Associations between age, sex and menopause with brain structure at middle and early old age

Dr Stephanie Than1,2, Dr Chris Moran1,2, Associate Professor Richard Beare1, Associate Professor Amanda Vincent3,4, Dr Wei Wang1, Professor Velandai Srikanth1,2

1Department of Academic Medicine, Peninsula Clinical School, 2Central Clinical School, Monash University, Department of Geriatric Medicine, Peninsula Health, 3Department of Endocrinology, Monash Health, 4Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University

Aims: Age and female sex are risk factors for dementia. Menopause, associated with cognitive dysfunction, may contribute to dementia risk. However, little is known whether menopausal status and age interact to amplify this risk. We aimed to study the associations of menopause, age and their interaction with imaging biomarkers of dementia.

Methods: Cross-sectional study of UK Biobank participants, a community-based cohort from the United Kingdom aged>40 years, with structural brain magnetic resonance imaging data. We explored the associations of age, sex and menopausal status with brain volumes, adjusting for APOE4 status. Analysis included descriptive statistics and linear regression modelling.

Results: Data were available for 1824 postmenopausal women, 231 premenopausal women and 2164 men (median age 63.3 years). The negative association of age with total brain volume (TBV) was greater in women than in men (p=0.01). The negative association of age with TBV was greater in post-menopausal women (β= -5.89, 95%CI:-10.68 to -1.11) than pre-menopausal women (β= -2.98, 95%CI:-5.35 to -0.61), p for age x menopause interaction=0.02.

Conclusions: Increasing age and menopause appears to have synergistic effects on brain structure. Further work is required to understand the mechanisms driving these associations, to develop ways to prevent or delay neurodegeneration and dementia.