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Interactions between age, sex, menopause, and brain structure at midlife: A UK biobank study


Than, S and Moran, C and Beare, R and Vincent, AJ and Collyer, TA and Wang, W and Callisaya, ML and Thomson, R and Phan, TG and Fornito, A and Srikanth, VK, Interactions between age, sex, menopause, and brain structure at midlife: A UK biobank study, Journal of Clinical Endocrinology and Metabolism, 106, (2) pp. 410-420. ISSN 0021-972X (2021) [Refereed Article]

Copyright Statement

Copyright 2020 The Authors

DOI: doi:10.1210/clinem/dgaa847


Objectives: Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife.

Methods: In this cross-sectional study of UK Biobank participants with brain magnetic resonance imaging (MRI), we explored the interaction of age with sex or menopausal status in explaining total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), white matter hyperintensity volume (WMHV), regional cortical volume , and subcortical volume.

Results: Data were available for 1827 postmenopausal women, 230 pre/perimenopausal women and 2165 men (median age 63.3 years). There was a significant interaction between age and sex (P = .024) for TBV, where the inverse association age with TBV was steeper in women (β = -5.35 mL/year) than in men (β = -4.77 mL/year). Similar age-sex interactions were also observed for GMV and WMV. In women, there was a significant interaction between age and menopausal status (P = .007) where the inverse association of age with TBV was steeper in postmenopausal (β = -5.89 mL/year) than in pre/perimenopausal women (β = -1.61 mL/year). Similar age-menopause interactions were found in predicting lower GMV and higher WMHV. Differences in the direction of these age-sex and age-menopause interactions were found for regional cortical and subcortical brain volumes.

Conclusion: Sex and menopause both interact with age during midlife in explaining MRI biomarkers of dementia. Further work is required to understand the mechanisms driving these interactions to develop strategies for delaying dementia.

Item Details

Item Type:Refereed Article
Keywords:MRI, all cognitive disorders/dementia, menopause, risk factors in epidemiology, sex differences
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Evaluation of health and support services
Objective Field:Determinants of health
UTAS Author:Callisaya, ML (Dr Michele Callisaya)
ID Code:147310
Year Published:2021
Web of Science® Times Cited:11
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-10-25
Last Modified:2022-08-23

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