PT  - JOURNAL ARTICLE
AU  - Martin J Prince
AU  - Daisy Acosta
AU  - Mariella Guerra
AU  - Yueqin Huang
AU  - Ivonne Z Jimenez-Velazquez
AU  - Juan J Llibre Rodriguez
AU  - Aquiles Salas
AU  - Ana Luisa Sosa
AU  - Kia-Chong Chua
AU  - Michael E Dewey
AU  - Zhaorui Liu
AU  - Rosie Mayston
AU  - Adolfo Valhuerdi
TI  - Reproductive period, endogenous estrogen exposure and dementia incidence among women in Latin America and China; a 10/66 population-based cohort study
AID  - 10.1101/137687
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 137687
4099  - http://biorxiv.org/content/early/2017/05/19/137687.short
4100  - http://biorxiv.org/content/early/2017/05/19/137687.full
AB  - Background Exposure to endogenous estrogen may protect against dementia, but evidence remains equivocal. Such effects may be assessed more precisely in settings where exogenous estrogen administration is rare. We aimed to determine whether reproductive period (menarche to menopause), and other indicators of endogenous estrogen exposure are inversely associated with dementia incidenceMethods Population-based cohort studies, of women aged 65 years and over in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, including ages at menarche, birth of first child, and menopause, and parity, with ascertainment of incident 10/66 dementia, and mortality, three to five years later.Results 9,428 women participated in the baseline phase, with response rates of 72–98% by site. The ‘at risk’ cohort comprised 8,466 dementia-free women. Mean age at baseline varied from 72.0 to 75.4 years, lower in rural than urban sites and in China than in Latin America. Mean parity was 4.1, generally higher in rural than urban sites and ranging from 2.4-7.2 by site. 6,854 women with baseline reproductive period data were followed up for 26,463 person years. There were 692 cases of incident dementia, and 895 dementia free deaths. Pooled meta-analysed fixed effects, per year, for reproductive period (Adjusted Sub-Hazard Ratio [ASHR] 1.001, 95% CI 0.988-1.015) did not support any association with dementia incidence, with no evidence also for any interaction between APOE genotype and reproductive period (ASHR 0.993, 95% CI 0.947-1.041, I2=39.3%). Similarly no association was observed between incident dementia and; ages at menarche, birth of first child, and menopause: nulliparity; or index of cumulative endogenous estrogen exposure. Greater parity was positively associated with incident dementia (ASHR 1.030, 95% CI 1.002-1.059, I2=0.0%).Conclusions We found no evidence to support the theory that natural variation in cumulative exposure to endogenous oestrogens across the reproductive period influences the incidence of dementia in late life.ASHRAdjusted Sub-Hazard Ratio APOE-Apolipoprotein ECERADConsortium to Establish a Registry for Alzheimer’s Disease CI-Confidence intervalCSI-DCommunity Screening Instrument for DementiaDSMDiagnostic and Statistical ManualEEEEndogenous estrogen exposureICEEEIndex of cumulative endogenous estrogen exposurePOFPremature ovarian failure