Unfortunately, although research is progressing and there are several promising treatment strategies, there is currently no cure for diseases that cause cognitive impairment and later dementia. However, there is symptom-relieving treatment that may be worth trying in Alzheimer's disease or mixed dementia (Alzheimer's disease in combination with vascular dementia). Since June 7, 2021, a new medicine called Aduhelm (Aducanemab) has also been approved in the United States for the treatment of Alzheimer's disease. Aduhelm is the first drug to affect what is thought to be the main disease process in Alzheimer's disease. A similar drug for Alzheimer's disease, Lecanumab, has been developed by a Swedish company (BioArctic) and has also received fast-track approval in the US on January 6, 2023 under the name Leqembi.
The three medicines - Donepezil (e.g. Aricept), Rivastigmine (e.g. Exelon) and Galantamine (e.g. Reminyl) - currently used in Alzheimer's disease, Lewy body dementia and Parkinson's disease with dementia are known as cholinesterase inhibitors. These three drugs inhibit the breakdown of the acetylcholine so that more acetylcholine can be used in signaling and contact between nerve cells, and the nerve cells function better. Memory is rarely affected but other cognitive abilities can be improved such as language, executive function, attention and orientation. However, this is very individual and depends on the stage of the disease process. However, the disease process itself is not affected. Over time, the disease worsens, despite treatment with symptom-relieving drugs. However, this does not mean that the drug is ineffective, despite the progression of the underlying disease. People should be allowed to stay on the drugs for as long as they are deemed effective. In later stages of the disease, they are often removed. These medicines were initially incorrectly called 'braking medicines', but nowadays they are more correctly referred to as symptom-relieving or symptom-limiting medicines. They are introduced in the early to moderate phase of the disease.
The fourth medicine is called Memantine (e.g. Ebixa) and it affects the function of nerve cells through another substance called glutamate. Memantine is also a symptom-relieving drug used in the same diseases as cholinesterase inhibitors. However, its use is in moderate to late stages of the disease. Studies on cholinesterase inhibitors and memantine have seen patients improve their cognitive functions, behavior and function better in daily life. A large Swedish study, the SATS study, showed that combination treatment with both cholinesterase inhibitors and memantine is most effective. In practice, one of the cholinesterase inhibitors is usually used first and after six months to a year, Memantine is added.
In very early stage Alzheimer's disease, vascular dementia or frontotemporal dementia, there is currently no scientific evidence that treatment with cholinesterase inhibitors or Memantine has any positive effect. However, it is not wrong to test treatment to see if certain symptoms can be improved after an individual assessment for each patient.
If a patient has vascular dementia, the strategy is to treat risk factors for vascular disease, i.e. treat blood pressure, blood lipids, blood sugar, smoking cessation, dietary advice and exercise, and optimize any diabetes treatment. In mixed forms of Alzheimer's disease and vascular dementia, drug treatment with cholinesterase inhibitors or Memantine and risk reduction as described above can be tried. It is possible to start treatment with drugs at any age.
Even at a late stage of the disease, treatment can be of value. In principle, it is always worth trying treatment. However, some people cannot be treated due to various reasons such as hypersensitivity or incompatibility with the other medicines used.
In general, treatment with cholinesterase inhibitors and/or Memantine should primarily be continued as long as the patient can interact with relatives/carers and can eat for himself, take care of their personal hygiene or move themselves. The big gain with drug treatment is improvement of cognitive symptoms and at best being able to postpone the need for other accommodation. When the patient is more dependent, the benefit of treatment is more uncertain.
If there are doubts about the effectiveness of the drug treatment, the treatment can be stopped and the patient's well-being evaluated within 2-4 weeks. Stopping treatment should be avoided when there are major changes in the patient's life, such as a move to a new home, as it is difficult to assess the cause of the deterioration. If a severe side effect is suspected, such as a slow heart rate, treatment should be stopped immediately, but this is rare.
In some cases, reducing the dose may be considered, for example, if there are problems with the stomach (nausea, hard or loose stools). When the patient is in a residential setting, some symptoms can sometimes be relieved by medicines and therefore drug treatment may be appropriate even then, but the benefits must always be weighed against the risks.
Treatment is usually completely terminated at the discretion of the doctor based on the assessment of the benefit and risk/disadvantages of continued treatment after close dialogue with relatives.
