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Background The importance of systemic inflammation, measured by C-reactive protein, in cognitive decline has been demonstrated; however, the role of vascular inflammation is less understood. Pentraxin 3 (PTX3) is a novel marker of vascular inflammation. Methods We followed adults 65 and older, free of cardiovascular disease (CVD) for up to 9 years (n = 1,547) in the Cardiovascular Health Study. We evaluated the relationship between PTX3 and change in cognitive function, measured using the Modified Mini-Mental State Examination (3MSE), and incident cognitive impairment (3MSE &amp;lt; 80). Mediation by CVD events, and effect modification by sex and apolipoprotein E ɛ4 allele (APOE4) were also examined. Results The average decline in 3MSE was 0.77 points per year. The association between PTX3 and change in 3MSE differed between women and men (p = .02). In the adjusted model, each standard deviation higher in PTX3 was associated with a 0.20 greater decline in 3MSE score per year in women over follow-up (95% CI: −0. 37, −0.03; p = .02), compared to no change in men (β = 0.07; 95% CI: −0.08, 0.22). CVD events had a minor effect on the associations. No effect modification by APOE4 was found, although we observed the association of PTX3 and cognitive impairment in women was attenuated and nonsignificant after adjustment for APOE4. There was a paradoxical protective association between PTX3 and reduced cognitive impairment in men, even after adjustment for APOE4. Conclusions We found that vascular inflammation was significantly associated with cognitive decline in older women, but not men.

Sex Differences in the Association Between Pentraxin 3 and Cognitive Decline: The Cardiovascular Health Study