Why are there more cases of Alzheimer's among women?

Almost 120 years have passed since the German doctor Alöis Alzheimer first described the neurodegenerative disease that today bears his name. It all started as a result of the case with a demented patient named Auguste Deter.

The latest data on Alzheimer's disease (AD) suggests that it was no coincidence that Auguste was a woman: Today we know that around two thirds of the affected people are.

Specifically, a study carried out in 2017 already showed that in Europe 3,31% of men suffer from Alzheimer's compared to 7,13% of European women – more than double. However, until relatively recently this difference had not been given all the importance it deserves.

Hormonal changes matter

The main risk factor for AD is age. Among the general population, it is more common for women to reach or exceed 85 years of age. Therefore, it had been assumed that they were more likely to suffer from it simply because they had a longer life expectancy.

However, we now know that this fact does not explain clinical reality. As with many other diseases, the answer could be found both in biological differences due to sex and in sociocultural differences (gender roles).

From a biological point of view, The hormonal changes typical of female aging have been in the focus of Alzheimer's research for many years. This is where estrogens come into play, steroid hormones produced mainly by the ovaries, but also by the adrenal glands, adipose tissue and the brain.

In addition to its role in reproduction, estrogens intervene in other signaling pathways, some related to cognitive functions or neuroprotection. Thus, they are molecules with antioxidant action, regulators of metabolism, the immune response, neurogenesis and synaptic plasticity, which are critical for brain aging.

Without going any further, the hippocampus has two types of estrogen receptors. And it just so happens that this brain region, which is involved in memory and learning, is severely affected in Alzheimer's patients from the early stages.

Therefore, it is evident that the loss of estrogen (hypoestrogenism) due to menopause seems to have a lot to say. So much so that women who have had their ovaries removed under the age of 50 also have a higher risk of suffering from cognitive impairment and Alzheimer's.

That is why for several decades research has been carried out to find out whether hormone replacement therapy (that is, providing estrogen in the form of medication at the beginning or during menopause) could have a neuroprotective function.

Work is also being done to optimize its application: the data suggest that there is a critical time window of administration in which this treatment could be most effective. Specifically, it could be more useful if applied in the initial stages of menopause or in cases of surgical menopause. However, there are conflicting data, so more studies are needed to clarify this issue.

The microbiota affects brain health

On the other hand, in this last decade the importance of populations of microorganisms that reside in the human body (microbiota) and their relationship with hormones and brain health.

Specifically, a subgroup of these bacteria, called estrobolome, actively participates in the regulation of systemic estrogen levels. Therefore, probiotic therapies could also have indirect beneficial effects on the brains of menopausal women.

In fact, the microbiota also presents sexual dimorphism, being different between men and women, which is known as microgenderome. These variations produce different degrees of susceptibility to suffering from certain pathologies.

Women's brains may be more vulnerable to stress

Stress is another known risk factor for developing Alzheimer's, which appears to affect women more than men. A recent study with animal models of this disease has shown that the brain of females is more vulnerable to the impact of stress than that of males., apparently due to a greater increase in the accumulation of beta-amyloid protein.

The incorporation of women into the world of work, along with household chores, care and family balance problems, means that, in general, they experience more stress than men. And this implies that social strategies aimed at eliminating gender differences could be very positive in reducing the risk of AD among women.

Towards 150 million patients

Alzheimer's is one of the main pandemics of the 21st century. It is expected that there will be around 150 million patients with this neurodegenerative disease by 2050. In Spain today there are more than 800 people who suffer from this type of dementia, and it is estimated that this figure will rise above 000 millions in the coming decades.

Unfortunately, at the moment there is no cure or truly effective treatment against this neurodegenerative disease. It is possible that overlooking differences due to sex and gender may have contributed in some way to this delay.

Precisely for this reason, Women's Brain Project (WBP) emerged, an international non-profit organization based in Switzerland, made up of experts in different scientific disciplines. WBP was born from this need to analyze the differences that depend on sex and gender in mental health and illnesses, in order to apply this knowledge for the sake of precision medicine.

What is increasingly clear is that sex is an important variable that, unfortunately, has not yet been given the deserved relevance, despite dividing the world population into two physiologically well-differentiated subgroups. This point could explain, at least in part, the failure to translate preclinical data into clinical trials, not only for Alzheimer's, but also for other diseases.

Source: The Conversation.

Authorship: Raquel Sánchez Varo. Doctor Assistant Professor of the Histology Area of ​​the Faculty of Medicine. She is a researcher at the CTS429 Medical Biology and Histology Group, at the CIBER in Neurodegenerative Diseases (CIBERNED) and at the Malaga Biomedical Research Institute (IBIMA), University of Malaga.