Education moderates inflammation-cognition associations after COVID-19 in younger but not older women: A sex- and age-stratified cross-sectional investigation

Cognitive reserve is known to support resilience against brain pathologies that affect older adults. However, the role of cognitive reserve proxies in moderating the link between post-COVID-19 cognitive dysfunction and systemic inflammation, particularly given sex differences and the potential influence of sex hormones, remains unclear. We investigated educational attainment, the most common proxy for cognitive reserve, as a moderator of the relationship between follow-up C-reactive protein (CRP) blood levels (an inflammation marker) and a composite cognitive score. Both measures were obtained during the same in-person assessment conducted between 6 and 11 months after hospitalization due to COVID-19 in a cross-sectional sample of adults stratified into four groups by sex and an age cutoff of 51 years, corresponding to the mean age of natural menopause. Regression and bootstrap analyses indicated a significant difference between women under 51 and those aged 51 or older, with higher educational attainment being associated with attenuation of the negative relationship between CRP and cognition only in women aged less than 51 years, consistent with the cognitive reserve hypothesis. Additional exploratory analyses showed a significant negative association between CRP and cognition in older men as well, but education did not moderate this association. The absence of this pattern in older women may suggest a role for sex hormones in the interplay between inflammation, cognitive reserve, and resilience. These results highlight the importance of considering sex and age-related hormonal status when evaluating post-COVID-19 cognitive outcomes.