Why is dementia different for women?

More women are affected by dementia than men. Worldwide, women with dementia outnumber men 2 to 1. Here we discuss the biology behind dementia risk.

Dementia risk is a complex puzzle. Understanding the differences of the sexes is one way that could help dementia researchers understand its causes and develop new treatments.

Dr Aoife Kiely, Research Communications Officer at Alzheimer's Society, explores why being male or female could affect dementia risk and diagnosis.

Two elder women smiling in conversation

Facts about women and dementia

  • More women are affected by dementia than men. Worldwide, women with dementia outnumber men 2 to 1.
  • Brain scans tell us that the rate at which brain cells are dying in the brain is faster in women than in men.
  • Women are more likely to live longer than men. However, although risk increases with age, dementia is caused by diseases of the brain not age alone.

The importance of female data in research

Animals are sometimes used in dementia research to understand the condition and develop new effective treatments.

We know data from female animals has generally been ignored in brain research. In the past, researchers have dismissed data from female animals or results from drugs trials that involved them.

The data was seen as too odd or inconvenient. Today, the use of female data has sparked debate among dementia researchers.

Jacqueline Mitchell, an Alzheimer’s Society funded researcher at King’s College London, says:

'We are very aware of sex-based differences – we always make sure to use a balance of male and female so that we can statistically compare any differences that arise in response to drug treatments.’

It might be a surprise that we haven’t learned more in the lab about how males and females respond differently to drug treatments.

However, women were only included in clinical trials from 1993.

Understanding the effect of oestrogen

Women have a lifelong relationship with the female hormone called oestrogen. Oestrogen affects the brain, mental health, the cardiovascular system, the liver and more. There have been some studies that show oestrogen might protect brain cells.

Some researchers have suggested 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.

Yet, before we can think of oestrogen as a wonder drug, it has some hurdles to overcome.

Hormone replacement therapy and dementia

Oestrogen is 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 when it was decided that the risks of heart and breast cancers outweigh any potential benefits on thinking and memory. Researchers are currently hard at work to develop better, more naturally-acting HRT. They are investigating whether starting HRT earlier could reduce dementia risk.

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. To assess this part of our memory we measures memory of a list of words or a short story.

Women keep these skills even if they have mild memory and thinking problems. The first step in dementia diagnosis is a verbal memory test. This poses a problem for men and women. As women have a strong verbal memory, they tend do well on memory tests, even if they have cognitive problems. This means they are under diagnosed with dementia.

Men 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-centred 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

Does heart health play a role in dementia risk?

We know that what is good for the heart is good for the head. Improving heart health seems to be a good way to lower dementia risk. The health of a heart affecting dementia risk might also be linked to sex. For example, high blood pressure in midlife is believed to increase risk in women but not men, even though it is more common in men.

Professor Patrick Kehoe is an Alzheimer’s Society funded researcher based at University of Bristol. He says:

'It is possible that the complex relationship of oestrogen to the renin angiotensin system, which regulates blood pressure and has roles in cognitive function, influences a woman’s risk of developing Alzheimer’s. Following menopause with the influence of oestrogen on this system a woman is at greater risk of high blood pressure and so perhaps also dementia, but we need to test this in more detail.’

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.

16 comments

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my wife has FTL dementia I spend a lot of time trying to work out why she has this, one thing I wonder is could being sterilised after having our children be a cause or other medical procedures ? There is nothing in her family.

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Hi David,
Thanks for getting in touch.
We are often asked by our supporters whether general anaesthetics used in surgical procedures might increase risk of dementia, but the research on this subject is not conclusive: https://www.alzheimers.org.uk/about-dementia/risk-factors-and-preventio…
In most cases, however, researchers think dementia is caused by a range of different factors, rather than one single cause. These include things such as genetics, lifestyle and other environmental factors.
It is very difficult to know for any individual exactly what may have caused their condition.
-
Alzheimer's Society Research team

