Reproductive factors and dementia risk

Pregnancy, long reproductive span, and older age at menopause are associated with a lower risk of dementia in women, according to a study publishing April 5^th in the open access journal PLOS Medicine. Inversely, hysterectomy, younger age of first birth, and younger or older than average age at first period were associated with greater dementia risk. The study suggests that reproductive and hormonal factors may be involved in dementia risk, but observed a similar association between the number of children and dementia risk in women and men, suggesting that the physical experience of childbearing may not account for risk variation.

Dementia rates are increasing around the world, with some studies reporting a higher incidence in women than men, yet there is a limited evidence base on reproductive factors and the risk of dementia. Jessica Gong at The George Institute for Global Health, Australia, and colleagues used data from the UK Biobank to examine the risk of all cause dementia and reproductive factors in 273,240 women as well as the number of children in those women and in 228,965 men.

After controlling for age, socioeconomic status, smoking, body mass index (BMI), and other elements, certain events related to shorter cumulative exposure to internally produced estrogen – such as older than average age at first period, younger than average age at menopause, and having a hysterectomy – were associated with higher dementia risk. Pregnancy, even aborted pregnancy, longer reproductive span, older age at menopause, and use of contraceptive pills were associated with a lower risk of all-cause dementia. For both men and women, compared with having two children, having no children or four or more were apparently associated with greater risk of dementia. 

The study has limitations including the retrospective reporting on reproductive factors that can be subject to bias, and the fact that UK Biobank is a relatively healthy cohort of affluent people of white British ancestry so may not be representative of a broader population.

Gong adds, “Reproductive events related to shorter exposure to endogenous estrogen in women were associated with higher dementia risk, and these findings highlight the vulnerability in dementia risk pertaining to women. However, the similar association between the number of children and dementia risk observed for women and men indicates that the risk variation in women may be more related to social and behavioural factors in parenthood, rather than biological factors involved in childbearing.”

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In your coverage, please use this URL to provide access to the freely available paper in PLOS Medicine:

http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003955

Citation: Gong J, Harris K, Peters SAE, Woodward M (2022) Reproductive factors and the risk of incident dementia: A cohort study of UK Biobank participants. PLoS Med 19(4): e1003955. https://doi.org/10.1371/journal.pmed.1003955

Author Countries: Australia, the Netherlands, United Kingdom

Funding: JG is supported by the Scientia PhD scholarship from the University of New South Wales, Sydney, Australia (https://www.scientia.unsw.edu.au/). SAEP is supported by a UK Medical Research Council Skills Development Fellowship [grant number: MR/P014550/1] (https://mrc.ukri.org/). MW is supported by an Australian National Health and Medical Research Council Investigator Grant [grant number APP1174120] and Program Grant [grant number: APP1149987] (https://www.nhmrc.gov.au/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.