Department of Anatomy and Neurobiology, UC Irvine Medical School, Irvine, California, 92697-3940; Department of Neurology, UC Irvine Medical School, Irvine, California, 92697-3940.
J Comp Neurol. 2013 Dec 15;521(18):4300-17. doi: 10.1002/cne.23418.
Noninvasive diagnostic tests for Alzheimer's disease (AD) are limited. Postmortem diagnosis is based on density and distribution of neurofibrillary tangles (NFTs) and amyloid-rich neuritic plaques. In preclinical stages of AD, the cells of origin for the perforant pathway within the entorhinal cortex are among the first to display NFTs, indicating its compromise in early stages of AD. We used diffusion tensor imaging (DTI) to assess the integrity of the parahippocampal white matter in mild cognitive impairment (MCI) and AD, as a first step in developing a noninvasive tool for early diagnosis. Subjects with AD (N = 9), MCI (N = 8), or no cognitive impairment (NCI; N = 20) underwent DTI-MRI. Fractional anisotropy (FA) and mean (MD) and radial (RD) diffusivity measured from the parahippocampal white matter in AD and NCI subjects differed greatly. Discriminant analysis in the MCI cases assigned statistical membership of 38% of MCI subjects to the AD group. Preliminary data 1 year later showed that all MCI cases assigned to the AD group either met the diagnostic criteria for probable AD or showed significant cognitive decline. Voxelwise analysis in the parahippocampal white matter revealed a progressive change in the DTI patterns in MCI and AD subjects: whereas converted MCI cases showed structural changes restricted to the anterior portions of this region, in AD the pathology was generalized along the entire anterior-posterior axis. The use of DTI for in vivo assessment of the parahippocampal white matter may be useful for identifying individuals with MCI at highest risk for conversion to AD and for assessing disease progression.
用于阿尔茨海默病（AD）的非侵入性诊断测试有限。死后诊断基于神经原纤维缠结（NFT）和富含淀粉样蛋白的神经突斑块的密度和分布。在 AD 的临床前阶段，内嗅皮层内的穿通途径的起源细胞是最早显示 NFT 的细胞之一，表明其在 AD 的早期阶段受到损害。我们使用弥散张量成像（DTI）来评估轻度认知障碍（MCI）和 AD 中海马旁回白质的完整性，作为开发早期诊断的非侵入性工具的第一步。AD（N=9）、MCI（N=8）或无认知障碍（NCI；N=20）受试者接受了 DTI-MRI 检查。AD 和 NCI 受试者的海马旁回白质的各向异性分数（FA）、平均（MD）和径向（RD）弥散度差异很大。MCI 病例的判别分析将 38%的 MCI 病例的统计成员分配给 AD 组。1 年后的初步数据显示，分配给 AD 组的所有 MCI 病例要么符合可能 AD 的诊断标准，要么表现出明显的认知下降。海马旁回白质的体素分析显示 MCI 和 AD 受试者的 DTI 模式发生了进行性变化：转换的 MCI 病例显示结构变化仅限于该区域的前部，而在 AD 中，病理学沿着整个前后轴普遍存在。DTI 用于评估海马旁回白质的体内评估可能有助于识别 MCI 中转换为 AD 风险最高的个体，并评估疾病进展。
