Gray matter volume in women with the BRCA mutation with and without ovarian removal

Witt, S. T.; Brown, A.; Gravelsins, L.; Engström, M.; Classon, E.; Lykke, N.; Lundqvist, E. A.; Theodorsson, E.; Ernerudh, J.; Kjölhede, P.; Einstein, G.

doi:10.1101/2023.11.14.566928

bioRxiv · 10.1101/2023.11.14.566928

Gray matter volume in women with the BRCA mutation with and without ovarian removal

Witt, S. T.·Brown, A.·Gravelsins, L.·Engström, M.·Classon, E.·Lykke, N.·Lundqvist, E. A.·Theodorsson, E.·Ernerudh, J.·Kjölhede, P.·Einstein, G.

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Abstract

ObjectiveOvarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimers disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counselled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM and this is in women without the BRCAm showing cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and BSO noted changes in cognition. MethodsThe present study looked at whole-brain changes in gray matter volume using high-resolution, quantitative MRI in women with BRCAm and intact ovaries (BRCA-preBSO) and after surgery with (BSO+ERT) and without (BSO) post-surgical estradiol hormone replacement therapy compared with agematched women (AMC) with their ovaries. ResultsThe BRCA-preBSO and BSO groups showed significant gray matter loss in left medial temporal and frontal lobe structures. BSO+ERT exhibited few areas of gray matter reductions compared to AMC. Novel to this study, we also observed that all three BRCAm groups exhibited gray matter increases compared with AMC, suggesting continued plasticity. ConclusionsThe present study provides evidence, through gray matter volume reductions, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, post-surgical ERT seems to ameliorate gray matter losses.

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Witt, S. T., Brown, A., Gravelsins, L., Engström, M., Classon, E., Lykke, N., Lundqvist, E. A., Theodorsson, E., Ernerudh, J., Kjölhede, P., Einstein, G.. 2023-11-16. Gray matter volume in women with the BRCA mutation with and without ovarian removal. https://doi.org/10.1101/2023.11.14.566928

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