Lost in space(s): multimodal neuroimaging of disorientation along the Alzheimer's disease continuum.
Lost in space(s): multimodal neuroimaging of disorientation along the Alzheimer's disease continuum.
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迷失空间：阿尔茨海默病连续体迷失方向的多模式神经影像。
DOI：
10.1101/2023.01.25.525587
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Arzy,Shahar
中科院分区：
文献类型：
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作者：
Peters-Founshtein,Gregory;Gazit,Lidor;Naveh,Tahel;Domachevsky,Liran;Korczyn,Amos;Bernstine,Hanna;Groshar,David;Marshall,GadA;Arzy,Shahar
定向是一种基本的认知能力，也是神经系统检查的基础。定向被定义为个体的内部表征与外部世界在空间、时间和社会领域之间的对齐。虽然空间定向障碍是阿尔茨海默病（AD）的公认标志，但对AD中空间以外的定向障碍知之甚少。本研究旨在探讨定向障碍在空间，时间和社会领域的沿着AD连续体。沿着AD连续体的51名参与者在进行功能性MRI时在空间、时间和社会领域执行生态定向任务。AD中的定向障碍遵循定向域、脑区和疾病阶段之间的三向关联。具体而言，早期遗忘型轻度认知障碍患者表现出时空定向障碍和颞顶区大脑活动减少，而AD痴呆患者表现出额外的社会定向障碍和额顶叶区大脑活动减少。此外，激活不足的模式重叠默认模式网络的不同子网络，氟脱氧葡萄糖代谢低下的模式，以及AD的皮质萎缩特征。我们的研究结果表明，AD可能包括定向障碍，其特征在于表现为早期时空和晚期社会定向障碍的双相过程。因此，定向障碍可能为AD的临床病理进展提供了一个独特的窗口。尽管对阿尔茨海默病（AD）进行了广泛的研究，但其核心认知缺陷仍然是一个有争议的问题。在这项研究中，我们调查是否定向，定义为在空间，时间和社会领域与外部世界对齐的内部表征的能力，构成了AD的核心认知缺陷。为此，我们使用PET-fMRI成像从51名参与者沿着AD连续体收集行为，功能和代谢数据。我们的研究结果表明，AD可能构成一种定向障碍，其特征是早期的时空定向障碍，随后是晚期的社会定向障碍，表现为任务诱发和神经退行性变化。我们认为，跨多个领域的定向障碍的概况提供了一个独特的窗口，进入AD的进展，因此可以大大有利于疾病的诊断，监测和治疗反应的评估。
Orientation is a fundamental cognitive faculty and the bedrock of the neurologic examination. Orientation is defined as the alignment between an individual's internal representation and the external world in the spatial, temporal, and social domains. While spatial disorientation is a recognized hallmark of Alzheimer's disease (AD), little is known about disorientation beyond space in AD. This study aimed to explore disorientation in spatial, temporal, and social domains along the AD continuum. Fifty‐one participants along the AD continuum performed an ecological orientation task in the spatial, temporal, and social domains while undergoing functional MRI. Disorientation in AD followed a three‐way association between orientation domain, brain region, and disease stage. Specifically, patients with early amnestic mild cognitive impairment exhibited spatio‐temporal disorientation and reduced brain activity in temporoparietal regions, while patients with AD dementia showed additional social disorientation and reduced brain activity in frontoparietal regions. Furthermore, patterns of hypoactivation overlapped different subnetworks of the default mode network, patterns of fluorodeoxyglucose hypometabolism, and cortical atrophy characteristic of AD. Our results suggest that AD may encompass a disorder of orientation, characterized by a biphasic process manifesting as early spatio‐temporal and late social disorientation. As such, disorientation may offer a unique window into the clinicopathological progression of AD.Significance statementDespite extensive research into Alzheimer's disease (AD), its core cognitive deficit remains a matter of debate. In this study, we investigated whether orientation, defined as the ability to align internal representations with the external world in spatial, temporal, and social domains, constitutes a core cognitive deficit in AD. To do so, we used PET‐fMRI imaging to collect behavioral, functional, and metabolic data from 51 participants along the AD continuum. Our findings suggest that AD may constitute a disorder of orientation, characterized by an early spatio‐temporal disorientation and followed by late social disorientation, manifesting in task‐evoked and neurodegenerative changes. We propose that a profile of disorientation across multiple domains offers a unique window into the progression of AD and as such could greatly benefit disease diagnosis, monitoring, and evaluation of treatment response.