Alzheimer’s Is a Disease That Discriminates: Why Women?

Dr. Murali Doraiswamy discusses the importance of exploring sex differences in Alzheimer’s.

For decades scientists have ignored crucial gender differences in the way men and women experience disease. With research on everything from stroke to cancer traditionally focused on men there is a sizeable dearth of knowledge when it comes to women’s health. Now, some scientists are trying to turn that around. Dr. Murali Doraiswamy, Professor of Psychiatry and Behavioral Sciences at Duke University, is probing the underlying mechanisms that distinguish how the sexes suffer from Alzheimer’s, a disease known to disproportionately affect women. He explains why it’s crucial to understand if women at risk for the disease truly do progress faster than men.

• Two-thirds of people who come down with Alzheimer’s disease are women

• Researchers looking to biomarkers to understand if there is a gender difference at different stages of Alzheimer’s

• Scientists look to X chromosome to as possible explanation for differences in Alzheimer’s

Being Patient: We know that two-thirds of people impacted by Alzheimer’s disease are women. Do we have any clue as to why?

Dr. Murali Doraiswamy: No, we don’t. This was not even fully appreciated from a scientific point of view until perhaps about four or five years ago. Interestingly the very first case of Alzheimer’s described 100 year ago was in a woman. That was the case where Dr. Alzheimer noticed the plaques and tangles, what are now considered the hallmarks of Alzheimer’s disease. It’s interesting that 100 years later now we’re discovering that there may be sex differences in the vulnerability for Alzheimer’s. It’s a huge public health priority for us to try to dig deep and try to see if it’s true or not.

“It’s interesting that 100 years later now we’re
discovering that there may be sex
differences in the vulnerability for Alzheimer’s.”

Being Patient: Do the genes or the chromosomes that women have perhaps make them more vulnerable to the disease?

Dr Murali Doraiswamy: For many years it was thought that women are more likely to have Alzheimer’s simply because they live longer. That myth, if you will, was struck a near body blow about five years ago when studies showed that the age-specific rates of Alzheimer’s in your sixties, and your seventies, and your eighties, at each of these decades was twice as high in women than it was in men, suggesting that it was not solely due to women living longer. That’s when researchers started digging in. We’re still in very early days, and so we still don’t fully know all the reasons.

Being Patient: Within your research what are you trying to address?

Dr Murali Doraiswamy: The first thing we are trying to do is to try to replicate these findings using what’s called a longitudinal naturalistic study. There is a large study that has been done in the US for the last 10 years, it’s called the Alzheimer’s Disease Neuroimaging Initiative. It’s a study that has followed about 1,500 individuals with and without Alzheimer’s over a 10 year period. It has tracked their cognitive scores, their functioning and a range of biomarkers – their blood tests, their genetic tests and brain scans. When subjects go to autopsy, [the study] also looked at their brains. This study, surprisingly, was not geared towards looking at sex differences. So we now have this treasure trove of data that I can go in and say: “Do women truly progress faster than men? What is the magnitude of differences? At which of the different stages of Alzheimer’s disease does the sex difference become most obvious?” Then I can dig deeper into their biomarkers to see what their possible mechanisms are.

“Undoubtedly there are different pathways
to disease in men versus women.”

Being Patient: Has there been any indication that the disease actually presents itself differently in women than in men?

Dr Murali Doraiswamy: It probably does because we know that on a variety of cognitive tests, men and women perform differently. Verbal abilities, for example, women tend to do a lot better than men. Women tend to do a little bit worse than men on some spatial abilities and certain types of math abilities. There’s also a tendency for women to be diagnosed at a slightly earlier stage because they come for treatment early, unless the man is in a high-powered job where the job is causing a lot of problems. The second difference is that certain behavioral problems associated with Alzheimer’s also tend to vary between men and women. Depression tends to be a little bit more common in women whereas certain types of verbal aggression, agitation … tend to be a little bit more common in men. Last but not least, women comprise most caregivers. Women bear the brunt of the disease, no matter who it affects.

Deborah Kan: Does it really matter that we know the reason behind more women getting the disease?

Dr Murali Doraiswamy: There are two things. Until about 25, 30 years ago, most clinical trials were done in men. For example, the famous study called the Aspirin Study, which is the basis for most people taking a low-dose aspirin to prevent heart attack, was done exclusively in men. We don’t know if aspirin, at that same dose, would work in women or not. The NIH (National Institutes of Health) in 1993 passed an act called the Revitalization Act mandating that women be included in clinical trials and that all clinical trials have a separate hypothesis to test whether men and women have different pathways to disease, and whether drugs benefit people differently.

“Until about 25, 30 years ago, most
clinical trials were done in men.”

We’ve learned there are tremendous variations between men and women. For example, women are much more vulnerable to side effects of drugs at the same dose … Their blood levels are different, their propensity for side effects is different. We also know that the biology of disease is very different. There are many diseases whose genes are housed on the X chromosome, making women more vulnerable to those genes. I think it’s very important for us to study this. Undoubtedly there are different pathways to disease in men versus women. For example, amongst non-smokers, women are much more likely to get lung cancer than men. If we truly find out that, say, men have a lower risk for a certain disease, or women have a lower risk for a certain disease, and we can identify that pathway, then we can target or develop drugs based on those mechanisms to help everybody.