On June 7, 2021, the US Food and Drug Administration (FDA) approved a new medicine, Aduhelm (aducanumab), for the treatment of patients with early-stage Alzheimer's disease. The approval was granted under a special procedure used to speed up the process when a drug has been shown to be effective in a way that suggests it will also have an effect on the symptoms and functions affected by Alzheimer's disease. The new drug, which needs to be started early in the disease process, increases the need for time-efficient validated methods for early cognitive assessment. Specifically, the drug Aduhelm has been shown to have an effect on and reduce the deposition of the protein beta-amyloid (plaque) in the brain, which is a typical finding in Alzheimer's disease and also one of the proteins thought to be the main cause of the development of Alzheimer's disease.
The WHO classifies Alzheimer's disease as one of the most serious public health problems of our time. Today, over 50 million people worldwide have the disease or one of the other cognitive disorders. If nothing is done to find effective drugs, this figure will grow to about 100 million by 2050. Until now, there has been no approved drug that claims to be able to affect the actual disease process of Alzheimer's disease. The approval thus marks a milestone in the search for effective drugs for Alzheimer's disease. How effective the drug will prove to be, however, remains to be seen in future studies.
This makes Aduhelm the fifth Alzheimer's disease medicine and the first to be approved since 2003.The key feature of Aduhelm is that it is the first treatment to target the underlying disease process in Alzheimer's disease. It is the first to show a reduction in the amount of plaque in the brain with Aducanemab treatments. In its assessment, the FDA assumes that it is reasonable to assume that as the amount of plaque in the brain is reduced, the symptoms of the disease will also be reduced or improved by treatment.
The approval is valid in the US and the company Biogen has now withdrawn its application for approval in the EU. Treatment in the US is estimated to cost around SEK 500,000 for one year of treatment, making it one of the most expensive treatments in the world.
There has been extensive debate and discussion prior to approval. The criticism has focused on the fact that the effect has been seen only on the plaques and not as clearly on the symptoms of the disease. The expert committee that advised the FDA's decision did not recommend approval. However, the FDA chose, as sometimes happens, to approve the drug despite this, precisely on the basis that given the effect on plaques in the brain that has been shown, it is reasonable to assume also an effect on disease symptoms when the right dose and treatment regimen are identified. The company behind Aduhelm says that during the study it turned out that patients who received higher doses also had an effect on symptoms. It remains for the company to show definitively in further studies that the drug also has an effect on symptoms. Such studies are planned for the future. Very few patients in the US have yet received Aduhelm because several health insurance systems have decided not to cover the treatment due to the unclear evidence of efficacy. As long as there is only a conditional approval, the drug will not be subsidized.
A similar drug for Alzheimer's disease, Lecanumab, has been developed by a Swedish company (BioArctic) and has also received fast-track approval in the US on January 6, 2023 under the name Leqembi. The expectation is that the European Medicines Agency, EMA, will also approve the drug for use in the EU. This drug does not cure the disease either, but has been shown in studies to reduce the plaques of beta-amyloid in the brain, which means that the symptoms are slowed down. The difference with Aduhelm is that the antibody in Leqembi binds to a precursor of beta-amyloid that forms the plaques in the brain. Studies have shown promising results in reducing the formation of plaques in the brain and improving cognitive symptoms, as well as avoiding deterioration of the disease over a period of time. The drug needs to be administered as a drip or injection directly into the bloodstream every two weeks. Continuous monitoring is necessary, as there may be a risk of some rare serious side effects such as swelling and bleeding in the brain. Further clinical trials are ongoing to evaluate the efficacy and safety of the drug.
In Sweden, health economic assessments of drugs are also carried out and may play a role in the decision on approval by the Swedish Medical Products Agency. Regardless, the progress of Aduhelm (Aducanumab) and Leqembi (Lecanumab) should be seen as a historic breakthrough as it is the first time a drug that affects the disease process itself has been approved. There are more than a hundred research studies underway on new medicines that hope to influence the disease process.
Treatment with Aduhelm or Leqembi will need to be started early in the disease process to be most effective. When these new and more effective drugs are introduced, it is even more important that a possible diagnosis can be established early so that treatment and care can be initiated and thus slow down the course of the disease.
