Alzheimer's Disease Medications

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For decades, Alzheimer’s disease, the most common form of dementia, could only be definitively diagnosed by brain biopsy or after death via autopsy, and we had no medications to treat it. Thirty years ago (1994), the FDA approved Cognex (tacrine), the first drug to treat Alzheimer’s disease. Over the next few years, three additional acetylcholinesterase inhibitors reached the market. Pervasive loss of neurons using acetylcholine characterizes Alzheimer’s, and these drugs boost levels of acetylcholine. But they don’t change the course of the disease, only slow progression of dementia by a tiny extent, and frequently have side effects.

A decade later, with the approval of memantine (Namenda), we had another way to try to combat Alzheimer’s. Memantine blocks the NMDA type of glutamate receptors, thereby reducing neuronal over-excitation and consequent cell death. But at best, the course of the disease is only slowed, not reversed.

More recently human monoclonal antibodies directed at amyloid-beta were approved by the FDA. However the makers of the first such drug aducanamab (Aduhelm) announced this month (February 2024) that they will cease production by the end of the year. Leqembi (Iecanemab), which has shown more benefit for preserving cognitive function, remains on the market. These drugs slow the rate of decline more definitively than the earlier drugs, but so far their ability to clear amyloid plaques from the brain is more robust than their clinical effect in improving the course of Alzheimer’s disease.

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References:

Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimer’s Disease: A comprehensive review (2024)

Aducanumab Therapy to Treat Alzheimer's Disease: A Narrative Review (2022)

Ultrasound Blood–Brain Barrier Opening and Aducanumab in Alzheimer’s Disease (2024)

2023 Alzheimer's disease facts and figures

Tacrine: First Drug Approved for Alzheimer's Disease (1994)

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