Mijalkov Mite, Veréb Dániel, Canal-Garcia Anna, Volpe Giovanni, Pereira Joana B
Neuro Division, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Physics, Goteborg University, Gotebörg, Sweden.
Neurosci Insights. 2023 Mar 29;18:26331055231161625. doi: 10.1177/26331055231161625. eCollection 2023.
Several studies have shown that amyloid-β (Aβ) deposition below the clinically relevant cut-off levels is associated with subtle changes in cognitive function and increases the risk of developing future Alzheimer's disease (AD). Although functional MRI is sensitive to early alterations occurring during AD, sub-threshold changes in Aβ levels have not been linked to functional connectivity measures. This study aimed to apply directed functional connectivity to identify early changes in network function in cognitively unimpaired participants who, at baseline, exhibit Aβ accumulation below the clinically relevant threshold. To this end, we analyzed baseline functional MRI data from 113 cognitively unimpaired participants of the Alzheimer's Disease Neuroimaging Initiative cohort who underwent at least one F-florbetapir-PET after the baseline scan. Using the longitudinal PET data, we classified these participants as Aβ negative (Aβ-) non-accumulators (n = 46) and Aβ- accumulators (n = 31). We also included 36 individuals who were amyloid-positive (Aβ+) at baseline and continued to accumulate Aβ (Aβ+ accumulators). For each participant, we calculated whole-brain directed functional connectivity networks using our own anti-symmetric correlation method and evaluated their global and nodal properties using measures of network segregation (clustering coefficient) and integration (global efficiency). When compared to Aβ- non-accumulators, the Aβ- accumulators showed lower global clustering coefficient. Moreover, the Aβ+ accumulator group exhibited reduced global efficiency and clustering coefficient, which at the nodal level mainly affected the superior frontal gyrus, anterior cingulate cortex, and caudate nucleus. In Aβ- accumulators, global measures were associated with lower baseline regional PET uptake values, as well as higher scores on the Modified Preclinical Alzheimer Cognitive Composite. Our findings indicate that directed connectivity network properties are sensitive to subtle changes occurring in individuals who have not yet reached the threshold for Aβ positivity, which makes them a potentially viable marker to detect negative downstream effects of very early Aβ pathology.
多项研究表明，淀粉样蛋白β（Aβ）沉积低于临床相关临界水平与认知功能的细微变化相关，并增加未来患阿尔茨海默病（AD）的风险。尽管功能磁共振成像对AD期间发生的早期改变敏感，但Aβ水平的亚阈值变化尚未与功能连接测量相关联。本研究旨在应用定向功能连接来识别认知未受损参与者的网络功能早期变化，这些参与者在基线时表现出低于临床相关阈值的Aβ积累。为此，我们分析了来自阿尔茨海默病神经影像倡议队列的113名认知未受损参与者的基线功能磁共振成像数据，这些参与者在基线扫描后至少接受了一次F-氟比他哌PET检查。利用纵向PET数据，我们将这些参与者分为Aβ阴性（Aβ-）非积累者（n = 46）和Aβ-积累者（n = 31）。我们还纳入了36名在基线时淀粉样蛋白阳性（Aβ+）并持续积累Aβ的个体（Aβ+积累者）。对于每个参与者，我们使用我们自己的反对称相关方法计算全脑定向功能连接网络，并使用网络分离（聚类系数）和整合（全局效率）测量来评估其全局和节点属性。与Aβ-非积累者相比，Aβ-积累者的全局聚类系数较低。此外，Aβ+积累者组的全局效率和聚类系数降低，在节点水平上主要影响额上回、前扣带回皮质和尾状核。在Aβ-积累者中，全局测量与较低的基线区域PET摄取值以及改良的临床前阿尔茨海默病认知综合评分较高相关。我们的研究结果表明，定向连接网络属性对尚未达到Aβ阳性阈值的个体中发生的细微变化敏感，这使其成为检测非常早期Aβ病理学负面下游效应的潜在可行标志物。
