Tondelli Manuela, Ballotta Daniela, Maramotti Riccardo, Carbone Chiara, Gallingani Chiara, MacKay Clare, Pagnoni Giuseppe, Chiari Annalisa, Zamboni Giovanna
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Neurologia, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
Front Aging Neurosci. 2024 Jun 5;16:1415994. doi: 10.3389/fnagi.2024.1415994. eCollection 2024.
Recent evidence suggests that anosognosia or unawareness of cognitive impairment in Alzheimer's Disease (AD) may be explained by a disconnection between brain regions involved in accessing and monitoring information regarding self and others. It has been demonstrated that AD patients with anosognosia have reduced connectivity within the default mode network (DMN) and that anosognosia in people with prodromal AD is positively associated with bilateral anterior cingulate cortex (ACC), suggesting a possible role of this region in mechanisms of awareness in the early phase of disease. We hypothesized that anosognosia in AD is associated with an imbalance between the activity of large-scale resting-state functional magnetic resonance imaging (fMRI) networks, in particular the DMN, the salience network (SN), and the frontoparietal network (FPN).
Sixty patients with MCI and AD dementia underwent fMRI and neuropsychological assessment including the Anosognosia Questionnaire Dementia (AQ-D), a measure of anosognosia based on a discrepancy score between patient's and carer's judgments. After having applied Independent Component Analysis (ICA) to resting fMRI data we performed: (i) correlations between the AQ-D score and functional connectivity in the DMN, SN, and FPN, and (ii) comparisons between aware and unaware patients of the DMN, SN, and FPN functional connectivity.
We found that anosognosia was associated with (i) weak functional connectivity within the DMN, in posterior and middle cingulate cortex particularly, (ii) strong functional connectivity within the SN in ACC, and between the SN and basal ganglia, and (iii) a heterogenous effect concerning the functional connectivity of the FPN, with a weak connectivity between the FPN and PCC, and a strong connectivity between the FPN and ACC. The observed effects were controlled for differences in severity of cognitive impairment and age.
Anosognosia in the AD continuum is associated with a dysregulation of the functional connectivity of three large-scale networks, namely the DMN, SN, and FPN.
近期证据表明，阿尔茨海默病（AD）中的失认症或对认知障碍的无意识状态，可能是由于参与获取和监测有关自我及他人信息的脑区之间的联系中断所致。已有研究表明，患有失认症的AD患者在默认模式网络（DMN）内的连接性降低，且前驱期AD患者的失认症与双侧前扣带回皮质（ACC）呈正相关，这表明该区域在疾病早期的意识机制中可能发挥作用。我们假设，AD中的失认症与大规模静息态功能磁共振成像（fMRI）网络，特别是DMN、突显网络（SN）和额顶叶网络（FPN）的活动失衡有关。
60例轻度认知障碍（MCI）和AD痴呆患者接受了fMRI和神经心理学评估，包括失认症问卷痴呆版（AQ-D），这是一种基于患者与照料者判断差异得分的失认症测量方法。在对静息fMRI数据应用独立成分分析（ICA）后，我们进行了以下操作：（i）AQ-D得分与DMN、SN和FPN功能连接性之间的相关性分析，以及（ii）对DMN、SN和FPN功能连接性方面有认知和无认知患者的比较。
我们发现，失认症与以下情况相关：（i）DMN内，特别是后扣带回和中扣带回皮质的功能连接性较弱；（ii）ACC中SN内以及SN与基底神经节之间的功能连接性较强；（iii）FPN功能连接性存在异质性效应，FPN与后扣带回皮质之间连接性较弱，而FPN与ACC之间连接性较强。所观察到的效应已针对认知障碍严重程度和年龄差异进行了校正。
AD连续体中的失认症与三个大规模网络，即DMN、SN和FPN的功能连接失调有关。
