Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 1724, New Orleans, LA, 70112, USA.
Department of Neurology, Center for Clinical Neurosciences, School of Medicine, Tulane University, New Orleans, LA, USA.
Geroscience. 2022 Jun;44(3):1479-1488. doi: 10.1007/s11357-022-00545-z. Epub 2022 Mar 20.
We examined the interactions between educational attainment and genetic susceptibility on dementia risk among adults over 60 years old. A total of 174,161 participants were free of dementia at baseline. The APOE ε4-related genetic risk was evaluated by the number of APOE ε4 alleles. The overall genetic susceptibility of dementia was evaluated by polygenetic risk score (PRS). Cox proportional hazards models were used to estimate the association between educational attainment and incident dementia. During a median of 8.9 years of follow-up, a total of 1482 incident cases of dementia were documented. After adjustment for covariates, we found that low education attainment was significantly associated with higher dementia risk in the APOE ε4 carriers, and such relation appeared to be stronger with the increasing number of ε4 alleles. In contrast, educational attainment was not associated with dementia risk in non-APOE ε4 carriers (P for multiplicative interaction = 0.006). In addition, we observed that the dementia risk associated with a combination of low educational attainment and high APOE ε4-related genetic risk was more than the addition of the risk associated with each of these factors (P for additive interaction < 0.001). We found similar significant interactions between educational attainment and PRS on both the multiplicative and additive scales on the dementia risk, mainly driven by the APOE genotype. These data indicate that higher educational attainment in early life may attenuate the risk for dementia, particularly among people with high genetic predisposition.
我们研究了受教育程度和遗传易感性在 60 岁以上成年人患痴呆症风险中的相互作用。共有 174161 名参与者在基线时无痴呆症。APOE ε4 相关的遗传风险通过 APOE ε4 等位基因的数量来评估。痴呆症的整体遗传易感性通过多基因风险评分（PRS）来评估。使用 Cox 比例风险模型来估计受教育程度与新发痴呆症之间的关联。在中位数为 8.9 年的随访期间，共记录到 1482 例新发痴呆症病例。在调整了协变量后，我们发现低教育程度与 APOE ε4 携带者发生痴呆症的风险显著相关，而且这种关系随着 ε4 等位基因数量的增加而变得更强。相比之下，教育程度与非 APOE ε4 携带者的痴呆症风险无关（乘法交互作用 P 值=0.006）。此外，我们观察到低教育程度和高 APOE ε4 相关遗传风险相结合与这两个因素各自的风险相关联所导致的痴呆症风险增加有关（加法交互作用 P 值<0.001）。我们在乘法和加法尺度上都发现了受教育程度和 PRS 与痴呆症风险之间的类似显著交互作用，主要由 APOE 基因型驱动。这些数据表明，早年的高教育程度可能会降低痴呆症的风险，尤其是在遗传易感性较高的人群中。
