AbstractContextMetabolic syndrome (MetS) affects cognitive function in late life, particularly in women. But longitudinal research is scarce on associations of MetS with cognitive function during midlife.ObjectiveTo determine associations between MetS exposure and cognitive function trajectories in midlife women.Design and SettingThis is a 17-year prospective, longitudinal study of multiracial/ethnic women in 7 US communities, with annual/biennial assessments.ParticipantsParticipants were 2149 US women traversing menopause.ExposureExposure consisted of MetS assessments (median 4 assessments over 4 years).Main Outcome MeasuresMain outcome measures were assessments of cognitive function in 3 domains: perceptual speed (symbol digit modalities test, SDMT), episodic memory (East Boston Memory Test, EBMT), and working memory (Digit Span Backward Test, DSB).ResultsBy their first cognitive assessment (age 50.7 ± 2.9 years), 29.5% met the criteria for MetS. Women completed a median (interquartile range [IQR]) of 6 (IQR 4–7) follow-up cognitive assessments over 11.2 (IQR 9.2–11.5) years. Women with MetS, compared with those without, had a larger 10-year decline in SDMT z-score (estimate –0.087, 95% confidence interval, –0.150 to –0.024; P = 0.007), after adjustment for cognitive testing practice effects, sociodemographics, lifestyle, mood, and menopause factors. As such, MetS accelerated the 10-year loss of perceptual speed by 24%. MetS did not differentially affect the rate of decline in either immediate (P = 0.534) or delayed (P = 0.740) episodic memory or in working memory (P = 0.584).ConclusionsIn midlife women MetS exposure was associated with accelerated decline in perceptual speed, but not episodic or working memory.