Forno Gonzalo, Saranathan Manojkumar, Contador Jose, Guillen Nuria, Falgàs Neus, Tort-Merino Adrià, Balasa Mircea, Sanchez-Valle Raquel, Hornberger Michael, Lladó Albert
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Laboratorio de Neuropsicología y Neurociencias Clínicas (LANNEC), Facultad de Medicina, Universidad de Chile, Chile.
Curr Res Neurobiol. 2023 Mar 24;4:100084. doi: 10.1016/j.crneur.2023.100084. eCollection 2023.
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Increasing evidence points to the thalamus as an important hub in the clinical symptomatology of the disease, with the 'limbic thalamus' been described as especially vulnerable. In this work, we examined thalamic atrophy in early-onset AD (EOAD) and late-onset AD (LOAD) compared to young and old healthy controls (YHC and OHC, respectively) using a recently developed cutting-edge thalamic nuclei segmentation method. A deep learning variant of Thalamus Optimized Multi Atlas Segmentation (THOMAS) was used to parcellate 11 thalamic nuclei per hemisphere from T1-weighted MRI in 88 biomarker-confirmed AD patients (49 EOAD and 39 LOAD) and 58 healthy controls (41 YHC and 17 OHC) with normal AD biomarkers. Nuclei volumes were compared among groups using MANCOVA. Further, Pearson's correlation coefficient was computed between thalamic nuclear volume and cortical-subcortical regions, CSF tau levels, and neuropsychological scores. The results showed widespread thalamic nuclei atrophy in EOAD and LOAD compared to their respective healthy control groups, with EOAD showing additional atrophy in the centromedian and ventral lateral posterior nuclei compared to YHC. In EOAD, increased thalamic nuclei atrophy was associated with posterior parietal atrophy and worse visuospatial abilities, while LOAD thalamic nuclei atrophy was preferentially associated with medial temporal atrophy and worse episodic memory and executive function. Our findings suggest that thalamic nuclei may be differentially affected in AD according to the age at symptoms onset, associated with specific cortical-subcortical regions, CSF total tau and cognition.
阿尔茨海默病（AD）是全球痴呆最常见的病因。越来越多的证据表明，丘脑是该疾病临床症状学中的一个重要枢纽，其中“边缘丘脑”被描述为特别脆弱。在这项研究中，我们使用一种最新开发的前沿丘脑核分割方法，将早发性AD（EOAD）和晚发性AD（LOAD）患者的丘脑萎缩情况与年轻和老年健康对照者（分别为YHC和OHC）进行了比较。采用丘脑优化多图谱分割（THOMAS）的深度学习变体，从88例生物标志物确诊的AD患者（49例EOAD和39例LOAD）以及58例AD生物标志物正常的健康对照者（41例YHC和17例OHC）的T1加权磁共振成像（MRI）中分割出每侧大脑半球的11个丘脑核。使用多变量协方差分析（MANCOVA）比较各组之间的核体积。此外，计算丘脑核体积与皮质 - 皮质下区域、脑脊液tau水平和神经心理学评分之间的Pearson相关系数。结果显示，与各自的健康对照组相比，EOAD和LOAD患者均存在广泛的丘脑核萎缩，与YHC相比，EOAD患者的中央中核和腹后外侧核出现额外萎缩。在EOAD中，丘脑核萎缩增加与顶叶后部萎缩及更差的视觉空间能力相关，而LOAD患者的丘脑核萎缩则优先与内侧颞叶萎缩及更差的情景记忆和执行功能相关。我们的研究结果表明，根据症状出现的年龄，AD患者的丘脑核可能受到不同程度的影响，且与特定的皮质 - 皮质下区域、脑脊液总tau水平和认知相关。
