Admin Supplement - Prevention of Alzheimer's disease in women: risks and benefits of hormone therapy
管理补充 - 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:10163429
- 负责人:
- 金额:$ 41.56万
- 依托单位:
- 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:
- 关键词:AffectAge of OnsetAgingAlkanesulfonatesAllelesAlzheimer disease preventionAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease riskAlzheimer&aposs disease therapyAmyloid beta-ProteinAromataseBenefits and RisksBiological AvailabilityBiologyBloodBlood VesselsBrainCYP1A2 geneCYP3A4 geneCYP3A5 geneCause of DeathClinical TrialsCognitionCognitiveCognitive agingCohort StudiesConjugated Equine EstrogensDataDementiaDiseaseDoseDouble-Blind MethodDrug KineticsESR1 geneESR2 geneEnrollmentEnzymesEstradiolEstrogen MetabolismEstrogen ReceptorsEstrogen TherapyEstrogensEtiologyExogenous Hormone TherapyFormulationGRIP1 geneGenesGenetic VariationGenotypeGoalsGrantHealthHealthcareHepatocyteHormone useHormonesHot flushesIndividualInterventionLeadLesionLinkMagnetic Resonance ImagingMeasuresMemoryMenopausal SymptomMenopauseMetabolismMoodsNCOA1 geneNeurologicNeurologic SymptomsNight SweatingOralOutcomeOvarian agingPathologicPathway interactionsPerimenopausePharmacodynamicsPlacebo EffectPlacebosPositron-Emission TomographyPostmenopausePreventionProteinsRandomizedRandomized Clinical TrialsReportingSafetySeveritiesSignal PathwaySignal TransductionSleep disturbancesSleeplessnessSourceStructureSulfateTREM2 geneThickUGT1A1 geneVariantWhite Matter HyperintensityWomanWomen&aposs Healthabeta depositionage relatedapolipoprotein E-4associated symptombasecognitive performanceenzyme activityestrogen sulfateexposure routegenetic analysisgenetic varianthormone therapyimaging biomarkerindividual variationindividualized medicineinsightolder womenpersonalized medicinepharmacokinetics and pharmacodynamicsphysical symptomprotein functionreceptorresponseresponse biomarkersulfotransferaseyoung woman
项目摘要
ABSTRACT
The use of exogenous hormones to treat the neurological symptoms associated with menopause as well as
diseases of aging such as Alzheimer's disease (AD) is controversial. This controversy arose from several
clinical trials including the Women's Health Initiative (WHI) memory study (WHIMS), the WHI study of cognitive
aging (WHISCA), the WHI study of memory in younger women (WHIMSY), Early vs Late Intervention
Treatment with Estrogen (ELITE) where menopausal hormone therapy (HT) either did not prevent dementia, or
increased dementia and adverse cognitive effects. Collectively, these results of these studies suggest that HT
may be effective if used within a critical window around menopause but not in in older women. The type of MT
and route of exposure (i.e. oral conjugated equine estrogen [oCEE] vs. transdermal E2 [tE2]) are also important
and studies such as the Kronos Early Estrogen Prevention Study (KEEPS), a double blind randomized clinical
trial, have investigated effects of these MT on cognitive when given within 3 years of the onset of menopause.
Variation in responses to HT may be related to pharmacokinetics and bioavailability associated with
administering an exogenous estrogen. For example, in the KEEPS cohort, genetic variants of two genes
encoding two different proteins involved in estrogen metabolism and transport i.e. SULTA1 and SLCO1B1
respectively, were associated with severity of menopausal hot flashes. In this supplemental grant, the goal is to
investigate genetic variation in women in the KEEPS continuation study, which aims to investigate the effects
of HT and any correlations to AD, thirteen years after the administration of HT. The genetic analysis will be
expanded to include additional genes involved in estrogen pharmacokinetics, as well as those encoding
proteins involved in estrogen signaling/pharmacodynamic pathways, which may impact response to hormone
therapy in relation to cognition and brain structure and function. The results from this study will lead to a better
understanding of the impact of genetic variation in estrogen pharmacokinetic and pharmacodynamic pathways,
provide insight to the controversy of HT for AD therapy, and lead the way to developing individualized
treatment approaches to AD.
摘要
项目成果
期刊论文数量(1)
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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CAREY E GLEASON其他文献
CAREY E GLEASON的其他文献
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{{ truncateString('CAREY E GLEASON', 18)}}的其他基金
Addressing Alzheimer's Disease and Related Dementias Disparities: The American Indigenous Cognitive Assessment (AMICA) Project
解决阿尔茨海默病和相关痴呆症的差异:美国土著认知评估 (AMICA) 项目
- 批准号:
10623223 - 财政年份:2022
- 资助金额:
$ 41.56万 - 项目类别:
Addressing Alzheimer's Disease and Related Dementias Disparities: The American Indigenous Cognitive Assessment (AMICA) Project
解决阿尔茨海默病和相关痴呆症的差异:美国土著认知评估 (AMICA) 项目
- 批准号:
10447514 - 财政年份:2022
- 资助金额:
$ 41.56万 - 项目类别:
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
- 批准号:
9422848 - 财政年份:2017
- 资助金额:
$ 41.56万 - 项目类别:
African AMERICANS Fighting Alzheimer's In Midlife
非裔美国人在中年时期与阿尔茨海默氏症作斗争
- 批准号:
10198394 - 财政年份:2016
- 资助金额:
$ 41.56万 - 项目类别:
African Americans Fighting Alzheimer’s in Midlife (AA-FAIM)
非裔美国人中年抗击阿尔茨海默病 (AA-FAIM)
- 批准号:
10589654 - 财政年份:2016
- 资助金额:
$ 41.56万 - 项目类别:
African AMERICANS Fighting Alzheimer's In Midlife
非裔美国人在中年时期与阿尔茨海默氏症作斗争
- 批准号:
9476898 - 财政年份:2016
- 资助金额:
$ 41.56万 - 项目类别:
African AMERICANS Fighting Alzheimer's In Midlife
非裔美国人在中年时期与阿尔茨海默氏症作斗争
- 批准号:
9913432 - 财政年份:2016
- 资助金额:
$ 41.56万 - 项目类别:
Alzheimer's Disease: Potential Benefit of Isoflavones
阿尔茨海默病:异黄酮的潜在益处
- 批准号:
7472379 - 财政年份:2004
- 资助金额:
$ 41.56万 - 项目类别:
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