What determines higher dementia risk for women?

23 July 2018

Dementia risk linked to pregnancies and reproductive history

More women than men are affected by dementia, and in the UK women make up two thirds of those living with the condition. While women can expect to live longer than men, this alone does not explain the difference in the numbers developing dementia, and scientists have been delving deeper into the biological variations that could be underlying this effect. Two studies presented at the Alzheimer’s Association International Conference 2018 have explored how reproductive history may be linked to dementia risk.

In the first study, researchers looked at the reproductive history of 14,595 women who were members of Kaiser Permanente, a US-based health care provider. The researchers looked at the women’s medical history, and whether they’d had children or miscarriages, their age at first period and at the onset of menopause, and whether they had received a dementia diagnosis.

They found that women who had three or more children had a 12% lower risk of developing dementia compared with women who had a single child. When they looked at those who had experienced a miscarriage, dementia risk increased by 9% for each additional miscarriage, with women who had three or more miscarriages having a 47% higher dementia risk. Women who had their first period at over 16 years of age were at a 22% increased risk of dementia compared with women who had their first period between the ages of 10 and 13 years old.

In the second study, researchers studied a group of 133 British women, looking at their reproductive history and whether they later developed Alzheimer’s disease. They analysed the data set by looking at the cumulative number of months a woman had spent pregnant, finding that each additional month a woman was pregnant was associated with a 5.5% reduction in dementia risk. When the researchers compared the effects of early versus late months of pregnancy, they found that the reduced dementia risk was associated with the first three months of pregnancy, and not with the last three months of pregnancy. The researchers thought this may indicate that there are important biological changes that take place in early pregnancy that may provide long-term protective effects to women’s brain health. They highlighted potential benefits to the immune system, a defence system that is thought to go rogue and contribute to damage to the brain in diseases like Alzheimer’s.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:

“With more women than men affected by dementia, it is important that we unravel the potential biological or social factors behind this difference. Changes in reproductive health over a woman’s lifetime could be having lasting impact on brain health, and by studying large groups of women, these new studies have shed light on links with dementia.

“While this research found that pregnancy was linked to lower dementia risk, women having their first period beyond the age of 15 or starting the menopause when younger than 45 were both associated with an increased risk of the condition.

“Unravelling what underlies this apparent link between pregnancy and cognitive health could help in the development of new treatments or risk reduction strategies, and this research suggests that future studies may need to focus on the first few months of pregnancy, the time which emerged as the most relevant to future dementia risk.”

Scientists study links between hormone therapy and cognition

There is conflicting evidence around the use of hormone replacement therapy in menopausal women and its knock-on effects on memory and thinking skills in later life, and a number of studies have indicated that hormone therapy use may be linked to a decline in cognitive health. In work presented at the Alzheimer’s Association International Conference 2018, a team of researchers have highlighted new evidence suggesting that the impact of hormone therapy may vary depending on when women begin the treatment and how healthy they are.

In one study, 662 women who had experienced the onset of menopause in the previous three years received either hormone therapy or placebo for four years. The researchers found that there was no difference in the memory and thinking skills of the women, but that hormone therapy was associated with improved mood, and lower levels of anxiety and depression. In another trial, two groups of women who were all in good health and either within six years of the onset of menopause, or over 10 years past menopause received hormone therapy for up to five years. There was no evidence of harm or benefit of the hormone therapy for either group.

The researchers also reanalysed data from WHIMS (Women’s Health Initiative Memory Study), this time looking at the age at when women began hormone therapy. They found that women who began hormone therapy aged 50-54 years did not exhibit any changes in memory or thinking skills, but that those who began hormone therapy aged 65-79 showed reductions in memory and thinking abilities over time, compared to those who did not receive hormone therapy. Additionally, women with type II diabetes showed increased risk of impairment in memory and thinking skills, compared to women without diabetes, or women with diabetes who took a placebo.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:

“Hormone replacement therapy provides important benefits to many women, helping to combat the disruptive symptoms that menopause brings, but it is important that we fully understand any other effects of these medicines, such as their impact on brain health. This study did not look at whether these women went on to develop dementia but does provide some useful insights into how hormone therapy may affect healthy brain ageing.

“These results suggest that the age at which a woman begins receiving hormone replacement therapy may impact future memory and thinking abilities and indicate that diabetes could play a role in the effects on the brain. Understanding the potential knock-on effects of hormone replacement therapy will aid discussions between doctors and patients, helping them to make informed decisions when trying to manage the symptoms of menopause.”

Women’s advantage in verbal skills may mask early dementia symptoms

A number of studies have shown that women tend to have an advantage in verbal memory skills compared to men. This difference may affect the way symptoms of Alzheimer’s are displayed in women. However, many of the memory and thinking tests used to diagnose Alzheimer’s are related to verbal memory skills, and so women’s verbal advantage may affect the results of these tests.

To explore this, a team of researchers in the US looked to the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a dataset collected from hundreds of people containing information from brain scans, genetic tests, memory and thinking tests, and other biological signatures of Alzheimer’s disease. The team used the brain scans to measure Alzheimer’s-related brain changes, looking at the size of hippocampi (the parts of the brain responsible for short term memory formation), energy usage in the brain and the amount of the hallmark Alzheimer’s protein, amyloid. They combined this information with results from verbal memory tests, to see if there were differences between men and women.

They found that in the early stages of Alzheimer’s disease, women showed better scores in verbal memory despite having similar levels of Alzheimer’s-related brain changes to men (smaller hippocampi, reduction in energy use and increased amyloid build-up). When they used sex-specific cut-off scores for the verbal memory tests, diagnostic accuracy increased for both men and women. The researchers suggest that women’s verbal advantage persists in the early stages of Alzheimer’s, and this could be masking symptoms. They also suggest that this masking effect may explain why women seem to show a more rapid decline as the disease progresses.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:

“This study suggests that women’s verbal advantage may be masking the early symptoms of Alzheimer’s, and this could be affecting the accuracy and timeliness of diagnosis. Currently, tests for Alzheimer’s and other forms of dementia don’t take sex-specific differences into account, but this new study suggests this could be a limitation in our approach.

“Doctors use clinical guidelines that set out cut-off points for scores on diagnostic memory and thinking tests, which help them to make a diagnosis. Emerging evidence of sex-specific differences will need extensive investigation and careful consideration by experts before being incorporated into diagnostic guidelines.”