Why Women are Affected by Alzheimer's disease more than Men? ~Dr. Domenico Pratico', MD, FCPP

Back in 1906, a German physician named Alois Alzheimer’s wrote a paper about a woman, August Dieter, who at the age of 51 was admitted in the hospital after experiencing memory loss and severe hallucinations. This is what we generally consider the first scientifically documented case of Alzheimer’s disease, and it was a woman. 

Fast-forward 120 years and today we know that there are more than 7 millions of American suffering from Alzheimer’s disease, and that nearly two-thirds of them are women. Moreover, we know that beside old age being a woman is probably the second greatest risk factor for developing late-onset Alzheimer’s disease.

We have been aware of these peculiar aspects of the disease for a while now, but for long time, they were often explained by the simple fact that women tend to live longer than men. However, recently the validity of this assumption has been under scrutiny and questioned.

So, why are women at extra risk to develop Alzheimer’s disease?

Is it something to do with genetics (the material we inherit from our parents)?

Or is it related to hormones differences?

Is that there are biological differences in how women age? or specific lifestyle factors specifically related to women?

All these are equally important questions that if answered could ultimately help not only to solve the mystery but most importantly find better preventative measures and hopefully therapeutic strategies geared towards women.

Here are some recent facts and numbers regarding women and Alzheimer’s disease.

Women who are cognitively healthy show a better resilience and have better memory than men as they age. However, if they develop the disease, women experience a faster cognitive decline, a more rapid shrinkage of certain areas that are linked to memory and executive functions and overall, a more aggressive form of it with more and faster disability.

After age 65, women have a 1-in-6 chance of developing Alzheimer's disease during the rest of their lives, compared with a 1-in-11 chance for men.

The different hormone make-up between women and men has been for years the driving hypothesis for the difference in Alzheimer’s risk between them. However, so far, no conclusive evidence has been produced, and the debate is still on.  For instance, the results of estrogen therapy replacement after 65 have been conflicting with both positive and negative outcomes.

One question that is still being addressed is whether menopause can be considered the tipping point that leaves certain women more vulnerable. In other words, is it possible that in a woman menopause change the brain and the way it reacts to various factors? One possibility is that since estrogen can help regulate the brain's ability to produce energy, a reduction in estrogen levels could create a deficit in the fuel necessary for proper cognitive function.

Research on genetics recently offers some intriguing new evidence on this topic. Analysis of more than 8,000 people for a form of gene (i.e., a piece of DNA) responsible for the production of a molecule named apolipoprotein E-4 (apoE4), known to increase Alzheimer's risk, showed that women whit a single copy of it are about twice as likely to develop Alzheimer's disease as women without the gene. By contrast, the risk for men with one copy of apoE4 is only minimally increased.

New research is now also shedding some light into the role of sex chromosomes. Female cells contain one active X chromosome from one parent, while the other is mainly silent. By contrast, male cells contain only maternal X and paternal Y chromosomes. The X chromosome is very rich in genes (piece of DNA) important for brain function and integrity, with a segment of it involved also in maintaining a cell clean and protecting from the accumulation of unwanted material like Amyloid beta anta pathologic tau proteins. Could this fact be responsible for the difference? 

Although the exact reason(s) for this difference are still unknown, the research field has finally started to pay attention to this important aspect of the disease risk by investing more and more in research. Awareness of this “inequality” can aid in the development of targeted preventative strategies, early detection initiatives and improve access to appropriate healthcare resources for women.

If you enjoyed this blog and are interested in reading more of my blogs:

https://www.praticolab.org/post/mitochondrial-abnormalities-among-earliest-indicators-of-alzheimer-s-disease-dr-domenico-pratico

Dr. Domenico Pratico' , MD, FCPP

Domenico Praticò, MD, holds the the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research and serves as a Professor and the Founding Director of the Alzheimer’s Center at Temple, as well as a Professor of Neural Sciences at Lewis Katz School of Medicine at Temple University.

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