Pajavand Amir Mohammad, Grothe Michel J, De Schotten Michel Thiebaut, Giorgi Filippo Sean, Vergallo Andrea, Hampel Harald
The National University of Iran (NUI), 19839-63113, Tehran, Iran.
Reina Sofia Alzheimer Center, CIEN Foundation-ISCIII, Madrid, Spain.
J Alzheimers Dis. 2024 Dec;102(4):1042-1056. doi: 10.1177/13872877241288710. Epub 2024 Nov 22.
Depression and circadian rhythm disruptions are non-cognitive neuropsychiatric symptoms (NPS) that can appear at any stage of the Alzheimer's disease (AD) continuum. Evidence suggests that NPS are linked to AD pathophysiology and hippocampal dysfunction.
To examine structural white matter (WM) connectivity and its association with gray matter (GM) atrophy and to identify specific AD-related neural networks linked to NPS in individuals with mild cognitive impairment (MCI).
Ninety-six older adults participants were divided into three groups based on the Global Depression Scale, Neuropsychiatric Inventory, Clinical Dementia Rating, and Mini-Mental Status Examination. Twelve individuals with MCI and NPS (MCI+) and 49 without NPS (MCI-) were classified, along with 35 age and gender-matched healthy individuals. Voxel-based morphometry and tract-based spatial statistics were employed to identify structural and microstructural alterations. Network-based statistics analyzed structural WM connectivity differences between MCI groups and healthy controls.
Significant structural WM connectivity and GM loss were exclusively observed in MCI+ individuals compared to controls. The hippocampus, amygdala, and sensory cortex showed GM atrophy (p < 0.05), while the thalamus, pallidum, putamen, caudate, hippocampus, and sensory and frontal cortices exhibited structural WM connectivity loss (p < 0.01). These data indicate early limbic system involvement even without GM atrophy.
Structural WM connectivity loss within the Papez circuit may precede and potentially predict GM atrophy in the temporal lobe of individuals with MCI+. These findings highlight the importance of investigating structural WM alterations in the prodromal phase of AD, which may inform diagnostic and therapeutic strategies in early AD.
抑郁和昼夜节律紊乱是非认知神经精神症状（NPS），可出现在阿尔茨海默病（AD）连续体的任何阶段。有证据表明，NPS与AD病理生理学及海马功能障碍有关。
研究轻度认知障碍（MCI）患者的白质（WM）结构连通性及其与灰质（GM）萎缩的关联，并确定与NPS相关的特定AD相关神经网络。
根据全球抑郁量表、神经精神科问卷、临床痴呆评定量表和简易精神状态检查表，将96名老年参与者分为三组。其中12名患有MCI和NPS的个体（MCI+）、49名无NPS的个体（MCI-）以及35名年龄和性别匹配的健康个体被纳入研究。采用基于体素的形态学测量和基于纤维束的空间统计学方法来识别结构和微观结构改变。基于网络的统计学分析了MCI组与健康对照组之间的WM结构连通性差异。
与对照组相比，仅在MCI+个体中观察到显著的WM结构连通性和GM丢失。海马体、杏仁核和感觉皮层出现GM萎缩（p<0.05），而丘脑、苍白球、壳核、尾状核、海马体以及感觉和额叶皮层出现WM结构连通性丢失（p<0.01）。这些数据表明，即使没有GM萎缩，边缘系统也会早期受累。
Papez回路内的WM结构连通性丧失可能先于并潜在预测MCI+个体颞叶的GM萎缩。这些发现凸显了在AD前驱期研究WM结构改变的重要性，这可能为早期AD的诊断和治疗策略提供依据。
