Internetwork Connectivity Predicts Cognitive Decline in Parkinson's and Is Altered by Genetic Variants.
Internetwork Connectivity Predicts Cognitive Decline in Parkinson's and Is Altered by Genetic Variants.
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DOI：
10.3389/fnagi.2022.853029
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发表时间：
2022
影响因子：
4.8
通讯作者：
Harrington DL
中科院分区：
文献类型：
--
作者：
Wei X;Shen Q;Litvan I;Huang M;Lee RR;Harrington DL
在帕金森病（PD）中，大脑功能的变化发生在显着的认知症状出现之前数年，但维持认知和预测未来认知下降的核心大规模网络却知之甚少。本研究调查了63名认知正常PD（PDCN）和43名健康对照者的视觉（VN），前后默认模式（aDMN，pDMN），左/右额顶叶（LFPN，RFPN）和显著性（SN）网络的网络间功能连接，这些人接受了静息态功能MRI。网络间耦合拓扑的功能相关性通过其与各组基线认知表现和PDCN子样本中2年认知变化的相关性进行测试。为了解开神经认知功能的异质性，我们还研究了α-突触核蛋白（SNCA）和微管相关蛋白tau（MAPT）变体是否会改变网络间的连接和/或加速认知能力的下降。我们发现，PDCN中的网络间连接在很大程度上得到了保留，除了减少的pDMN-RFPN/LFPN耦合，这与较差的基线整体认知相关。保留的网络间耦合也与特定领域的认知相关，但两组不同。在PDCN中，更强的正网络间耦合拓扑结构与基线时更好的认知相关，这表明了一种补偿机制，该机制源于支持健康对照认知的网络部署效率较低。然而，更强的正网络间耦合拓扑结构通常预测更大的纵向下降，在大多数认知领域，这表明它们是神经元脆弱性的替代标记。在这方面，更强的aDMN-SN、LFPN-SN和/或LFPN-VN连接预测注意力、工作记忆、执行功能和视觉认知的纵向下降，这是痴呆的风险因素。一些互联网络拓扑结构的耦合强度改变了遗传变异。SNCA风险等位基因的PDCN携带者显示SN和VN/pDMN之间的放大的连接关系，这支持健康对照的认知，但加强了pDMN-RFPN连接，这保持了纵向的视觉记忆。PDCN携带者的MAPT风险等位基因表现出更大的纵向下降的工作记忆和增加VN-LFPN连接，这反过来又预示着更大的下降，在视觉空间处理。总的来说，这些结果表明，认知是通过大规模网络间通信的功能重构来维持的，这些功能重构部分地被遗传风险因素改变，并预测未来特定领域的认知进展。
In Parkinson’s disease (PD) functional changes in the brain occur years before significant cognitive symptoms manifest yet core large-scale networks that maintain cognition and predict future cognitive decline are poorly understood. The present study investigated internetwork functional connectivity of visual (VN), anterior and posterior default mode (aDMN, pDMN), left/right frontoparietal (LFPN, RFPN), and salience (SN) networks in 63 cognitively normal PD (PDCN) and 43 healthy controls who underwent resting-state functional MRI. The functional relevance of internetwork coupling topologies was tested by their correlations with baseline cognitive performance in each group and with 2-year cognitive changes in a PDCN subsample. To disentangle heterogeneity in neurocognitive functioning, we also studied whether α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) variants alter internetwork connectivity and/or accelerate cognitive decline. We found that internetwork connectivity was largely preserved in PDCN, except for reduced pDMN-RFPN/LFPN couplings, which correlated with poorer baseline global cognition. Preserved internetwork couplings also correlated with domain-specific cognition but differently for the two groups. In PDCN, stronger positive internetwork coupling topologies correlated with better cognition at baseline, suggesting a compensatory mechanism arising from less effective deployment of networks that supported cognition in healthy controls. However, stronger positive internetwork coupling topologies typically predicted greater longitudinal decline in most cognitive domains, suggesting that they were surrogate markers of neuronal vulnerability. In this regard, stronger aDMN-SN, LFPN-SN, and/or LFPN-VN connectivity predicted longitudinal decline in attention, working memory, executive functioning, and visual cognition, which is a risk factor for dementia. Coupling strengths of some internetwork topologies were altered by genetic variants. PDCN carriers of the SNCA risk allele showed amplified anticorrelations between the SN and the VN/pDMN, which supported cognition in healthy controls, but strengthened pDMN-RFPN connectivity, which maintained visual memory longitudinally. PDCN carriers of the MAPT risk allele showed greater longitudinal decline in working memory and increased VN-LFPN connectivity, which in turn predicted greater decline in visuospatial processing. Collectively, the results suggest that cognition is maintained by functional reconfiguration of large-scale internetwork communications, which are partly altered by genetic risk factors and predict future domain-specific cognitive progression.
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