生命的本质8，2型糖尿病和痴呆症的多基因风险：来自英国生物库的证据
Life's Essential 8, Polygenic Risk for Type 2 Diabetes, and Dementia: Evidence from the UK Biobank.
摘要(中文译文)
目前尚不清楚坚持健康指南能否改变2型糖尿病多基因风险评分（PRS）与痴呆之间的关联。本研究旨在探讨2型糖尿病PRS、生命必需8项（LE8）指标与痴呆之间的相互关系。我们纳入了2006年至2010年间年龄≥40岁的437,732名英国生物银行参与者。2型糖尿病PRS通过累加加权遗传变异效应计算。截至2022年12月，通过登记记录识别新发的全因痴呆和特定病因痴呆。LE8评分分为低水平与中高水平。应用Cox回归和限制性立方样条进行分析。在平均13.27年（标准差=2.27）的随访期间，9425名参与者发生痴呆。观察到PRS与血管性痴呆之间存在剂量-反应关系，风险在超过第95百分位数后急剧上升。在2型糖尿病PRS的所有取值范围内，LE8低水平个体的全因痴呆风险始终高于LE8中高水平个体。ε4占痴呆人群归因风险的35%以上，而2型糖尿病PRS仅贡献1%。即使考虑ε4后，通过维持中高水平LE8行为组分，全因痴呆的人群归因风险仍可进一步降低5.91%至10.46%。2型糖尿病PRS与痴呆之间存在剂量-反应关系，尤其是血管性痴呆。坚持最佳LE8指标，尤其是行为组分，可能有助于跨遗传分层的痴呆预防。这些发现强调了多领域生活方式干预在痴呆预防中的重要性。
Abstract
It is unclear if adherence to healthy guidelines can modify the association between polygenic risk score (PRS) for type 2 diabetes and dementia. This study aimed to investigate interrelationships between PRS for type 2 diabetes, Life's Essential 8 (LE8) metrics, and dementia. We included 437,732 UK Biobank participants aged ≥40 years between 2006 and 2010. PRS for type 2 diabetes was calculated by summing weighted genetic variant effects. Incident all-cause and cause-specific dementias were identified using registry records up to December 2022. LE8 scores were classified as low vs. moderate-to-high levels. Cox regression and restricted cubic splines were applied. Over an average follow-up of 13.27 years (SD = 2.27), 9425 participants developed dementia. A dose-response relationship was observed between PRS and vascular dementia, with risk rising sharply beyond the 95th percentile. Individuals with low LE8 constantly showed a higher risk of all-cause dementia than those with moderate-to-high LE8 across all values of PRS for type 2 diabetes. ε4 accounted for more than 35% of the population-attributable risk of dementia, whereas the PRS for type 2 diabetes contributed only 1%. The population-attributable risk of all-cause dementia could be further reduced by 5.91% to 10.46% through maintaining moderate-to-high LE8 behavioral components, even after considering ε4. A dose-response relationship exists between PRS for type 2 diabetes and dementia, particularly vascular dementia. Adherence to optimal LE8 metrics, particularly behavioral components, may contribute to dementia prevention across genetic strata. These findings highlight the importance of multidomain lifestyle interventions in dementia prevention.
如何引用
AMA
Yuanjing Li, Örjan Ekblom, Bikram Bucha, Ariana Cojocari, Hui-Xin Wang, Rui Wang. Life's Essential 8, Polygenic Risk for Type 2 Diabetes, and Dementia: Evidence from the UK Biobank.. Nutrients. 2026; doi:10.3390/nu18132080.
APA
Yuanjing Li, Örjan Ekblom, Bikram Bucha, Ariana Cojocari, Hui-Xin Wang, Rui Wang (2026). Life's Essential 8, Polygenic Risk for Type 2 Diabetes, and Dementia: Evidence from the UK Biobank.. Nutrients. https://doi.org/10.3390/nu18132080
GB/T 7714
Yuanjing Li, Örjan Ekblom, Bikram Bucha, Ariana Cojocari, Hui-Xin Wang, Rui Wang. Life's Essential 8, Polygenic Risk for Type 2 Diabetes, and Dementia: Evidence from the UK Biobank.[J]. Nutrients, 2026 doi:10.3390/nu18132080.
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