Abstract Disclosure: J. Yu: None. K. Han: None. J. Yun: None. S. Lee: None. Risk of dementia according to the reproductive factors in postmenopausal women with diabetes Jin Yu[1], Kyungdo Han[2], Jae-Seung Yun[3], Seung-Hwan Lee[1],[4] [1]Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea[2]Department of Statistics and Actuarial Science, Soongsil University[3]Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea[4]Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Background: Previous studies have suggested a possible association between endogenous estrogen exposure and decreased risk of cognitive impairment or dementia. We aimed to investigate the impact of reproductive factors on the risk of dementia in women with diabetes. Methods:166,245 postmenopausal women with type 2 diabetes aged over 40 who underwent health examination in 2009 were identified from the National Health Information Database. Information regarding reproductive factors were collected through self-administered questionnaires. Incident dementia was defined using diagnosis codes and anti-dementia drug prescription. Cox proportional hazards regression analyses were performed to evaluate the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia according to reproductive factors including age at menarche, age at menopause, reproductive lifespan, parity, and use of hormone replacement therapy (HRT). Results: The mean age and reproductive lifespan were 64.5 ± 8.0 and 33.4 ± 4.7 years, respectively. During the median follow-up of 8.3 years, 25,330 cases of any dementia, including 20,817 cases of Alzheimer's disease and 2,756 cases of vascular dementia were developed. The hazard ratios (95% CI) of all-cause dementia were 1.28 (1.06-1.56) for age at menarche >16 years compared with ≤12 years, 0.71 (0.66-0.77) for age at menopause ≥55 years compared with <40 years, and 0.72 (0.68-0.76) for reproductive lifespan ≥40 years compared with <30 years, respectively. The risk of all-cause dementia was decreased by 11% in women with parity ≥2 compared with 0, and by 16% in women with HRT for more than 5 years compared without HRT. Similar findings were observed for Alzheimer’s disease and vascular dementia. Conclusion: Longer reproductive lifespan was associated with lower risk of dementia in postmenopausal women with diabetes. Presentation: 6/2/2024