Mehta Rashi I, Keith Cierra M, Teixeira Camila Vieira Ligo, Worhunsky Patrick D, Phelps Holly E, Ward Melanie, Miller Mark, Navia R Osvaldo, Pockl Stephanie, Rajabalee Nafiisah, Coleman Michelle M, D'Haese Pierre-François, Rezai Ali R, Wilhelmsen Kirk C, Haut Marc W
Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown, WV 26505, United States.
The Departments of Neuroradiology, 1 Medical Center Dr. PO Box 8063 Morgantown, WV 26506, United States.
Cereb Cortex. 2024 Dec 3;34(12). doi: 10.1093/cercor/bhae475.
Early-onset Alzheimer's disease (EOAD) is less investigated than the more common late-onset Alzheimer's disease (LOAD) despite its more aggressive course. A cortical signature of EOAD was recently proposed and may facilitate EOAD investigation. Here, we aimed to validate this proposed MRI biomarker of EOAD neurodegeneration in an Appalachian clinical cohort. We also compared differences in EOAD signature atrophy in participants with biomarker-positive EOAD, LOAD, early-onset non-AD pathologies, and cognitively normal individuals. Cortical thinning was reliably detected in eight of nine signature areas of persons with EOAD relative to cognitively normal individuals despite very early disease stage. Additionally, individuals with EOAD showed thinner cortex in most signature regions relative to those with early-onset non-AD pathologies. EOAD and LOAD showed similar cortical atrophy within most EOAD signature regions. Whole-brain vertex-wise cortical analyses supported these findings. Furthermore, signature cortical atrophy showed expected relationships with measures of global and specific cognitive and functional status. This investigation further validates and expands upon the recently defined EOAD signature and suggests its robustness within a rural population, even at early disease stage. Larger scale and longitudinal studies employing this marker of EOAD neurodegeneration are needed to further understand clinical effects and appropriate management of persons with EOAD.
早发性阿尔茨海默病（EOAD）尽管病程更为凶险，但与更常见的晚发性阿尔茨海默病（LOAD）相比，其研究较少。最近提出了一种EOAD的皮质特征，这可能有助于EOAD的研究。在此，我们旨在验证这一提出的EOAD神经退行性变的MRI生物标志物在阿巴拉契亚临床队列中的有效性。我们还比较了生物标志物阳性的EOAD患者、LOAD患者、早发性非阿尔茨海默病病理患者以及认知正常个体在EOAD特征性萎缩方面的差异。尽管疾病处于非常早期阶段，但与认知正常个体相比，在EOAD患者的九个特征区域中的八个区域可靠地检测到了皮质变薄。此外，与早发性非阿尔茨海默病病理患者相比，EOAD患者在大多数特征区域的皮质更薄。在大多数EOAD特征区域内，EOAD和LOAD表现出相似的皮质萎缩。全脑顶点-wise皮质分析支持了这些发现。此外，特征性皮质萎缩与整体及特定认知和功能状态的测量结果呈现出预期的关系。这项研究进一步验证并扩展了最近定义的EOAD特征，并表明其在农村人群中即使在疾病早期阶段也具有稳健性。需要进行更大规模的纵向研究，采用这种EOAD神经退行性变的标志物，以进一步了解EOAD患者的临床影响和适当管理。
