Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States of America.
PLoS One. 2011;6(10):e26286. doi: 10.1371/journal.pone.0026286. Epub 2011 Oct 17.
The volume of the hippocampus measured with structural magnetic resonance imaging (MRI) is increasingly used as a biomarker for Alzheimer's disease (AD). However, the neuropathologic basis of structural MRI changes in the hippocampus in the elderly has not been directly assessed. Postmortem MRI of the aging human brain, combined with histopathology, could be an important tool to address this issue. Therefore, this study combined postmortem MRI and histopathology in 100 elderly subjects from the Rush Memory and Aging Project and the Religious Orders Study. First, to validate the information contained in postmortem MRI data, we tested the hypothesis that postmortem hippocampal volume is smaller in subjects with clinically diagnosed Alzheimer's disease compared to subjects with mild or no cognitive impairment, as observed in antemortem imaging studies. Subsequently, the relations of postmortem hippocampal volume to AD pathology, Lewy bodies, amyloid angiopathy, gross infarcts, microscopic infarcts, and hippocampal sclerosis were examined. It was demonstrated that hippocampal volume was smaller in persons with a clinical diagnosis of AD compared to those with no cognitive impairment (P = 2.6 × 10(-7)) or mild cognitive impairment (P = 9.6 × 10(-7)). Additionally, hippocampal volume was related to multiple cognitive abilities assessed proximate to death, with its strongest association with episodic memory. Among all pathologies investigated, the most significant factors related to lower hippocampal volume were shown to be AD pathology (P = 0.0018) and hippocampal sclerosis (P = 4.2 × 10(-7)). Shape analysis allowed for visualization of the hippocampal regions most associated with volume loss for each of these two pathologies. Overall, this investigation confirmed the relation of hippocampal volume measured postmortem to clinical diagnosis of AD and measures of cognition, and concluded that both AD pathology and hippocampal sclerosis affect hippocampal volume in old age, though the impacts of each pathology on the shape of the hippocampus may differ.
使用结构磁共振成像（MRI）测量海马体体积，正日益被用作阿尔茨海默病（AD）的生物标志物。然而，尚未直接评估老年人中 MRI 海马体体积变化的神经病理学基础。衰老人脑的死后 MRI 与组织病理学相结合，可能是解决这一问题的重要工具。因此，本研究结合了来自 Rush 记忆与衰老项目和宗教秩序研究的 100 名老年受试者的死后 MRI 和组织病理学数据。首先，为了验证死后 MRI 数据中包含的信息，我们检验了一个假设，即与生前影像学研究中观察到的轻度或无认知障碍的受试者相比，临床诊断为 AD 的受试者的死后海马体体积更小。随后，我们研究了死后海马体体积与 AD 病理学、路易体、淀粉样血管病、大梗死、微梗死和海马硬化之间的关系。结果表明，与无认知障碍（P = 2.6×10(-7))或轻度认知障碍（P = 9.6×10(-7))的受试者相比，临床诊断为 AD 的受试者的海马体体积更小。此外，海马体体积与死亡前最近评估的多种认知能力相关，与情景记忆的相关性最强。在所研究的所有病理学中，与较低海马体体积最相关的因素是 AD 病理学（P = 0.0018)和海马硬化（P = 4.2×10(-7))。形态分析可以可视化与这两种病理学相关的海马体体积损失最相关的区域。总体而言，本研究证实了死后 MRI 测量的海马体体积与 AD 的临床诊断和认知测量之间的关系，并得出结论，AD 病理学和海马硬化都会影响老年人的海马体体积，但每种病理学对海马体形状的影响可能不同。
