Vannini Patrizia, Hanseeuw Bernard, Munro Catherine E, Amariglio Rebecca E, Marshall Gad A, Rentz Dorene M, Pascual-Leone Alvaro, Johnson Keith A, Sperling Reisa A
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA; Athinoula A. Martinos Center for Biomedical Imaging and the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Athinoula A. Martinos Center for Biomedical Imaging and the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Radiology, Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Neurology, Saint-Luc University Hospital, Institute of Neuroscience, Université Catholique de Louvain, 1200 Brussels, Belgium.
Neuroimage Clin. 2017 May 25;15:408-414. doi: 10.1016/j.nicl.2017.05.020. eCollection 2017.
Anosognosia, or loss of insight of memory deficits, is a common and striking symptom in Alzheimer's disease (AD). Previous findings in AD dementia patients suggest that anosognosia is due to both functional metabolic changes within cortical midline structures involved in self-referential processes, as well as functional disconnection between these regions. The present study aims to extend these findings by investigating the neural correlates of anosognosia in the prodromal stage of AD. Here, we used regional brain metabolism (resting state 18-F fluorodeoxyglucose positron emission tomography (FDG-PET)) to unravel the metabolic correlates of anosognosia in subjects with amnestic mild cognitive impairment (aMCI) and subsequently resting state functional magnetic resonance imaging (rs-fMRI) to investigate the intrinsic connectivity disruption between brain regions. Thirty-one subjects (mean age: 74.1; Clinical Dementia Rating (CDR) global score: 0.5) with aMCI, and 251 cognitively normal (CN) older adults (mean age: 73.3; CDR: 0) were included as a reference group for behavioral and FDG data. An anosognosia index was obtained by calculating a discrepancy score between subjective and objective memory scores. All subjects underwent FDG-PET for glucose metabolism measurement, and aMCI subjects underwent additional rs-fMRI for intrinsic connectivity measurement. Voxel-wise correlations between anosognosia and neuroimaging data were conducted in the aMCI subjects. Subjects with aMCI had significantly decreased memory awareness as compared to the CN older adults. Greater anosognosia in aMCI subjects was associated with reduced glucose metabolism in the posterior cingulate (PCC) cortices and hippocampus. Intrinsic connectivity analyses revealed a significant association between anosognosia and attenuated functional connectivity between the PCC seed region and orbitofrontal cortex (OFC) as well as bilateral inferior parietal lobes (IPL). These findings provide further evidence that implicates cortical midline structures and hippocampus in the awareness of memory deficits. Investigating neuroimaging changes that co-vary with memory awareness may improve our ability to identify the cause of anosognosia and ultimately increase our chances for its treatment.
疾病失认症，即对记忆缺陷缺乏洞察力，是阿尔茨海默病（AD）中一种常见且显著的症状。先前对AD痴呆患者的研究结果表明，疾病失认症是由于参与自我参照过程的皮质中线结构内的功能代谢变化，以及这些区域之间的功能断开所致。本研究旨在通过调查AD前驱期疾病失认症的神经关联来扩展这些发现。在此，我们使用区域脑代谢（静息态18-F氟脱氧葡萄糖正电子发射断层扫描（FDG-PET））来揭示遗忘型轻度认知障碍（aMCI）患者疾病失认症的代谢关联，随后使用静息态功能磁共振成像（rs-fMRI）来研究脑区之间的内在连接中断情况。31名aMCI患者（平均年龄：74.1岁；临床痴呆评定量表（CDR）总体评分：0.5）和251名认知正常（CN）的老年人（平均年龄：73.3岁；CDR：0）被纳入作为行为和FDG数据的参照组。通过计算主观和客观记忆评分之间的差异分数获得疾病失认症指数。所有受试者均接受FDG-PET以测量葡萄糖代谢，aMCI患者还接受额外的rs-fMRI以测量内在连接。在aMCI患者中进行了疾病失认症与神经影像数据之间的体素级相关性分析。与CN老年人相比，aMCI患者的记忆意识显著降低。aMCI患者中更严重的疾病失认症与后扣带回（PCC）皮质和海马体的葡萄糖代谢降低有关。内在连接分析显示，疾病失认症与PCC种子区域与眶额皮质（OFC）以及双侧下顶叶（IPL）之间的功能连接减弱之间存在显著关联。这些发现提供了进一步的证据，表明皮质中线结构和海马体与记忆缺陷的意识有关。研究与记忆意识共同变化的神经影像变化可能会提高我们识别疾病失认症病因的能力，并最终增加我们治疗它的机会。
