Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, USA.
Department of Health Sciences Research, Mayo Clinic Alix School of Medicine, Phoenix, AZ, USA.
Neurobiol Aging. 2024 Jan;133:67-77. doi: 10.1016/j.neurobiolaging.2023.10.002. Epub 2023 Oct 20.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. Two of 3 patients with AD are biologically female; therefore, the biological underpinnings of this diagnosis disparity may inform interventions slowing the AD progression. To bridge this gap, we conducted analyses of 1078 male and female participants from the Alzheimer's Disease Neuroimaging Initiative to examine associations between levels of cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes. The Chow test was used to quantify sex differences by determining if biological sex affects relationships between the studied biomarkers and outcomes. Multiple magnetic resonance imaging (whole brain, entorhinal cortex, middle temporal gyrus, fusiform gyrus, hippocampus), position emission tomography (AV45), and CSF (P-TAU, TAU) biomarkers were differentially associated with cognitive and functional outcomes. Post-hoc bootstrapped and association analyses confirmed these differential effects and emphasized the necessity of using separate, sex-stratified models. The studied imaging/CSF biomarkers may account for some of the sex-based variation in AD pathophysiology. The identified sex-varying relationships between CSF/imaging biomarkers and cognitive/functional outcomes warrant future biological investigation in independent cohorts.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是记忆和功能受损。AD 患者中有 3 人是女性；因此，这种诊断差异的生物学基础可能为减缓 AD 进展的干预措施提供信息。为了弥补这一差距，我们对来自阿尔茨海默病神经影像学倡议的 1078 名男性和女性参与者进行了分析，以检查脑脊髓液（CSF）/神经影像学生物标志物与认知/功能结果之间的关联。Chow 检验用于通过确定生物性别是否影响所研究生物标志物与结果之间的关系来量化性别差异。多个磁共振成像（全脑、内嗅皮层、颞中回、梭状回、海马体）、正电子发射断层扫描（AV45）和 CSF（P-TAU、TAU）生物标志物与认知和功能结果存在差异关联。事后 bootstrap 和关联分析证实了这些差异效应，并强调了使用单独的、按性别分层的模型的必要性。研究中的成像/CSF 生物标志物可能解释了 AD 病理生理学中一些基于性别的变化。CSF/成像生物标志物与认知/功能结果之间的已识别性别变化关系需要在独立队列中进行进一步的生物学研究。
