Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease
Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease
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功能网络的分离与阿尔茨海默病的认知弹性相关
DOI：
10.1093/brain/awab112
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发表时间：
2021-03-16
期刊：
影响因子：
14.5
通讯作者：
Franzmeier, Nicolai
中科院分区：
文献类型：
--
作者：
Ewers, Michael;Luan, Ying;Franzmeier, Nicolai
认知弹性是阿尔茨海默病认知功能下降的重要调节因素，但支持认知弹性的大脑功能机制仍然难以捉摸。鉴于之前在正常衰老中的发现，我们检验了这一假设，即大脑连接体到不同功能网络的更高分离代表了阿尔茨海默病认知弹性的功能机制。使用静息状态功能磁共振，我们评估了静息状态功能磁共振全球系统隔离，即网络间连接到网络内连接的平衡，以及模块化的替代指数Q作为认知弹性的预测因子。我们在两个独立的样本中进行了所有分析以进行验证：(I)108名常染色体显性遗传性阿尔茨海默病患者和71名非携带者对照；(Ii)156名散发性阿尔茨海默病患者和184名淀粉样阴性对照的淀粉样蛋白PET阳性受试者。在常染色体显性遗传性阿尔茨海默病样本中，疾病严重程度是根据症状出现的估计年数来评估的。在散发的阿尔茨海默病样本中，通过颞叶tau-PET(即跨越Braak I期和III期的复合区域)来评估疾病阶段。在这两个样本中，我们测试了疾病严重程度对认知的影响是否在功能网络分离的较高水平上减弱。对于常染色体显性阿尔茨海默病，我们发现，功能磁共振评估的系统隔离程度较高，与从症状开始到全球认知的估计年限的减弱相关(P=0.007)。同样，对于散发性阿尔茨海默病患者，每增加一次颞叶tau-PET，功能磁共振评估的系统分离度越高，总体认知(P=0.001)和情景记忆(P=0.004)的减退越少。使用另一种模块化指数Q的验证性分析显示了一致的结果。总而言之，功能连接到不同大规模网络的更高分离支持了阿尔茨海默病的认知弹性。
Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease.Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer's disease and 184 amyloid-negative controls.In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer's disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results.In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease.