memories.
- Music and Arts Therapy: Utilizing creative outlets for expression and engagement.
- Environmental Modifications: Adjusting the living space to be calm and predictable.
These methods can be used alongside medication to provide more holistic support.
Future directions in dementia treatment
The field of dementia research continues to explore new targets and therapies, including those aimed at tau pathology and neuroinflammation. Ongoing studies are also investigating different formulations and delivery methods for existing drug types. The momentum in developing disease-modifying treatments suggests a future with more personalized and effective interventions.
Conclusion
The recent FDA approvals of lecanemab, donanemab, and brexpiprazole represent significant progress in treating dementia. These new prescriptions offer ways to slow the progression of early Alzheimer's and manage associated agitation. However, these treatments require careful selection, monitoring for side effects like ARIA, and should be part of a comprehensive care plan that includes non-pharmacological support. As research advances, the integration of new medications with supportive care will be key to enhancing the lives of those affected by dementia.
Visit the Alzheimer's Association website for resources and support.
