Reproductive period, endogenous estrogen exposure and dementia incidence among women in Latin America and China; a 10/66 population-based cohort study

Abstract

BackgroundExposure 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 incidence MethodsPopulation-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. Conclusions. CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/137687 doi: bioRxiv preprint first posted online May. 19, 2017; 4 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.

Towards an understanding of women's brain aging: the immunology of pregnancy and menopause

“…For instance, endogenous E2 exposure has been suggested to be neuroprotective [73,74] and to lower the risk for AD [75], but a recent population-based study found no evidence of an effect of endogenous E2 exposure on incident dementia [76]. Endogenous sex-hormone exposure can be estimated based on factors such as length of reproductive span (time from menarche to menopause) [76] and parity, including age at first birth [77] and duration of breastfeeding [75]. Some studies also include postmenopausal weight or body mass index, number or occurrence of abortions and miscarriages, as well as duration of oral contraceptive (OC) use and hormonal replacement therapy (HRT) to approximate cumulative estrogen exposure [75,77].…”

Women’s brain aging: effects of sex-hormone exposure, pregnancies, and genetic risk for Alzheimer’s disease

“…Results from the Esprit study in France showed an association between longer reproductive span and better cognitive performance, but no relationship was observed between reproductive span and cognitive decline across four years (9). A recent meta-analysis found no link between endogenous estrogen exposure and incident dementia (8). Findings from the Rotterdam cohort showed that women with longer reproductive span had an increased risk of dementia, but the association was only evident in women carrying the apolipoprotein E type 4 (APOE e4) genotype (12).…”

“…However, other studies have found no association between endogenous exposure and dementia risk (8,9) or cognitive performance (9,10). Only a small number of studies have been population-based (8), and among those, findings are mixed. Results from the Guangzhou Biobank Cohort Study in China showed that longer reproductive span, i.e.…”

“…Estrogen may also have beneficial effects on cognition (4,5), and studies have shown a link between endogenous estrogen exposure and less cognitive decline in older age (6,7). However, other studies have found no association between endogenous exposure and dementia risk (8,9) or cognitive performance (9,10). Only a small number of studies have been population-based (8), and among those, findings are mixed.…”

“…Parity represents a complex addition to the estimation given the role of immune factors in pregnancy such as the proliferation of regulatory T cells (39), which is suggested to protect against AD (40). In addition, estrogen levels rise up to 300-fold throughout pregnancy (41) and fall 100-1000 fold postnatally (42), often in relation to breastfeeding (8), of which the duration influences the number of total menstrual cycles within a woman's reproductive years (11,43). Parous women may also have shorter menstrual cycles and lower levels of estradiol than nulliparous women (44,45), indicating that age at first birth also influences lifetime estrogen exposure.…”