Takamiya Akihiro, Radwan Ahmed, Christiaens Daan, Van Cauwenberge Margot, Vande Casteele Thomas, Laroy Maarten, Vansteelandt Kristof, Sunaert Stefan, Koole Michel, Van den Stock Jan, Van Laere Koen, Bouckaert Filip, Vandenbulcke Mathieu, Emsell Louise
Department of Neurosciences, Neuropsychiatry, KU Leuven, Leuven, Belgium.
Department of Neurosciences, KU Leuven, Leuven Brain Institute, Leuven, Belgium.
Psychol Med. 2025 Feb 4;55:e10. doi: 10.1017/S0033291724003362.
Late-life depression (LLD) is characterized by medial temporal lobe (MTL) abnormalities. Although gray matter (GM) and white matter (WM) differences in LLD have been reported, few studies have investigated them concurrently. Moreover, the impact of aetiological factors, such as neurodegenerative and cerebrovascular burden, on tissue differences remains elusive.
This prospective cross-sectional study involved 72 participants, including 33 patients with LLD (mean age 72.2 years, 23 female) and 39 healthy controls (HCs) (mean age 70.6 years, 24 female), who underwent clinical and positron emission tomography (PET)-magnetic resonance imaging (MRI) assessments. High-resolution 3D T1-weighted and T2-weighted FLAIR images were used to assess MTL GM volumes and white matter hyperintensities (WMHs), a proxy for cerebrovascular burden. Diffusion kurtosis imaging metrics derived from multishell diffusion MRI data were analyzed to assess WM microstructure in the following MTL bundles reconstructed using constrained spherical deconvolution tractography: uncinate fasciculus, fornix, and cingulum. Standardized uptake value ratio of 18F-MK-6240 in the MTL was used to assess Alzheimer's disease (AD) type tau accumulation as a proxy for neurodegenerative burden.
Compared to HCs, patients with LLD showed significantly lower bilateral MTL volumes and WM microstructural differences primarily in the uncinate fasciculi bilaterally and right fornix. In patients with LLD, higher vascular burden, but not tau, was associated with lower MTL volume and more pronounced WM differences.
LLD was associated with both GM and WM differences in the MTL. Cerebrovascular disease, rather than AD type tau-mediated neurodegenerative processes, may contribute to brain tissue differences in LLD.
老年期抑郁症（LLD）的特征是内侧颞叶（MTL）异常。尽管已有报道LLD患者存在灰质（GM）和白质（WM）差异，但很少有研究同时对二者进行调查。此外，神经退行性和脑血管负担等病因因素对组织差异的影响仍不明确。
这项前瞻性横断面研究纳入了72名参与者，包括33例LLD患者（平均年龄72.2岁，23名女性）和39名健康对照者（HCs）（平均年龄70.6岁，24名女性），他们接受了临床及正电子发射断层扫描（PET）-磁共振成像（MRI）评估。高分辨率三维T1加权和T2加权液体衰减反转恢复（FLAIR）图像用于评估MTL的GM体积和白质高信号（WMH），后者可作为脑血管负担的指标。对多壳扩散MRI数据得出的扩散峰度成像指标进行分析，以评估使用约束球形反卷积纤维束成像重建的以下MTL束中的WM微观结构：钩束、穹窿和扣带束。MTL中18F-MK-6240的标准化摄取值比率用于评估阿尔茨海默病（AD）型tau蛋白积累，作为神经退行性负担的指标。
与HCs相比，LLD患者双侧MTL体积显著降低，WM微观结构差异主要存在于双侧钩束和右侧穹窿。在LLD患者中，较高的血管负担而非tau蛋白与较低的MTL体积和更明显的WM差异相关。
LLD与MTL中的GM和WM差异均有关。脑血管疾病而非AD型tau蛋白介导的神经退行性过程可能导致LLD患者的脑组织差异。
