Akbarian Niki, Ebrahimi Mahbod, Dos Santos Fernanda C, Afjeh Sara Sadat, Abdelhack Mohamed, Sanches Marcos, Diaconescu Andreea O, Rajji Tarek K, Felsky Daniel, Zai Clement C, Kennedy James L
Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
Behav Sci (Basel). 2024 Sep 29;14(10):876. doi: 10.3390/bs14100876.
Cognitive decline is a public health concern affecting about 50 million individuals worldwide. Neuroticism, defined as the trait disposition to experience intense and frequent negative emotions, has been associated with an increased risk of late-life cognitive decline. However, the underlying biological mechanisms of this association remain unknown. This study investigated the relationship between genetic predisposition to neuroticism, computed by polygenic risk score (PRS), and performance in cognitive domains of reasoning, processing speed, visual attention, and memory in individuals over age 60. The sample consisted of UK Biobank participants with genetic and cognitive data available (N = 10,737, 4686 females; mean age = 63.4 ± 2.71). The cognitive domains were assessed at baseline for all participants and seven years later for a subset (N = 645, 262 females; mean age = 62.9 ± 2.44). Neuroticism PRS was not associated cross-sectionally with cognitive measures ( > 0.05). However, the trajectory of change for processing speed (β = 0.020; 95% CI = [0.006, 0.035], adjusted = 0.0148), visual attention (β = -0.077; 95% CI = [-0.0985, -0.0553], adjusted = 1.412 × 10), and memory (β = -0.033; 95% CI = [-0.0535, -0.0131], adjusted = 0.005) was significantly associated with neuroticism PRS. Specifically, a higher genetic predisposition to neuroticism was associated with less decline in these cognitive domains. This trend persisted after sensitivity analysis using complete cases, although it only remained nominally significant for visual attention.
认知能力下降是一个影响全球约5000万人的公共卫生问题。神经质被定义为体验强烈且频繁负面情绪的特质倾向，它与晚年认知能力下降风险增加有关。然而，这种关联的潜在生物学机制仍不清楚。本研究调查了通过多基因风险评分（PRS）计算的神经质遗传易感性与60岁以上个体在推理、处理速度、视觉注意力和记忆等认知领域表现之间的关系。样本包括有可用基因和认知数据的英国生物银行参与者（N = 10737，4686名女性；平均年龄 = 63.4 ± 2.71）。所有参与者在基线时评估认知领域，七年后对一个子集（N = 645，262名女性；平均年龄 = 62.9 ± 2.44）进行评估。神经质PRS与认知测量在横断面分析中无关联（> 0.05）。然而，处理速度（β = 0.020；95%置信区间 = [0.006, 0.035]，校正 = 0.0148）、视觉注意力（β = -0.077；95%置信区间 = [-0.0985, -0.0553]，校正 = 1.412 × 10）和记忆（β = -0.033；95%置信区间 = [-0.0535, -0.0131]，校正 = 0.005）的变化轨迹与神经质PRS显著相关。具体而言，较高的神经质遗传易感性与这些认知领域中较小的下降相关。在使用完整病例进行敏感性分析后，这种趋势仍然存在，尽管仅在视觉注意力方面名义上仍显著。
