Impact of menopause associated adrenal aging on cognitive function and Alzheimer dementia neuroimaging biomarkers
更年期相关肾上腺老化对认知功能和阿尔茨海默氏痴呆神经影像生物标志物的影响
基本信息
- 批准号:10558589
- 负责人:
- 金额:$ 15.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AccelerationAdrenal GlandsAffectAgeAgingAlzheimer&aposs DiseaseAndrogensBilateralBiological AssayBiological MarkersBloodBrainBrain imagingCardiovascular DiseasesCenters of Research ExcellenceClinicDataDevelopmentDexamethasoneEndocrineEnvironmentEpigenetic ProcessGeneticGlucocorticoidsHormonalHydrocortisoneImpaired cognitionImpairmentInflammationMachine LearningMeasuresMenopauseMorbidity - disease rateOperative Surgical ProceduresOutcomeOvarian hormonePostmenopauseProcessRecording of previous eventsReportingResearchSalivarySalpingo-OophorectomySex DifferencesShort-Term MemorySpecialized CenterSteroidsStructureTechniquesTissuesUrineWomancerebral atrophycognitive changecognitive functioncognitive performanceexecutive functionexperiencehippocampal atrophyhypothalamic-pituitary-adrenal axisinsightmenmetabolomemortalityneuroimaging markernovelprematureprocessing speed
项目摘要
PROJECT SUMMARY
Aging is associated with both physical and cognitive decline. Endocrine-wise, impairment in the hypothalamic-
pituitary-adrenal axis has been reported, including elevated diurnal cortisol concentrations, abnormal
suppression of cortisol following dexamethasone administration, and increased salivary cortisol. Previous
studies reported association between higher cortisol concentrations and poor overall cognitive performance
and structural changes in the brain, with cortical and hippocampal atrophy, as well as Alzheimer Disease (AD)
development. However, these studies used suboptimal assessment of adrenal steroid metabolome, mainly
concentrating on cortisol (only 1% of steroid metabolome). As we show in our preliminary data, steroid
metabolome (as assessed by a novel steroid profiling assay) changes with age, differentially in women versus
men, with decreased androgens and increased glucocorticoid metabolites, increasing with age
glucocorticoid/androgen ratio, and steroid ratio changes suggestive of increased tissue exposure of cortisol.
Previous studies reported that menopause accelerates epigenetic aging of blood, and that later age of natural
menopause is associated with decreased mortality. Women undergoing bilateral salpingo-oophorectomy
(BSO) prior to the age of natural menopause experience a higher degree of accelerated aging with increased
rates of multiple morbidities, most notably cardiovascular disease, cognitive decline, and increased mortality.
As shown in our preliminary data, most significant change in steroid metabolome occurs in women after
menopause. We further show that abnormal steroid metabolome in menopausal women is associated with
decline in executive function, processing speed, and working memory. In our proposed research, our
hypothesis is that adrenal aging (as measured by the 24h urine steroid metabolome) is accelerated with
menopause; BSO accelerates adrenal aging which, in turn, impacts cognitive function and brain structures. In
our proposed research, we will take advantage of the ongoing study in the Mayo Clinic Specialized Center of
Research Excellence (SCORE) on sex differences to assess how abrupt loss of ovarian hormones caused by
BSO affects adrenal aging (Aim 1). In addition, through a machine learning analysis, we propose to determine
whether abnormal steroid metabolome is associated with cognitive decline and AD structural changes on brain
imaging (Aim 2).
This project will deliver the insight into BSO-related changes in steroid metabolome and will estimate the
impact of adrenal aging on cognitive changes and structural changes of AD on brain imaging. A specific steroid
signature will be identified to potentially serve as biomarker of aging and cognitive decline.
项目摘要
衰老与身体和认知能力的下降有关。内分泌方面,下丘脑受损-
垂体-肾上腺轴已报告,包括昼夜皮质醇浓度升高,异常
地塞米松给药后皮质醇抑制和唾液皮质醇增加。先前
研究报告称,皮质醇浓度较高与整体认知能力较差有关
和脑结构变化,皮质和海马萎缩,以及阿尔茨海默病(AD)
发展然而,这些研究使用了肾上腺类固醇代谢组的次优评估,主要
集中于皮质醇(仅占类固醇代谢组的1%)。正如我们在初步数据中显示的那样,类固醇
代谢组(通过一种新的类固醇分析法评估)随年龄变化,女性与
男性,雄激素减少,糖皮质激素代谢产物增加,随年龄增长而增加
糖皮质激素/雄激素比率和类固醇比率的变化提示皮质醇的组织暴露增加。
以前的研究报告说,更年期加速了血液的表观遗传老化,
绝经与死亡率降低有关。接受双侧输卵管卵巢切除术的女性
(BSO)在自然绝经年龄之前经历更高程度的加速衰老,
多发病率,最明显的心血管疾病,认知能力下降,死亡率增加。
正如我们的初步数据所示,类固醇代谢组的最显著变化发生在女性中,
绝经我们进一步表明,绝经期妇女类固醇代谢组异常与
执行功能、处理速度和工作记忆下降。在我们的研究中,我们
假设肾上腺老化(通过24小时尿类固醇代谢组测定)加速,
绝经期; BSO加速肾上腺老化,这反过来会影响认知功能和大脑结构。在
我们的研究计划,我们将利用正在进行的研究,在马约诊所专业中心,
卓越研究(SCORE)的性别差异,以评估如何突然失去卵巢激素造成的
BSO影响肾上腺老化(目的1)。此外,通过机器学习分析,我们建议确定
类固醇代谢组异常是否与认知功能下降和AD脑结构改变有关
成像(Aim 2)。
该项目将深入了解BSO相关的类固醇代谢组学变化,并将估计
肾上腺老化对AD认知功能改变和脑影像结构改变的影响。一种特殊的类固醇
将鉴定标记以潜在地用作衰老和认知衰退生物标志物。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Irina Bancos其他文献
Irina Bancos的其他文献
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{{ truncateString('Irina Bancos', 18)}}的其他基金
Impact of abnormal steroid metabolome on cellular senescence, frailty and cognition
类固醇代谢异常对细胞衰老、虚弱和认知的影响
- 批准号:
10586100 - 财政年份:2022
- 资助金额:
$ 15.44万 - 项目类别:
Impact of abnormal steroid metabolome on cellular senescence, frailty and cognition
类固醇代谢异常对细胞衰老、虚弱和认知的影响
- 批准号:
10425564 - 财政年份:2022
- 资助金额:
$ 15.44万 - 项目类别:
Impact of menopause associated adrenal aging on cognitive function and Alzheimer dementia neuroimaging biomarkers
更年期相关肾上腺老化对认知功能和阿尔茨海默氏痴呆神经影像生物标志物的影响
- 批准号:
10371283 - 财政年份:2022
- 资助金额:
$ 15.44万 - 项目类别:
Skeletal Consequences of Mild Autonomous Cortisol Secretion
轻度自主皮质醇分泌对骨骼的影响
- 批准号:
9803313 - 财政年份:2019
- 资助金额:
$ 15.44万 - 项目类别:
Skeletal Consequences of Mild Autonomous Cortisol Secretion
轻度自主皮质醇分泌对骨骼的影响
- 批准号:
10160897 - 财政年份:2019
- 资助金额:
$ 15.44万 - 项目类别:
Skeletal Consequences of Mild Autonomous Cortisol Secretion
轻度自主皮质醇分泌对骨骼的影响
- 批准号:
10405659 - 财政年份:2019
- 资助金额:
$ 15.44万 - 项目类别:
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