Sex-specific relations of ceramides and white matter hyperintensities in the Rhineland study

TL;DR

This study finds that ceramides are more strongly linked to brain changes called white matter hyperintensities in women than in men.

Contribution

The study reveals novel sex-specific associations between ceramides and white matter hyperintensity burden, particularly in women.

Findings

Multiple ceramides, ceramide ratios, and a ceramide score were associated with increased white matter hyperintensity load.

Associations between ceramides and white matter hyperintensities were significantly stronger in women than in men.

Menopausal status did not influence the observed associations between ceramides and white matter hyperintensities.

Abstract

Women have a higher white matter hyperintensity (WMH) burden compared to men of a similar age, but the causes of this remain unclear. Ceramide (CER) levels differ between men and women and were previously linked to WMH, suggesting they could underlie these sex differences. Therefore, we associated twelve CERs, CER totals, six CER ratios, and a CER score reflecting the CERs most strongly associated with cardiovascular disease, with WMH load in 3,283 participants (30–95 years) of the community-based Rhineland Study. We assessed sex-specific relations between CERs and WMH by including an interaction term and performing sex-stratified analyses. We further investigated the influence of menopause by comparing relations in pre- and postmenopausal women of the same age. Multiple CERs, CER ratios, and the CER score were associated with increased WMH load, with most associations being significantly stronger in women than in men. We found no influence of menopausal status on the associations between CERs and WMH. Thus, we showed novel and strong associations of CERs, CER ratios and the CER score with WMH burden, especially in women. This study suggests that CERs may play an important role in the observed sex differences in WMH burden.

The online version contains supplementary material available at 10.1038/s41598-025-06911-z.

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