High Volume of Healthy Vascular Fat During Menopause Associated With Better Brain Health Later in Life

Samar R El Khoudary, PhD, MPH, BPharm, FAHA

In a long-term follow-up study, Samar R. El Khoudary, PhD, MPH, BPharm, FAHA, and colleagues investigated how the quantity and quality of cardiovascular fat in women with Alzheimer disease measured during the transition to menopause are related to their cognitive function later in life.

Additional Resource:
Qi M, Janssen I, Barinas-Mitchell E, et al. The quantity and quality of cardiovascular fat at mid-life and future cognitive performance among women: The SWAN cardiovascular fat ancillary study. Alzheimers Dement. 2023;19(9):4073-4083. doi:10.1002/alz.13133


Consultant360: What was the impetus for this study? So why now?

Samar R. El Khoudary, PhD: Yeah, so almost two-thirds of Alzheimer disease patients older than 65 are women, so this kind of study underlines the need to focus on this population and better understand the risk factors in this population. Also, the midlife is a critical time for women where, actually, women experience the menopause transition. And during the menopause transition, women experience multiple changes, specifically relevant to heart health. We know that the risk factors related to heart health are common risk factors for Alzheimer's disease and cardiovascular fat has been viewed in our work as a novel risk factor that actually has been linked to the menopause transition and we believe that it could also be related to the brain health, and that's where we found the passion to look at the cardiovascular fat as a potential risk factor for cardiovascular disease and Alzheimer's disease.

Consultant360: How does this study fill a current gap in our knowledge?

Dr El Khoudary: Yes. So there are very few studies which looked at the cardiovascular fat. However, these studies very limited in perspective that none focus on midlife women and also they utilized a very simple metric of cardiovascular fat, which is the thickness of this fat using echocardiography. Now we do have CT scans, which actually we usually use to measure the calcification in the coronary arteries. Those CT scans, we can go back to them and then we can use them to quantify cardiovascular fat. We can get from those CT scans that quantity as the volume, and volume much better than the thickness because it can show you the variability across the participants. And then a measure of the quality, which is very novel here, and we referring to the radiodensity coming from those CT scans has been actually used in the literature as a measure of the quality.

So with that being said, the current study looked at the Study of Women's Health Across the Nation that's by far the largest study of the menopause transition in the United States. It has been initiated since 1996. We included 531 women for whom we had a CT scan done to measure the calcification. So we looked at those again and we measured the cardiovascular fat at three different locations. So we measured the epicardial fat, that's the fat close to the heart within the epicardial sac. And then we measured the pericardial fat, the fat outside of the pericardial sac. And then we measured the perivascular fat of the descending aorta, what we called PVAT in this study. And then for those women, we had subsequently measured cognitive function using three different tests that measure the processing speed, the working memory, and the episodic memory in those women over almost 14 years of follow-up. So that's how we filled those gaps in the literature.

Consultant360: Can you provide an overview of your study results, and were you surprised by what you found?

Dr El Khoudary: In this study, we actually were able to find that not all fat around the heart and the vasculature contribute similarly to cognitive function. Interestingly, only the fat surrounding the descending aorta found in our study to be relevant to cognitive function at the quantity and the quality level. For the quantity level, we found that more of this fat actually associated with better episodic memory while higher radiodensity of this fat associated with lower episodic memory and working memory in our women.

I have to say that the findings were of surprise for us because we were expecting more of a negative association with the volume of the fat. But the findings suggest that PVAT is good when you talk about cognitive function. But at the same time, the quality of this fat matter because if you have more of this fat, the quality may not be at the level you are thinking. So that way, it showed the opposite direction in this association.

Consultant360: Why is the menopause transition age range such an important timeframe when considering heart and brain health in women?

Dr El Khoudary: The midlife and the menopause transition is very critical because we have been studying this for years and years and we identify this stage as a window of opportunity, literally, where women start to experience changes in multiple risk factors that if we don't make our women aware of them, then they would impact their future for heart health as well as brain health. Also, the dementia, which is the largest contributor here when we talk about Alzheimer disease, could be tracked back to midlife to early changes that could happen as early as midlife. So if we focus on this period of women, we are able to apply early interventions, hopefully, that can delay the progression of the disease in the future.

Consultant360: What gaps in our knowledge still remain regarding the volume and quantity of certain vascular fat for women in mid-life and cognitive function?

Dr El Khoudary: We have not done any clinical trial in this study, and it was just an epidemiological study where we looked at the relationship between two factors. But since the study showed a link between the volume of this fat and cognitive function and then the quality of this fat and this function, you would think of the prevention could be in light of lifestyle changes applied in that perspective. Because as I mentioned, the quality results that we found point out that too much of this fat could be actually detrimental. And we know that this fat is kind of an ectopic fat, which mean that it's accumulate and expand once your body not able to store the fat in the subcutaneous areas. So it's more of us thinking of whether if there is too much of this fat, the implication would be bigger and then we want to make sure that we are staying in the normal range. So lifestyle changes such as dieting and exercise has been found to be related to the volume of these fats. So a future study, I would say, which we have not done in this study, could look at the implication of reducing this fat among obese patient and how that could impact their cognitive function in the future.

Consultant360: Do you have a plan for future studies? What's next for this topic?

Dr El Khoudary: I would say what's next now, as I mentioned, the finding about the quality and quantity were quite novel and kind of come into opposite, suggesting that we need to know more about PVAT, why the perivascular fat around the descending aorta was the only fat that was relevant to cognitive function, how this fat talk with the brain. So we want to understand the mechanistic pathway through which this fat is relevant. And then the quantity, sorry, the quality, as I mentioned, we use radiodensity as a measure of the quality. And radiodensity is just a number coming from CT scans. I would say that basic research that enable us to better characterize the quality of this fat can enable us to better understand where we can intervene.

So all what I would say, our explanation in the paper, was more of speculation because all what we have, just the association that we were able to observe in this study and also going back to the literature. However, we want to know if for example, this fat as it expand become dysfunctional? Would this fat become more a product of inflammatory marker? And then you would think would medications like for example, statin, which has been shown to have some anti-inflammatory effect on ectopic fat, could be a potential candidate here to help those participants or those patients. And then a statin, for example, has been viewed as a way to reduce risk factor for dementia, in some studies.

Consultant360: What are the overall takeaways from your study?

Dr El Khoudary: These kind of studies would be very helpful for a health care provider because it enable them to point out to a population at risk for a future regression in their cognitive function so they can educate their patients that if you are in that group of participants or patients, then we need to pay attention to your brain health. And with that perspective, definitely, it'll enable early prevention. And then of course the findings that we have reported highlight that connection between the brain and the heart and give us a big message, "If you take care of your heart, you will be able to take care of your brain at the same time," which is a win-win case in that situation.


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