Call to factor gender into Alzheimer’s research

In 2005, the New York Times ran a story that caused an extra frisson of fear in roughly 48% of its readers. It reported a study that found regular aspirin did not prevent a first heart attack in women under 65, as it did in men.

The finding, since confirmed in a number of studies, was something of a touchstone in the increasing push to include sex as a variable in research design, now mandated by the US National Institutes of Health and the European Commission.

A new paper from the Society for Women’s Health Research in Washington DC in the US, however, suggests that when it comes to Alzheimer’s research, we have a bit of catching up to do.

“A growing body of research shows us that Alzheimer’s disease differs between women and men,” says Pauline Maki from the University of Illinois at Chicago, a co-author on the paper, which is published in the journal Alzheimer’s & Dementia.

Some of those differences place women at a striking disadvantage from the disease, which blights more than 5.5 million Americans over 65 with memory loss, muddled thinking and social withdrawal.

Scan a city sidewalk and around 10 to 15% of folk will be carrying a version of the Apolipoprotein E (APOE) gene known as E4. That genetic tweak puts people at higher risk of depositing a protein in the brain called amyloid beta, the main component of the plaques found in Alzheimer’s. If you’re a woman aged between 65 and 75 with the E4 variant, your risk of Alzheimer’s is four times higher than the menfolk. The reason isn’t known.

The APOE4 gene also rears its head in the conflicting literature on hormone replacement therapy (HRT). Some studies suggest that starting HRT soon after menopause protects against cognitive decline, while others find no such effect. Critically, the authors note, one recent study found women with the E4 variant who got oestrogen replacement had fewer amyloid deposits on brain scans.

That’s probably good because, in another confounding result, for any given degree of pathological brain change, a woman’s risk of getting the symptoms of Alzheimer’s is more than six-fold that of men. As with the preceding findings, the reasons remain maddeningly unclear.

The gender disparity doesn’t end there. Once women get Alzheimer’s they decline more quickly than men.

On this there is at least a theory. Women rate better than blokes on verbal memory across their lifespan. That means women can start slipping yet still perform adequately on memory screening tests. This masks the disease, which gets diagnosed later, hampering prevention efforts and leading to faster deterioration.

The upshot, say the authors, is that sex-specific screening tests should be well and truly on the agenda.

Nearly two-thirds of Alzheimer’s sufferers are women, a fact partially explained by age being a risk factor for the disease, and women living longer. But longevity does not fully explain the gender difference and it is time, say the authors, for researchers to step up to the plate and fill the knowledge gap.

Among a raft of recommendations, they call for gender to be included in the massive data-crunching exercises of precision medicine, to re-examine past dementia studies for differential effects between men and women.

“To improve the diagnosis of the disease and to speed the development of new treatments and interventions, we must better understand how the biological and sociocultural differences between women and men are influencing the development, progression, and treatment of Alzheimer’s,” said Maki.

The article comes as the Australian Government releases its own progress report on the $200 million Boosting Dementia Research Initiative. Among a range of innovative Alzheimer’s treatments being researched are ultrasound, music therapy and the effects of reducing iron levels in the blood. The mainstay of treatment for Alzheimer’s continues, however, to be drug therapy. There is no known cure.