Vande Casteele Thomas, Laroy Maarten, Van Cauwenberge Margot, Vanderlinden Greet, Vansteelandt Kristof, Koole Michel, Dupont Patrick, Van Den Bossche Maarten, Van den Stock Jan, Bouckaert Filip, Van Laere Koen, Emsell Louise, Vandenbulcke Mathieu
Department of Neurosciences, Neuropsychiatry (TVC, ML, MVC, MVDB, JVDS, FB, LE, MV), KU Leuven, Leuven Brain Institute, Leuven, Belgium.
Department of Neurosciences, Neuropsychiatry (TVC, ML, MVC, MVDB, JVDS, FB, LE, MV), KU Leuven, Leuven Brain Institute, Leuven, Belgium.
Am J Geriatr Psychiatry. 2025 Jan;33(1):47-62. doi: 10.1016/j.jagp.2024.07.005. Epub 2024 Jul 18.
To investigate whether tau accumulation is higher in late life depression (LLD) compared to non-depressed cognitively unimpaired (CU) older adults. To situate these findings in the neurodegeneration model of LLD by assessing group differences in tau and grey matter volume (GMV) between LLD, non-depressed CU and mild cognitive impairment due to Alzheimer's Disease (MCI).
Monocentric, cross-sectional study.
University Psychiatric hospital, memory clinic and outpatient neurology practice.
A total of 102 adults over age 60, of whom 19 currently depressed participants with LLD, 19 with MCI and 36 non-depressed CU participants completed neuropsychological testing and tau PET-MR imaging.
PET-MRI: 18F-MK-6240 tracer SUVR for tau assessment; 3D T1-weighted structural MRI derived GMV in seven brain regions (temporal, cingulate, prefrontal and parietal regions); amyloid PET to assess amyloid positivity; Neuropsychological test scores: MMSE, RAVLT, GDS, MADRS. ANCOVA and Spearman's rank correlations to investigate group differences in tau and GMV, and correlations with neuropsychological test scores respectively.
Compared to non-depressed CU participants, LLD patients showed lower GMV in temporal and anterior cingulate regions but similar tau accumulation and amyloid positivity rate. In contrast, MCI patients had significantly higher tau accumulation in all regions. Tau did not correlate with any neuropsychological test scores in LLD.
Our findings suggest AD-type tau is not higher in LLD compared to non-depressed, cognitively unimpaired older adults and appears unlikely to contribute to lower gray matter volume in LLD, further underscoring the need to distinguish major depressive disorder from depressive symptoms occurring in early AD.
研究与非抑郁认知未受损（CU）的老年人相比，晚年抑郁症（LLD）患者的tau蛋白积累是否更高。通过评估LLD、非抑郁CU和阿尔茨海默病所致轻度认知障碍（MCI）患者之间tau蛋白和灰质体积（GMV）的组间差异，将这些发现置于LLD的神经退行性变模型中。
单中心横断面研究。
大学精神病医院、记忆门诊和门诊神经科诊所。
共有102名60岁以上的成年人，其中19名目前患有LLD的抑郁参与者、19名患有MCI的参与者和36名非抑郁CU参与者完成了神经心理学测试和tau蛋白PET-MR成像。
PET-MRI：使用18F-MK-6240示踪剂SUVR评估tau蛋白；从三维T1加权结构MRI得出七个脑区（颞叶、扣带回、前额叶和顶叶区域）的GMV；淀粉样蛋白PET评估淀粉样蛋白阳性；神经心理学测试分数：简易精神状态检查表（MMSE）、雷氏听觉词语学习测验（RAVLT）、老年抑郁量表（GDS）、蒙哥马利-阿斯伯格抑郁评定量表（MADRS）。分别采用协方差分析和斯皮尔曼等级相关分析来研究tau蛋白和GMV的组间差异，以及与神经心理学测试分数的相关性。
与非抑郁CU参与者相比，LLD患者在颞叶和前扣带回区域的GMV较低，但tau蛋白积累和淀粉样蛋白阳性率相似。相比之下，MCI患者在所有区域的tau蛋白积累均显著更高。在LLD患者中，tau蛋白与任何神经心理学测试分数均无相关性。
我们的研究结果表明，与非抑郁、认知未受损的老年人相比，LLD患者的AD型tau蛋白并不更高，而且似乎不太可能导致LLD患者灰质体积降低，这进一步强调了区分重度抑郁症与早期AD中出现的抑郁症状的必要性。
