Introduction to Current Alzheimer's Treatment
For decades, treatments for Alzheimer's disease primarily focused on managing symptoms. Medications like cholinesterase inhibitors (e.g., donepezil) and glutamate inhibitors (e.g., memantine) addressed cognitive and behavioral symptoms but did not halt the progression of the disease. The landscape of treatment is undergoing a significant shift with the development and approval of disease-modifying therapies, which target the presumed root causes of the disease. The newest treatments focus on removing amyloid-beta proteins from the brain.
New Disease-Modifying Anti-Amyloid Therapies
Over the past few years, the U.S. Food and Drug Administration (FDA) has granted approval to new anti-amyloid therapies for individuals in the early stages of Alzheimer's. These therapies represent a major milestone, offering the first real hope of slowing the disease's progression.
Lecanemab (Leqembi®)
Lecanemab received traditional FDA approval in 2023 for patients with mild cognitive impairment or mild dementia due to Alzheimer's disease.
- Mechanism: It is a monoclonal antibody that targets and clears aggregated, soluble amyloid-beta protofibrils and plaques from the brain.
- Efficacy: Clinical trials, like the Clarity AD study, showed that lecanemab slowed the rate of cognitive decline by approximately 27% over 18 months compared to a placebo group. Real-world data presented at AAIC 2025 suggests benefits may continue to grow with longer treatment durations. A potential at-home subcutaneous option is also in development.
- Administration: Typically given as a biweekly intravenous infusion.
- Side Effects: Potential side effects include infusion-related reactions and amyloid-related imaging abnormalities (ARIA), which can involve temporary brain swelling or small brain bleeds. Regular MRI monitoring is required.
Donanemab (Kisunla™)
Donanemab received traditional FDA approval in 2024 for the treatment of early Alzheimer's disease.
- Mechanism: This monoclonal antibody targets a specific form of amyloid plaque called N3pE-Aβ. It works to clear existing plaques from the brain.
- Efficacy: The TRAILBLAZER-ALZ 2 clinical trial found that donanemab slowed cognitive and functional decline by up to 35% in patients with early Alzheimer's with low-medium tau pathology. A key feature is that treatment can potentially be stopped once imaging confirms amyloid plaques have been cleared. Long-term extension studies continue to show growing benefit.
- Administration: Administered as an intravenous infusion, typically on a monthly basis.
- Side Effects: Similar to other anti-amyloid therapies, it carries a risk of ARIA and requires careful monitoring via MRI. Carriers of the APOE e4 gene may have a higher risk of ARIA with both donanemab and lecanemab.
Comparison of Lecanemab and Donanemab
These two therapies have distinct characteristics, which influence patient eligibility and treatment plans.
| Feature | Lecanemab (Leqembi) | Donanemab (Kisunla) |
|---|---|---|
| Target | Amyloid-beta protofibrils and plaques | A specific, aggregated form of amyloid plaque (N3pE-Aβ) |
| Frequency | Biweekly intravenous infusion | Monthly intravenous infusion |
| Treatment Duration | Ongoing, potential for less frequent maintenance | Can be stopped once amyloid is cleared from brain scans |
| Effect on Tau | Shown to decrease phosphorylated tau levels in CSF | Shown to decrease phosphorylated tau levels in CSF |
| Screening | Confirmed presence of amyloid pathology via PET or CSF | Confirmed presence of both amyloid and tau pathology |
| Potential At-Home Option | Subcutaneous auto-injector is in development | Ongoing infusions needed, but potentially for a limited time |
Promising Research and Future Directions
Research beyond amyloid is actively underway, investigating other mechanisms involved in Alzheimer's progression.
- Tau-Targeting Therapies: Clinical trials are exploring therapies that target the tau protein, the other key protein involved in the formation of neurofibrillary tangles. New antibodies and antisense oligonucleotide therapies are in development to reduce tau accumulation and spread.
- Anti-Inflammatory Approaches: Chronic, low-level inflammation is a feature of Alzheimer's. Researchers are studying drugs, such as sargramostim, that may stimulate the immune system to protect the brain from harmful proteins.
- Combination Therapies: The future may involve a cocktail of drugs, targeting multiple pathways (e.g., both amyloid and tau) to achieve a more significant clinical benefit. Studies suggest that a combination of existing medications for blood pressure and cholesterol may also offer some cognitive protection.
- Blood Biomarkers: Advancements in blood tests, measuring p-tau217 and other markers, are revolutionizing diagnosis and monitoring. In 2025, the Alzheimer's Association released new guidelines on their use, paving the way for faster and less invasive diagnostic pathways.
Managing Symptoms and Non-Drug Approaches
Even with the new disease-modifying therapies, managing symptoms remains a critical part of comprehensive care. These non-pharmacological strategies can improve quality of life for both patients and caregivers.
- Lifestyle Interventions: The U.S. POINTER study presented at AAIC 2025 showed that lifestyle interventions, including increased physical activity, a healthy diet (like the MIND diet), and cognitive and social engagement, improved cognition in older adults at risk. Exercise, particularly walking, was found to be highly beneficial, especially for those with a high genetic risk.
- Cognitive Stimulation and Memory Care: Programs that use Montessori-inspired techniques and structured creative therapies, such as crochet, are designed to stimulate cognitive abilities and enhance social inclusion.
- Behavioral Management: Therapies and techniques exist to help manage behavioral changes such as agitation, depression, and anxiety that can accompany the disease. The FDA has also approved specific medications, like brexpiprazole (Rexulti®), for the agitation associated with dementia due to Alzheimer's.
- Caregiver Support: A person-centered approach, such as Compassionate Touch, helps reduce stress for caregivers and patients by fostering comfort and connection.
Conclusion
The latest treatments for Alzheimer's, particularly the disease-modifying anti-amyloid antibodies lecanemab and donanemab, mark a pivotal moment in the fight against this devastating disease. These therapies, while not cures, represent the first to effectively slow disease progression by targeting the underlying pathology. However, they are most effective in the disease's early stages and come with risks and significant costs. The treatment landscape continues to evolve, with promising research into tau-targeting therapies and non-pharmacological interventions offering hope for more effective, combination-based approaches in the future. A holistic approach, combining new medical treatments with lifestyle interventions and compassionate support, offers the best path forward for patients and their families.
To learn more about ongoing research and support resources, visit the official website of the Alzheimer's Association.
