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

The menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology.

In this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40-70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline.

Postmenopausal females showed higher levels of baseline blood lipids (HDL $\beta$ = 0.14, p < 0.001, LDL $\beta$ = 0.20, p < 0.001, triglycerides $\beta$ = 0.12, p < 0.001) and HbA1c ($\beta$ = 0.24, p < 0.001) compared to premenopausal women, beyond the effects of age. Over time, BMI increased more in the premenopausal compared to the postmenopausal group ($\beta$ = -0.08, p < 0.001), while WHR increased to a similar extent in both groups ($\beta$ = -0.03, p = 0.102). The change in WHR was however driven by increased waist circumference only in the premenopausal group. While the group level changes in BMI and WHR were in general small, these findings point to distinct anthropometric changes in pre- and postmenopausal females over time. Higher baseline measures of BMI, WHR, triglycerides, blood pressure, and HbA1c, as well as longitudinal increases in BMI and WHR, were associated with larger WMH volumes ($\beta$ range = 0.03-0.13, p ≤ 0.002). HDL showed a significant inverse relationship with WMH volume ($\beta$ = -0.27, p < 0.001).

Our findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years.