焦虑作为阿尔茨海默病相关神经退行早期表现的网络定位
Network Localization of Anxiety as an Early Manifestation of Alzheimer's Disease-related Neurodegeneration
目的 焦虑是临床前阿尔茨海默病（AD）中突出的神经精神症状，但连接焦虑与AD的神经环路尚未被阐明。我们评估了临床前AD中的焦虑是否与AD相关神经退行性变独立相关，并定位于一个共同的焦虑网络。方法 在具有3T MRI和淀粉样蛋白β PET的认知正常（CU）老年人（N=1,775）中，我们检验了一个既有的AD相关萎缩网络是否与焦虑（STAI-6）相关。随后，使用萎缩网络映射（ANM），该方法将个体皮层萎缩模式映射到规范功能连接组（N=1000）上，我们推导出一个焦虑网络。我们检验了其1）与AD网络以及与源自病灶和神经调控数据的因果焦虑网络的空间收敛性，2）相对于抑郁的特异性，3）在来自AD和帕金森病独立队列样本中的可推广性（总n=878），以及4）与纵向结局的关联。结果 在CU老年人中，更大的AD网络萎缩与更高的焦虑相关，且独立于抑郁、认知、皮层萎缩和淀粉样蛋白负荷。焦虑定位于一个与AD网络（r=0.74，p=0.04）和因果焦虑网络（r=0.72，p=0.02）高度相似的网络。这种收敛性跨越AD连续谱并延伸至帕金森病队列，且相对于抑郁为焦虑所特有。更大的焦虑网络萎缩与4.6年间的认知下降相关。结论 焦虑定位于一个类似于AD相关萎缩网络的脑环路，在AD连续谱中保持一致，并可能延伸至AD之外。这些发现支持焦虑作为早期AD相关神经退行性变的独立标志物。
把焦虑映射到与阿尔茨海默病萎缩网络高度重合的脑网络，为早期神经退行提供独立于抑郁的影像线索。
Objective Anxiety is a prominent neuropsychiatric symptom in preclinical Alzheimer's disease (AD), but the neural circuitry linking anxiety and AD remains uncharacterized. We assessed whether anxiety in preclinical AD is independently associated with AD-related neurodegeneration and localizes to a common anxiety network. Methods In cognitively unimpaired (CU) older adults with 3T MRI and amyloid-beta PET (N=1,775), we examined whether an established AD-related atrophy network is associated with anxiety (STAI-6). Then, using Atrophy Network Mapping (ANM), which maps individual cortical atrophy patterns onto a normative functional connectome (N=1000), we derived an anxiety network. We tested its 1) spatial convergence with the AD network and with a causal anxiety network derived from lesion and neuromodulation data, 2) specificity relative to depression, 3) generalizability in samples from independent cohorts with AD and Parkinson's disease (total n=878), and 4) association with longitudinal outcomes. Results In CU older adults, greater AD-network atrophy was associated with higher anxiety, independent of depression, cognition, cortical atrophy, and amyloid burden. Anxiety localized to a network closely resembling the AD network (r=0.74, p=0.04) and the causal anxiety network (r=0.72, p=0.02). This convergence extended across the AD continuum and to the Parkinson's disease cohort and was specific to anxiety relative to depression. Greater anxiety-network atrophy was associated with cognitive decline over 4.6 years. Conclusion Anxiety localizes to a brain circuit resembling the AD-related atrophy network, is consistent across the AD continuum and may extend beyond AD. These findings support anxiety as an independent marker of early AD-related neurodegeneration.
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来源：bioRxiv · Neuroscience · biorxiv.org