Prevention of Alzheimer's disease in women: risks and benefits of hormone therapy

预防女性阿尔茨海默病：激素治疗的风险和益处

基本信息

批准号：
9422848
负责人：
CAREY E GLEASON
金额：
$ 1063.89万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9422848
关键词：
Address Age Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease risk Amyloid beta-Protein Attention Auditory Benefits and Risks Biological Biological Markers Blinded Blood Vessels Brain Cerebrovascular Disorders Clinical Trials Cognition Cognitive Conjugated Equine Estrogens Data Decision Making Dementia Doctor of Philosophy Early Diagnosis Early treatment Elderly Enrollment Epidemic Estradiol Estrogen Therapy Estrogens Exposure to Formulation Functional disorder Funding Funding Opportunities Genotype Health Hormone use Image Impaired cognition Knowledge Language Life Expectancy Long-Term Effects Magnetic Resonance Imaging Measures Memory Menopausal Symptom Menopause Menstruation Modeling Moods Nerve Degeneration Nervous System Physiology Neurons Oral Outcome Participant Pathology Pharmaceutical Preparations Placebos Population Study Positioning Attribute Positron-Emission Tomography Postmenopause Premature Menopause Prevention Prevention strategy Preventive Intervention Publishing Randomized Research Risk Risk Factors Safety Scientific Advances and Accomplishments Short-Term Memory Site Social Impacts Societies Speed Structure TNFRSF5 gene Time United States National Institutes of Health Verbal Learning Visual attention White Matter Disease White Matter Hyperintensity Woman Women&apos s Health abeta deposition brain volume cerebrovascular cerebrovascular lesion clinical practice cognitive change cognitive performance disorder prevention economic impact economic implication flexibility follow-up hormone therapy imaging biomarker insight men middle age mild cognitive impairment non-invasive imaging older women prevent primary outcome rate of change risk variant social implication

项目摘要

PROJECT SUMMARY / ABSTRACT With the growing social and economic impact of dementia on the society, the emphasis is shifting from early diagnosis and treatment to the prevention of cognitive impairment and dementia. The social and economic implications of this epidemic will be greatest in women because of their longer life expectancy and elevated risk for dementia compared to men. Neuroprotective effects of estrogens offer the possibility of preventing or delaying mild cognitive impairment and dementia in postmenopausal women. However, oral conjugated equine estrogen treatment in older women who were more than a decade past their menopause did not prevent dementia, and there is controversy as to whether or not estrogen can preserve neurological function and decrease the risk of dementia when administered early in menopause defined as the “critical window”. This project is proposed as a continuation to the Kronos Early Estrogen Prevention Study (KEEPS), a nationwide, multi-center, randomized blinded study of menopausal hormone therapy in newly postmenopausal women. Our objective is to assess the long-term risks and benefits of menopausal hormone therapy on Alzheimer's disease pathophysiology, cerebrovascular lesion load, cognitive and mood health in women who were treated with transdermal 17β-estradiol and oral conjugated equine estrogen compared to placebo within 36 months of their last menses; hypothesized as the “critical window“ for menopausal hormone therapy. Furthermore, we will investigate whether the Alzheimer's disease risk allele APOE ε4 and vascular risk factors influence the differences in Aβ deposition, brain structure, and cognition between each of the menopausal hormone therapy formulations and placebo, in order to provide insight into the mechanisms of cognitive and imaging biomarker changes associated with early menopausal hormone therapy. This project addresses an important and controversial problem regarding whether two commonly-used formulations of menopausal hormone therapy, administered during immediate postmenopausal years preserves cognition, neuronal integrity, and protects against cerebrovascular and Alzheimer's disease-related pathology. It is expected that the findings will hold the premise to significantly advance scientific knowledge and clinical practice by providing insight into the effects of early menopausal hormone therapy on long-term cognitive health.

项目概要/摘要随着痴呆症对社会和经济的影响日益加大，人们的关注重点已从早期诊断和治疗可预防认知障碍和痴呆。这种流行病对女性的经济影响最大，因为她们的预期寿命较长与男性相比，雌激素的神经保护作用增加了患痴呆症的风险。预防或延缓绝经后妇女的轻度认知障碍和痴呆。对十多岁的老年妇女进行口服结合马雌激素治疗更年期并不能预防痴呆症，关于雌激素是否可以预防痴呆症存在争议在更年期早期服用时，可以改善神经功能并降低痴呆症的风险，定义为该项目被提议作为 Kronos 早期雌激素预防的延续。研究 (KEEPS)，一项针对绝经期激素治疗的全国性、多中心、随机盲法研究我们的目标是评估绝经后的长期风险和益处。激素治疗对阿尔茨海默病病理生理学、脑血管病变负荷、认知和功能的影响接受透皮 17β-雌二醇和口服结合马烯治疗的女性的情绪健康状况末次月经后 36 个月内使用雌激素与安慰剂进行比较；此外，我们将调查更年期激素治疗是否有患阿尔茨海默病的风险。等位基因 APOE ε4 和血管危险因素影响 Aβ 沉积、大脑结构和每种更年期激素治疗制剂和安慰剂之间的认知，以便提供深入了解与早期相关的认知和影像生物标志物变化的机制该项目解决了一个重要且有争议的问题。两种常用的绝经期激素治疗配方是否在立即给药绝经后几年可以保留认知、神经元完整性，并预防脑血管和预计这些发现将为阿尔茨海默病相关病理学提供显着的前提。通过提供对早期更年期影响的深入了解，科学知识和临床实践激素疗法对长期认知健康的影响。