Sex differences in dementia are only just being recognized – but the consequences could change the way we fight the disease.
By Laura Oliver12 July 2018
Diagnosed with Alzheimer’s in 2015, 75-year-old Brenda Whittle still enjoys jigsaws, sewing, and dancing. New activities are less appealing, but participating in Alzheimer’s research and drug trials is an exception. She’s so at ease with loud brain scans, she even falls asleep during them.
Brenda is one of more than 50 million people worldwide living with dementia – a catch-all category of diseases affecting memory and brain processing, including Alzheimer’s. That number is rising quickly. Globally, experts estimate that 75 million people will live with dementia by 2030 and 131.5 million by 2050.
Most are women.
In Australia, nearly two-thirds of all dementia-related deaths were women; in the US, two-thirds of those living with the disease are women, too. In some cases, dementia even outstrips more famously ‘female’ diseases: US women over 60are twice as likely to develop Alzheimer’s disease as breast cancer. (Breast cancer remains the leading cause of death for UK women aged 35 to 49).
“This can’t be sustained by any medical health system – it is too much in terms of numbers, says Antonella Santuccione-Chadha, a physician and Alzheimer’s specialist based in Switzerland. “And as women are more confronted by the disease, we need to investigate the differences between the male and female specifics of it.”
Much of the gender gap comes down to one of dementia’s biggest risk factors: age. The older you are, the more likely you are to develop late-onset Alzheimer’s. Women typically live longer than men, so more have dementia.
But recent research hints that we would be wrong to assume that aging means Alzheimer’s is inevitable. Results from two major Cognitive Function and Ageing Studies (CFAS) suggest that over the last 20 years, new dementia cases in the UK have dropped by 20% – driven mostly by a fall in incidence among men over 65 years old.
Over the past 20 years, new dementia cases in the UK have dropped by 20% – driven mostly by a fall in incidence among men over 65
Experts say this may be because of public health campaigns targeting heart disease and smoking. Both are risk factors for Alzheimer’s. But because men tend to get heart disease younger and smoke more than women, these campaigns also may have helped stave off these risk factors more for men than women.
Meanwhile, other risk factors for the disease affect women more than men. For example, more women develop depression – and depressed mood has been linked to the onset of Alzheimer’s. Other risk factors affect only women, such as surgical menopause and pregnancy complications like pre-eclampsia, both of which have been linked to cognitive decline in later life.
Social roles, such as caregiving, also may increase the chance of developing dementia. Some research has shown that being a caregiver is, in itself, a risk factor for Alzheimer’s disease, says Annemarie Schumacher, a health psychologist. In the UK, some 60-70% of all unpaid caregivers looking after someone with dementia, in particular, are women.
“Sex-specific prevention might start from having more of this information about female-specific risk factors,” says Maria Teresa Ferretti, a biomedical researcher in the field of Alzheimer’s disease at the University of Zurich.
This idea is gaining momentum. Advocacy group the Women’s Brain Project (WBP), co-founded by Santuccione-Chadha, Ferretti, and Schumacher as well as chemist Gautam Maitra, has just published a major review analyzing a decade’s worth of scientific literature on Alzheimer’s, revising existing data and asking scientists to stratify it by sex for the first time.
“The most obvious differences that come out of the literature are in the display and progression of cognitive and psychiatric symptoms between men and women with Alzheimer’s disease. Based on these new studies we can design new hypotheses and figure out new ways to improve treatment of patients,” says Ferretti.
Currently, for example, Alzheimer’s is detected by looking for two toxic proteins that have accumulated in the brain. Evidence suggests no difference in the levels of these proteins, or ‘biomarkers’, in men and women with Alzheimer’s disease. But the women show a greater cognitive decline.
As a result, the biomarkers “might have a different predictive value in men and women,” says Ferretti: “We might need to adjust imaging, biochemical and neuropsychological biomarkers for men and women or find gender-specific biomarkers.”
Another question for researchers is why the disease progresses faster in women than men after diagnosis
Another question for researchers is why the disease progresses faster in women than men after diagnosis. One school of thought suggests that estrogen protects women’s brains when they’re younger, but that those benefits drop off, as does estrogen, after a certain age.
Other research suggests women perform better on the initial tests used, which can lead to missed diagnoses at an early stage and which may also lead doctors to underestimate the disease’s severity. If that is the case, diagnostic exams may need to be changed to reflect the neuropsychological differences between men and women.
Another challenge has been with how clinical trials for Alzheimer’s medications are designed. Expensive and long, they tend to have a near-even gender split, even though more women deal with the disease.
For other conditions, like depression and multiple sclerosis, “prevalence is often reflected,” Santuccione-Chadha says. “If more women are affected by those diseases, more women are usually included in the trials.” That approach seems to have worked: “in these disease areas, we have been witnessing successful drugs,” she says. Most clinical trials for medications for Alzheimer’s in the past decade, on the other hand, have failed.
Compared to other diseases, research on dementia also remains underfunded. Historically in the UK, 8p is spent on researching new dementia treatments for every £10 spent caring for those with the disease, according to research from Oxford University. By comparison, £1.08 goes to cancer.
The funding discrepancy is repeated elsewhere: in 2017 in the US, data from the National Institutes of Health (NIH) suggests around $3.03bn (£2.29bn) was spent on research into Alzheimer’s and related diseases, while $9.87bn (£7.47bn) went to cancer research.
Funding for research is growing year-on-year helped by recent high-profile pledges, such as Bill Gates’ donation of $50 million (£38m). But “there is still ground to make up”, says Hilary Evans, CEO of Alzheimer’s Research UK. “We must see further significant funding drives to ensure we make the same advances for people with dementia that we’ve seen for cancer and heart disease in recent years.”
As for Brenda, she manages with the help of a GPS tracker – prompted after a trip on the wrong train – and with reminder notes stuck around the house by her husband Stephen. Both say they plan to continue to involve themselves in discussions and research.
The involvement of couples like Brenda and Stephen is essential. Research conducted with sex and gender at the forefront is already raising new possibilities for how we detect, treat and support the growing number of people living with the disease. Pinning down any differences could help solve one of the greatest medical mysteries of our time – a chance, experts agree, we’d be foolish not to take.
Source: BBC News