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

项目2 - 双侧卵巢切除术研究阿尔茨海默病和脑血管疾病的影像生物标志物

• 批准号: 10414014
• 负责人: KEJAL KANTARCI
• 金额: $ 39.54万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10414014
• 关键词: Address; Age; Aging; Alzheimer associated neurodegeneration; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Apolipoprotein E; Atrophic; Bilateral; Bilateral oophorectomy; Cerebrovascular Disorders; Cognitive; Dementia; Diffuse; Doctor of Medicine; Endocrine disruption; Enrollment; Etiology; Evaluation; Functional disorder; Genotype; Goals; Healthcare; Hormonal; Image; Impaired cognition; Lesion; Life Expectancy; Long-Term Effects; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Medial; Menopause; Outcome; Ovarian; Ovarian hormone; Ovary; Pathology; Perfusion; Pittsburgh Compound-B; Positron-Emission Tomography; Premenopause; Prophylactic treatment; Recording of previous events; Research; Risk; Salpingo-Oophorectomy; Sampling; Temporal Lobe; Testing; Time; Woman; cerebrovascular pathology; cognitive function; cognitive testing; cohort; dementia risk; early detection biomarkers; economic implication; follow-up; imaging biomarker; insight; men; middle age; multiple chronic conditions; nervous system disorder; neuroimaging marker; non-invasive imaging; population based; primary outcome; sex; social implication; tau Proteins; uptake; white matter

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.

项目2：总结/摘要Kejal Kantarci，M.D. 痴呆症的社会和经济影响在女性中最大，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升高。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基因型修饰。妇女 在绝经前接受双侧输卵管卵巢切除术（BSO）的女性， 多吗啡的积累，与衰老相关的神经系统疾病的风险增加，包括 痴呆双侧输卵管卵巢切除术（BSO）如何影响痴呆症的风险仍不清楚， 因为据估计，八分之一的美国妇女切除了卵巢， 才能达到自然绝经期导致认知障碍的最常见病理 和痴呆症的女性是阿尔茨海默病（AD）和脑血管疾病（CVD）。确定 绝经前BSO对痴呆风险的影响需要几十年的随访;或者， 非侵入性成像生物标志物可以潜在地评估卵巢激素突然丧失对 在较短的时间内降低AD和CVD病理的风险。我们在项目2中的目标是了解 在接受BSO的女性中，卵巢激素突然中断对AD和CVD病理生理的影响 通过生物标记物成像。我们将招募100名BSO女性和100名推荐人 这些妇女将从一个特征明确的、以人口为基础的群体中选出。我们假设 AD和CVD病理生理学的成像生物标志物在接受过治疗的女性中会更异常， 绝经前BSO，与年龄匹配的女性对照队列相比， 绝经前BSO，这种差异是由APOE ε4调节的。我们将进一步调查 成像生物标志物与项目1中测量的认知结果的关系。 拟议的研究将解决这个问题，通过应用最先进的成像和认知测试，在一个 以人口为基础的妇女群体。评估这一样本的妇女，其中年历史， 绝经前BSO的特点很好，提供了一个独特的机会，以澄清的长期影响， 通过影像学生物标志物研究卵巢激素突然中断对认知能力下降和痴呆风险的影响 早期病理学对于考虑使用BSO预防癌症的女性来说，这些发现将提供关键的 洞察力，指导他们的医疗决策。