Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

Abstract

The menopause transition involves changes in oestrogens and adipose tissue distribution, which may influence female brain health post-menopause. Although increased central fat accumulation is linked to risk of metabolic diseases, adipose tissue also serves as the primary biosynthesis site of oestrogens post-menopause. It is unclear whether different types of adipose tissue play diverging roles in female brain health post-menopause, and whether this depends on lifetime oestrogen exposure, which can have lasting effects on the brain and body even after menopause. Using the UK Biobank sample, we investigated associations between brain characteristics and visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) in 10,251 post-menopausal females, and assessed whether the relationships varied depending on length of reproductive span (age at menarche to age at menopause). To parse the effects of common genetic variation, we computed polygenic scores for reproductive span. The results showed that higher VAT and ASAT were both associated with higher grey and white matter brain age, and greater white matter hyperintensity load. The associations varied positively with reproductive span, indicating more prominent associations between adipose tissue and brain measures in females with a longer reproductive span. The results could not be fully explained by genetic variation or relevant confounders. Our findings indicate that associations between abdominal adipose tissue and brain health post-menopause may partly depend on individual differences in cumulative oestrogen exposure during reproductive years, emphasising the complexity of neural and endocrine ageing processes in females.

Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later

“…17 participants were excluded due to implausible menopause status data or age at menopause outliers (see Section 2.2 for details). 794 participants with known brain disorders were excluded based on ICD10 diagnoses including Alzheimer's disease and dementia, mild cognitive disorder, neurodegenerative diseases, stroke, mental and behavioural disorders (36,48). 9,882 participants were included in the final dataset.…”

“…Participants answering "no" at baseline were classed as premenopausal, and those answering "yes" at baseline were classed as postmenopausal. Premenopausal females who were older than 63 at baseline and postmenopausal females who were younger than 39 at baseline were excluded (n = 4), based on outlier estimations for the variable 'age at menopause' conducted on all UK Biobank females in our previous work (36). 13 participants were removed due to implausible menopause status data (e.g., responses indicating postmenopausal status at baseline and premenopausal status at timepoint 2).…”

“…Both cross-sectional and longitudinal studies indicate that the menopause transition poses a risk for accumulation of abdominal adipose tissue (6,(26)(27)(28) and an unfavourable lipid profile (4,5,29,30), beyond the risk related to advancing age. However, higher levels of abdominal adiposity, blood lipids, blood pressure (BP), and blood glucose are generally linked to greater WMH volumes (8,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41), and it is challenging to disentangle menopause-specific risks from those linked to increasing age (6). In addition, recent studies show age-and sex-specific associations between cardiometabolic risk factors and brain measures (24,42,43), indicating dynamic body-brain relationships across the lifespan.…”