This transcript has been edited for clarity.
Dear colleagues, I’m Christoph Diener from the faculty of medicine at the University of Duisburg-Essen, in Germany. In this month’s video, I would like to concentrate on the topic of dementia.
We made tremendous progress in the diagnosis of Alzheimer’s disease, not only at a time when patients show symptoms but also in the preclinical phase of the disease.
Biomarkers and Lifestyle
We have new biomarkers in cerebrospinal fluid with amyloid and tau PET, and more recently, we have now biomarkers in plasma. One is p-tau217, and this has shown a high sensitivity for the diagnosis of Alzheimer’s disease and a good correlation with cerebrospinal fluid markers, as published recently in Neurology.
A second aspect is we know that there are about 14 different lifestyle factors and comorbidities that increase the risk for mild cognitive impairment, dementia, and in particular, Alzheimer’s disease. The most frequent ones — as you know — are vascular risk factors, hearing loss, smoking, high alcohol intake,obesity, and nutrition.
Unfortunately, for most of these correlations, there have been no prospective randomized trials to show that management or treatment of these risk factors or comorbidities would really decrease the risk of Alzheimer’s disease.
Just to give you an example, there is one study from the US published in Neurologywith more than 100,000 participants, and they showed that consumption of red meat significantly increases the risk of dementia. We have in the past not really considered lifestyle factors enough to prevent Alzheimer’s disease.
Herpes Zoster and Cognitive Impairment
There are very interesting findings on the correlation between Herpes zoster and the increased risk of cognitive impairment and dementia.We have now several studies with hundreds of thousands of patients in the US, in the UK and Australia, which showed that, if someone has Herpes zoster infection, over the next 13 years, the risk of dementia is increased between 15% and 30%.
The more interesting feature is that obviously vaccination against Herpes zoster reduces the risk of dementia.There have been several studies, including one in Wales with almost 300,000 participants. When the vaccination was introduced, participants born before 1933 were not vaccinated, while 50% of those born after 1933 were vaccinated. After 7 years, the diagnosis of dementia was reduced by 3.5% in vaccinated individuals.The relative risk reduction for dementia was 20%.
Another aspect is which vaccine. The study from the United States with more than 100,000 people observed over 6 years showed that recombinant vaccine is more effective in preventing cognitive impairment and dementia compared to the traditional live vaccine. The risk reduction was 17%.
GLP-1 Drugs and Anti-Amyloids
We have a totally new class of medicines to treat diabetes and obesity: the GLP-1 receptor agonists. There is indirect evidence that they might also be beneficial for the prevention of dementia. One publication in JAMA Neurology looked at a database of more than 33,000 patients treated with GLP-1 receptor agonistsand 34,000 treated with SGLT2 inhibitors compared with standard therapy.
For both substances, there was a 35%-45% reduction in the risk of Alzheimer’s dementia and other dementias compared to standard therapy. This has to be shown in one of the ongoing trials with GLP-1 receptor agonists.
Let me mention the new beta-amyloid antibodies, lecanemab and donanemab. They have been approved both in the United States and in Europe for the treatment of early stages of Alzheimer’s disease. This is a complicated business because you need biomarkers and amyloid PET for the diagnosis, you need regular intravenous administration, and you need MR controls to check for Amyloid-related imaging abnormalities.
At the recent Alzheimer’s Congress in Toronto, for both substances, long-term data were presented for a time period of three to 4 years. They showed that with increasing time of treatment, there is also an increase, obviously, in efficacy if the data are compared with a database, not within the randomized trials, because these were open-label, long-term studies.
With donanemab, it was interesting that, in more than 75% of the patients, there was no longer amyloid detected on PET. The other important issue is that there is now a new application of donanemab that is subcutaneous.
Spend Money on Lifestyle
At the end of the day. I’m not really sure whether this is an effective treatment if we consider cost and risk, and I think a healthcare system would be better advised to invest all this money into teaching of at-risk persons, in particular, to have an impact on lifestyle.
I’m aware that, in low-income people, this is extremely difficult, because they cannot afford healthy food and they cannot afford to pay for a gym for regular exercise. I think we can do much better, in particular, in treating comorbidities like obesity, diabetes, hypertension, high cholesterol, and so on.
Dear colleagues, this is a short update on what has happened recently in the field of dementia. I’m Christoph Diener from the University of Duisburg-Essen Medical School. Thank you very much for listening and watching.