Institute of Cognitive Neuroscience, University College London, London WC1N 3AZ, United Kingdom;
Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom.
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):2228-2233. doi: 10.1073/pnas.1712268115. Epub 2018 Feb 12.
The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults. We show that older adults with reduced structural LC integrity show poorer subsequent memory. This effect is more pronounced for emotionally negative events, in accord with a greater role for noradrenergic modulation in encoding salient or aversive events. In addition, we found that salient stimuli led to greater pupil diameters, consistent with increased LC activation during the encoding of such events. Our study presents novel evidence that a decrement in noradrenergic modulation impacts on specific components of cognition in healthy older adults. The findings provide a strong motivation for further investigation of the effects of altered LC integrity in pathological aging.
蓝斑（LC）是大脑中去甲肾上腺素的主要来源。LC 的完整性在健康的老年人个体之间有很大差异，据推测，这与衰老过程中认知功能的改变有关。在这里，我们使用一种已知易受去甲肾上腺素调节的偶然记忆任务来检验这一假设。我们使用 MRI 神经黑色素（NM）成像来评估 LC 的结构完整性，并使用瞳孔测量法作为 LC 激活的一个可能指标，分别在年轻和老年成年人中进行评估。我们发现，LC 结构完整性降低的老年人随后的记忆能力较差。对于情绪负面的事件，这种影响更为明显，这与去甲肾上腺素调节在编码突出或厌恶事件中的更大作用一致。此外，我们发现，突出的刺激会导致瞳孔直径增大，这与在编码此类事件时 LC 激活增加一致。我们的研究提供了新的证据，表明去甲肾上腺素调节的降低会影响健康老年人认知的特定成分。这些发现为进一步研究病理性衰老中 LC 完整性改变的影响提供了强有力的动力。
