Why is dementia different for women?

Whilst we know a lot about what happens in the brain in the different diseases that cause dementia, the exact causes remain elusive. Understanding the differences between the sexes is one way that could help dementia researchers understand its causes and develop new treatments.

Dementia affects more women

More women are affected by dementia than men. Worldwide, women with dementia outnumber men 2 to 1. This is mostly due to the fact that Alzheimer’s disease affects more women than men. Other dementias such as dementia with Lewy bodies, vascular dementia and frontotemporal dementia tend to affect slightly more men, though Alzheimer’s disease affect more people than these three combined.

Age is the biggest driver of a person’s chance of developing dementia. Women are known to live longer than men. However, this alone is does not fully explain why women are more likely to develop dementia.

One study has shown how women between 40 and 65 have more amyloid, more brain shrinkage and lower energy levels in the brain than men of the same age.

Understanding the effect of oestrogen

One of the main theories as to why dementia affects women more is to do with the hormone oestrogen. As well as being involved in the reproductive cycle, oestrogen also affects many other parts of the body including the brain. There have been some studies that show oestrogen might protect brain cells.

Some studies have shown that if a woman has more oestrogen throughout her life, she might be less likely to develop dementia. For example, if she starts her periods at a younger age, has at least one child or goes through menopause later.

Hormone replacement therapy and dementia

Oestrogen and progesterone are commonly used in hormone replacement therapy (HRT). Some women going through menopause choose this to help relieve some of the symptoms, such as hot flushes and anxiety.

HRT fell out of favour after a Women’s Health Initiative study in 2002 found that it increased the level of risk of heart disease, and breast cancers. However, since then different types of HRT have been developed that are much safer. Now that HRT carries less risk, there are less concerns about its safety when considering its potential benefits for dementia risk.

Previous research into the link between HRT and dementia risk is conflicting with studies producing mixed results. However, in 2021 a large study of nearly 400,000 women, found both new and old HRT drugs reduced the risk of diseases that cause dementia. The study found that the effects differed based on many things: dose, type of medication, length of treatment, age and time from menopause. Now, researchers are currently working to understand the link better, to clarify whether HRT really does reduce dementia risk.

This includes work that has found HRT reduces that shrinkage of certain regions of the brain in people with the main Alzheimer’s disease risk gene (called APOE E4).

How sex impacts dementia diagnosis

Oestrogen affects how a woman’s brain grows and functions. Researchers think this might be why women have a better memory for words and verbal items than men. This poses a problem for men and women.

Research suggests that diagnostic tests specifically designed for men and women might led to less misdiagnosis than using the same test for both sexes. This is because women tend to have a stronger verbal memory than men, so may do well on memory tests, even if they have cognitive problems. This means they are under-diagnosed with dementia. Men on the other hand are more likely to be incorrectly diagnosed with dementia because their verbal memory skills might not be as strong.

At Alzheimer’s Society, we champion person-centered care. This must begin with a method of diagnosis that takes into account certain factors. These could include things such as cultural background, education, on and off days and sex.

The importance of female data in research

Animals are used in research to understand different diseases and develop new effective treatments. Unfortunately, female animals are used much less frequently in studies. In the neuroscience field, studies using male animals out number studies with female animals by five to one.

This has come from assumptions that female animals are more variable than males. The reproductive cycle of female animals has been blamed for this. However, an analysis of 293 different experiments disputes this, finding that the experiments using female animals have no more variation than those using males.

Additionally, carrying out experiments with both male and female mice may will require more animals to be used, to account for the variability between sexes.

The focus on male animals for research is another form of discrimination against women. Whilst it is now acknowledged as a problem there is still a long way to go for women to have equal rights in terms of the understanding of their own bodies and healthcare.

Fortunately, nowadays human trials seem to be well balanced between male and female participants.

Looking to the future

The G8 and the Prime Minister’s Challenge have committed to finding a disease modifying therapy for dementia by 2025.

With women being 65 per cent of the people affected by dementia, we must make sure that any new therapy works for them as well as men.

From lab to the pharmacy, it’s important dementia research, care and treatment can improve the lives of both men and women.

Acknowledgements

This blog was originally written by Dr Aoife Kiely in 2018, and has since been brought up to date