Roberta Diaz Brinton, PhD, is the director of the UA Center for Innovation in Brain Science at the University of Arizona Health Sciences. Dr. Brinton is a leading neuroscientist in the field of Alzheimer’s, the aging female brain and regenerative therapeutics. Dr. Brinton has been the recipient of several WAM Research Grants since 2016.. We caught up with her on what she’s been up to in the lab this year.

WAM: Your 2021 WAM Research Grant is taking a close look at how therapies to control cholesterol might reduce a risk for developing Alzheimer’s—and how women respond differently to statin therapy than men. What are you finding?
Dr. Brinton: First, we are finding that statins are very effective at reducing the risk of Alzheimer’s disease. They are slightly more effective in men compared to women, but the preventive effect in women is still quite strong, reducing risk by 50%
. This slight difference between women and men in responsivity is largely driven by women who have cardiovascular disease in addition to the elevated cholesterol being treated by statin therapy.

It is critical to reduce the number of systems that are not healthy. Having one problem is controllable, having 2 is more complex and demanding, having 3 systems that are dysregulated is even more challenging to keep functioning well and within a healthy range. We are preparing the results of this WAM-supported study for publication in an open access scientific journal so that both women and their health care providers have access to the results of our analyses.

WAM: How does this grant build on what you’ve learned over the past 6 years from previous WAM Research Grants?
Dr. Brinton: We have consistently asked the question: What factors are increasing the risk of Alzheimer’s in women, and could treatment for those risk factors reduce the risk of Alzheimer’s in women? Our WAM project on the impact of statins is one example of our approach as dyslipidemia, or elevated cholesterol, increases the risk of AD.
Another example is the impact of hormone therapy on risk of AD. Because we know that loss of estrogen is associated with increased risk of Alzheimer’s disease, we investigated whether menopausal hormone therapy could prevent the risk of Alzheimer’s. Results of these analyses indicated that hormone therapy reduces the risk of Alzheimer’s by 50-60%. We went onto investigate whether some hormone therapies were better than others in reducing Alzheimer’s risk. Outcomes of those analyses indicated that hormone therapies that contain the same molecules that the body produces, 17beta-estradiol and progesterone, were best at reducing risk of Alzheimer’s.

Based on these findings, we then on to ask – If estrogen menopausal therapy reduces the risk of Alzheimer’s, what would be the impact of breast cancer anti-estrogen therapies? Outcomes of our WAM investigation were somewhat surprising. We discovered that several breast cancer therapies, especially tamoxifen and exemestane, were associated with a significant decrease in the risk of Alzheimer disease.

WAM: How do you anticipate this study may help the average woman as she looks at managing her risk for Alzheimer’s?
Dr. Brinton: Our WAM project goal is to provide women with scientific knowledge they can use to make informed decisions about how best to reduce their risk of Alzheimer’s disease. We have investigated factors that increase the risk of AD and determined the best therapeutic strategies to reduce that risk. We have very purposely published our findings in scientific journals that are accessible to women and their health care providers. With the information about health conditions that increase risk of AD, women can take necessary action to prevent these conditions. If they have conditions that increase the risk of AD, we have provided women and their health care providers with scientific data that can inform their therapeutic decisions for selecting drug therapies that are effective in treating the condition while also reducing the risk of AD! Real Science that Really Matters for Real People!

WAM: How has getting a WAM seed grant benefitted the work you are doing in understanding women’s increased risk for Alzheimer’s?
Dr. Brinton: WAM-supported projects have greatly increased our understanding of the clinical conditions that increase the risk of AD and, more importantly, the best treatments for those conditions for reducing the risk of AD and sustaining an AD free life! Outcomes of our WAM research has also contributed to securing funding from the NIH National Institute on Aging to investigate the biology underlying differences between women and men in their risk for AD and for their response to therapies to reduce the risk of AD.