Gray matter volume in women with the BRCA mutation with and without ovarian removal: evidence for increased risk of late-life Alzheimer's disease or dementia.

IF 2.8 3区 医学 Q1 OBSTETRICS & GYNECOLOGY
Suzanne T Witt, Alana Brown, Laura Gravelsins, Maria Engström, Elisabet Classon, Nina Lykke, Elisabeth Åvall-Lundqvist, Elvar Theodorsson, Jan Ernerudh, Preben Kjölhede, Gillian Einstein
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引用次数: 0

Abstract

Objective: Ovarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimer's disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counseled 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 showing women without the BRCAm had cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and bilateral salpingo-oophorectomy (BSO) noted changes in cognition.

Methods: The present, cross-sectional study examined whole-brain differences in gray matter (GM) volume using high-resolution, quantitative magnetic resonance imaging in women with BRCAm and intact ovaries (BRCA-preBSO [study cohort with BRCA mutation prior to oophorectomy]; n = 9) and after surgery with (BSO + estradiol-based therapy [ERT]; n = 10) and without (BSO; n = 10) postsurgical estradiol hormone therapy compared with age-matched women (age-matched controls; n = 10) with their ovaries.

Results: The BRCA-preBSO and BSO groups showed significantly lower GM volume in the left medial temporal and frontal lobe structures. BSO + ERT exhibited few areas of lower GM volume compared with age-matched controls. Novel to this study, we also observed that all three BRCAm groups exhibited significantly higher GM volume compared with age-matched controls, suggesting continued plasticity.

Conclusions: The present study provides evidence, through lower GM volume, 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, postsurgical ERT seems to ameliorate GM losses.

有 BRCA 基因突变并切除或未切除卵巢的妇女的灰质体积:晚年阿尔茨海默病或痴呆症风险增加的证据。
目的:在自发/自然绝经(SM)之前切除卵巢与包括阿尔茨海默病在内的晚期痴呆症风险增加有关。这种风险的增加可能与内源性雌二醇的突然和过早丧失有关。建议乳腺癌基因突变(BRCAm)的女性在绝经前接受输卵管切除术,以显著降低患乳腺癌、卵巢癌和宫颈癌的风险。关于在 SM 年龄之前切除卵巢对神经系统影响的有限证据显示,没有 BRCAm 的女性颞叶内侧结构的皮质变薄。另一项针对 BRCAm 和双侧输卵管卵巢切除术(BSO)女性的研究则发现了认知能力的变化:本横断面研究使用高分辨率定量磁共振成像检查了 BRCAm 和卵巢完好女性(BRCA-preBSO [卵巢切除术前 BRCA 基因突变的研究队列],n = 9)的全脑灰质(GM)体积差异;n = 9)、术后接受(BSO + 雌二醇疗法 [ERT];n = 10)和不接受(BSO;n = 10)术后雌二醇激素疗法的女性与卵巢完整的年龄匹配女性(年龄匹配对照组;n = 10)进行比较。结果:BRCA-preBSO组和BSO组的左侧内侧颞叶和额叶结构的GM体积明显较低。与年龄匹配的对照组相比,BSO + ERT 组的 GM 体积较小。与本研究不同的是,我们还观察到,与年龄匹配的对照组相比,所有三个 BRCAm 组的 GM 体积都明显增大,这表明可塑性仍在继续:本研究通过较低的基因组容积提供了证据,支持 BRCAm(单独)和早年 BSO 可能在增加晚年痴呆症风险方面发挥作用的可能性。至少对于伴有 BSO 的 BRCAm 患者来说,手术后的 ERT 似乎可以改善 GM 的损失。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.40
自引率
7.40%
发文量
330
审稿时长
3-8 weeks
期刊介绍: ​Menopause, published monthly, provides a forum for new research, applied basic science, and clinical guidelines on all aspects of menopause. The scope and usefulness of the journal extend beyond gynecology, encompassing many varied biomedical areas, including internal medicine, family practice, medical subspecialties such as cardiology and geriatrics, epidemiology, pathology, sociology, psychology, anthropology, and pharmacology. This forum is essential to help integrate these areas, highlight needs for future research, and enhance health care.
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