ESOC 2026 | Understanding sex differences in cognitive decline: blood pressure variability and incident stroke

Prior studies have shown that there are sex differences in cognitive decline, with women generally having faster cognitive decline as compared to men. However, the reasons for these underlying sex differences are not fully understood. There are a variety of factors that are likely playing a role, including sociodemographic factors, genetic factors, lifestyle factors, and vascular risk factors, especially cumulative vascular risk factors throughout the life course like cumulative systolic blood pressure. But there are a couple of factors in particular which have not been fully evaluated in prior studies. These include blood pressure variability, which is a variation in blood pressure from visit to visit over the long term. And we know that blood pressure variability is associated with an increased risk of dementia and we also know that increased blood pressure variability tends to increase in women after menopause, so it may be one factor that could potentially help explain these differences. Another factor is incident stroke, so we know that after stroke there’s an acute decline in cognition, and then that’s followed by a persistent decline in the years following. We also know that the incidence of stroke varies by sex throughout the life course, with women generally having a higher incidence in later years. So again, this might be another factor that could be relevant to this question. So to study this, we pooled data from five major US longitudinal cohort studies, and we came up with over 20,000 participants, 55% of which were women. And we performed a sequential modeling approach to add variables sequentially into the model to help explain this association. So what we found was that after adding BP variability and incident stroke into the model, it actually didn’t change the sex difference all that much. So our main hypothesis actually, you know, we found that these factors did not explain the sex difference, but we did find a couple of really interesting findings. We found that the association between blood pressure variability and cognitive decline still held, even after accounting for all these other various factors that we talked about. So that was one major finding. The other was that there was an effect modification by sex in the association between acute stroke incidence and cognitive decline, meaning that after an incident stroke, women tended to have a faster cognitive decline as compared to men. So that was also a really interesting finding, particularly because we had many other variables in the equation at this point. So this was independent of all those factors. So in conclusion, we found that, again, there are still these sex differences in cognitive decline that we don’t fully understand the reason why they occur. But we did find that this should be an area for future research. And we also found this interesting finding that women tend to have faster cognitive decline after stroke compared to men, which also deserves future research.

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