During my medical residency in neurology at the Hospital of Federal Fluminense University (UFF) in Rio de Janeiro/Brazil we often faced the following question: some medications commonly prescribed in routine neurology practice (for patients with Parkinson's syndrome, depression or urinary alterations) inhibited the neurotransmitter acetylcholine, important for the formation and maintenance of memory. Since one of the proposals for the pharmacological treatment of Alzheimer's disease is precisely to increase the concentration of acetylcholine in the brain, the use of drugs that inhibit this neurotransmitter seemed contradictory and threatening to us.
With the project "Knowledge stops Dementia", the German Foundation for Health Information and Prevention (Deutsche Stiftung für Gesundheitsinformation und Prävention DSGiP), together with the Academy for Human Medicine (Akademie für menschliche Medizin), presents a broad spectrum of lifestyle-oriented measures for the prevention and therapy of Alzheimer's disease. In addition to Alzheimer's dementia, however, other neurodegenerative diseases such as multiple sclerosis and Parkinson's disease also pose a major challenge for those affected, their relatives and, ultimately, the healthcare system, since the prospect of a cure through pharmaceutical approaches is still a long way in the future. But the good news is, individualized lifestyle concepts seem to be effective also in these diseases.
Our brain is one of the largest glucose consumers in our body. Not all areas of the brain need the hormone insulin to take up glucose and thus operate insulin-independently. However, this is different in the neurons of the hippocampus, the brain region responsible for our memory consolidation and one of the first to be affected by Alzheimer's and dementia: here - as researchers have recently discovered - insulin is needed to provide the neurons with sufficient glucose supply during times of increased energy demand. Thus, it's not surprising that when insulin resistance is present, for example during developing or established type-2 diabetes, the brain can also suffer from a glucose deficiency. This impaired glucose utilization and the associated energy crisis in the brain have also been visualized in imaging techniques, the so-called PET scan, in Alzheimer's patients.
Positive news from clinical Alzheimer's research is rare. In hardly any other indication do pharmaceutical companies have to accept as many setbacks as here. To date, pharmacological approaches to treating Alzheimer's have been almost uniformly unsuccessful, with more than 400 failed clinical trials. Since 2002, there has been no new approval in the field of neurodegenerative diseases. That changed on June 7, 2021, when the drug Aducanumab, from U.S. biotech Biogen (and its Japanese research partner Eisai), was approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer's disease. The drug, which is administered intravenously to patients, will be available in the U.S. under the trade mark Aduhelm. Aduhelm works on the basis of passive immunization. It is a monoclonal antibody that targets amyloid-ß, a protein characteristic of Alzheimer's disease. These amyloid-ß proteins make up the deposits in the brain, known as plaques, which are associated with the destruction of neurones. Aduhelm's mechanism of action is based on promoting the breakdown of β-amyloid, thereby reducing the harmful plaques.
It has been known for quite some time that a disturbance in blood glucose and insulin metabolism plays a central role not only in diabetes, but also in Alzheimer's disease. When insulin, which is important for glucose utilization, can no longer work properly due to missing or damaged insulin receptors, the so-called insulin resistance occurs. This also applies to the brain, where it is called cerebral insulin resistance. If this occurs, our central nervous system may experience an energy deficiency despite high glucose levels in the blood. The resulting starvation state of the brain gradually leads to the cessation of its specific functions and the death of brain cells, which is particularly noticeable in the impairment of memory. Therefore, maintaining or restoring the energy metabolism of the brain is of crucial importance, especially at the beginning of Alzheimer's disease.
It's been a long road for Dr. Dale Bredesen in Alzheimer's research: He worked for years as a scientist and studied dying brain cells, fruit flies with "Alzflymer" and transgenic mice with "Mouzheimer's." But his applications for clinical trials that could demonstrate proof of efficacy of his research concepts in patients were first rejected in 2011 and again in 2018. Instead, he published treatment successes in his patients in 2014, 2016 and 2018. Finally, in 2019, he received approval to conduct a clinical trial, which was then completed last year.
It seems like a miracle: a late-stage Alzheimer's patient, completely immersed in dementia and cut off from his environment and his own identity. But when he hears the sounds of familiar pieces of music selected for him from his former life, he wakes up from his apathy, starts to laugh, talk, move and becomes 'alive' again!
The relation between lifestyle and Alzheimer’s disease has been previously described in many studies. It has become well established that lifestyle interventions can prevent the onset of the disease in about 40% (as we reported in a previous NF based on the 12 Alzheimer’s disease prevention factors listed by The Lancet commission on Dementia). The Finnish FINGER study (Finnish Geriatric Intervention Study 2015) has also already impressively shown these correlations
Can aerobic exercises reduce cognitive decline in Alzheimer’s patients? – Results from a new randomized controlled trial.
Physical exercise is an important part of a healthy lifestyle, contributing to general fitness, muscle control and coordination, and to a sense of wellbeing. Physical exercise is also essential for maintaining adequate blood flow to the brain and may stimulate brain cell growth and survival. Evidence of the effects of physical exercise in the prevention of dementia have been supported by many observational studies. The results of randomized trials suggest that exercise leads to increases in brain tissue, including the hippocampus and elevate blood levels of brain derived neurotrophic factor (BDNF), stimulating the formation of new nerve cells.
To date, there is no effective drug to treat Alzheimer's disease. The currently available drug treatment options are limited to acetylcholinesterase inhibitors and memantines, each of which is used depending on the stage of the disease and directly influences the action of neurotransmitters in the brain. It is hard to believe, but these pharmacological approaches are still based on the findings of the 1970s and 1980s.