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Hi Georgina, a good link to begin with is:
Does Brain Development in Childhood Set the Stage for Dementia?
Series - Alzheimer's Association International Conference 2015:
20 Aug 2015
It’s clear by now that in dementia, a disease mostly of old age, trouble starts decades earlier—but how early? Well—how about in the womb? Data presented at the Alzheimer's Association International Conference, 2015, held July 18-23 in Washington, D.C., lend some support to this radical idea. Scientists presented epidemiological, imaging, and even genetic studies that drew associations between early brain development and some atypical forms of Alzheimer's disease.
They also grappled with what those associations mean. “Might how your brain is wired in early stages influence how it degenerates later in life? That’s an extremely interesting concept,” said Jonathan Schott, University College London. Zachary Miller, from the University of California, San Francisco, stressed that early developmental patterns are not necessarily risk factors for later disease. "A more parsimonious explanation is that if you are going to get some form of dementia, then where it presents first, or the ‘locus of least resistance,’ might be determined by how your brain has developed," he told Alzforum. Whatever the cause and effect, researchers agreed that studying how learning disabilities and brain development influence later dementia could yield valuable insights into the disease processes, and even provide an opportunity for very early intervention.

Researchers have suspected for some time that there is a connection between learning problems and dementia. In 2008, researchers led by Marsel Mesulam at Northwestern University, Chicago, reported that people with learning disabilities..

The rest of the article is online..
My focus of interest is now on the daily and seasonal circadian rhythm, if you google Images for serotonin and melatonin it speaks volumes about insomnia.

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It would be really useful to have a link to the research studies mentioned in the articles to read. Apologies if I have missed it!

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Obviously a lot of factors that need to be controlled for and investigated. Some of the data analysis is too crude e.g. the number of children doesn’t factor in the number of years on the pill, miscarriages etc which will also change the Oestrogen levels and maybe even if you breastfed for over a year. But the sleep thing is really interesting as snoring husbands have a much bigger and longer impact than pregnancy or menopause, shitty as the later is. I wonder whether that is being taken into account or whether it’s too politically incorrect to raise it ?

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What about B12 and Pernicious Anemia? A lot of study is now been seen showing that low levels of Iron and B12 over your life time effects neurology. One of the first signs of Pernicious Anemia is what they call “brain fog”. Women suffer higher instances of Iron and B12 Anemia than men. Is there not something in this? If so how easy would it be to make sure your B12 levels are high and not deficient.

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With research suggesting that sleep plays an important role in flushing the brain of harmful waste products such as amyloid beta which are associated with dementia, could the prolonged lack of sleep associated with pregnancy and the menopause be a contributing factor?

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Why do more women than men get AZ DM? it makes more sense biologically if the male and female difference in fat to muscle protein is considered, because I suggest what happens in the AZ DM progression is much the same as what happens when faced with famine starvation or as in a diabetic coma the body uses up its fat stores before using muscle protein.

It is known for example that mid life obesity is a risk indicator yet when AZ DM is diagnosed it is more often in later life a few years after the person has become very thin due to weight loss, this is thought to be because a hormone called Leptin is to low.
Here the fact that most of the body s fatty cholesterol is stored in the brain says to me the body is using up that fat reserve up as well as its body fat before it begins to use the body s muscle protein.
But lets not forget AZ DM is not just about the body s hormones and metabolism its about the person who can slowly fade away before your eyes..the latest health and well being advise is that changing our lifestyle will minimize the risk by about 30% which means the usual diet and exercise changes, and some now argue that because AZ DM risk is higher among the less well educated more education will statistically protect you.
Now lets also consider the late 20th century Nuns study which found on autopsy that those Nuns that had the unmistakably loss of brain mass including its cholesterol content, were able to function normally within the family orientated ethos of the organisation, why? because they were valued as human beings and not as just a collection of hormones and that I believe is what makes all the difference for the quality of life even if AZ DM does visit your family. Hate the disease but love the person.
True enough those Nuns were well read people but more importantly they felt loved and valued for who they were not how much they had learnt and that is a powerful motivation.

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My hypothesis is that more women have dementia then men in the traditional generation ( age 75 to 85 ). Because of the mental abuse they took for 50 years of there life from there husbands. Wish there could be a study on this. No one in my moms family had dementia. She has it and took mental ( no physical abuse) from my dad for 60 years.

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My mother recently was diagnosed with sun down dementia. I have several other friends whose mothers are also going thru this same thing as I am with my mom. I was wondering is there any studies that show if you have a hysterectomy before the age of 50 that it can lead to dementia.

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My mum died of Lewy Body dementia 2014. Like Claire White’s mum she was a healthy person. Low BP, good BMI (underweight if anything) ate fish. No history of diagnosed mental illness except PND 50 years previously. Generally happy disposition. She could be histrionic at times and spent a considerable time in hospital as a child which could have affected her mental health and attachment in relationships. She had TB in her spine as a child. She had insomnia throughout her life known to be ironing in the early hours. I’d like to see more research linking insomnia, previous life history, diseases in childhood especially nervous system to dementia.

