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Dr. Isaacson:
Welcome to another episode of the Frontline of Alzheimer's Care, where we tackle interesting questions from real clinicians about the use of amyloid-targeting therapies in Alzheimer's disease. I'm Dr. Richard Isaacson, and here with me today are doctors Gayatri Devi and Pierre Tariot to help answer these questions. Let's have a question now from Ms. Grigaitis-Reyes.
Ms. Grigaitis-Reyes:
There have been reports that in the clinical trial data for lecanemab, it demonstrated no statistically significant results in the primary outcome measure when looking at women as a group. So my question is, do you discuss this with your female patients? And how do you respond if they ask about that?
Dr. Isaacson:
So, Dr. Devi you have a lot of experience here. Tell us about your thoughts about the differences between men and women. And, Dr. Tariot, I would really love your input as well. Dr. Devi?
Dr. Devi:
Generally, women tend to suffer more from Alzheimer's disease, both in terms of the prevalence of Alzheimer's disease in women, as well as women as caregivers as people most likely to take care of patients with Alzheimer's. I believe Alzheimer's is more - there's more heterogeneity in Alzheimer's in women. There may be less or more cardiovascular risk. There may be less or more use of hormone replacement in women which may be associated with risk for Alzheimer's disease. Early versus late menopause, as well, and exposure to estrogen. Endogenous estrogen may also affect risk. So there are a multitude of different reasons why the group may not be quite as homogenous as men with Alzheimer's disease.
Having said that, I personally am not aware of any studies that show a difference in terms of plaque load between men and women differentially affecting functioning. And I believe the clearance is the same in terms of plaque from the monoclonal antibodies and treatment of Alzheimer's plaques and clearance of Alzheimer's plaques. So I have found in my practice, that there's not much difference in terms of efficacy between men and women who are on either aducanumab or lecanemab. They seem to be very little differential response, although in the clinical trial looking at lecanemab, it appears that lecanemab was less effective in women.
Dr. Isaacson:
Dr. Tariot, any concluding comments?
Dr. Tariot:
Yeah, I come at it a little differently. It's a very astute question, by the way. There are three monoclonal antibody development programs. This glitch was only seen in the lecanemab program. Remember that if you do a large number of statistical comparisons, you are going to get positive or negative results by chance alone. And I think this was very likely a play-of-chance issue. That said, I really appreciate the nuances that Dr. Devi raised just now.
Dr. Isaacson:
Great, well, thank you to Ms. Grigaitis-Reyes for that fantastic question. And to our viewers, watch our other episodes for more important questions like this, about the clinical use of amyloid-targeting therapies. Thanks for joining us.
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