INTRODUCTION: Current findings of the relative influence of social isolation and loneliness on dementia are contradictory, and the potential neurobiological mechanisms are unclear. METHODS: We utilized the UK Biobank to investigate the relationships of social isolation and loneliness with dementia (n = 462,619). Neuroanatomical correlates were identified in a subset of participants (n = 32,263). The transcriptomic signatures of related brain changes were characterized by gene enrichment analysis. RESULTS: After full adjustment, social isolation but not loneliness was associated with dementia (hazard ratio: 1.28, 95% confidence interval: 1.17-1.39). Isolated individuals had reduced gray matter volumes in temporal, frontal, occipital and subcortical regions (e.g., hippocampus and amygdala). Relevant brain changes were spatially correlated with genes involved in mitochondrial dysfunction and oxidative phosphorylation, and down-regulated Alzheimer's disease-related genes. DISCUSSION: Social isolation is an independent risk factor for dementia, which could be partly explained by related structural changes coupling with altered molecular functions.

中文翻译：

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社会孤立、孤独和全因痴呆：英国生物银行队列的纵向和成像遗传研究

引言：目前关于社会孤立和孤独对痴呆症的相对影响的研究结果是相互矛盾的，潜在的神经生物学机制尚不清楚。方法：我们利用英国生物银行来调查社会孤立和孤独与痴呆的关系（n = 462,619）。在一部分参与者（n = 32,263）中确定了神经解剖学相关性。相关大脑变化的转录组特征通过基因富集分析进行表征。结果：完全调整后，社交孤立而非孤独与痴呆症相关（风险比：1.28，95% 置信区间：1.17-1.39）。孤立的个体在颞叶、额叶、枕叶和皮层下区域（例如，海马和杏仁核）的灰质体积减少。相关的大脑变化与参与线粒体功能障碍和氧化磷酸化的基因在空间上相关，并下调阿尔茨海默病相关基因。讨论：社会孤立是痴呆症的一个独立危险因素，部分原因是相关的结构变化与分子功能的改变相结合。