There is both clinical and neuroanatomical variability at the single-subject level in Alzheimer's disease, complicating our understanding of brain-behaviour relationships and making it challenging to develop neuroimaging biomarkers to track disease severity, progression, and response to treatment. Prior work has shown that both group-level atrophy in clinical dementia syndromes and complex neurological symptoms in patients with focal brain lesions localize to brain networks. Here, we use a new technique termed 'atrophy network mapping' to test the hypothesis that single-subject atrophy maps in patients with a clinical diagnosis of Alzheimer's disease will also localize to syndrome-specific and symptom-specific brain networks. First, we defined single-subject atrophy maps by comparing cortical thickness in each Alzheimer's disease patient versus a group of age-matched, cognitively normal subjects across two independent datasets (total Alzheimer's disease patients = 330). No more than 42% of Alzheimer's disease patients had atrophy at any given location across these datasets. Next, we determined the network of brain regions functionally connected to each Alzheimer's disease patient's location of atrophy using seed-based functional connectivity in a large (n = 1000) normative connectome. Despite the heterogeneity of atrophied regions at the single-subject level, we found that 100% of patients with a clinical diagnosis of Alzheimer's disease had atrophy functionally connected to the same brain regions in the mesial temporal lobe, precuneus cortex, and angular gyrus. Results were specific versus control subjects and replicated across two independent datasets. Finally, we used atrophy network mapping to define symptom-specific networks for impaired memory and delusions, finding that our results matched symptom networks derived from patients with focal brain lesions. Our study supports atrophy network mapping as a method to localize clinical, cognitive, and neuropsychiatric symptoms to brain networks, providing insight into brain-behaviour relationships in patients with dementia.

中文翻译：

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阿尔茨海默病临床、认知和神经精神症状的网络定位。

阿尔茨海默病在单个受试者水平上存在临床和神经解剖学变异，这使我们对大脑行为关系的理解变得复杂，并使开发神经影像生物标志物来跟踪疾病的严重程度、进展和治疗反应变得具有挑战性。先前的研究表明，临床痴呆综合征中的群体水平萎缩和局灶性脑损伤患者的复杂神经系统症状都局限于大脑网络。在这里，我们使用一种称为“萎缩网络图谱”的新技术来检验这样的假设：临床诊断为阿尔茨海默病的患者的单受试者萎缩图谱也将定位于特定综合征和特定症状的大脑网络。首先，我们通过比较两个独立数据集（阿尔茨海默病患者总数 = 330）中每个阿尔茨海默氏病患者与一组年龄匹配、认知正常的受试者的皮质厚度来定义单受试者萎缩图。在这些数据集中，不超过 42% 的阿尔茨海默病患者在任何给定位置出现萎缩。接下来，我们使用大型（n = 1000）规范连接组中基于种子的功能连接来确定与每个阿尔茨海默病患者萎缩位置功能连接的大脑区域网络。尽管萎缩区域在单个受试者水平上存在异质性，但我们发现 100% 临床诊断为阿尔茨海默病的患者的内侧颞叶、楔前叶皮层和角回的相同大脑区域存在功能性萎缩。结果与对照受试者相比是特定的，并且在两个独立的数据集中复制。最后，我们使用萎缩网络映射来定义记忆受损和妄想的症状特异性网络，发现我们的结果与来自局灶性脑损伤患者的症状网络相匹配。我们的研究支持萎缩网络映射作为一种将临床、认知和神经精神症状定位到大脑网络的方法，从而深入了解痴呆症患者的大脑行为关系。