P3-565: endogenous estrogen exposure and dementia incidence: a 44-year longitudinal population study of women

Dementia incidence is higher among women than among men, especially in the very old. Estrogen has been proposed as a possible explanation for this difference. However, few studies have investigated the longitudinal effect of endogenous estrogen exposure (EEE) on dementia incidence. We aimed to study the longitudinal effect of EEE on dementia incidence, measured as length of the reproductive period, number of pregnancies and months of breastfeeding, among women with natural menopause followed up to 44 years. We used a population-based sample of 1410 women from the Gothenburg H70 Birth Cohort Studies, born 1908, 1914, 1918, 1922 and 1930, followed from 1968 – 2012. Information about age at menarche, menopause, type of menopause, number of pregnancies and months of breastfeeding, were obtained at four examinations (1968, 1974, 1980 and 1992). We calculated the reproductive period as the time from age at menarche to age at menopause. During follow-up, dementia (n=228), Alzheimer's disease (AD) (n=112) and dementia with CVD (n=98) were diagnosed according to established criteria. Length of reproductive period and number of pregnancies were independently associated with dementia incidence (HR 1.2; 95% CI 1.05 – 1.36, HR 0.9; 95% CI 0.79 – 0.99, respectively), after adjustment for age. Only reproductive period remained associated with increased risk of dementia (HR 1.1; 95% CI 1.01 – 1.28), and AD (HR 1.3; 95% CI 1.06 – 1.48) after adjustment for multiple covariates. Taking age at onset into account, the associations with reproductive period were only found in those with age at onset after 85 years (HR versus 1st quartile for the 2nd quartile 7.8; 95% CI 1.67 – 36.16, for the 3rd quartile 5.2; 95% CI 1.11 – 24.00, 4th quartile 6.4; 95% CI 1.43 – 29.02). The APOE genotype had no effect on these findings. Among women with natural menopause, number of pregnancies were associated with reduced risk of dementia, while length of the reproductive period was related to an increased risk of dementia and AD. Length of the reproductive period had an especially strong association with the risk of AD with onset after the age of 85.