Project 2 - Bilateral Oophorectomy on Imaging Biomarkers of Alzheimer's and Cerebrovascular Diseases

项目2：摘要/摘要Kejal Kantarci，医学博士。 痴呆症对社会和经济的影响对女性的影响最大，因为她们的寿命更长 与男性相比，预期和由此导致的痴呆症风险增加。女性患痴呆症的风险可能是， 部分受卵巢激素调节，并受载脂蛋白E(ApoE)ε4基因修饰。女人 在绝经开始前接受双侧输卵管卵巢切除术(BSO)的患者有加速 多发病累积，与衰老有关的神经系统疾病风险增加，包括 痴呆症。目前尚不清楚双侧输卵管卵巢切除术(BSO)如何影响痴呆症的风险，但 需要解决的问题，因为据估计，每八名美国女性中就有一人切除卵巢 在达到自然更年期之前。导致认知障碍的最常见的病理因素 女性的痴呆症是阿尔茨海默病(AD)和脑血管疾病(CVD)。确定 绝经前服用BSO对痴呆症风险的影响需要数十年的随访；或者， 非侵入性成像生物标记物可以潜在地评估卵巢激素突然丧失对 在较短的时间内发生AD和CVD的风险。我们在项目2中的目标是了解 卵巢激素突然阻断对BSO患者AD和CVD病理生理的影响 在到达更年期之前通过成像生物标记物。我们将招收100名女性BSO和100名推荐人 妇女将从特征良好和以人口为基础的队列中挑选出来。我们假设 AD和CVD病理生理的成像生物标记物在接受 绝经前的BSO与年龄匹配的未绝经女性的参照组比较 这种差异是由载脂蛋白ε4调节的。我们将进一步研究 成像生物标志物与项目1中测量的认知结果的关系。 拟议的研究将通过将最先进的成像和认知测试应用于 以人口为基础的女性队列。对这一样本女性的评估，她们的中年病史 绝经前BSO的特点很好，提供了一个独特的机会来阐明长期影响 通过成像生物标志物研究卵巢激素突然紊乱对认知功能减退和痴呆风险的影响 早期病理学的特征。对于考虑将BSO用于癌症预防的女性来说，这一发现将提供关键的 洞察力，指导他们的医疗保健决策。

PROJECT 2: SUMMARY/ABSTRACT Kejal Kantarci, M.D. The social and economic implications of dementia will be greatest in women because of their longer life expectancy and resulting elevated risk for dementia compared to men. This risk of dementia in women may be, in part, modulated by ovarian hormones and modified by the apolipoprotein E (APOE) ε4 genotype. Women who undergo bilateral salpingo-oophorectomy (BSO) before the onset of menopause have an accelerated accumulation of multimorbidity, with an increased risk of aging-related neurological diseases including dementia. How bilateral salpingo-oophorectomy (BSO) influences the risk of dementia remains unknown, but needs to be addressed, because it is estimated that one in eight U.S. women have their ovaries removed before reaching natural menopause. The most common pathologies that contribute to cognitive impairment and dementia in women are Alzheimer's disease (AD) and cerebrovascular disease (CVD). Determining the effects of BSO before menopause on the risk of dementia would require decades of follow-up; alternatively, non-invasive imaging biomarkers can potentially assess the effects of an abrupt loss of ovarian hormones on the risk of AD and CVD pathologies in a shorter time frame. Our goal in Project 2 is to understand the effects of abrupt disruption of ovarian hormones on AD and CVD pathophysiology in women who underwent BSO before reaching menopause through imaging biomarkers. We will enroll 100 women with BSO and 100 referent women that will be drawn from a well-characterized and established population-based cohort. We hypothesize that imaging biomarkers of AD and CVD pathophysiology will be more abnormal in women who underwent BSO before reaching menopause, compared to an age-matched referent cohort of women who did not undergo premenopausal BSO, and that this difference is modulated by APOE ε4. We will further investigate the relationship of imaging biomarkers with cognitive outcomes as measured in Project 1.The results of the proposed research will address this problem by applying state-of-the art imaging and cognitive testing in a population-based cohort of women. Evaluation of this sample of women, whose midlife history of premenopausal BSO is well-characterized, provides a unique opportunity to clarify the long-term effects of abrupt ovarian hormonal disruption on the risk of cognitive decline and dementia through imaging biomarkers of early pathology. For women considering BSO for cancer prophylaxis, the findings will provide critical insights, guiding their health care decisions.