Fifteen Eighty Four

The media have been busy in discussion with the results of a large clinical trial that is a new monoclonal antibody therapy, designed to treat patients with the early stages of Alzheimer’s disease. On November 29^th, the data was released from the clinical trial, developed by Eisai and Biogen. The outcomes show that the antibody, named Lecanemab, was highly effective in removing the amyloid beta protein from the brain. Unfortunately, the cognitive response to the treatment was less substantial than the improvement in the amyloid biomarker. Cognitive decline over 18 months of treatment was reported to be slowed by a quarter in the group receiving Lecanemab. As this is a small response, it may not be recognised by patients, caregivers or clinicians.

The history of development in Alzheimer’s disease treatments over the past twenty years has been disappointing. Due to not knowing what the target is, the field has been limited. Is it the deposition in the brain of improperly folded proteins? The failure of clearance of these molecules? Or the nature of the immune response to their presence?

As we wait for effective therapies to develop, we should be taking advantage of what we can do now. The risk of getting Alzheimer’s is not entirely genetic. Although this factor is important, it is not the cause of the disease in 99% of cases. Environmental factors are critical as there are several potential modifiable risks. There is extensive evidence to show that what we do in our lives, makes a difference.

Age and gender are nonmodifiable risk factors in Alzheimer’s. On the other hand, modifiable factors may include the following:

• High in saturated fat diet
• Smoking
• Alcohol
• Hypertension
• Diabetes
• Lack of physical activity
• Lack of mental demands at work/home
• Low levels of education
• Obesity
• Poor sleep
• Depression

These risk factors operate at all phases in life, from childhood to adulthood. The lack of attention to these modifiable factors may delay the progress of the disease because of the late onset in most cases.

A particularly new and exciting area of research involves the gut bacteria. We all have a complex population of microbes comprised of bacteria, viruses, fungi and other organisms. These organisms have developed alongside humanity throughout the past billion years and have strong influences on our metabolism, immunity and disease conditions.

Most notably, it is critical to recognise that our microbial communities are determined by what we eat. A diet high in saturated fat, salt and sugar, leads to excessive activity of the immune system, contributing to higher occurrence of Alzheimer’s, strokes, heart disease and cancer. However, a high fiber diet enhances the growth of bacteria in the gut which helps the immune system to be more tolerant and less aggressive. There is considerable evidence to suggest that a diet with a low intake of meat and high intake of fiber-rich foods, lowers the risk of developing late life neurodegenerations, such as Alzheimer’s. Other important factors include avoiding head injuries and high levels of physical and mental activity.

With hope that effective Alzheimer therapies develop soon, we must continue to utilise the information we currently have to prevent the disease.  The great Harvard psychologist, William James, once said, “Act as if whatever you do makes a difference. It does.”

These concepts are further explored in my book “Unaging: The Four Factors That Impact How You Age”. (Cambridge University Press, October 2022).

Robert P. Friedland MD

Rudd Chair and Professor

University of Louisville School of Medicine

Louisville, Kentucky

[email protected]

1-502-548-9905