PDF(Pubmed)
Abstract：
BACKGROUND: Females represent approximately 70% of the Alzheimer\'s disease (AD) cases and the literature has proposed a connection between the decreased estrogen levels during menopause and an increased AD risk. Previous investigations have predominantly focused on assessing how hormone therapy (HT) affects the likelihood of AD development and cognitive deterioration. However, as the research framework has shifted toward a biomarker-defined AD and alterations in specific biomarkers could take place years before cognitive decline becomes discernible, it is crucial to examine how HT influences AD biomarkers. The main goal of this study was to evaluate the impact of HT on AD biomarker-informed pathophysiology in both cognitively unimpaired (CU) and cognitively impaired (CI) post-menopausal females across the aging and AD spectrum.
METHODS: This cross-sectional study included post-menopausal females without HT history (HT-) and with HT (HT+) at the time of PET imaging assessment from two cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, and the Alzheimer\'s Disease Neuroimaging Initiative (ADNI). Participants underwent magnetic resonance imaging (MRI), positron emission tomography (PET) and biofluid collection. Voxel-based t-tests were performed to assess the differences in amyloid-β (Aβ) and tau neurofibrillary tangles (NFTs) loads between HT- and HT + females. Linear regression models with interaction terms were also conducted to examine the interactive effects of HT and Aβ-PET on regional tau-PET.
RESULTS: HT + females demonstrated significantly lower tau-PET standardized uptake value ratio (SUVR) in Braak I-II ROIs (P < 0.05, Hedges\' g = 0.73), Braak III-IV ROIs (P < 0.0001, Hedges\' g = 0.74) and Braak V-VI ROIs (P < 0.0001, Hedges\' g = 0.69) compared to HT- females. HT + females also showed significantly lower CSF p-tau181 (P < 0.001) and plasma p-tau181 (P < 0.0001) concentrations. Additionally, results from multivariate linear regression models indicated that HT interacts with cortical Aβ and is associated with lower regional NFT load.
CONCLUSIONS: Overall, findings from this observational study suggest that HT is associated with lower tau neuroimaging and fluid biomarkers in postmenopausal females. Due to the close link between tau and cognition, this study highlights the need for large randomized controlled trials designed to systemically study the influences of HT on AD biomarkers and disease progression.
METHODS: This cross-sectional study included post-menopausal females without HT history (HT-) and with HT (HT+) at the time of PET imaging assessment from two cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, and the Alzheimer\'s Disease Neuroimaging Initiative (ADNI). Participants underwent magnetic resonance imaging (MRI), positron emission tomography (PET) and biofluid collection. Voxel-based t-tests were performed to assess the differences in amyloid-β (Aβ) and tau neurofibrillary tangles (NFTs) loads between HT- and HT + females. Linear regression models with interaction terms were also conducted to examine the interactive effects of HT and Aβ-PET on regional tau-PET.
RESULTS: HT + females demonstrated significantly lower tau-PET standardized uptake value ratio (SUVR) in Braak I-II ROIs (P < 0.05, Hedges\' g = 0.73), Braak III-IV ROIs (P < 0.0001, Hedges\' g = 0.74) and Braak V-VI ROIs (P < 0.0001, Hedges\' g = 0.69) compared to HT- females. HT + females also showed significantly lower CSF p-tau181 (P < 0.001) and plasma p-tau181 (P < 0.0001) concentrations. Additionally, results from multivariate linear regression models indicated that HT interacts with cortical Aβ and is associated with lower regional NFT load.
CONCLUSIONS: Overall, findings from this observational study suggest that HT is associated with lower tau neuroimaging and fluid biomarkers in postmenopausal females. Due to the close link between tau and cognition, this study highlights the need for large randomized controlled trials designed to systemically study the influences of HT on AD biomarkers and disease progression.
摘要：
背景：女性约占阿尔茨海默病（AD）病例的70％，文献提出了绝经期间雌激素水平降低与AD风险增加之间的联系。以前的研究主要集中在评估激素疗法（HT）如何影响AD发展和认知恶化的可能性。然而,随着研究框架已经转向生物标志物定义的AD，特定生物标志物的改变可能发生在认知衰退变得明显之前的几年，研究HT如何影响AD生物标志物至关重要.这项研究的主要目标是评估HT对认知未受损（CU）和认知受损（CI）绝经后女性在衰老和AD谱中的AD生物标志物信息病理生理学的影响。
方法：这项横断面研究纳入了在PET成像评估时无HT病史（HT-）和有HT（HT+）的绝经后女性，来自两个队列：衰老和痴呆转化生物标志物（TRIAD）队列，和阿尔茨海默病神经影像学倡议（ADNI）。参与者接受了磁共振成像（MRI），正电子发射断层扫描（PET）和生物流体收集。进行了基于体素的t检验，以评估HT和HT雌性之间淀粉样蛋白β（Aβ）和tau神经原纤维缠结（NFT）负荷的差异。还进行了具有相互作用项的线性回归模型，以检查HT和Aβ-PET对区域tau-PET的相互作用。
结果：HT+女性在BraakI-IIROI中表现出显著较低的tau-PET标准化摄取值比率（SUVR）（P<0.05，Hedges\'g=0.73），BraakIII-IVROI(P<0.0001,Hedges\'g=0.74)和BraakV-VIROI(P<0.0001,Hedges\'g=0.69)与HT-女性相比。HT+雌性还显示显著较低的CSFp-tau181(P<0.001)和血浆p-tau181(P<0.0001)浓度。此外,多元线性回归模型的结果表明，HT与皮质Aβ相互作用，并与较低的区域NFT负荷相关。
结论：总体而言，这项观察性研究的结果表明,在绝经后女性中,HT与较低tau神经影像学和液体生物标志物相关.由于tau和认知之间的紧密联系，本研究强调需要大型随机对照试验,旨在系统研究HT对AD生物标志物和疾病进展的影响.
方法：这项横断面研究纳入了在PET成像评估时无HT病史（HT-）和有HT（HT+）的绝经后女性，来自两个队列：衰老和痴呆转化生物标志物（TRIAD）队列，和阿尔茨海默病神经影像学倡议（ADNI）。参与者接受了磁共振成像（MRI），正电子发射断层扫描（PET）和生物流体收集。进行了基于体素的t检验，以评估HT和HT雌性之间淀粉样蛋白β（Aβ）和tau神经原纤维缠结（NFT）负荷的差异。还进行了具有相互作用项的线性回归模型，以检查HT和Aβ-PET对区域tau-PET的相互作用。
结果：HT+女性在BraakI-IIROI中表现出显著较低的tau-PET标准化摄取值比率（SUVR）（P<0.05，Hedges\'g=0.73），BraakIII-IVROI(P<0.0001,Hedges\'g=0.74)和BraakV-VIROI(P<0.0001,Hedges\'g=0.69)与HT-女性相比。HT+雌性还显示显著较低的CSFp-tau181(P<0.001)和血浆p-tau181(P<0.0001)浓度。此外,多元线性回归模型的结果表明，HT与皮质Aβ相互作用，并与较低的区域NFT负荷相关。
结论：总体而言，这项观察性研究的结果表明,在绝经后女性中,HT与较低tau神经影像学和液体生物标志物相关.由于tau和认知之间的紧密联系，本研究强调需要大型随机对照试验,旨在系统研究HT对AD生物标志物和疾病进展的影响.