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As with the poor diagnosis and treatment of heart disease in women (BHF, 2019) and many other aspects of women’s health, the fact that women are nearly twice as likely to develop Alzheimer’s Disease (AA, 2014) receives little attention. It is often noted that “Studies looking at whether replenishing oestrogen levels using HRT can reduce women's risk of dementia have been inconclusive and contradictory” (AS, 2019) and that it might depend on when treatment is started. This suggests that HRT is an entirely effective treatment for the menopause, BUT it is well known that it isn’t – it helps some people with some of the symptoms to some extent (nobody has bothered to document this in any detail) – it doesn’t return things to pre-menopause. In addition, focus is entirely on oestrogen, as if this is the only thing that matters; but there are several hormones involved. One prominent one is progesterone, which could help a common symptom of the menopause, insomnia. Poor sleep in middle age is a known risk factor for AD, because of reduction in glymphatic drainage (Holzman, 2017; cf Yo-el et al, 2017, lliff et al, 2012; Glymphatic system, Maiken Nedergaard as described in Konnikova, 2014; Walker, 2017). There is evidence that oral progesterone can help with disturbed sleep (Caufriez et al, 2011); “studies have shown that hormonal changes in the menstrual cycle can and do interfere with sleep for an average 2-3 days per monthly cycle……. A second time of disrupted sleep occurs as progesterone levels fall towards the end of the menstrual cycle” (LSC, 2018); women have been shown to be more easily disturbed during sleep (Horne, 2006).
Oral progesterone to relieve menopausal insomnia is recommended by the British Menopause Society (WHC, 2018). Progestogens are commonly used in combined HRT rather than progesterone, and Panay (2014) of the National Association for Premenstrual Syndrome recommends body identical hormones to be used in HRT and states: “whilst progesterone has a mild sedative effect through its intermediate metabolites, progestogens tend to cause anxiety and irritability”.

So it’s no surprise that HRT, especially when started late, and when containing progestogens, has little impact of the development of AD in women. This is something that needs serious attention, given the rising numbers of people with AD.

Most people don’t get the opportunity to try oral progesterone or body identical HRT even though it is recommended by the BMS and Panay; it has definitely improved my sleep after 20 years of chronic insomnia but it was a real struggle to get it. Menopausal insomnia should be treated, it is very unpleasant and a risk factor for AD. Until the medical profession takes a serious look into effective HRT, and takes seriously insomnia as a symptom of menopause (Vahration, 2017) rather than ignoring it, and tries to actually treat it, it won’t have any effect in reducing the high levels of AD suffered by women.

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I feel there is a link with anxiety/depression in earlier life that increases the risk of having dementia later in life. A bit like brain overload & eventually something that is a big worry will trigger the Dementia. My Mum had a very healthy lifestyle with no medical problems apart from post natal depression (prescribed valium) after her second child. I believe she suffered from anxiety but it was not diagnosed. Her Alzheimer's was diagnosed at the age of 64 after a trip to New Zealand & 2 extremely worrying life incidents to family. Is the link the drugs given to people who suffer with anxiety & depression, ie. the effect they have on serotonin levels. Or is it the natural make up of the brain & the brain disease is triggered by a life experience? I too suffer from anxiety & have taken Prozac, will be interesting to see what happens to me considering Mum's age when diagnosed with Dementia. I would have thought I would be a prime candidate for research lol.

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In the first large-scale epidemiological look at dementia risk and reproductive history, Paola Gilsanz, a scientist with Kaiser Permanente Northern California, and Rachel Whitmer, professor of epidemiology at the University of California, Davis, evaluated data on nearly 15,000 women between the ages of 40 to 55 collected over nearly a decade to find that women with three or more children had a 12 percent lower risk of dementia compared with women who had only one child. (There was a small, but not significant, benefit for having had two kids.)

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I thought the information about the differences between women and men in relation to Dementia most interesting. Many thanks. HC

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Hi. There is the psychological side to consider too.
Women tend to talk more than men about health problems, e.g. in a crowd one will say she is having a problem remembering and then others join in and it snowballs, this happens on a regular basis, my theory is if you keep telling yourself you can’t remember in these circumstances it will send a signal to the brain and therefore you won’t remember. So, don’t talk yourselves into it.

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