Gender Differences in Alzheimer’s Disease

In this episode, we’re fortunate enough to be joined by Dr. Sanjay Asthana, the director and founder of the Wisconsin Alzheimer’s Disease Research Center. Dr. Asthana has published extensive research in the field of hormones and brain health and will be discussing some of his work, which looks at the gender differences that exist in Alzheimer’s disease.

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Sanjay Asthana head shot
Dr Sanjay Asthana

Transcript

Intro: Welcome to Dementia Matters, a podcast created by the Wisconsin Alzheimer's Disease Research Center. It's our goal to humanize Alzheimer's research so that our community, our patients, our participants, and anyone else interested can get a better understanding of the work that's happening to fight back against this disease. My name is Nathaniel Chin, and I'm a geriatric memory clinic physician at the University of Wisconsin. I'm also the family member of someone living with dementia. I'll be serving as your host for this podcast and asking the questions I believe are in the minds of many in our community. Thanks for joining us.

Chin: Today we welcome Dr. Sanjay Asthana, the director and founder of the Wisconsin Alzheimer's Disease Research Center located in Madison, Wisconsin and the associate dean of gerontology at the University of Wisconsin School of Medicine and Public Health. In addition to overseeing the work done here at the ADRC, Dr. Asthana has published extensive research in the field of hormones and cognition. We'll be talking more about research and take a closer look at the sex differences that exist in Alzheimer's disease. So, welcome Dr. Asthana to Dementia Matters.

Asthana: Thank you.

Chin: You were a part of the Alzheimer's Association expert think-tank on gender and biologic sex differences in Alzheimer's disease. A consensus statement came out in 2015 in one major journal of Alzheimer's and dementia describing some of these differences, but really just asking the question, what is going on here?

Asthana: Yes, and thank you for highlighting this meeting to really rethink why women are at a higher risk for Alzheimer's disease. So, there are a number of studies that indicate that women, and this is correcting for the fact that women live longer than men—even if you take away that fact—they still seem to be at a higher risk for developing Alzheimer's disease. We don't quite know what the major reasons are for that increased risk for women, but one of the reasons that may be true—and I think personally it is true—is that women undergo menopause, and as they go through menopause, their estrogen levels drop rather precipitously, as compared to in men when they go through andropause their testosterone levels fall slowly, but in women the estrogen levels fall rather quickly, and the sudden decline in estrogen levels after menopause has been thought to be at least one of the reasons why women are at a high risk for Alzheimer's disease. This think-tank relief tried to identify potential reasons why women are at high risk for Alzheimer's disease so that we can do more research and reduce the risk of Alzheimer's in women.

Chin: So, you mentioned estrogen and hormones. I think a common question in our community would be well then should women be on hormone replacement therapy to fight against this risk of Alzheimer's disease?

Asthana: This is one of the most common questions I get when I talk about my research in Alzheimer's and estrogen. That's very true, but, unfortunately, as a number of studies over years have done some estrogen treatment research in women with Alzheimer's and without Alzheimer's disease the results of those studies are not confirmatory that estrogen is good for Alzheimer's or that it reduces the risk for Alzheimer's disease. Now, there are a number of problems with many of those studies—the way they were designed, the form of estrogen that was used. So, to counteract those previously known deficits in prior studies we, myself and a number of other investigators in the country, conducted an NIH funded study—four years of treatment with two forms of estrogen, oral and patch form, and women who were going through menopause; they were not quite menopausal, but they were transitioning into menopause. The results of those studies have been published, but even those results, although they were not focused on Alzheimer's, but they certainly found that estrogen treatment did not improve their cognitive test performance, but it did improve their mood and depression symptoms that are very common as women go through menopause. So, there are those beneficial effects on mood, but we did not see any effects on memory or thinking. So, the field is a bit controversial. There’s no hard evidence that estrogen should be taken to prevent Alzheimer's disease or treat Alzheimer's disease so neither I nor any other person in this field uses them routinely for that purpose.

Chin: So, there are other reasons a woman could be on hormone replacement therapy, but based on the good data that you have, it should not be used specifically for cognition.

Asthana: Absolutely, either for cognition or prevention of Alzheimer's disease, there's no evidence really, as of now, to do that.

Chin: In addition to hormones, are there any other major theories being discussed as to why women develop Alzheimer's at a greater rate than men?

Asthana: Yes, and one of the things that has come up in the area of research is a gene. It is known as ApoE4 gene. There are decades of research data suggesting that anyone with either a single or two copies of this gene are at a higher risk of getting Alzheimer's disease. It seems that in women who have this gene, they are at a higher risk for Alzheimer's than men who may have this gene. So, it remains to be seen why women are more prone to getting Alzheimer's if they have the ApoE4 gene compared to men. Another reason is the testosterone hormone, which is present both in men and women, but certainly much higher concentration in men. As I mentioned earlier, it goes down rather slowly after men go through their menopause, so-called andropause, as compared to the sudden fall of estrogen in women. So, maybe that slow decline is one of the reasons that men have reduced, perhaps, risk for Alzheimer’s, as compared to women.

Chin: Now, how are women affected differently? Do you have any data or statistics that we could share with our listeners?

Asthana: In terms of estrogen and Alzheimer's risk, yeah, I think some studies will say anywhere from one and a half to two-fold increase risk actually in women, compared to men, especially after menopause. So, this is a significant risk, and as we better understand why that is the case, then I think we might be able to reduce this risk for women. Really, this area of research is gaining more significance based on some findings from new studies, and I think it will be very important for the field of Alzheimer's disease.

Chin: Excellent, well, thank you again Dr. Asthana for coming in for our podcasts. We appreciate having you.

Asthana: Yeah, my pleasure. It was really wonderful to talk to you. Thank you.

Credits: Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center. The Wisconsin Alzheimer's Disease Research Center combines academic, clinical, and research expertise from the University of Wisconsin School of Medicine and Public Health, and the geriatric research education and clinical center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from private, university, state, and national sources, including a grant from the National Institutes of Health for Alzheimer's Disease Centers. This episode was produced by Rebecca Wasieleski and recorded and edited by Alex Wehrli. Our musical jingle is "Cases to Rest," by Blue Dot Sessions. Check out our website at adrc.wisc.edu. You can also follow us on Twitter and Facebook. If you have any questions or comments, email us at dementiamatters@medicine.wisc.edu. Thanks for listening.