Bueichekú Elisenda, Diez Ibai, Gagliardi Geoffroy, Kim Chan-Mi, Mimmack Kayden, Sepulcre Jorge, Vannini Patrizia
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Commun Med (Lond). 2024 Apr 5;4(1):65. doi: 10.1038/s43856-024-00497-9.
Unawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer's Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and progression. Here, we use in-vivo multi-modal neuroimaging to profile the brain phenotype of individuals presenting altered self-awareness of memory during aging.
Amyloid- and tau-PET (N = 335) and resting-state functional MRI (N = 713) imaging data of individuals from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4)/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study were used in this research. We applied whole-brain voxel-wise and region-of-interest analyses to characterize the cortical intersections of tau, amyloid, and functional connectivity networks underlying unawareness in the aging brain compared to aware, complainer and control groups.
Individuals with unawareness present elevated amyloid and tau burden in midline core regions of the default mode network compared to aware, complainer or control individuals. Unawareness is characterized by an altered network connectivity pattern featuring hyperconnectivity in the medial anterior prefrontal cortex and posterior occipito-parietal regions co-locating with amyloid and tau deposition.
Unawareness is an early behavioral biomarker of AD pathology. Failure of the self-referential system in unawareness of memory decline can be linked to amyloid and tau burden, along with functional network connectivity disruptions, in several medial frontal and parieto-occipital areas of the human brain.
无意识状态是一种行为状况，其特征是对客观记忆衰退缺乏自我意识。在阿尔茨海默病（AD）的背景下，无意识状态可能在痴呆前期阶段出现，并导致疾病的严重程度和进展。在此，我们使用体内多模态神经成像来描绘在衰老过程中记忆自我意识发生改变的个体的脑表型。
本研究使用了来自无症状阿尔茨海默病抗淀粉样蛋白治疗（A4）/淀粉样蛋白风险与神经退行性变纵向评估（LEARN）研究中个体的淀粉样蛋白和tau蛋白PET（N = 335）以及静息态功能MRI（N = 713）成像数据。我们应用全脑体素级和感兴趣区域分析，以表征与有意识、有抱怨症状和对照组相比，衰老大脑中无意识状态背后的tau蛋白、淀粉样蛋白和功能连接网络的皮质交叉点。
与有意识、有抱怨症状或对照个体相比，无意识个体在默认模式网络的中线核心区域呈现出升高的淀粉样蛋白和tau蛋白负荷。无意识状态的特征是网络连接模式改变，以内侧前额叶前皮质和枕顶叶后部区域的超连接为特征，这些区域与淀粉样蛋白和tau蛋白沉积共定位。
无意识状态是AD病理学的一种早期行为生物标志物。记忆衰退无意识状态下自我参照系统的失效可能与人类大脑几个内侧额叶和顶枕叶区域的淀粉样蛋白和tau蛋白负荷以及功能网络连接中断有关。
