Dementia Treatment Options - 30 years ago and now
Alzheimer's disease is a complex and multifactorial neurodegenerative disease that affects the brain and results in progressive memory loss, cognitive decline, and behavioral changes. There is currently no cure for Alzheimer's disease, and the available drugs only offer modest benefits in terms of symptom management.
It is remarkable is that the history of Alzheimer's drug development is more than 30 years long. The first cholinesterase inhibitors were approved for the treatment of Alzheimer's disease in the 1990s. Tacrine was the first drug in this class to receive approval from the U.S. Food and Drug Administration (FDA) in 1993. However, due to its potential liver toxicity, tacrine was later replaced by other cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, which have fewer side effects and are better tolerated by patients. These drugs have been shown to slightly improve cognitive function, activities of daily living, and behavior in some patients with Alzheimer's disease.
One reason why cholinesterase inhibitors like donepezil and galantamine are ineffective is that they target the symptoms of the disease rather than the underlying causes. They increase the levels of the neurotransmitter acetylcholine in the brain, which can improve memory and cognitive function in some patients with Alzheimer's disease. However, these drugs do not address the underlying neurodegenerative processes that cause the disease.
Among the causal approaches, anti-amyloid immunotherapy leads the way.
In 2021 FDA approved the first component Aducanumab. Aducanumab shows a small clinical effect at a high dose. Although it is an FDA-approved treatment, many American neurologists are cautious about prescribing Aducanumab because of its severe side effects.
At the CTAD Congress in December 2022, two more antibodies were presented: gantenerumab and Lecanemab. Gantenerumab is for subcutaneous application every two weeks. The clinical study results showed only a low effect on amyloid clearance.
Lecanemab therapy showed a mild improvement compared to the placebo, particularly in patients in the early stages of the disease with mild cognitive symptoms. However, the side effects of the Lecanemab are severe and include brain swelling and bleeding.
The reason why Alzheimer's drug development takes scientists so long and only shows limited results is that the disease is highly heterogeneous, with different patients exhibiting different patterns of neuronal damage and neuroinflammation.
This leads to two conclusions:
A one-size-fits-all approach to drug development may not be effective in treating all patients with Alzheimer's disease.
There is a need for effective and sustainable approaches to dementia prevention and risk reduction.
