Reproductive risk factors for Alzheimer's disease dementia and pathology

阿尔茨海默氏病痴呆的生殖危险因素和病理学

• 批准号: 9250532
• 负责人: Michelle M Mielke
• 金额: $ 397.5万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9250532
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Attention; Bilateral oophorectomy; Brain; Brain Pathology; Brain imaging; Cardiovascular Diseases; Child; Clinic; Clinical; Clinical Trials; Cognition; Cognitive; Comorbidity; Confounding Factors (Epidemiology); Data; Dementia; Development; Diagnosis; Dose; Enrollment; Epidemiology; Exposure to; Future; Genotype; Goals; Gonadal Steroid Hormones; Gynecologic Surgical Procedures; High Prevalence; Hormonal; Hormonal Change; Impaired cognition; Individual; Infarction; Language; Lesion; Literature; Long-Term Effects; Longevity; Magnetic Resonance Imaging; Measures; Medical; Medical Record Linkage; Memory; Menarche; Menopause; Multimodal Imaging; Nerve Degeneration; Observational Study; Operative Surgical Procedures; Pathology; Performance; Population Study; Positron-Emission Tomography; Pre-Eclampsia; Pregnancy; Premature Menopause; Recording of previous events; Research; Research Infrastructure; Risk; Risk Factors; Severities; Sex Characteristics; Structure; System; Testing; Thick; United States National Institutes of Health; Visuospatial; White Matter Hyperintensity; Woman; aging brain; brain morphology; brain size; brain volume; cerebrovascular; cognitive function; disorder subtype; fluorodeoxyglucose positron emission tomography; gray matter; hormone therapy; imaging study; indexing; men; mild cognitive impairment; neuroimaging; pregnancy disorder; processing speed; reproductive; sex; white matter

PROJECT SUMMARY/ABSTRACT Recent estimates suggest that almost two-thirds of the individuals diagnosed with Alzheimer’s disease [AD] are women. The National Institutes of Health and the Alzheimer’s Association have highlighted the critical need to understand sex differences in the risk factors and clinical progression of AD. Reproductive and hormonal factors may be particularly important for women. Hypertensive pregnancy disorders [HPD] have been associated with subjective cognitive complaints or white matter lesions five to ten years after the HPD, but the long-term effects of HPD on brain structure and cognitive function are unknown. Population-based studies are needed to assess the contribution of HPD and subtype (i.e., preeclampsia) to the risk of cognitive decline, AD, and neuroimaging measures of amyloid-beta [Aβ], neurodegeneration, and cerebrovascular pathologies. Further, observational studies and clinical trials have examined the effects of early menopause (natural or surgically-induced) and hormonal therapy [HT] on the risk of AD and other dementias. However, it is not currently known whether the effects of early menopause, HT use, and their interactions with APOE genotype, are associated with specific type(s) of brain pathology (i.e., Aβ, neurodegeneration, cerebrovascular) because multi-modal imaging studies have not been conducted. The overall aims of this proposal are to elucidate the impact of two hormonally-related sex-specific factors for women, pregnancy (e.g., number of pregnancies, HPD) and menopause (surgically-induced or natural), on the risk of cognitive decline, AD, and neuroimaging measures of Aβ, neurodegeneration, and cerebrovascular pathologies. Because the literature and our preliminary data suggest that risk scores for cardiovascular disease and dementia are less predictive in women compared to men, we also propose to incorporate these sex-specific factors to develop a more predictive risk score of mild cognitive impairment and AD for women. To accomplish our goals, we will utilize two existing infrastructures at the Mayo Clinic: the Mayo Clinic Study of Aging (MCSA; U01 AG006786) and the Rochester Epidemiology Project medical records-linkage system (REP; R01 AG034676). Using the REP, we will newly abstract information on pregnancy and menopause for 2,370 women enrolled in the MCSA. Because few studies assessing pregnancy and menopause have also adjusted for putative confounding variables, we will also abstract this data using the REP to determine whether these sex-specific conditions are independent predictors of cognitive decline, AD, and neuroimaging measures of specific brain pathologies. Successful completion of these aims will be a key step towards understanding whether these sex-specific factors are associated with the risk of AD in women, to understanding whether these factors are related to a specific type of brain pathology (i.e., Aβ, neurodegeneration, cerebrovascular), and to developing a better risk score for predicting cognitive impairment, dementia, and specific brain changes in women.

项目摘要/摘要 最近的估计表明，被诊断为阿尔茨海默氏病的人中，几乎三分之二[AD] 是妇女。 了解危险因素和临床程序的繁殖和荷尔蒙的程序进展 因素对女性尤为重要。 与主观认知投诉或白质病变相关，五十个十个toter hpd，但你 HPD对大脑结构和认知功能的长期影响尚不清楚 需要评估HPD和亚型（即先兆子痫）对认知能力下降的风险，AD，AD，， 淀粉样蛋白β[Aβ]，神经退行性变性和脑血管病理的神经影像学测量。 此外，观察性研究和临床试验已经检查了更年期早期的影响（自然或 /或 手术引起的）和荷尔蒙治疗[HT]关于AD其他痴呆症的风险。 目前知道更年期，HT使用以及与ApoE基因型的相互作用的影响， 与脑病理学的特定类型有关（即Aβ，神经变性，脑血管） 多模式成像研究尚未进行。 两种与荷尔蒙相关的性别因素对妇女的影响，怀孕（例如，怀孕人数， HPD）和更年期（外科手术引起或自然），就认知能力下降，AD和神经影像的风险 Aβ，神经退行性的度量和脑血管病理。 初步数据表明，女性的心血管疾病和痴呆的风险评分较低 与男性相比，我们还建议将这些特定的因素合并为发展更具预测性的风险 为了实现我们的目标的轻度认知障碍和广告的得分。 Mayo诊所的基础设施：梅奥诊所的衰老研究（MCSA； U01 AG006786）和Rochester 流行病学项目医疗记录连接系统（REP; R01 AG034676）。 MCSA入学的2370名妇女的怀孕和更年期的抽象信息 评估怀孕和更年期的研究还针对推定的混杂变量进行了调整，我们将 还要抽象使用以确定这些特定条件是否独立的数据 认知能力下降，AD和神经影像学指标的预测因素。 目标的压缩将是Tewing的关键步骤，这些特定因素是否是 与妇女的广告风险相关，以了解与特定类型有关的因素 大脑病理学（即Aβ，神经退行性，脑血管），并为更高的风险评分增长 预测女性的认知障碍，痴呆症和特定的大脑变化。