Research

Why is dementia different for women?

In this blog, we use the term ‘women’ to refer to those born with female sex, including female chromosomes and hormones, rather than gender.

We currently have very little research evidence specific to people with less common gender status, such as transgender or intersex.​

Do women have a higher risk of dementia? 

Yes. Women have a greater risk of developing dementia during their lifetime.

In fact, around twice as many women have Alzheimer’s disease – the most common type of dementia – compared to men.

The main reason for this greater risk is because women live longer than men and old age is the biggest risk factor for this disease.

It’s much less clear if men and women of the same age have different levels of dementia risk.

Some studies have suggested that women over 80 years may be more likely to have Alzheimer’s disease than men of the same age. However, up until this age the risk appears to be about the same for both sexes.

Other studies have found no difference in dementia risk between men and women – even in the oldest age groups. So, it’s really not at all clear whether being a woman means that you’re more likely to develop dementia than a man of your age.

This doesn’t necessarily mean that sex isn’t an important factor in understanding dementia risk. It seems quite likely that each sex has a different blend of risk factors.

Why might women have different dementia risk factors?

Over the course of a lifetime, women tend to have very different experiences than men – particularly women from older generations.

Some of these are caused by differences in biology, such as menstruation, pregnancies and menopause.

Others are more related to traditional differences in gender roles, such as education, work and lifestyle. Many of these have an impact on dementia risk.

For example, we know that having a full education and opportunities for lifelong mental stimulation helps to delay dementia in old age – something known as ‘cognitive reserve’.

Historically, opportunities to go to university or work for many years in highly-skilled occupations have been less available to women, which has led some scientists to wonder if this might be an important risk factor for women.

Women may also be more severely affected by some risk factors than men.

Genetics

An important example of this is women’s greater risk when they have the ‘ApoE4’ gene variant.

Genes are the second biggest risk factor for dementia.

Nearly two thirds of people with Alzheimer’s disease – the most common types of dementia – have at least one copy of the ApoE4 gene.

Although men and women are just as likely to have the ApoE4 gene variant, its effect on dementia risk seems to be greater in women than it is in men. The reasons for this difference are not fully understood.

However, it could be extremely important for understanding how future medicines for treating dementia might have different levels of effectiveness for men and women.

Brain injury

Traumatic brain injury (TBI) is another dementia risk factor where there may be important differences between the sexes.

Women are more vulnerable to concussion and its long-term effects on the brain. This has led some to call for greater priority to be given to preventing concussion in women’s sport, such as football and rugby.

Sex, menopause and dementia risk

Risks of dementia associated with menopause

A major difference between older men and women is the menopause. This is when levels of sex hormones, such as oestrogen and progesterone, fall dramatically in women during late middle age.

Oestrogen is thought to have a range of protective effects on brain health, including an ability to block some of the harmful effects of substances involved in Alzheimer’s disease.

This has led some researchers to suggest that if a person has more exposure to oestrogen throughout their life, they might be less likely to develop dementia. For example, if they:

• start periods at a younger age
• have at least one pregnancy (when levels of oestrogen are greatly increased)
• start menopause later.

By contrast, a very early menopause caused by surgical treatments for cancer may increase the risk of dementia in later years.

We also now know that most of the diseases causing dementia start developing in the brain around 10-20 years before clinical symptoms show, which for many women is around the time of their menopause.

It’s tempting therefore to connect the loss of this brain-protecting hormone with the start of processes in the brain that ultimately lead to dementia.

However, the relationships between sex, menopause and dementia risk are extremely complex and until recently researchers have not prioritised menopause as an opportunity to learn more about dementia. We need a lot more research before we can draw any firm conclusions.

Hormone replacement therapy and dementia

The sex hormones oestrogen and progesterone are commonly used as medicines to treat the symptoms of menopause, such as hot flushes, sleep problems, anxiety and brain fog. This is sometimes called ‘hormone replacement therapy’ (HRT).

During the early days of HRT, there was concern that treatment might have health risks for women in later life, including a greater risk of dementia.

One major study from the US initially suggested this might indeed be the case but further studies found no effect or even a protective effect on dementia risk.

Over the last two decades, the way HRT is provided has been made safer and more efficient, so the potential for long-term risks has been greatly reduced.

Now most of the public interest is focused on whether HRT might actually reduce the risk of dementia.

Sex and dementia research

The importance of dementia research that can see differences between the sexes

It may surprise most people to find out that the vast majority of experiments and clinical trials carried out by dementia researchers have not been designed to see differences between male and female participants.

This runs all through the research process. Most older studies involving mice used only males and the first phase of some clinical trials also only recruit male human volunteers.

Most of the time there is a good reason for this bias towards male participants.

Experiments involving animals try to control the situation as tightly as possible so that the only difference between groups of animals is the subject of the research – for example, whether they’ve been treated with a drug or not.

We also need to protect younger women who might be pregnant in case a new experimental drug is unsafe for their baby.

However, the wider implications of doing research like this is that we still have a poor understanding of how diseases causing dementia might work differently in females.

Things are slowly improving as scientists start to appreciate the importance of sex differences in dementia research, but it will take a while to catch up.