Why Alzheimer’s Hits Women Harder: A Q+A with Dr. Natasha Rajah

Abridged Interview:

Leslie Andrachuk (LA): We often hear that almost two-thirds of people with Alzheimer’s are women. For years, the explanation was simply that women live longer. Is that the whole story?

Dr. Rajah: Not at all. Longevity is only part of the picture. We now know that sex-specific biology plays a major role — particularly hormones like estrogen. Women’s reproductive history — when they begin menstruating, how long they are fertile, the age of menopause — all affect brain aging. The longer a woman’s reproductive span, the lower her risk of Alzheimer’s later in life. In addition to this, genetics, access to higher education, career and socioeconomic status, as well as traumatic brain injury may contribute.

LA: What are the key hormonal risk factors researchers are uncovering?

Dr. Rajah: Premature menopause, which happens before age 40, and early menopause, between 40 and 44, both increase risk. Surgical removal of the ovaries before 50 is another big one. Estrogen has neuroprotective effects, and when it’s lost suddenly or too early, the brain is left more vulnerable.

Pregnancy also matters. Having one to three children appears to lower risk, likely because of beneficial hormonal changes that occur during those pregnancies.

LA: How does genetics come into play?

Dr. Rajah: One of the strongest genetic risk factors is the APOE4 variant. Both men and women with this variant are at higher risk, but women are affected more strongly. Their risk of developing Alzheimer’s is significantly higher than men carrying the same gene.

LA: You’ve also spoken about how women may mask symptoms early on. Can you explain?

Dr. Rajah: Women tend to have stronger verbal memory skills, which means they can compensate for early declines in memory. Standard tests often miss those subtle changes so we’ve been looking at different ways to diagnose women and we may be getting to a stage where we have a task that’s sensitive for differentiating females that are at different levels of risk.

This is important as without the right diagnostic tools, women may not be diagnosed until the disease has already progressed further, which limits treatment options.

LA: Why has research on women and Alzheimer’s lagged so far behind?

Dr. Rajah: Historically, women were excluded from clinical trials. They were considered “too complicated” because of complex hormonal cycles. That bias left us with decades of data based on men – who also have hormones, by the way. We’re now playing catch-up. Only recently have funding agencies and researchers started prioritizing sex and gender in brain health.

LA: How is this new knowledge shaping prevention and treatment?

Dr. Rajah: We’re moving toward more personalized approaches. That could mean earlier screening for women who experience premature or early menopause, or tailoring hormone therapies to individual histories. As I said before, it also means adjusting diagnostic tools, so women’s memory strengths don’t mask early symptoms.

LA: If a woman in her 40s or 50s asked you how to protect her brain health, what would you say?

Dr. Rajah: Stay physically active, eat a healthy diet, and keep socially and mentally engaged. If you’re facing early menopause or had your ovaries removed, speak with your doctor about whether hormone therapy might be appropriate. And advocate for yourself — if you notice changes in memory, push for assessment.

LA: Finally, if you had unlimited funding, what’s the first question you’d want to answer?

Dr. Rajah: I would want to understand exactly how estrogen and reproductive history interact with brain aging over a woman’s lifetime. That could open the door to precise prevention strategies — and perhaps even disease-modifying treatments — that specifically protect women’s brains.