Censi S, Sestieri C, Punzi M, Delli Pizzi A, Ferretti A, Gambi F, Tomassini V, Delli Pizzi S, Sensi S L
Stefano Delli Pizzi, Department of Neuroscience, Imaging, and Clinical Sciences, University «G. d'Annunzio» of Chieti-Pescara, Via Polacchi, 11 Chieti 66100, Italy,
J Prev Alzheimers Dis. 2024;11(4):1030-1040. doi: 10.14283/jpad.2024.42.
Patients with Alzheimer's Disease (AD) exhibit structural alterations of the thalamus that correlate with clinical symptoms. However, given the anatomical complexity of this brain structure, it is still unclear whether atrophy affects specific thalamic nuclei and modulates the clinical progression from a prodromal stage, known as Mild Cognitive Impairment (MCI), to full-fledged AD.
To characterize the structural integrity of distinct thalamic nuclei across the AD spectrum, testing whether MCI patients who convert to AD (c-MCI) show a distinctive pattern of thalamic structural alterations compared to patients who remain stable (s-MCI).
Investigating between-group differences in the volumetric features of distinct thalamic nuclei across the AD spectrum.
Prodromal and clinical stages of AD.
We analyzed data from 84 healthy control subjects (HC), 58 individuals with MCI, and 102 AD patients. The dataset was obtained from the AD Neuroimaging Initiative (ADNI-3) database. The MCI group was further divided into two subgroups depending on whether patients remained stable (s-MCI, n=22) or progressed to AD (s-MCI, n=36) in the 48 months following the diagnosis.
A multivariate analysis of variance (MANOVA) assessed group differences in the volumetric features of distinct thalamic nuclei obtained from magnetic resonance (MR) images. A stepwise discriminant function analysis identified which feature most effectively predicted the conversion to AD. The corresponding predictive performance was evaluated through a Receiver Operating Characteristic approach.
AD and c-MCI patients showed generalized atrophy of thalamic nuclei compared to HC. In contrast, no significant structural differences were observed between s-MCI and HC subjects. Compared to s-MCI, c-MCI individuals displayed significant atrophy of the nucleus reuniens and a trend toward significant atrophy in the anteroventral and laterodorsal nuclei. The discriminant function analysis confirmed the nucleus reuniens as a significant predictor of AD conversion, with a sensitivity of 0.73 and a specificity of 0.69.
In line with the pathophysiological relevance of the nucleus reuniens proposed by seminal post-mortem studies on patients with AD, we confirm the pivotal role of this nucleus as a critical hub in the clinical progression to AD. We also propose a theoretical model to explain the evolving dysfunction of subcortical brain networks in the disease process.
阿尔茨海默病（AD）患者表现出丘脑的结构改变，且这些改变与临床症状相关。然而，鉴于该脑结构的解剖复杂性，目前仍不清楚萎缩是否影响特定的丘脑核团，以及是否能调节从前驱期（即轻度认知障碍，MCI）到典型AD的临床进展。
描述AD谱系中不同丘脑核团的结构完整性，测试转化为AD的MCI患者（c-MCI）与病情保持稳定的患者（s-MCI）相比，是否表现出独特的丘脑结构改变模式。
研究AD谱系中不同丘脑核团体积特征的组间差异。
AD的前驱期和临床期。
我们分析了来自84名健康对照者（HC）、58名MCI个体和102名AD患者的数据。该数据集取自AD神经影像学倡议（ADNI-3）数据库。MCI组根据患者在诊断后的48个月内病情是否保持稳定（s-MCI，n=22）或进展为AD（c-MCI，n=36）进一步分为两个亚组。
多变量方差分析（MANOVA）评估从磁共振（MR）图像获得的不同丘脑核团体积特征的组间差异。逐步判别函数分析确定哪个特征最有效地预测向AD的转化。通过受试者工作特征曲线方法评估相应的预测性能。
与HC相比，AD和c-MCI患者表现出丘脑核团的广泛性萎缩。相比之下，s-MCI和HC受试者之间未观察到明显的结构差异。与s-MCI相比，c-MCI个体的 reunien核显著萎缩，前腹侧核和背外侧核有显著萎缩的趋势。判别函数分析证实reunien核是AD转化的重要预测指标，敏感性为0.73，特异性为0.69。
与对AD患者进行的开创性尸检研究所提出的reunien核的病理生理相关性一致，我们证实该核在AD临床进展中作为关键枢纽的关键作用。我们还提出了一个理论模型来解释疾病过程中皮质下脑网络不断演变的功能障碍。
