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.
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.