Not much is known about why women develop dementia. That’s about to change

The first patient to be treated with Alzheimer’s disease, in the German city of Frankfurt in 1901, was a 51-year-old woman named Auguste.

Despite this, and although Alzheimer’s is twice as prevalent in women, more than 120 years later research remains largely focused on men.

Among studies that include men and women, only 42 per cent conduct analysis of the differences between the sexes.

The reason often given for women’s exclusion in research is their increased hormonal variability. Now, it is precisely this hormonal variability that researchers want to examine.

A new $US50 million global program ($77 million) has the goal of halving the lifetime risk of Alzheimer’s disease in women through funding research into sex-specific biomarkers and interventions.

One of the 16 recipients of funding is Professor Kaarin Anstey, the director of the University of New South Wales Ageing Futures Institute and a conjoint senior principal research scientist at Neuroscience Research Australia.

Anstey and her colleague Professor Kristine Yaffe, from the University of California, plan to explore the relationship between dementia risk and neuroendocrine factors – women’s reproductive health factors that affect the brain.

For instance, early menopause (under the age of 45) is associated with a higher risk of Alzheimer’s and all-cause dementia. The basic concept is that reduced exposure to the neuroprotective hormone oestrogen may increase their risk.

“But we need to do much more science and proper work around it,” Anstey says. “What we need is really detailed research looking at the hormonal changes women go through and how that affects their brain and later their dementia risk.”

Those reproductive changes include the onset of menarche; breastfeeding and number of viable pregnancies; so-called “baby brain”; onset of menopause; menopausal “brain fog”; and exogenous hormones such as hormone replacement therapy (HRT), infertility treatments and contraceptives.

“We don’t know much about these reproductive factors in relation to brain health and even things like the fact that women are exposed to hormones on and off through their life,” she explains.

Some observational evidence on HRT suggests it may be protective, but evidence from the few randomised controlled trials that look at cognitive outcomes are inconclusive.

As for terms like “baby brain”, menopausal “brain fog” and complaints of cognitive difficulties, they could provide important clues into their brain health, Anstey says: “But they’ve just been dismissed.”

About two-thirds of women report experiencing brain fog during menopause.

“With over five million Australian women over 40, a better understanding of menopause, and its cognitive effects is critical,” says Associate Professor Caroline Gurvich, head of the Cognition and Hormones Group at Monash University. “We don’t know what the long-term consequences of menopausal brain fog are (if any).”

While researchers work to understand the complex interactions between women’s hormones, lifestyles and brain health, signs of cognitive decline can be passed off as “women’s issues”.

‘Maybe it’s menopause, maybe it’s depression’

When Terry Kitay, a previously happy, kind and caring mother-of-three, became withdrawn and nervous, her family was confused. The 53-year-old stopped attending her book club, no longer wanted to drive, and sat quietly through boisterous family dinners.

“There were definitely conversations around ‘maybe it’s menopause, maybe it’s depression’,” says her daughter Keri. “There was no history of dementia in our family, and she was in her early 50s. It was honestly not even on our radar.”

Then Terry, who had worked as the receptionist at her husband’s dental clinic for more than 15 years, forgot how to book an appointment. But it was a phone call from their accountant, who noticed that her bookkeeping suddenly looked like a “dog’s breakfast”, that prompted further investigation.

“He said ‘something is wrong with Terry’,” Keri recalls.

An appointment with the GP and a referral to a neurologist followed. In June 2011, 18 months after her first symptoms appeared, a PET-scan revealed amyloid build-up in the frontal temporal lobe of her brain. Terry, by then 54, was diagnosed with early-onset Alzheimer’s disease. The cause remains unknown.

Women’s lives and hormones are complex, says Professor Susan Davis, the director of the Women’s Health Research Program at Monash University.

For instance, she questions whether the increased dementia risk in women who go through early menopause or who have low oestrogen before 45 is because of reduced exposure to oestrogen or because of an underlying pathology that causes early menopause or low oestrogen.

“It’s not simple to determine if ‘brain fog’ at menopause predicts dementia – there are so many other variables to address,” Davis adds.

Last year, The Lancet Commission on dementia prevention indicated that nearly half of all dementia cases worldwide could be prevented or delayed by addressing 14 modifiable risk factors.

They are low education, midlife hearing loss, untreated high blood pressure, smoking, obesity, untreated depression, physical inactivity, diabetes, excessive alcohol, traumatic brain injury, air pollution, social isolation, high cholesterol and untreated vision loss.

Keri Kitay admits she has anxiety about getting dementia. “Having witnessed what somebody goes through … I wouldn’t wish that on my worst enemy,” says the Sydneysider, who wrote a memoir about her family’s experience, titled The Long Goodbye: Lessons on humanity from the grips of Alzheimer’s.

Terry died nine years after her diagnosis, aged 63.

The knowledge that much of the risk can be prevented, however, gives Keri heart.

“I just have to try and be as physically active and healthy as I can be, try and reduce my stress, eat properly and enjoy having a whisky, but I don’t have one every day, or every week.”

With the new body of research, Anstey hopes we will also get a clearer picture of how the modifiable risk factors affect men and women differently. The effect of particular risk factors might be greater in men than women, and vice versa, but needs teasing out.

She says: “The more we can understand, the more we can intervene to prevent it.”

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