J E Yoo1, D W Shin2,3, K Han4, D Kim5, H-S Won6, J Lee7,8, S Y Kim9, G E Nam10, H S Park11. 1. Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea. 2. Department of Family Medicine and Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 3. Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea. 4. Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea. 5. Department of Medical Statistics, Catholic University of Korea, Seoul, Korea. 6. Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 7. Department of Economics and Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA. 8. RANC Corporation, Santa Monica, CA, USA. 9. Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Korea. 10. Department of Family Medicine, Korea University College of Medicine, Seoul, Korea. 11. Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Abstract
BACKGROUND AND PURPOSE: The aim was to investigate whether female reproductive factors are associated with dementia. METHODS: In all, 4 696 633 post-menopausal women without dementia were identified using the Korean National Health Insurance System database. Data on reproductive factors were collected using a self-administered questionnaire. Dementia was determined using dementia diagnosis codes and anti-dementia drug prescription. Cox proportional hazards regression was conducted to assess the hazard ratio (HR) for dementia according to reproductive factors. RESULTS: During a median follow-up of 5.74 years, there were 212 227 new cases of all-cause dementia (4.5%), 162 901 cases of Alzheimer's disease (3.5%) and 24 029 cases of vascular dementia (0.5%). The HR of dementia was 1.15 [95% confidence interval (CI) 1.03-1.16] for menarcheal age ≥17 years compared with menarcheal age 13-14 years, 0.79 (0.77-0.81) for menopausal age ≥55 years compared with menopausal age <40 years, and 0.81 (0.79-0.82) for fertility duration ≥40 years compared with fertility duration <30 years. Whilst being of parity one (HR 0.89, 95% CI 0.85-0.94) and breastfeeding <6 months (HR 0.92, 95% CI 0.88-0.95) was associated with lower risk of dementia, being of parity two or more (HR 1.04, 95% CI 0.99-1.05) and breastfeeding ≥12 months (HR 1.14, 95% CI 1.01-1.07) was associated with a higher risk of dementia than women without parity or breastfeeding history. Use of hormone replacement therapy and oral contraceptives independently reduced the dementia risk by 15% and 10%, respectively. CONCLUSIONS: Female reproductive factors are independent risk factors for dementia incidence, with higher risk associated with shorter lifetime endogenous estrogen exposure.
BACKGROUND AND PURPOSE: The aim was to investigate whether female reproductive factors are associated with dementia. METHODS: In all, 4 696 633 post-menopausal women without dementia were identified using the Korean National Health Insurance System database. Data on reproductive factors were collected using a self-administered questionnaire. Dementia was determined using dementia diagnosis codes and anti-dementia drug prescription. Cox proportional hazards regression was conducted to assess the hazard ratio (HR) for dementia according to reproductive factors. RESULTS: During a median follow-up of 5.74 years, there were 212 227 new cases of all-cause dementia (4.5%), 162 901 cases of Alzheimer's disease (3.5%) and 24 029 cases of vascular dementia (0.5%). The HR of dementia was 1.15 [95% confidence interval (CI) 1.03-1.16] for menarcheal age ≥17 years compared with menarcheal age 13-14 years, 0.79 (0.77-0.81) for menopausal age ≥55 years compared with menopausal age <40 years, and 0.81 (0.79-0.82) for fertility duration ≥40 years compared with fertility duration <30 years. Whilst being of parity one (HR 0.89, 95% CI 0.85-0.94) and breastfeeding <6 months (HR 0.92, 95% CI 0.88-0.95) was associated with lower risk of dementia, being of parity two or more (HR 1.04, 95% CI 0.99-1.05) and breastfeeding ≥12 months (HR 1.14, 95% CI 1.01-1.07) was associated with a higher risk of dementia than women without parity or breastfeeding history. Use of hormone replacement therapy and oral contraceptives independently reduced the dementia risk by 15% and 10%, respectively. CONCLUSIONS: Female reproductive factors are independent risk factors for dementia incidence, with higher risk associated with shorter lifetime endogenous estrogen exposure.