Key takeaways

  • New disease-modifying medications like donanemab (Kisunla) and lecanemab (Leqembi) work by clearing beta-amyloid plaques in the brain and can slow cognitive decline.
  • Auvelity is the first non-antipsychotic medication approved specifically to treat agitation associated with Alzheimer’s disease, offering a safer alternative to traditional antipsychotics.

The landscape of Alzheimer’s disease treatments has shifted dramatically. For nearly two decades, medications only managed symptoms, such as memory loss or confusion, without attacking the root cause of the disease.

Today, the focus has shifted to disease-modifying therapies that slow disease progression, along with new options for managing behavioral symptoms.

Disease-modifying drugs are monoclonal antibodies designed to target and clear beta-amyloid plaques. These are toxic protein clumps that build up in the brains of people with Alzheimer’s disease.

They are approved for people in the early stages of the disease (mild cognitive impairment or mild dementia). Examples include:

  • Donanemab (Kisunla): This drug was approved in 2024. It is a monthly IV infusion that was shown to slow cognitive decline by about 35% over 18 months. People may eventually stop treatment with Kisunla once their brain scans show their amyloid plaques have been cleared.
  • Lecanemab (Leqembi): This drug was approved in 2023. Leqembi has been shown to slow the progression of the disease by about 27%. Leqembi is also available as a subcutaneous injection (injection under the skin) option under the name Leqembi Iqlik that people can self-administer at home. Leqembi can also be given as a monthly IV maintenance option after the initial plaque-clearing phase.
Safety consideration

While these drugs are a major milestone, they come with risks including a boxed warning. They require regular MRI monitoring for a side effect known as ARIA (Amyloid-Related Imaging Abnormalities), which involves temporary swelling or minor bleeding in the brain.

Alzheimer’s affects more than just memory; it can also cause profound behavioral changes. Historically, doctors used powerful, off-label antipsychotics to manage these changes, but safer options have emerged.

  • Dextromethorphan-bupropion (Auvelity): This drug was recently approved specifically to treat agitation associated with Alzheimer’s disease. It is the first non-antipsychotic option for this symptom.
  • Brexpiprazole (Rexulti): This drug is an atypical antipsychotic that is also approved specifically used to treat severe agitation associated with Alzheimer’s disease.

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There is still a lot of research going on around Alzheimer’s disease. Here are a few examples of things on the horizon:

  • Tau Protein Inhibitors: Tau protein forms tangles inside brain cells, increasing the likelihood of cell death. Tau-targeting therapies are being studied.
  • GLP-1 Drugs: Researchers are studying whether GLP-1 medications, such as semaglutide, can protect the brain. Initial data suggest they may reduce neuroinflammation and metabolic dysfunction in the brain.
  • Blood-Based Biomarkers: Highly sensitive new blood tests, such as Lumipulse and Elecsys, may allow doctors to detect Alzheimer’s pathology. These tests can give people access to new, early-stage medications much faster.

If you or someone you care for has Alzheimer’s disease, talk with your doctor about what options are available. They can help recommend the best treatment options for you.

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