1 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK2 Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, UK
3 Institute of Neurology, University College London, London, WC1N 3BG, UK.
Brain. 2014 Aug;137(Pt 8):2303-11. doi: 10.1093/brain/awu143. Epub 2014 Jun 11.
Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short-term memory associated with GBA mutation and with Parkinson's disease. Identification of the specific pattern of cognitive impairment in GBA mutation versus Parkinson's disease is potentially important as it might help to identify individuals at risk of developing Parkinson's disease.
携带溶酶体酶葡萄糖脑苷脂酶 (GBA) 基因突变的个体患帕金森病伴认知缺陷的风险显著增加。我们研究了视觉短期记忆障碍是否也存在于 GBA 阳性个体中，包括患有和不患有帕金森病的个体。使用序列顺序任务测量视觉工作记忆的准确性，在该任务中，参与者观察四个条形，每个条形的颜色和方向均不同，依次显示在屏幕中心。之后，要求他们调整彩色探针条的方向，使其与序列中同色条的方向匹配。额外的注意力“过滤”条件测试了患者选择性编码四个条形之一而忽略其他条形的能力。使用相同刺激的感觉运动任务控制了感知和运动因素。与健康对照组相比，GBA 阳性个体（无论是否患有帕金森病）以及 GBA 阴性帕金森病患者的记忆精度均存在显著缺陷。患有帕金森病的 GBA 阳性个体的记忆召回最差。尽管所有组在视觉短期记忆方面均受损，但与 GBA 突变和帕金森病相关的错误来源存在双重分离。在 GBA 阳性个体中观察到的缺陷，无论其是否患有帕金森病，都可以通过记忆中其他项目特征的系统干扰增加来解释：错误绑定错误。相比之下，无论 GBA 状态如何，帕金森病患者的损伤都可以通过随机反应的增加来解释。GBA 阳性且患有帕金森病的个体同时患有这两种类型的错误，表现出最差的表现。这些发现为与 GBA 突变和帕金森病相关的视觉短期记忆领域中的可分离特征缺陷提供了证据。在 GBA 突变与帕金森病中识别认知损伤的特定模式可能很重要，因为它可能有助于识别有患帕金森病风险的个体。
